How to Grow Taller

Grow Taller 4 Idiots

Darwin is the creator of this system. He was once a victim of shortness and is well conversant with the daily lonely and depressed life. His techniques have been tested and tried by thousands of people and have proven to work. His product can, therefore, be trusted as he is the living proof of the results of his techniques. This product has the following features; Formulas for how you can make a growth cocktail at home, without having to purchase an expensive drink. Categorically outlined stretching exercises that are fully illustrated to show you what you should do. Height increase potential is much likely to be observed in younger people, however, the old should also see a noticeable difference after going through the system. If you are a short guy, and you are troubled at work, school or even at home and you would wish to gain more height, this book guide is the solution for you. By following the methods and techniques highlighted in it, you will be able to gain your desirable heights. The first observations you will be able to notice in just a couple of weeks! This product is presented to you in a digital format; an e-book that is PDF. The system is designed to help those who wish to grow taller, both men and women of all ages. More here...

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Highly Recommended

I've really worked on the chapters in this ebook and can only say that if you put in the time you will never revert back to your old methods.

Overall my first impression of this ebook is good. I think it was sincerely written and looks to be very helpful.

Effects of growth hormone and insulinlike growth factor 1 deficiency on ageing and longevity

Abstract Present knowledge on the effects of growth hormone (GH) insulin-like growth hormone (IGF)1 deficiency on ageing and lifespan are reviewed. Evidence is presented that isolated GH deficiency (IGHD), multiple pituitary hormone deficiencies (MPHD) including GH, as well as primary IGF1 deficiency (GH resistance, Laron syndrome) present signs of early ageing such as thin and wrinkled skin, obesity, hyperglycemia and osteoporosis. These changes do not seem to affect the lifespan, as patients reach old age. Animal models of genetic MPHD (Ames and Snell mice) and GH receptor knockout mice (primary IGF1 deficiency) also have a statistically significant higher longevity compared to normal controls. On the contrary, mice transgenic for GH and acromegalic patients secreting large amounts of GH have premature death. In conclusion longstanding GH IGF1 deficiency affects several parameters of the ageing process without impairing lifespan, and as shown in animal models prolongs longevity. In...

Congenital multiple pituitary hormone deficiencies MPHD including growth hormone

In 1988, we had the opportunity to examine six out of 10 living dwarfed patients, part of 24 related patients recorded on the island of Krk in the Adriatic Sea. They belong to two villages near to each other, and were known to have existed since the end of the 19th century (Hanhart 1925). DNA from these patients revealed a mutation in the PROP1 gene (a transcription factor) causing MPHD (thyroid-stimulating hormone, prolactin, luteinizing hormone, follicle-stimulating hormone and GH deficiencies) (Krzisnik et al 1999). They were treated by thyroxine, which some took irregularly. Only one 14 year old girl received GH. The five adult patients ranged from 47 to 68 years (3 males, 2 females). In addition to short stature (120 139 cm), they were obese, sexually immature and had a very wrinkled skin (Fig. 1). Notably the patients did not have any grey hair despite their advanced adult age. This was also seen on a picture of a 70 year old patient found on his tombstone (Fig 2). The...

Secondary sexual characteristics absent short stature

In pure Turner syndrome the chromosome complement is 45X and here a syndrome of short stature and ovarian failure lead to the typical features of this syndrome. These children usually present in the teenage years, either because of failure of development of secondary sexual characteristics or more commonly referred from growth clinics for induction of secondary sexual characteristics. Attempts to improve height have proved difficult to achieve.

Growth hormone axis

In the acute phase circulating levels of growth hormone (GH) are elevated. The peak GH levels as well as interpulse concentrations are high (Ross et al 1991, Voerman et al 1992) and the GH pulse frequency is increased. Serum insulin-like growth factor (IGF)1 concentrations are low, (Ross et al 1991). The combination of high GH levels and low IGF1 levels has been interpreted as resistance to GH, which may be related to decreased GH receptor expression (Hermansson et al 1997). The other GH-dependent peptides IGF binding protein (IGFBP)3 and acid labile subunit (ALS) are also decreased in the circulation (Baxter 1997, Timmins et al 1996), preceded by a drop in the GH binding protein (GHBP). Circulating levels of the small IGFBPs such as IGFBP1, IGFBP2 and IGFBP6 are elevated (Baxter et al 1998, Rodrigues-Arnao et al 1996). It has been suggested that these changes are brought about by the effects of cytokines such as tumour necrosis factor (TNF)a, interleukin (IL)1 and IL6. The hypothesis...

Contemporary Endocrinology

Mendelson, 2000 Sports Endocrinology, edited by Michelle P. Warren and Naama W. Constantni, 2000 Gene Engineering in Endocrinology, edited by Margaret A. Shupnik, 2000 Endocrinology of Aging, edited by John E. Morley and Lucreta van den Berg, 2000 Human Growth Hormone Research and Clinical Practice, edited by Roy G. Smith and

Endocrine aspects of healthy ageing in men

Frailty is characterized by generalized weakness, impaired mobility and balance and poor endurance. Loss of muscle strength is an important factor in the process of frailty, and is the limiting factor for an individual's chances of living an independent life until death. In men, several hormonal systems show a decline in activity during ageing. Serum bioavailable testosterone and oestradiol, dehydroepiandrosterone and its sulfate, and growth hormone and insulin-like growth factor 1 concentrations all decrease during ageing in men. Physical changes during ageing have been considered physiologic, but there is evidence that some of these changes are related to this decline in hormonal activity. Studies on hormone administration in the elderly appear to be promising. However, until now, hormone replacement has not yet been proven to be beneficial and safe.

Why offlabel use of drug should be avoided

In recent years, the government has attempted to regulate off-label promotion in response to subtle efforts by industry to conceal direct incentive payments to clinicians, questionable consultant contracts, and all-expense paid 'educational' trips. The alleged deceptive off-label marketing of gabapentin (Neurontin) was settled for 468 million.1 A more recent example is human growth hormone, which was never approved either to spur growth in children who were not hormone-deficient, or to slow the aging process in adults. Yet it has been widely prescribed for both indications.

HIVSpecific Diseases Lipodystrophy

Lipodystrophy is extremely difficult to manage, as specific treatments including rosiglitazone do not appear to be effective. Switching therapy from a thymidine analog to abacavir has shown modest improvement but not resolution of lipodystrophy. Recombinant growth hormone may

Delirium And Intoxications

Criteria for probable sporadic CJD The clinical diagnosis of CJD is currently based on the combination of progressive dementia, myoclonus, and multifocal neurological dysfunction, associated with a characteristic periodic electroencephalogram (EEG). However, new variant CJD, most growth hormone-related iatrogenic cases, and up to 40 of sporadic cases are not noted to have the characteristic EEG appearance. This hampers clinical diagnosis, and hence surveillance, and illustrates the need for additional diagnostic tests. Proposed criteria for probable sporadic CJD

Characterization of Protein Ligand Binding Sites

Other approaches are also available to determine the arrangements of residues in a binding site. One involves a laborious process of systematic derivatization and mutation of residues of a peptide or protein ligand, in order to determine the effects of these changes on a biological response, which then provide spatial information about the binding surface and the characteristics of that surface. One version of this process that is widely used for detecting and analyzing binding interfaces is that of alanine scanning mutagenesis 40, 41, 42, 43 . This technique, which was first applied to the human growth hormone and its receptor, consists of the systematic mutation of surface residues to Ala, with concomitant measurement of the effect on the binding constant for the protein-ligand interaction 3 . The seminal work on the human growth hormone receptor complex showed that a few hydrophobic interactions contribute a significant portion of the binding affinity in this largely hydrophilic...

Genetic Engineering and Society

Policies were used to restrict immigration of certain Asian and European populations that were termed genetically inferior. Eugenics had its ultimate expression when it provided the scientific basis for the racial policies of the Nazis before and during World War II. Where the capability exists, so will the temptation. Will parents seek to amplify the gene for human growth hormone in their offspring so that their children could become heftier football linemen or taller basketball players The ability to select the gender of one's offspring by amniocentesis and abortion is already causing problems in some cultures.

Trials to determine best chemotherapy regimen

Chemotherapy to reduce the dose of cranial-spinal radiation. This effort is due to the very real risk of long-term deficits produced by the radiation to the cranial-spinal axis. There have been a number of studies that indicate that 30-35 Gy to the whole brain can produce deficiencies, including growth hormone, thyroid deficiencies and, more significantly, intellectual deficit, especially in children less than 7 years old.

Iatrogenic Transmission Of Creutzfeldtjakob Disease

Over the last three decades, approximately 270 cases of iatrogenic CJD have been observed. 11 By far, the most frequently involved medical interventions were the surgical use of dura mater grafts (114 cases) and treatment with pituitary-derived human growth hormone (139 cases). In a few cases each, treatment with pituitary-derived gonadotropin, corneal transplantation, or the use of neurosurgical equipment such as stereotactic electrodes was implicated.

Diagnostic Potential Of The M129v Polymorphism

Although all vCJD cases investigated so far have been found to be M M homozygous at codon 129, the deferral of such potentially higher risk donors from blood or plasma donation is not feasible based on the already strained supply of these products and the large proportion of the population displaying this genotype. Also, any risk associated with the use of these products remains purely hypothetical at this point, and again there is mounting evidence against any risk being associated with their use. 14 However, for products carrying an identified level of risk and are needed in lower quantities, exclusion based on an identified genetic predisposition for disease development might be an option. Human growth hormone from cadaveric pituitary glands, a product that has historically led to many CJD transmissions, has already been replaced by recombinant versions of the product. Dura mater, another of the products implicated earlier, 11 is no longer in clinical use and has been widely...

Danger Transmission Mediated Through The Anaphylatoxic Peptides C3a And C5a

Several reports in the literature suggest AT effects that are independent of AT receptor ligation. This is particularly true for C3a and its degradation product C3adesArg. The latter is devoid of binding to C3aR however, similar to C3a, it can suppress LPS-induced cytokine production from tonsil-derived B cells and monocytes86-88. Further, C3adesArg stimulates pituitary cells to release prolactin, growth hormone, and adrenocorticotropic9. C3adesArg has also been termed acylation-stimulating protein (ASP) by one group referring to its role in triacylglycerol synthesis in human adipocytes90. All of the C3adesArg biology has been enigmatic, as it does not fit in our mechanistic understanding of biological functions as receptor mediated entities. Although a recent publication suggests that C5L2 may be the missing link, C3adesArg binding to this receptor

Structure Of Cytokine Receptor Complexes

The composition of cytokine receptor complexes varies considerably 11 . The simplest case is realized for growth hormone (GH) a member of the hematopoietin family (see Figure 3.1A). One GH molecule binds to two identical receptor (GHR) molecules 12 . Interestingly, two complete different interaction sites (site I and site II) of GH interact with nearly the same residues in the two GHR molecules. Binding of the two receptor molecules happens sequentially, site I of the GH molecules first contacts one receptor molecule, followed by the contact of site II of GH and a second GHR 12 .

Clinical Description

This rare condition is inherited as an autosomal recessive condition. The clinical picture is characterized by premature rupture of the membranes, extreme skin fragility and laxity, easy bruising, large fontanels, umbilical hernia, short stature and characteristic facies with epi-canthic folds, downslanting palpebral fissures, puffy eyelids, blue sclerae, and micrognathia. During childhood and puberty, increased bruising and severe skin fragility predominate the clinical picture. Wound healing is not delayed and initial scar formation is only minimal. 19 In older patients, however, more typical atrophic scarring with pigmentation is seen, probably because of repeated skin tearing and bruising. Joint hypermobility, although not obvious during the first years of life, seem to become more important with age. Fragility of internal tissues is an important feature during childhood, as is illustrated by spontaneous bladder rupture at the age of 5 years in two children with the...

Receptor Specific Nuclear Actions Genomic Actions

T3 binds to TR-a and TR-( resulting in nuclear gene expression. The receptors are ligand-regulatable transcription factors that recognize and interact with specific DNA sequences (thyroid hormone response elements) in the promoter region of target genes leading to consequent effects on transcription 95, 96 (fig. 5a). The transcriptional activity of target genes is either increased or decreased. Examples of target genes that are positively regulated by TH are fatty acid synthetase, growth hormone, lysosome silencer, malic enzyme, type I 5'-deiodinase and negative regulated epidermal growth factor receptor, prolactin, TSH, thyrotropin-releasing hormones, type II 5'-diodinase 96 The genomic effects have response times of hours to days. After TR binding to TH

Mechanisms of conjoint failure of the somatotropic and gonadal axes in ageing men

Endogenous growth hormone (GH) production falls by 50 every 7 years and bioavailable testosterone concentrations decline concomitantly by 12 15 every decade in ageing men. Despite this temporal parallelism, the neuroendocrine bases of the somatopause and gonadopause are not known. This knowledge deficit contrasts with the recent unfolding of new insights into the nature of oestrogen-dependent control of the GH insulin-like growth factor (IGF)1 axis in pre- and postmenopausal women. The present overview examines the postulate that the pathophysiology of somatopause and gonadopause in ageing men is bidirectionally linked. According to this broader thesis, hyposomatotropism accentuates Leydig cell steroidogenic failure and, conversely, progressive androgen deficiency exacerbates the decline in GH IGF1 output in ageing. Clinical features of ageing include variably impaired psychological well being, cognitive function and quality of life decreased libido and or sexual function...

Investigation and management of fetal growth disorder

The concept of symmetric and asymmetric IUGR have been taken to describe early onset (chromosomal genetic) and later onset (uteroplacental) IUGR respectively. Thus poor fetal growth before 24 weeks is more commonly associated with genetic and chromosomal abnormalities or fetal infection whereas after 24 weeks fetal growth is determined to a far greater extent by maternal influences and uteroplacental function. As ultrasound techniques have advanced, it has become clear that the symmetric asymmetric IUGR is somewhat of an oversimplification. The growth restriction thought to be inherent to chromosomal and genetic conditions may in fact be mediated by uteroplacental insufficiency hence severely growth restricted trisomy 18 babies in the third trimester frequently exhibit asymmetrical growth restriction with abnormal uteroplacental and fetal Doppler. Conversely, ultrasound assessment of fetuses with severe early onset uteroplacental insufficiency often reveals symmetrically reduced...

Appropriate Uses of Gene Therapy

How do researchers determine which disorders or traits warrant gene therapy Unfortunately, the distinction between gene therapy for disease genes and gene therapy to enhance desired traits, such as height or eye color, is not clear-cut. No one would argue that diseases that cause suffering, disability, and, potentially, death are good candidates for gene therapy. However, there is a fine line between what is considered a disease (such as the dwarfism disorder achondroplasia) and what is considered a trait in an otherwise healthy individual (such as short stature). Even though gene therapy for the correction of potentially socially unacceptable traits, or the enhancement of desirable ones, may improve the quality of life for an individual, some ethicists fear gene therapy for trait enhancement could negatively impact what society considers normal and thus promote increased discrimination toward those with the undesirable traits. As the function of many genes continue to be discovered,...

Intrauterine growth restriction

Ultrasound is the primary tool for monitoring growth in multiple pregnancies for two reasons. First, they are at high risk of intrauterine growth restriction (IUGR), with 25 of twins being small for gestational age at birth. In most cases IUGR will be discordant affecting one twin only. Second, abdominal palpation and symphysis-fundal height measurement are unreliable as indices of individual fetal growth as, instead, they reflect total intrauterine growth.

Twintwin transfusion syndrome

Chronic TTTS occurs in 15 of MC twins and is responsible for 15-20 of perinatal death in twins. The patho-physiology involves chronic net shunting of blood from the donor to recipient twin. The donor becomes growth restricted, oliguric and develops anhydramnios ('stuck twin') and the recipient becomes polyuric with polyhy-dramnios and can go on to develop cardiac sequelae and hydrops. TTTS usually presents in the mid- but sometimes the third trimester, with gross discordance in amniotic fluid volume, with polyhydramnios in the recipient's and oligohydramnios in the donor's sac. The usual placental configuration comprises unbalanced deep artery to vein anastomoses with absent or inadequate compensation along superficial anastomoses 44 . Thus Doppler detection of a compensatory artery-to-artery anastomosis antenatally substantially reduces the chance of developing TTTS, and where it does develop, predicts better prognosis 42,45 .

Mechanisms of Cell Damage

Lytic infections of neural cells cause regional destruction of brain or lysis of specific cell populations. Noncyto-pathic infections of neural cells also occur and lead to persistent infection with no disease or disorders without obvious histological changes. For example, neuroblastoma cells in culture infected with noncytopathic viruses such as rabies can show normal morphology growth rates and protein synthesis, but reduced synthesis of specific neu-rotransmitters or receptors. These have been termed 'luxury functions', although in vivo the ability of neurons to synthesize transmitters or receptors would hardly be considered a luxury. Analogous noncytopathic infection has been demonstrated in mice congenitally infected with lymphocytic choriomeningitis virus. Congenitally infected mice are usually 'runts', but recent studies have shown selective infection of cells of the anterior pituitary which normally generates growth hormone. The animals are actually pituitary dwarfs responsive...

Summary And Conclusions

L. monocytogenes has been recognized as a human pathogen for more than 50 yr. It primarily causes abortion, infections of the central nervous system or septicemia, mainly in certain well-defined high-risk groups, including immunocompromised persons and pregnant women. The widespread use of immunosuppressive medications for treatment of malignancy and management of organ transplantation, has expanded the immuno-compromised population at increased risk of listeriosis. Also consumer life styles have changed with less time for food preparation, more ready-to-eat, and take-away foods. Changes in food production and technology have led to the production of foods with long shelf life that are typical Listeria risk foods, because the bacteria have time to multiply, and the food does not undergo a listericidal process such as cooking before consumption. Increased mass production means outbreaks can change from being small and confined to a community or region, to large, affecting hundreds of...

Regulation Of The

Significantly decreased the creatine uptake rate but did not alter the CRT content (55- and 58-kDa bands). Creatine depletion from P-GPA supplementation increased creatine uptake capacity in the soleus and red gastrocnemius muscle, a change accompanied by 70-150 increases in CRT protein. However, the creatine uptake rate of white gastrocnemius muscle was unchanged, even though its CRT content increased by 230 , suggesting that total CRT content is unrelated to creatine uptake activity. It should be noted that unlike the previous study, this study determined the total rather than the plasma membrane content of the CRT. The relationship between creatine content and the levels of CRT remains unclear. In a human study, moderate supplementation with creatine increased creatine content of skeletal muscle without significant changes in levels of CRT protein or mRNA (Tarnopolsky et al., 2003). Disease states also affect the CRT content of skeletal and heart muscle. In humans, the CRT content...

Importance for Medicine and Industry

The ability to clone a gene is not only valuable for conducting biological research. Many important pharmaceutical drugs and industrial enzymes are produced from cloned genes. For example, insulin, clotting factors, human growth hormone, cytokines (cell growth stimulants), and several anticancer drugs in use are produced from cloned genes.

Long Acting Somatostatin Analogs

Effect of octreotide or placebo on hourly growth hormone (GH) levels in acromegaly. Mean percentage changes ( SE of basal values) of serum GH concentrations in patients with acromegaly treated with either 100 g octreotide subcutaneously every 8 h (n 52 a) or placebo (n 47 b) subcutaneously every 8 h. Blood was sampled before an injection and every hour for 8 subsequent h before treatment (baseline), at the end of wk 2 and 4 of treatment, and 4 wk after discontinuation of treatment (washout). Octreotide or placebo was administered just after the 0-h sampling. (Reproduced from Ezzat S, Snyder PJ, Young WF, et al. Octreotide treatment of acromegaly a randomized multicenter study. Ann Intern Med 1992 117 711-718.) Fig. 7. Effect of octreotide or placebo on hourly growth hormone (GH) levels in acromegaly. Mean percentage changes ( SE of basal values) of serum GH concentrations in patients with acromegaly treated with either 100 g octreotide subcutaneously every 8 h (n 52 a) or...

Duplications Of 17p112

Estimated prevalence of 1 20,000, is characterized by mental retardation, neurobehavioral abnormalities, sleep disorders, speech and motor delays, midface hypoplasia, short stature, and brachydactyly. 3 The same deletion is seen in 90 of patients. Only recently has it been recognized that a reciprocal duplication also exists. The dup(17)(p11.2p11.2) syndrome is characterized by borderline to mild mental retardation, behavioral problems, short stature, dental anomalies, normal facies, and lack of major organ malformations 4,5 This syndrome typifies a milder phenotype that was not recognized as a syndrome until connected to the microduplication.

Peptide Mapping Analysis

As in the case of amino acid analysis, a key factor influencing the success of peptide mapping experiments is the optimization and control of the conditions during enzymatic digestion. Ruggedness of this step of the analysis is influenced by many factors including temperature, pH, type of buffer used, purity and lot-to-lot consistency of the enzyme, length of digest, stability of the fragments and protein concentration. Low or inconsistent purity of the enzyme can lead to non-selective cleavage due to contamination by other endo and exoproteases. Care must be taken to assure that the peptide fragments are not lost during sample handling due to nonspecific adsorption to glass, filters or other surfaces, with which the sample may come in contact. The addition of surfactants may be necessary, particularly for hydrophobic proteins, to improve recoveries and consequently, reproducibility of the peptide maps. For large proteins, digestion conditions need to be optimized such that the...

Regulation Of Metabolism During Feeding And Fasting

When either growth hormone or glucocorticoids are present in excess for prolonged periods, diabetes mellitus often results. Approximately 30 of patients suffering from excess GH (acromegaly) and a similar percentage of persons suffering from Cushing's disease (excess gluco-corticoids) experience diabetes mellitus as a complication of their disease. Most of the others have some decrease in their ability to Growth hormone (I) intestinal hormones, especially glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), which are potent secretagogues for insulin. Finally, the beta cells respond directly to increased glucose and amino acids in arterial blood (see Chapter 41). During the postprandial period the concentration of insulin in peripheral blood may rise from a resting value of about 10 mUnits mL to perhaps as much as 50 mUnits mL. Glucagon secretion may also increase at this time in response to amino acids in arterial blood. Dietary amino acids may also...

Regulation Of The Jakstat Pathway Suppressors of Cytokine Signaling

Little is known about specificity within the SOCS family of proteins. To date, most studies of SOCS function have depended on the use of in vitro overexpression systems. These studies have shown that expression of SOCS-1 suppresses signaling in response to a variety of cytokines, including LIF, on-costatin M (OSM), IFNy, TPO, and growth hormone (GH) in addition to IL-6 (46,51,53,61-63). SOCS-3 expression also inhibits signaling in response to IL-6, LIF, GH, and IFN-y (54,61,63,64) in addition to blocking leptin-induced signal transduction (65). CIS expression suppresses cell proliferation in response to IL-3 and EPO cell proliferation (50). However, SOCS-2 has yet to be shown to inhibit cytokine signal transduction pathways.

C Capillary Electrophoresis

It is clear that CE is an indispensable technique for protein analysis as evidenced by its extensive use in various facets of drug development from in process control during fermentation to stability monitoring of protein drug products. Although CE is still primarily being used in a research mode, its utility in providing reliable analysis in a quality control environment is rapidly being realized. Capillary electrophoresis has been shown to be equivalent to RP-LC for the analysis of human growth hormone in terms of its linearity of response, precision and sensitivity. In addition, use of internal reference standards have been demonstrated to significantly improve reproducibility of migration times and detector response between injections. More recently, CE was shown to have adequate accuracy, precision, selectivity, linearity of response and limit of detection to assay the concentration of an oligonucleotide drug product for quality control release as well stability 62 , As more...

Other Hormones Affecting Calcium Balance

In addition to the primary endocrine regulators of calcium balance discussed earlier, it is apparent that many other endocrine and paracrine factors influence calcium balance. Bone growth and remodeling involve a still incompletely understood interplay of local and circulating cytokines, growth factors and hormones including insulin-like growth factor-1, growth hormone (see Chapter 44), the cytokines interleukin 1 (see Chapter 40), interleukin 6, interleukin 11, TNFa, TGF , and doubtless many others. The prostaglandins (see Chapter 40) also have calcium mobilizing activity and stimulate bone lysis. Production of prostaglandins and interleukins is increased in a variety of inflammatory conditions and can lead to systemic or localized destruction of bone. Many of the systemic hormones directly or indirectly have an impact on calcium balance. Obviously, special demands are imposed on overall calcium balance during growth, pregnancy, and lactation. All of the hormones that govern growth,...

Clinical Management

The management of OI focuses on minimizing fractures and maximizing function in all aspects of the child's life. Until recently, the correction of deformities, intramedul-lary rodding of long bones, orthotic support, muscle strengthening, and mobility devices, such a wheelchairs, were the mainstays of treatment. 11 The recombinant human growth hormone has been used to augment growth and bone mass. The greatest potential currently resides in bisphosphonate therapy. Bisphosphonates as potent inhibitors of bone resorption have been shown to be highly effective in improving bone mass in children with severe forms of OI. 12 As a consequence, the fracture rate was reduced significantly and quality of life increased in all patients. However, in long-term therapy, bone turnover is suppressed to levels lower than those in healthy children, and the consequences of chronically low bone turnover in children with OI are unknown.

AWhole animal bioassays

In this approach, live animals that are capable of expressing the desired biological effect in man are employed to ascertain that the biopharmaceutical sample of interest has statistically significant relative potency when compared with that of the reference standard. Whole animal bioassays are generally used only because an alternative in vitro or biochemical assay has not been demonstrated to be predictive of the activity of the drug of interest. Live animal assays are difficult to validate requiring large numbers of animals per dose treatment group due to poor animal-to-animal reproducibility. Precision in the range of 30 - 100 RSD are not uncommon. In addition, the validation efforts required are expensive and require extraordinary lengths of time as each bioassay requires several days or several weeks to detect a measurable biological effect after dosing with the drug. Although validation of such assays is achievable as evidenced by the whole animal bioassays that have been...

Detection Of Human Platelet Antigens

Quence at the site of allelic variation, a PCR product will be generated. However, when the 3' nucleotide of the primer is mismatched, the amplification of the template will not occur or will proceed with very low efficiency. For the detection of each HPA allele, two sets of primers are designed, each set containing an allele-specific primer and a common primer. After gel electrophoresis of the PCR product, DNA is stained and analyzed under UV light. The HPA genotype is then determined by the absence or presence of a DNA fragment. As an internal control for the success of the PCR reaction, an additional pair of primers for the amplification of the human growth hormone gene or another gene is usually added to each reaction.

The Plan Of The Revised Edition

Much water has passed under the bridge with respect to debate over biotechnology since the first edition appeared. I have tried to update discussion of the debate to reflect more recent controversies in a few cases, but I have not tried to do so in anything like the detail (which was not intended to be exhaustive, in any case) in the original edition of the book. While the first edition made some attempt to document the popular, regulatory and intellectual debate over food biotechnology, any extended attempt to update this aspect of the original book would have resulted in a totally different book. In fact, the revised edition has eliminated a number of pages documenting the debate over biotechnology. In some cases, especially environmental risks, the debate has progressed to the point that some of the sources (dating back to the 1980s) discussed in the original edition no longer seem relevant. When the original manuscript was written, the most significant debate over food...

Primary Nursing Diagnosis

Often, preeclampsia occurs before the fetus is term. The goals of treatment are to prevent seizures, intracranial hemorrhage, and serious organ damage in the mother and to deliver a healthy term infant. The only cure for preeclampsia is delivery of the infant however, if the infant is preterm, care is balanced between preventing maternal complications and allowing the fetus more time in utero. If the symptoms in preeclampsia are mild, often the patient is treated at home on bedrest, with careful instructions and education on the danger signs and frequent prenatal visits to monitor progression of the disorder. Antihypertensives are usually not prescribed for mild preeclamptics no differences in gestational age or birthweight have been noted, and growth-restricted infants were twice as frequent in mothers who took labetalol than those treated with bedrest hospitalization alone. Mild preeclampsia is really a misnomer, because it can become severe very rapidly. Frequent tests of fetal...

Pseudohypoparathyroidism

PHP-Ia is characterized by resistance to PTH and skeletal and developmental abnormalities termed Albright's hereditary osteodystrophy. These abnormalities include short stature, round face, obesity, brachydactyly, and mental retardation. PTH resistance is caused by inactivating mutations of Gsa (50) inherited

Phenotype and Genotype

An organism's observable characteristics, such as height, hair texture, skin color, or ear shape, are known as the phenotype of that organism. The phenotype is determined partly by the environment and partly by the set of genes that the organism inherited from its parents. Adult height, for instance, is due partly to nutrition (an environmental influence), and partly to a set of genes governing things such as rates of bone growth, sensitivity to specific hormones, and the like. Phenotype includes not only large-scale characteristics such as height, but every expressed trait, including the types and amounts of all the proteins produced in each cell in the body.

Classification of Epimutations

Characterized by neonatal muscular hypotonia, hypogonadism, hyperphagia and obesity, short stature, small hands and feet, sleep apnoea, behavioural problems and mild to moderate mental retardation (estimated prevalence, 1 25,000 newborns). PWS is caused by the loss of function of imprinted genes which are active on the paternal chromosome only. Although all of the genes in the critical region are known, it is unclear which are the PWS genes. In patients with an imprinting defect, which is found in approximately 1 of cases, all paternally expressed genes are silent. Of these patients, 10 have a PWS-SRO deletion, whereas 90 have a primary epimutation (see Sect. 2.2). Almost all of the other PWS patients have a large paternally derived chromosomal deletion, or maternal uniparental disomy.

Vivien Bonert md and Shlomo Melmed md

Growth Hormone Releasing Factor

Acromegaly is a chronic, insidious, disfiguring disorder of adulthood caused by excess circulating growth hormone (GH) secretion occurring after epiphyseal closure with protean clinical manifestations affecting almost every major organ system. GH hypersecretion stimulates increased hepatic insulin-like growth factor (IGF-1) production, and both GH and IGF-1 contribute to the clinical features of hypersomatotrophism. Fig. 1. (A) Normal GH IGF-1 feedback loop. Growth hormone (GH), insulin-like growth factor-I (IGF-1), growth hormone-releasing hormone (GHRH), and somatostatin (SRF) feedback loop in the control of somatic growth. A stimulatory effect of GHRH and inhibitory effect of SRF interact to result in GH secretion from the anterior pituitary. GH stimulates IGF-1 production from the liver. This, in turn, has a negative feedback effect on pituitary GH secretion and a positive feedback effect on hypothalmic SRF release. Pituitary GH secretion has a negative autoregulatory feedback...

Secondary sexual characteristics absent normal height

The gonad is described as dysgenetic if it is abnormal in its formation. This encompasses a spectrum of conditions which vary with the degree of differentiation. The commonest is Turner syndrome, which is a single X chromosome giving 45X as the karyotype. The missing chromosome may be either X or Y. There are other circumstances in which the gonadal dysgenesis may be associated with a mosaic. Here two cell lines exist within one individual, the most common being 45X 46XX. There are other structural chromosomal anomalies associated with gonadal dysgenesis known as deletions. If the deletion involves the part of the long arm of the X chromosome or the short arm then loss of this genetic material may affect gonadal development. In Turner's syndrome ovarian development is normal until 20 weeks' of gestation and at this stage oocytes are found in the ovaries. However, further maturation is impaired and a massive atresia occurs during the latter part of pregnancy. The ovaries in most...

Endocrine regulation of fetal growth

Fetal growth is critically regulated by the insulin-like growth factors (IGFs). There are two IGFs, numbered I and II. There are two main receptors for the IGFs, numbered 1 and 2. The type-1 IGF receptor mediates most of the major biological effects of IGF-I and IGF-II and it binds the two growth factors with similar affinity. The type-2 IGF receptor appears mainly to be involved in clearance of IGF-II. Mice lacking IGF-I, IGF-II or the type-1 IGF receptor are growth restricted at birth. Mice lacking the type-2 receptor are large at birth. Following birth, IGF levels are stimulated by growth hormone (GH). However, in fetal life, levels of the IGFs appear largely independent of GH and are stimulated by human placental lactogen. The effects of IGFs are influenced by six distinct IGF binding proteins (IGFBP). Binding of IGF to an IGFBP may decrease or enhance its physiological effect. A number of IGFBP proteases exist, such as pregnancy associated plasma protein A (PAPP-A), a protease...

Definition of fetal growth disorder

Fetal growth disorder is strictly defined as the failure of a fetus to grow according to its genetic potential. In practice this is never known and fetal growth is defined on the basis of the expected dimensions of the infant in relation to its gestational age. At birth, these measurements can be made directly. In fetal life, ultrasound is employed (see p. 164). Defining whether a given value of a continuous variable is normal, whether weight or an ultrasonic measurement, involves identifying a value which is thought to be the limit of the normal range. Often, measurements which are within two standard deviations of the mean are regarded as normal this includes approximately 95 of the population. It follows that approximately 2.5 of the population will be regarded as small and 2.5 large, assuming a normal distribution. In practice, due to error in estimating gestational age, inaccuracy in weight estimation, and variation in true genetic potential, there will be no cut off that...

Cardiotocography and biophysical assessment

Umbilical Artery Doppler Normal Values

Chronic uteroplacental insufficiency may lead to hypoxia and in severe cases to acidaemia. The short-term variation (STV) in FHR, assessed by computerized analysis, is the best indicator of fetal compromise in this context. STV increases with gestational age the 2.5th centile is approximately 4.4 ms at 26 weeks and 6 ms at 34 weeks. It is very rare for there to be fetal acidaemia at values above these whereas reduced STV correlates well with fetal hypoxia and metabolic acidaemia. Successive recordings of an 'at risk' growth restricted fetus over days or weeks will often show a gradual reduction in STV in parallel with other findings such as reduced amniotic fluid, reduced fetal movements and raised umbilical artery resistance with centralization of blood flow. Spontaneous decelerations seen on cardiotocography (CTG) are a relatively late finding and usually coincide with reduced STV on computerized recordings. Unprovoked CTG decelerations are...

Physiology Of The Anterior Pituitary Gland

There are six anterior pituitary hormones whose physiologic importance is clearly established. They include the hormones that govern the function of the thyroid and adrenal glands, the gonads, the mammary glands, and bodily growth. They have been called trophic or tropic from the Greek trophos, meaning to nourish,'' or tropic, meaning to turn toward.'' Both terms are generally accepted. We thus have, for example, thyro-trophin, or thyrotropin, which is also more accurately called thyroid-stimulating hormone (TSH). Because its effects are exerted throughout the body or soma in Greek, growth hormone (GH) has also been called the somato-tropic hormone (STH), or somatotropin. Table 1 lists the anterior pituitary hormones and their various synonyms. The various anterior pituitary cells are named for the hormones they contain. Thus we have thyrotropes, corticotropes, somatotropes, and lactotropes. Because a substantial number of growth hormone-producing cells also secrete prolactin, they...

Somatic theories of sleep function

One possible explanation for the link between sleep and physical health is that sleep regulates metabolic endocrine systems that control energy balance in the body 44,55,56,57,58 . NREM sleep is associated with increases in growth hormone (GH) release, and substances which increase GH concentrations in the brain (in some studies) increase NREM sleep 46,55,56 . NREM sleep is also associated with a suppression of the hypothalamic-pituitary-adrenal (HPA) axis, and it is believed that an interplay between growth hormone-releasing hormone (GHRH) and corticotropin-releasing hormone (CRH) influences the quality of sleep 46,55,56 . More recently, it has been shown that prolonged total sleep deprivation in rodents reduces thyroid hormone levels and the pulsatile release of GH and prolactin that normally occurs during NREM sleep 52 . A very intriguing series of

Diagnostic categories in infertility

Amenorrhoea with elevated serum FSH and low or unde-tectable oestrogen levels signify ovarian failure. Known causes include Turners Syndrome (XO), Turner mosaic (XO, XX, XX) gonadal dysgenesis, autoimmune disorders, irradiation or chemotherapy. In many cases the cause is unknown. Turner's syndrome is characterized by a kary-otype of 45 (XO) and phenotypic abnormalities including short stature, webbing of the neck, shield chest and cubitus valgus. By puberty the gonads can be identified as 'streak' ovaries with no functioning follicles by the age

Role of Leptin as a Signal of Starvation

The receptor for leptin was identified by expression cloning in 1995. Sequencing of the original mouse cDNA demonstrated that it coded for a single membrane spanning protein of the class I cytokine receptor family residing on chromosome 4 (human 1p31). It consists of 20 exons, of which the first 2 are noncoding (46). This family includes gp130, G-CSF, interleukin-6, and leukemia inhibitory factor receptors among its members and is consistent with predictions that leptin itself was a helical cytokine structurally homologous to growth hormone and interleukin-2. There are several isoforms of the leptin receptor (ObRa-e) in both mice and humans arising from alternative RNA splicing at the most C-terminal coding exon of the leptin receptor gene. All isoforms have a common extracellular domain but differ in the length of their intracytoplasmic domain (46-48). One isoform (OBRe) is predicted to be a soluble receptor, as it lacks the transmembrane domain (48). The long isoform of the leptin...

Men1 3ps parathyroid pancreas and pituitary tumors

Anterior pituitary tumors associated with MEN-1 occur in approximately 30 of patients. Prolactinomas are the most common pituitary tumor, constituting approximately 60 of the total (3). They are multicentric and large but usually respond well to dopamine agonists (e.g., bromocriptine or cabergiline). Growth hormone-producing tumors are the second most common pituitary tumor, affecting 10-25 of patients (3). Overproduction of growth hormone results in acromegaly in adults and gigantism in children. Nonfunctional tumors and corticotrophinomas account for less than 15 of associated pituitary MEN-1 tumors (3). In general, pituitary tumors are expressed much less frequently than neuroendocrine pancreatic tumors.

Examples Involving Site Directed Mutagenesis

Growth hormone Biotropin Genetropin Humatrope Neutropin* Norditropin Protropin Saizen Serostim** Growth hormone-releasing factor Sermorelin growth hormone Regranex Growth hormone deficiency in children* and for use in adults and in Turner's syndrome** AIDS-related wasting and for pediatric HIV patients Evaluation and use in pediatric growth hormone deficiency

Prions And Prion Diseases

In this respect they resemble the neurodegeneration of Alzheimer's disease (see Section 21.10). In other respects they differ. Most importantly they differ from Alzheimer's in their trans-missibility. CJD, for instance, can be transmitted by poor medical practice (growth hormone from infected pituitaries, infected surgical instruments, etc.) or by cannibalism (kuru New Guinea). Many (not all) animal encephalopathies can (like kuru) be transmitted, often by ingesting contaminated food.

Industries Affected by Phage Infection

A relatively new aspect of the fermentation industry is the use of bacteria to produce proteins encoded by genes derived from other sources. Examples of eucaryotic proteins now produced by bacteria include chymosin, interferon, bovine somatotropin, insulin, human growth hormone, blood clotting factors and tissue plasminogen activator. This list is not complete and is expanding rapidly. Much effort has been placed on the development of efficient expression systems for these foreign genes, and inadvertent product loss through phage infection is troublesome. Although this industry is much better suited to control phage through using sterile production media, sterile air and aseptic fermentation technique, its reliance on single unique production strains increases susceptibility. Scientists involved with the scale-up of processes to production size should be aware of the threat of phage infection and design equipment, processes and production facility layout to provide a measure of...

Physiology of lactation

Structure Breast Lactation

At puberty, the milk ducts which lead from the nipple to the secretory alveoli are stimulated by oestrogen to sprout, branch and form glandular tissue buds from which milk-secreting glands will develop (Fig. 10.2). During pregnancy, this breast tissue is further stimulated so that pre-existing alveolar-lobular structures hypertrophy and new ones areformed. At thesametimemilk-collecting ducts also undergo branching and proliferation. Both oestrogen and progesterone are necessary for mammary development in pregnancy but prolactin, growth hormone and adrenal steroids may also be involved. During pregnancy only minimal amounts of milk are formed in the breast despite high levels of the lactogenic hormones, pro-lactin and placental lactogen. This is because the actions of these lactogenic hormones are inhibited by the secretion of high levels of oestrogen and progesterone from the placenta and it is not until after delivery that copious milk production is induced.

Motor Neuron Disease Mnd Amyotrophic Lateral Sclerosis

Spinobulbar Muscular Atrophy

Figure 21.3 Inactivation of neurofibromin affects the balance between growth and differentiation. The figure shows how NF1 and receptor-activated GAP compete for p21ras. The NF1 route leads to differentiation the receptor-activated GAP route leads to growth. The balance is represented by a set of scales at the bottom of the figure. G growth hormone NF1 neurofibromin R receptor. Other abbreviations and acronyms as before. Further explanation in text. Figure 21.3 Inactivation of neurofibromin affects the balance between growth and differentiation. The figure shows how NF1 and receptor-activated GAP compete for p21ras. The NF1 route leads to differentiation the receptor-activated GAP route leads to growth. The balance is represented by a set of scales at the bottom of the figure. G growth hormone NF1 neurofibromin R receptor. Other abbreviations and acronyms as before. Further explanation in text.

Hormonal Interactions During Exercise

FIGURE 9 Concentrations of glucose in the plasma of normal subjects (Control) and patients suffering from isolated deficiency of GH (shown in blue) while eating normally and while fasting. Some GH-deficient patients were untreated while others were given 5 mg of human GH per day (treated). Fasting began after collection of blood on day 2. From Merimee, TJ, Felig, P, Marliss, E, Fineberg, SE, Cahill, GF Jr. (1971). Glucose and lipid homeostasis in absence of human growth hormone. J. Clin. Invest. 50 574-582. With permission.

Cultural and Religious Influences

Eysenck in his book Genius (1995) noted that only 3 of the U.S. population is Jewish, but that 27 of U.S. Nobel Laureates are Jewish. Thus, according to Eysenck, a person has a much higher chance of winning a Nobel Prize if he or she comes from a Jewish home than from a Christian or Muslim home. To explain this large discrepancy, Eysenck provided two postulates differences in culture and differences in intelligence. He concluded the discussion of this anomaly by stating that there are studies that show Jewish children have higher IQs than non-Jewish children, and it is this higher intelligence that leads to more Jews being extremely creative. Correlation does not necessarily imply causation. For example, the observation that the pants worn by tall men are longer than those worn by short men does not prove that wearing long pants caused them to be tall. The observation that American Jews appear to be intelligent and creative might be related not to genetic-hereditary factors but rather...

Physiological changes occurring in sleep stages

Several hormones are released during sleep. Growth hormone (GH) secretion occurs early in the night, and peaks during SWS 28 , while prolactin is usually released in the middle of the night 29 . Both of these hormones have feedback effects on sleep GH on SWS 30 , prolactin on REM 31 . Adrenocorticotropic hormone (ACTH) and cortisol, two hormones of the hypothalamic-pituitary-adrenal (HPA) axis, are downregulated at sleep onset but increase and peak toward the end of sleep, when they likely contribute to morning arousal 32 . In contrast, the secretion of thyroid-stimulating hormone (TSH) is maximal in the evening before sleep onset, inhibited by sleep, and enhanced by sleep deprivation 33 . Melatonin, whose secretion by the pineal gland is permitted only at night by the circadian system, is also inhibited by light and promoted by darkness, thus providing information to the brain regarding seasonal day length. Melatonin is often used as a sleep-promoting agent,

Physiologic Effects Of Thyroid Hormones

One of the most striking effects of thyroid hormones is on bodily growth (see Chapter 44). Although fetal growth appears to be independent of the thyroid, growth of the neonate and attainment of normal adult stature require optimal amounts of thyroid hormone. Because stature or height is determined by the length of the skeleton, we might anticipate an effect of thyroid hormone on growth of bone. However, there is no evidence that T3 acts directly on cartilage or bone cells to signal increased bone formation. Rather, at the level of bone formation, thyroid hormones appear to act permissively or synergistically with growth hormone, insulin-like growth factor (see Chapter 44), and other growth factors that promote bone formation. Thyroid hormones also promote bone growth indirectly by actions on the pituitary gland and hypothalamus. Thyroid hormone is required for normal growth hormone synthesis and secretion.

Brief Survey Of Major Cytokine Families

A number of important cytokines form the type I cytokine or hematopoietin family 37 . Although these cytokines show little or no significant homology in their primary structure, they share the presence of four a-helical bundles in a spatially similar arrangement 38-40 . (These features are also shared by erythropoietin and human growth hormone.) In addition, many of these cytokines show a similar genomic organization and many of their structural genes are located in close proximity to one another on human chromosome 5 and mouse chromosome 11 41 . Furthermore, these and some other cytokines bind to the so-called class I cytokine or hematopoietic receptors 42,43 . The characteristic feature of these receptors is that their extracellular regions contain a domain with two conserved pairs of cysteine residues and a membrane proximal tryptophan-serine doublet separated by an intervening amino acid (WSXWS motif). This group can be subdivided into type I long (further subdivided in groups 1,...

Exercise and Immune Function

Aging affects the muscle precursor cells (satellite cells or myobloasts) and their regeneration after exercise (Grounds 1998). Aging may also affect proliferation and fusion of myoblasts in response to injury signaling molecules that stimulate satellite cells with aging host environment, inflammatory cells, growth factors and their receptors, and the extracellular matrix. There is a reduction in growth hormone, total and free testosterone, and cortisol, both at baseline and after exercise. The decreased anabolic effects on muscles may explain the loss of muscle mass and strength with aging (Hakkinen et al., 1998). The more primitive components of immune defense, including natural killer cells, phagocytes, acute-phase proteins, and regulatory cytokines, may be altered in elderly. Several investigators have found that the proportion of neutrophils will be increased in the circulation following physical exercise. An increase in neutrophils has been correlated with an increase in plasma...

Polymerase Chain Reaction Primer Design

The melting annealing temperature of a primer can be predicted from the nearest-neighbor model described above. The first requirement is that the primer pair must have closely similar annealing temperatures because extension of both strands occurs simultaneously under the same reaction conditions. The primers, being small and mobile, outcompete the complementary target strands and anneal forming a short double-stranded section with a long 5' single-strand overhang. The annealing temperature chosen for the PCR reaction is usually 5-10 C less than the melting temperature of the primer pair to promote stable hybridization between the primers (which typically exist in excess numbers) and the amplicon to obtain high yield in each cycle.

Biological Activities of Carotenoids and Vitamin A in

Concerning growth and development it should be mentioned, that both vitamin A excess and vitamin A deficiency are known to cause birth defects. Retinol and retinoic acid are essential for embryonic development. Additionally, retinoic acid has been found to regulate expression of the gene for growth hormone.

Prevalence And Clinical Diversity

OI is an autosomal genetic disorder characterized by brittleness of bones and susceptibility to bone fractures from very mild trauma. Fractures may be rare or frequent (more than 200 prior to puberty), and bone fragility may be accompanied by reduced life span and various connective tissue abnormalities short stature, blue sclerae, joint laxity, dentinogenesis imperfecta, easy bruising, and hearing loss. OI represents extreme variation in severity from lethal perinatal to barely detectable. These clinical features, along with radiological and genetic criteria, were used to separate four major clinical types of OI. 1 The patients affected with the mildest (type I) OI have blue sclerae, osteopenia, slight growth retardation or normal height, and premature deafness dentinogenesis imperfecta is less common. Fractures are not commonly observed at birth, but begin with am-bulation and decrease following puberty. Type II is the lethal perinatal form infants exhibit multiple intra-uterine...

Focal dermal hypoplasia

Present at birth, almost exclusively in females skin findings - symmetric, linear, reticulated, frequently tender, pink or red, thin skin involved areas angular, atrophic, slightly raised, or depressed macules, with telangiectasias lesions follow the lines of Blaschko prominent involvement on the lower extremities, forearms, and cheeks hernia-like outpouchings of fatty tissue multiple raspberry-like papillomas arising at junctions between the mucosa and the skin (i.e. perioral, perivulvar, perianal, peri-ocular junctions) apocrine nevi multiple hydrocystomas hypohidrosis scalp and body hair usually sparse hair sometimes brittle dysmorphic facial features other abnormalities, include short stature, skeletal abnormalities, mental retardation, dys-morphic ears, and ocular abnormalities

Ubiquitin Proteasome System

This system participates in the endocytosis of growth hormone receptors and prolonged JAK activation by proteasome inhibitors has been reported (21,22). In addition, it was found that INF-y-activated STAT1 is conjugated to ubiquitin, and degradation of the STAT1 is reduced by treatment of the cells with a proteasome inhibitor (23). These findings suggest that the ubiquitin-proteasome system participates not only in the receptor level, but also at the STAT transcription factor level.

Stat Transcription Factors

Confirmed by the analysis of STAT5-deficient mice. Consistent with its isolation as a mammary growth factor, mice lacking STAT5A are unable to lactate and do not develop normal breast tissue (41). Mice lacking STAT5B undergo normal lactation but display abnormalities resulting from a block in growth hormone signaling, including growth retardation (42). STAT3, on the other hand, plays an essential role during early development, since STAT3 deficiency leads to early embryonic lethality (39).

Prolonged Responses to Cytokines andor Hormones

Hormones such as growth hormone have been shown to reduce phagocytic and metabolic function in neutrophils. This is the result of reduced TNF production (35). Glucocorticoids have also been shown to block PAF-induced downregulation of CD62L and upregulation of CD11 CD18 on neutrophils. This suggests that ligation of glucocorticoid receptors has an anti-inflammatory effect on cells by the inhibition of leukocyte accumulation at sites of tissue injury (36).

Endocrinology of ageing

The third endocrine system that gradually declines in activity with ageing is the growth hormone (GH) insulin-like growth factor 1 (IGF1) axis (Corpas et al 1993). Mean pulse amplitude, duration, and free fraction of GH secreted, but not pulse frequency, gradually decrease during ageing. In parallel, there is a progressive fall in circulating IGF1 levels (Corpas et al 1993). The IGF1

DNA Vaccination Techniques

This innovation in vaccination strategy was discovered some years ago, but the active development of this technology only began after Stephen Johnston's group at the University of Texas Southwestern Medical Center demonstrated that plasmid DNA can induce the formation of antibodies against an encoded protein in 1992. Johnston's group was able to show that when mice are innoculated with plasmid DNA encoding human growth hormone, the mice produce antibodies against the hormone.

Introduction to Biopharmaceuticals

Advances in molecular biology, genetic engineering, process purifications, analytical chemistry and related disciplines have led to the production of large quantities of highly purified proteins facilitating drug development efforts. A number of these proteins such as insulin, human growth hormone (HGH), a-interferon, y-interferon, tissue plasminogen activator (TPA), granulocyte colony stimulating factor (G-CSF), granulocyte macrophage colony stimulating factor (GM-CSF), Interleukin-2, erythropoietin, hepatitis B-vaccine and murine monoclonal antibody have already been

Revolution in Biology

The fusion of traditional industrial microbiology and genetic engineering in the late 1970s led to the development of the modern biotechnology industry. Using recombinant DNA technology, this industry has brought a long and steadily growing list of products into the marketplace. Human insulin produced by genetically engineered bacteria was one of the first of these products. It was followed by human growth hormone an anti-viral protein called interferon the immune stimulant called interleukin 2 a tissue plasminogen activator for dissolving blood clots two blood-clotting factors, labeled VIII and IX, which are administered to hemophiliacs and many other products.

Insulinlike Growth Factor1 IGF1

Growth hormone and IGF-I have been suspected of playing a role in the progression of diabetic retinopathy. In a previous era, hypophysectomy was shown to lead to regression of proliferative retinopathy in a study of 100 patients . Similarly, diabetic dwarfs with low systemic IGF-I levels due to growth hormone deficiency have a reduced incidence of proliferative DR compared with age- and sex matched diabetic patients. Such observations have raised interest in the use of growth hormone-inhibitory and antiproliferative somatostatin analogs to treat severe proliferative DR, however, a growth hormone receptor antagonist, pegvisomant, failed to induce regression of neovascularization . This negative result may have occurred because the treatment was initiated too late treatment may need to have started prior to the development of proliferative DR. In another small-scale trial (23 patients), octreotide (a somatostatin analog) treatment reduced the requirement for laser photocoagulation...

Bromocriptine Parlodel

Additionally, Parlodel is also prescribed to treat a wide variety of other medical conditions that are not related to fertility or women's health at all. Examples include Parkinson's disease, which is a neurological condition, and acromegaly, which is a rare condition where the body produces too much growth hormone.

Insulin like Growth Factor IGFI

IGF-I is a polypeptide showing high similarity to insulin. Two different forms are distinguished IGF-I and IGF-II. IGF-I circulates in blood in the form of IGF-binding protein (IGF-BP), probably inhibiting activity of free IGF. IGF-I is a pivotal growth factor secreted as a result of stimulation by human growth hormone. Both in vivo and in vitro studies indicate its anti-apoptotic and anti-inflammatory properties (Goes et al., 1996 Sukhanov et al., 2007 Sun et al., 2010). There are reports that IGF-I has protective actions in ischaemic rat kidney due to inhibition of inflammatory cytokine production (Goes et al., 1996) and anti-apoptotic in Parkinson disease via inhibition of GSK-3P signalling pathway (Sun et al., 2010). IGF-I exerts its protective actions also in central nervous system and cardiomyocytes (Sun et al., 2010). In premature babies a small concentration of IGF-I is a risk factor of retinopathy of prematurity (Perez-Munuzuri et al., 2010). IGF-I deficiency after birth may...

Creation Of Receptor Antagonists By Modifying Cytokines

Growth Hormone Receptor Structure

The selective modification of receptor-binding sites was first applied to the generation of receptor antagonists for human growth hormone (GH) receptor. To form a functional receptor complex, each molecule of GH binds two Figure 1 Schematic representation of a single molecule of growth hormone bound to two molecules of GHR, based on the crystalline structure of the cocomplex (48). The receptor binding sites on GH are topologically separated. The first receptor to bind, shown on the right, occupies site 1. The receptor on the left subsequently occupies site 2. Preserving site 1 while disabling site 2 creates a competitive antagonist (1). Figure 1 Schematic representation of a single molecule of growth hormone bound to two molecules of GHR, based on the crystalline structure of the cocomplex (48). The receptor binding sites on GH are topologically separated. The first receptor to bind, shown on the right, occupies site 1. The receptor on the left subsequently occupies site 2. Preserving...

Androgen effects

Following the adage that when one's only tool is a hammer, remarkably soon all problems turn into nails, it is an understandable that androgen administration is proposed for older men. Such proposals long pre-date the first availability of testosterone (Hamilton 1937) with many bouts of rejuvenation quackery associated with the names of Brown-Sequard, Steinach and Voronoff into the early 20th century. Standard clinical endocrine practice includes replacement therapy for unequivocal hormonal deficiencies of the pancreas (insulin), thyroid (thyroxine), adrenal (glucocorticoid, mineralocorticoid) and gonads (oestrogen, androgen). Conversely, hormone replacement is not provided for other classical hormones such as prolactin, glucagon, somatostatin, calcitonin, calcitonin-gene related peptide and adrenalin, and other hormones (thyroid-stimulating hormone, LH, FSH, parathyroid hormone) are not replaced but substituted by simpler non-peptide end products. Generally, the criteria for a...

Prenatal Development

The placenta also has important endocrine functions. Soon after implantation, chorionic gonadotropin (CG) is produced. This maintains the corpus luteum so that progesterone production is continued. Progesterone maintains the thick endometrium. After month three or four of the pregnancy, CG drops sharply and the placenta produces progesterone itself the corpus luteum is allowed to degrade. The placenta also produces large amounts of estrogens, especially estriol, from testosterone produced by the fetal adrenal glands. The high levels of progesterone and estrogen are thought to contribute to the morning sickness'' experienced by some pregnant women. The hormone human placental lactogen, placental prolactin, plus maternal hormones prolactin and thyroid hormones prepare the mammary glands for milk production and has other effects similar to growth hormone. The peptide hormone relaxin prepares for birth by causing dilation of the cervix and suppressing oxytocin production by the...

Clinical Findings

The hallmarks of the disease are hepatomegaly, hypoglycemia, lactic acidosis, hyperuricemia, hyperlipidemia, and growth retardation. Long-term complications include short stature, osteoporosis, gout, renal disease, pulmonary hypertension, and hepatic adenomas. Virtually all females have ultrasound findings consistent with poly-cystic ovaries. 6 Hepatic adenomas develop in a significant number of patients, and malignant transformation

Acknowledgements

Omerovic, E., Bollano, E., Lorentzon, M., Walser, M., Mattsson-Hulten, L., and Isgaard, J., 2003, Growth hormone induces myocardial expression of creatine transporter and decreases plasma levels of IL-1beta in rats during early postinfarct cardiac remodeling. Growth Horm. IGF Res. 13 239-245.

Fetal assessment

Early onset pre-eclampsia is particularly involved with placental insufficiency, and more than half of babies born before 34 weeks will be growth restricted 35 . This also explains why abruption is more common, occurring in about 1 in 20 of these early onset cases. Fetal well-being should always be carefully considered in all cases of pre-eclampsia, and includes a symphyseal fundal height assessment, as well as a general enquiry as to fetal movements. At early gestations an ultrasound scan must be performed to assess fetal growth, and should include determination of the amniotic fluid index and umbilical artery Doppler waveforms. A non-reactive CTG with decelerations or a fetal condition that is deteriorating warrants delivery, as it is unlikely to improve with time and may worsen with antihypertensive therapy.

Cell Proliferation

Growth hormone receptor, which is a member of the same receptor family as the PRL receptor, activates the JAK-SHC pathway in 3T3-F442A cells (43). In breast cells, both normal and malignant, the author et al. have shown that PRL can phosphorylate SHC proteins within 1 min of hormone treatment, followed by association with the Grb2-Sos complex. Also, JAK2 is phosphorylated and associated with SHC protein upon PRL activation in these mammary ECs (44). Possible crosstalk between MAPK pathway and the JAK-STAT pathway has been suggested (45).

Growth Disorders

Growth, which usually refers to skeletal growth since it determines final adult height, is an extremely complex process. As such, it is susceptible to a wide range of genetic and physiologic disturbances. Indeed, growth is adversely affected by many if not most chronic diseases of childhood, through many different mechanisms.

Endocrine Disorders

Growth hormone (GH) is produced by the pituitary gland at the base of the brain and is a major regulator of growth. Deficiency of the hormone is the prototype of the inherited endocrine disorders of growth. Although normal in size at birth, infants with GH deficiency exhibit severe postnatal growth deficiency while maintaining normal body proportions. If untreated, children typically have a baby-doll facial appearance and a high-pitched voice that persists after puberty.

Human BC

Immunologically detectable PRL appears in 60-85 of human BC biopsies (76,77) specific PRLRs have been demonstrated in more than 70 of biopsy samples (9-12). However, there is no clear correlation between circulating PRL levels and the etiology or prognosis of the BC (69,78,79). When patients were treated with PRL-inhibiting ergot drugs, which significantly diminish circulating pituitary PRL, no change in disease state was observed (80,81). Operating on the assumption that the lack of effect may have been caused by the presence of human growth hormone (hGH), which is also a lactogen, Manni et al. (82) administered a combination therapy of bromocriptine and a somatostatin analog to a group of women with advanced BC. Circulating levels of PRL, detected by a single assay, were abolished nearly completely in 8 9 patients hGH levels were suppressed in 7 9 patients during treatment. Although overall antitumor effects could not be assessed reliably, because the patients entering the study had...

Praderwilli Syndrome

Prader-Willi syndrome (PWS) is a rare neuro-behavioral genetic disorder that affects numerous organ systems. It occurs in approximately 1 in 10,000 to 30,000 births and affects all races and genders. PWS impacts the functioning of the hypothalamus, a regulation center located in the brain, resulting in decreased growth hormone, altered reproductive Characteristic physical features (e.g., short stature, small hands, small feet, almond-shaped eyes, small mouth with thin upper lip and down-turned corners, fair skin and hair)

Glucagon

In the intestine and the hypothalamus, the principal cleavage products are the glucagon-likepeptide 1 (GLP-1), which has important effects on islet function (see later discussion), and glucagon-like peptide 2 (GLP-2), whose major actions are exerted on the intestine. GLP-1 may also regulate the rate of gastric emptying and feeding behavior. Proglucagon is a member of a superfamily of genes that encodes gastrointestinal hormones and neuro-peptides including secretin, vasoactive inhibitory peptide (VIP), pituitary adenylyl cyclase activating peptide (PACAP), glucose-dependent insulinotropic peptide (GIP), and the growth hormone-releasing hormone, GHRH. Glucagon is packaged, stored in membrane-bound granules, and secreted by exocytosis like other peptide hormones.

Transgenic Animals

Although many researchers had previously studied the behavior of animal cells in vitro, the first application of such cells which led to a useful product was the production in 1949 of the polio virus. Today, many products are generated from cultured animal cells, including virus vaccines, cellular chemicals (interferons, interleukin-2, thymosin, urokinase), immunobiolog-icals (monoclonal antibodies), hormones (e.g., growth hormone, prolactin, ACTH), and virus predators (insecticides), among others. While it is unlikely that animal-cell-based processes for the generation of live virus vaccines will be superseded by processes based on genetically engineered bacteria, it is clear that some animal cell products such as insulin and interferons can be produced from modified bacteria (Spier, 1987). However, transgenic animals are becoming more common and useful tools because they provide an in vivo look at the capabilities and impact of foreign gene expression in a biological system....

Analysis of variance

Let us think through an experiment in which we want to investigate the effects of several different concentrations of a growth hormone on the growth of plant sections. To conduct a fair test we need to include a control in which the media used for containing the plants would not have any growth hormone present. Then, instead of designing a series of experiments in which a single concentration of hormone would be investigated against a control, we would design an experiment in which several different concentrations were compared simultaneously. So we may have a design in which we have

Somatostatin

Somatostatin was originally isolated from hypotha-lamic extracts that inhibited the secretion of growth hormone. Somatostatin is widely distributed in many neural tissues where it presumably functions as a neurotransmitter. It is found in many secretory cells (delta cells) outside of the pancreatic islets, particularly in the lining of the gastrointestinal tract. Somatostatin is stored in membrane-bound vesicles and secreted by exocytosis. Measurable increases in the somatostatin concentration can be found in peripheral blood after ingestion of a meal rich in fat or protein, with the vast majority secreted by intestinal cells rather than islet cells. It is cleared rapidly from the blood and has a halflife of only about 3 min.

Human Prion Diseases

Human prion disease should be considered in any patient who develops a progressive subacute or chronic decline in cognitive or motor function. Typically, adults between 40 and 80 years of age are affected. The young age of more than 30 people who have died of vCJD in Britain and France has raised the possibility that these individuals were infected with bovine prions that contaminated beef products. Over 100 young adults have also been diagnosed with iatrogenic CJD between 4 and 30 years after receiving human growth hormone (hGH) or gonadotropin derived from cadaveric pituitaries. The longest incubation periods (20-30 years) are similar to those associated with more recent cases of kuru.

Expression vectors

The small size of the insulin molecule (and gene) and the size of the potential market made it a prime early candidate for production by recombinant DNA technology. Most insulin used in the treatment of diabetes nowadays is produced in this way. Systems based on E. coli have also been used to synthesise other small human proteins with therapeutic potential such as human growth hormone, Y-interferon and tumour necrosis factor (TNF).

Placental Hormones

And electrolytes between maternal and fetal circulations. In humans, the placenta is also a major endocrine gland capable of producing large amounts of both steroid and peptide hormones and neurohormones. The placenta is the most recently evolved of all mammalian organs, and its endocrine function is highly developed in primates. It is unique among endocrine glands in that, as far as is known, its secretory activity is autonomous and not subject to regulation by maternal or fetal signals. In experimental animals such as the rat, pregnancy is terminated if the pituitary gland is removed during the first half of gestation or if the ovaries, and consequently the corpora lutea, are removed at any time. In primates, the pituitary gland and ovaries are essential only for a brief period after fertilization. After about 7 weeks, the placenta produces enough progesterone to maintain pregnancy. In addition, it also produces large amounts of estrogen, human chorionic gonadotropin (hCG), and...

Lactation

Prenatal growth and development of the mammary glands are independent of sex hormones and genetic sex. Until the onset of puberty, there are no differences in the male and female breast. With the onset of puberty, the duct system grows and branches under the influence of estrogen. Surrounding stromal and fat tissue also proliferate in response to estrogens. Progesterone, in combination with estrogen, promotes growth and branching of the lobuloalveolar tissue, but for these steroids to be effective prolactin, growth hormone, IGF-1, and cortisol must also be present. Lobuloalveolar growth and regression occur to some degree during each ovarian cycle. Growth, differentiation, and proliferation of mammary alveoli are pronounced during pregnancy, when estrogens, progesterone, prolactin, and hCS circulate in high concentrations.

Diarrhea

If effective, consideration must be given to using monthly im injections of a long-acting octreotide preparation to make it more comfortable to the patients. Attention must be given to reduce insulin dosage needs on account of inhibition of release of glucagon, growth hormone, and other peptides by octreotide. Potential for hypoglycemic episodes exists.

Yggdrasil

Its branches, like the bodies of tiny men, recalling the practice of hanging sacrificial victims from trees (Davidson). It is pointed out, too, that the ash has wide-spreading roots, and the roots of Yggdrasil are said to spread to different parts of the underworld. There are three roots to support the tree, one stretching to the world of death, another to the world of frost giants, and the third to the world of men. Three wells lay at the base of the tree, one under each root. Yggdrasil is the centre of the divine world, where the gods sit in council every day. It rises to the sky, and its branches spread over the whole world. It is known too as the Guardian Tree, for it nourishes, and at the same time suffers from, the animals that inhabit it, feed on it, and attack it. The dragon Nidhogg gnaws the roots (Crossley-Holland).

Ultrasound biometry

Growth parameters, primarily biparietal diameter (BPD), head circumference (HC), femur length (FL) and abdominal circumference (AC), are plotted on charts which delineate the normal range of growth within a population. In an attempt to refine identification of true IUGR, ultrasound growth charts that adjust for baseline maternal and fetal characteristics have been devised. They also allow the differentiation between fetuses that are small, but have normal growth rate (hence might have been mis-labelled 'growth restricted' using normal population centile charts) from those whose growth was originally within the normal range but has fallen below a given centile.

Approach to therapy

Images Algorithm Hypopituitarism

Action of growth hormone (GH) receptor antagonist. (A) Normally a single molecule of GH binds two GH receptors through sites 1 and 2, and the GH signal transduction pathway is activated. (B) Pegvisomant increases binding of the GH receptor to site 1 and blocks binding at site 2 to prevent functional GH receptor dimerization, initiation of GH action, and induction of IGF-1 synthesis and secretion. The peripheral effects of excess GH are antagonized at the cellular level, independent of the presence of somatostatin or dopamine receptors on the pituitary tumor. (Adapted from ref. 124.) Fig. 9. Action of growth hormone (GH) receptor antagonist. (A) Normally a single molecule of GH binds two GH receptors through sites 1 and 2, and the GH signal transduction pathway is activated. (B) Pegvisomant increases binding of the GH receptor to site 1 and blocks binding at site 2 to prevent functional GH receptor dimerization, initiation of GH action, and induction of IGF-1 synthesis and...

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