bluuebunny/crossref_metadata_2025 huggingface dataset:
MITOCHONDRIAL PROTEIN SYNTHESIS IN HeLa CELLS
Authors: Attardi Giuseppe , Costantino Paolo , England James , Lederman Muriel , Ojala Deanna , Storrie Brian
Published: October 2009

HeLa cell mitochondrial polysomes, estimated to consist of two to seven 60S monomers, exhibit an unusual resistance to RNase and EDTA, possibly related to the strongly hydrophobic nature of their polypeptide products which makes the nascent chains particularly "sticky". Mitochondria-specific ribosomal and 4S RNA are coded for by mitochondrial DNA (mit-DNA): there is one gene for each ribosomal RNA (rRNA) species and nine genes for 4S RNA on the heavy (H) mit-DNA strand, and three 4S RNA genes on the light (L) strand. The existence of messenger RNA (mRNA) transcribed from mit-DNA is strongly suggested by the occurrence in mitochondria of poly(A) stretches, 60 to 80 residues long, most of which are covalently linked to RNA molecules coded for by mit-DNA. Mitochondrial poly(A) is not a transcription product of mit-DNA.

The in vivo and in vitro products of mitochondrial protein synthesis exhibit by polyacrylamide gel electrophoresis a group of not well resolved components in the molecular weight range from 12 000 to 25 000 daltons, and another group, more abundant, in the range from 40 000 to 55 000 daltons. A strong constraint appears to exist in the pattern of amino acid utilization by HeLa cell mitochondria, with a very low level, if any, of incorporation of the charged polar amino acids, and a predominant utilization of the most hydrophobic ones.

Block of mitochondrial protein synthesis by chloramphenicol for up to four generations of cell growth has no effect on mitochondrial growth and replication, on the rate of mitochondrial nucleic acid synthesis, and on the formation of a functional protein synthesizing apparatus; however, mitochondrial protein synthesis is required for the formation of a functional cytochrome c oxidase.

No significant differences in the rate of mitochondrial protein synthesis per unit of cell mass, nor in the size distribution of the protein products, were found in HeLa cells in different phases of the cell cycle.
OESTROGEN INDUCED SYNTHESIS OF A PROTEIN IN AVIAN LIVER
Authors: Talwar G. P. , Jailkhani B. L. , Narayanan P. R. , Narasimhan Chitra
Published: October 2009

Oestrogens have a dual role. In organisms exposed to the hormone for the first time, they act as differentiating agents directing the division and recruitment of precursor cells to those competent to make hormone dependent products. Data are given for the induction of the synthesis of an egg yolk protein, phosvitin, in immature pullets and roosters. The hormone is also required for the expression of the differentiated function in the committed cells.

The paper also reviews briefly the salient features of the action of oestradiol in the ovariectomized rat uterus. The hormone is recognized by "receptor" proteins present in the cytoplasm. The hormone-receptor complex migrates rapidly to the nucleus. A derepression of RNA synthesis is observed as an early event.
METABOLISM OF SYNTHETIC STEROIDS BY ANIMALS AND MAN
Authors: Fotherby K.
Published: October 2009

The metabolism of naturally occurring oestrogens in humans is outlined and compared with that in other species and with the metabolism of synthetic oestrogens. There is a close similarity in humans between the metabolism of the naturally occurring oestrogens and that of ethynyl-oestradiol with the exception that the latter is less extensively metabolised than the former. With the exception of the baboon, the metabolism of oestrone and oestradiol appears to differ significantly in other species from that of the human. Our knowledge of the metabolism of oestrone and oestradiol and the synthetic oestrogens in the baboon is still meagre and much more information is required before one can ascertain to what extent metabolism in this species can serve as a model for that in humans.

Little information is available concerning the metabolism of synthetic progestogens in species other than man and rabbits. There are many similarities between these two species both in the metabolism of progesterone and of synthetic progestogens related both to 19-nortestosterone and to 17α-hydroxyprogesterone. Insufficient information is available to know how far these similarities extend.

Little is known about the in vitro metabolism of either the synthetic oestrogens or synthetic progestogens. Such information as is available does not suggest that in vitro metabolic studies, with their well-known limitations, are likely to be helpful.
MONITORING SIDE EFFECTS OF CONTRACEPTIVES
Authors: Hill Austin Bradford
Published: October 2009

The problems of identifying and assessing the frequency of adverse reactions to contraceptives are discussed. The ways and means of solving them are critically reviewed, e. g. by clinical trial, by prospective and retrospective inquiry, by monitoring.

Evidence that oral contraceptives can cause thromboembolic diseases is set out. It is based upon five retrospective inquiries conducted in different ways, different places and with reactions of differing severity but nevertheless giving concordant results. The amount of oestrogen in the formulation has been shown to increase the risk. Association has also been shown between oral contraception and cerebral thrombosis and, probably, coronary thrombosis and with hypertension. The actual incidence of all these adverse reactions is difficult to measure accurately but is undoubtedly small with the lower oestrogen formulations.

Retrospective studies have shown no increased neoplasia of the breast or cervix in women using oral contraception. Firm conclusions must await the passage of more years of use.

With other forms of contraception good evidence on the incidence of adverse reactions is generally scanty.

With all forms of contraception there is a need for more monitoring and for carefully conducted investigations arising from it. Observations over more parts of the world and in differing populations are required.
SPECIAL REQUIREMENTS FOR TOXICITY TESTING OF ORAL COMPOUNDS ADMINISTERED CONTINUOUSLY OR CYCLICALLY
Authors: Overbeek G. A. , Hornstra H. W. , van Julsingha E. B. , Mumford J. P. , Zayed I.
Published: October 2009

The authors feel that several reasons exist for considering contraceptives as a special class of drugs, which therefore require special safety studies. Apart from the usual short and long term studies, particular attention should be paid to the reversibility of the induced infertility, and to its possible consequences for subsequent offspring. A possible risk of damage to the foetus is partially outweighed by the low risk of pregnancy during the treatment periods with oral contraceptives. The procedures used in the Organon laboratories are briefly described. Principles on which we base the choice of dose levels and the duration of the various studies are discussed. The paucity of available data from toxicity studies in animals has prevented the presentation of a summary allowing an appraisal of the predictive value of the current methods in toxicology. Nevertheless, a few examples are given which demonstrate the need for more predictive methods. The present lack of knowledge on side effects in humans after prolonged treatment with oral contraceptives has created a feeling of uneasiness. This in its turn has resulted in some excessive regulatory requirements for very long term animal studies. In our opinion, the predictive value of these studies is extremely low because of the inadequacy of the available animal models.

More value can be attached to the monitoring of side effects in humans and efforts in this direction should be increased. The Organon system of monitoring the side effects of its marketed preparations is briefly described. It is not considered feasible to standardize regulatory toxicity requirements for the time being, which should not prevent us from aiming at reasonable, more generally accepted methods of study.
ENZYME INHIBITION BY ANTIBODIES
Authors: Arnon Ruth
Published: October 2009

The interest in the inhibition of enzymes by their specific antibodies stems mainly from the fact that these systems can serve as suitable models in the study of neutralization of biologically active molecules in general. The interaction of enzymes with their specific antibodies generally leads to a reduction in their enzymatic activity. The mechanism of this inhibition is rarely a direct combination of the antibodies with the catalytic site, but is rather due to steric hindrance, namely, barring the access to the active site. In several systems the mechanism of the antibody effect is by conformational changes which it induces on the enzyme. In these cases, the interaction with the antibody may result either in inhibition or in enhancement of the enzymatic activity. In every instance, however, the effect of the antibody is dependent on its narrow specificity, namely, on the regions of the enzyme to which it is directed. The extent of inhibition or enhancement is, therefore, a reflection of the nature and distribution of the various antigenic determinants on the enzyme molecule.

Antibodies specific exclusively to defined regions of an enzyme molecule can be prepared. This has been performed for both lysozyme and staphylococcal nuclease by two procedures: a) Selective separation of the relevant antibodies from the anti-enzyme serum by an immunoadsorbent containing a particular immunologically active fragment of the enzyme, b) The use of an isolated antigenic fragment of the enzyme, or a conjugate of it, for immunization. The antibodies thus prepared, specific toward a unique defined region of the lysozyme molecule (residues 60–83, denoted "loop") recognize the structural conformation of the fragment and are reactive with the intact enzyme molecule. Furthermore, a chemically synthesized loop-like derivative was proved immunologically identical with the natural fragment, and when forming a part of a completely synthetic conjugate, elicited conformation-specific antibodies, reactive with native lysozyme.

These findings are relevant to the topic of an immunological approach to fertility control from two different viewpoints: In the first place they are informative regarding the specific inhibition by antibodies of sperm enzymes which partake in the fertilization process. Secondly, they encourage the synthetic approach for induction of an immune response toward hormones which are crucial in fertilization or implantation.
THE USE OF ANTIBODIES DEVELOPED BY INFERTILE WOMEN TO IDENTIFY RELEVANT ANTIGENS
Authors: Jones Warren R.
Published: October 2009

In the first half of this century several studies demonstrated that temporary infertility may be induced by immunizing women with semen. Isolated examples of acute hypersensitivity reactions to sexual intercourse provide dramatic evidence that natural isoimmunization to semen occurs in man. The afferent immunological pathway in this process can be influenced by adjuvant effects of genital tract infection. This may be important in assessing the significance of antisperm antibodies in infertile women.

In immunological studies of female infertility, the 3 most commonly used tests for humoral antisperm activity are microagglutination, macroagglutination and immobilization (complement dependent cytotoxicity). The sperm microagglutination test detects both antibody and non-antibody activity. The macroagglutination and immobilization tests both detect antibodies but to date the latter has provided the more meaningful results in infertile women.

A prospective study of reproductive patterns in infertility patients indicated a lower subsequent fertility rate and a markedly higher abortion rate in women with antisperm antibodies compared to those without them. However, the association of antisperm antibodies with continuing infertility only reached a statistically significant level in women with a past history of unexplained infertility of at least 3 years' duration. Occlusion (condom) therapy in patients with antisperm antibodies has proved unsuccessful when compared with the natural reproductive patterns in untreated patients.

Immunofluorescence studies are described and correlated with results of other tests for antisperm antibodies in serum and cervical mucus. The results of these and of other studies of naturally occurring antibodies in infertile women have identified antigens of actual or potential relevance to infertility and fertility control. These include (i) intrinsic spermatozoal antigens, (ii) seminal plasma antigens, (iii) blood group antigens, (iv) histocompatibility antigens and (v) nucleoprotein antigens.
VI. EFFECTS OF THE ANTI-ANDROGEN TSAA-291 AND ITS RELATED COMPOUNDS ON THE IN VITRO FORMATION OF 5α-DHT-RECEPTOR COMPLEX IN THE CYTOSOL OF RAT VENTRAL PROSTATES
Authors: Sudo Katsuichiro , Yoshida Keiji , Nakayama Ryo
Published: October 2009

Inhibitory effect of a synthetic steroidal anti-androgen TSAA-291 (16β-ethyl-17β-hydroxy-4-oestren-3-one) on the in vitro formation of 5α-dihydrotestosterone(5α-DHT)-receptor complex was examined. An aliquot of the cytosol from rat ventral prostates was incubated with [3H]5α-DHT in the presence of various amounts of the anti-androgen. By means of dextran-coated charcoal assay and sucrose density-gradient centrifugation analysis, TSAA-291 was demonstrated to inhibit directly, in a competitive manner, the binding of 5α-DHT to a component analogous in its properties to the cytosol androgen receptor. Further, displacing study using a variety of TSAA-291 analogues was undertaken to examine which of the functional groups of TSAA-291 is important for the affinity to the 5α-DHT binding component, and elucidated that 3-hydroxy or 5α-dihydro derivatives of TSAA-291 and others having axial methyl group at C-10 were less potent competitors for [3H]5α-DHT binding than TSAA-291. Furthermore, using other steroids including androgens and anti-androgens, considerable knowledge was obtained about structural requirements for a steroid molecule to displace the bound [3H] 5α-DHT, and this displacing activity of the steroids was discussed in terms of their anti-androgenic activity.
Diabetic neuropathy: Epidemiological, pathogenetic, and clinical aspects with special emphasis on type 2 diabetes mellitus
Authors: Matikainen E. , Juntunen J.
Published: October 2009

ABSTRACT. Peripheral neuropathy is a frequent complication of diabetes mellitus. Alterations of the peripheral nervous system in diabetics have been studied in numerous investigations. There are many factors known to participate in the development of this complication, e.g. the age of the patient, duration of the diabetes, quality of the diabetic control etc. The role of different types of diabetes in development of neuropathy is still largely unclear since investigations on this aspect are few. It seems, however, that peripheral neuropathy in type 2 (non-insulin dependent) diabetes is common but often mild. The differential diagnosis of the peripheral neuropathy in type 2 diabetics is more difficult than in type 1 (insulin dependent) diabetics, since these patients tend to be older and also may have other concomitant disorders. In this paper the clinical features and pathogenetic mechanisms of neuropathy in type 2 diabetes are briefly discussed.
Serum lipids and Lipoproteins in type 2 diabetes
Authors: Taskinen Marja-Riitta , Harno Kari , Nikkilä Esko A.
Published: October 2009

ABSTRACT. Serum lipids, lipoproteins and lipolytic enzymes were studied (a) before and (b) after six weeks of glipizide treatment in ten (4 men, 6 women) newly diagnosed type 2 diabetic patients. Improved glycemic control during glipizide therapy (HbA1:11.2±0.5 % vs 9.6 ± 0.4%;P<0.01)had no effect on serum or lipoprotein triglyceride, whereas both serum total cholesterol (4.60 ± 0.29 mmol/l vs 4.37 ± 0.30 mmol/l; P<0.05) and LDL cholesterol (3.16 ± 0.18 mmol/l vs 2.98 ± 0.24 mmol/l; P<0.05) decreased after six weeks of glipizide. HDL cholesterol, the composition and concentration of HDL subfractions HDL2 and HDL3 and lipolytic enzymes were uninfluenced by glipizide therapy. In conclusion, low HDL levels in type 2 diabetic patients do not appear to be due to sulphonylurea treatment, but rather represent a basic abnormality of HDL metabolism.
The history of anabolic steroids and a review of clinical experience with anabolic steroids
Authors: Kopera H.
Published: October 2009

Metabolism is the term employed to embrace the various physical and chemical processes occurring within the tissues upon which the growth and heat production of the body depend and from which the energy for muscular activity, for the maintenance of vital activity and for the maintenance of vital functions is derived (Best & Taylor 1950). The destructive processes by which complex substances are converted by living cells into more simple compounds are called catabolism. Anabolism denotes the constructive processes by which simple substances are converted by living cells into more complex compounds, especially into living matter.

Catabolism and anabolism are part of all metabolic processes, the carbohydrate, fat and protein metabolism. The term anabolic refers only to substances that exert an anabolic effect on protein metabolism and are unlikely to cause adverse androgenic effects. They shift the equilibrium between protein synthesis and degradation in the body as a whole in the direction of synthesis, either by promoting protein synthesis or reducing its breakdown. The protein anabolic effect of anabolic steroids is not restricted to single organs but is the result of stimulated biosynthesis of cellular protein in the whole organism.
Anabolic steroids in aplastic anemia
Authors: Gardner Frank H.
Published: October 2009

Abstract. Despite the successful recovery of young patients with aplastic anemia following bone marrow transplants, additional patients have had benefit from immune suppression therapy, predominantly antithymus globulin (ATG). There exists a large residual pool of patients who have not been able to benefit from these modalities because of 1) lack of compatible siblings, 2) age, 3) duration of illness prior to diagnosis. Historically oral androstanes have been helpful in the treatment of chronic aplastic anemia. The long-range survival in large cooperative groups of patients treated with androstanes have indicated that both severe and chronic aplastic anemia have had responses similar to immune suppressive therapy. There is a need to have further investigations to seek the most effective anabolic agents. Many group studies have shortened treatment schedules when an erythropoietic response has been obtained, rather than continue therapy until the maximum platelet count is achieved. Such abbreviation of therapy may hasten a hematological relapse. Clinics also should evaluate parenteral androstanes since they appear to be more hematopoietic. Also the investigation of different androstane metabolites, i.e. etiocholanolone, should be pursued to determined if a more effective stimulus of stem cell proliferation can be achieved. In the recovery phase of the aplastic anemia patients treated with immune suppression or androstanes the peripheral blood reflects an altered proliferation of the marrow stem cell. The majority of these patients continue to have abnormalities in red cells (macrocytosis) and decreased platelet size.
Diabetes and Coronary Heart Disease
Authors: Pyörälä Kalevi
Published: October 2009

Abstract. Clinically manifest coronary heart disease (CHD) is not uncommon in diabetics with insulin-dependent type of the disease below the age of 40, particularly when the duration of diabetes is long.

Clinically manifest CHD is very common in diabetics with maturity-onset, non-insulin-dependent type of the disease, and in this type of diabetes the frequency of CHD shows little or no relation to the duration of diabetes.

Premenopausal female diabetics have a clinically manifest CHD almost as often as male diabetics of the same age - a situation in sharp contrast to that in non-diabetics with large excess of CHD in males.

The incidence of all manifestations of CHD (sudden and non-sudden CHD death, non-fatal myocardial infarction, »silent« myocardial infarction, and angina pectoris) is increased in diabetics as compared to non-diabetics, but the excess of CHD mortality in diabetics is especially marked, being 3 to 4 times higher than in non-diabetics.

The incidence of congestive heart failure is markedly increased in diabetics and this is in part independent of increased occurrence of CHD and hypertension among diabetics. Subclinical abnormalities of left ventricular function are common in diabetics and these abnormalities appear to show some relationship to the metabolic control of diabetes and in insulin-dependent diabetics also to the presence of microangiopathy.

Diabetes is associated with changes in general CHD risk factors to atherogenic direction. These changes include abnormalities in the levels and composition of plasma lipids and lipoproteins and increased frequency of hypertension.

The impact of general risk factors on CHD risk appears to be similar in diabetics and non-diabetics. The major part of the excess CHD in diabetics, however, is not explained by the effect of diabetes on general cardiovascular risk factors, but is due to an independent effect of diabetes itself through mechanisms which are far from solved.
Insulin receptors in normal pregnant women and women with gestational diabetes
Authors: Andersen Ole , Kühl Claus , Buch Inge
Published: October 2009

Abstract. In a serial study of insulin receptor binding to monocytes from normal pregnant women, a significant increase in insulin binding in mid pregnancy followed by a significant decrease in late pregnancy at tracer insulin concentration was found. No changes in the insulin concentration necessary to reduce tracer binding by 50% (ID50) were observed. At delivery, binding to isolated adipocytes was significantly lower in normal pregnant women than in non-pregnant normal controls while no difference in ID50 was observed. No differences in insulin binding at tracer insulin concentration to monocytes and adipocytes between normal weight women with gestational diabetes and healthy non-diabetic pregnant controls were found, but the ID50 was significantly lower in women with gestational diabetes diagnosed in late pregnancy than in pregnant controls at the same weeks of gestation.
Treatment of pregnant insulin-dependent diabetic women
Authors: Fuhrmann K.
Published: October 2009

Abstract. The treatment of 620 insulin-dependent diabetic pregnant women is reported. The goal of treatment was to achieve a normal blood glucose concentration as soon as possibly during early, or even before pregnancy. When intensified conventional insulin therapy was started before conception, about 88% of the patients achieved normal blood glucose levels during the first weeks of pregnancy. In only about 20% of the pregnant diabetics without intensified preconceptional treatment a normal blood glucose level was obtained during their first hospitalization in pregnancy. The rate of congenital malformations was 1.1% in the former and 7.1% in the latter group.
Vasopressin and oxytocin their presence in the central nervous system and their functional significance in brain processes related to behaviour and memory
Authors: van Wimersma Greidanus Tj. B. , Burbach J. P. H. , Veldhuis H. D.
Published: October 2009

Abstract. Vasopressin and oxytocin exert pronounced effects on behaviour by a direct action on the brain. A single injection of vasopressin results in a long-term inhibition of extinction of a conditioned avoidance response suggesting that vasopressin triggers a long-term effect on the maintenance of a learned response, probably by facilitation of memory processes. In addition vasopressin improves passive avoidance behaviour, delays extinction of appetitive discrimination tasks, affects approach behaviour to an imprinting stimulus in ducklings, improves copulation rewarded behaviour of male rats in a T-maze, prevents or reverses amnesia induced by electroconvulsive shoch. CO2 inhalation, pentylenetetrazol or puromycin. The majority of these effects of vasopressin in the various and sometimes relatively complex tasks may be explained by stimulatory influences of this neuropeptide on memory processes. Generally oxytocin exerts effects which are opposite to those of vasopressin and it has been suggested that oxytocin may be an amnesic neuropeptide. Various limbic system structures seem to act as the anatomical substrate for the bevavioural effects of vasopressin. In particular the amygdala, the dentate gyrus of the hippocampal complex, the ventral hippocampus and the dorsal septum seem to be involved. Evidence has been obtained from experiments with homozygous diabetes insipidus rats and from experiments in which antisera were applied that endogenous vasopressin and oxytocin play a physiological role in brain processes related to memory. It appears that highly active fragments can be generated from vasopressin and experiments in which a fragment of vasopressin ([pGlu4, Cyt6]AVP-(4–8)) as well as an AVP-antagonist were used, reveal that the vasopressin receptors mediating the behavioural effects are situated in the brain and differ in specificity from the peripheral (blood pressure) vasopressin receptors. Generally the clinical data obtained so far with vasopressin treatment are in agreement with the results from animal experiments and they support the notion on the involvement of vasopressin in memory function. The sometimes reported conflicting results on vasopressin effects in certain patients (Korsakoff or Alzheimer) may have to do with the wide-spread pathology in these diseases.
Continuous subcutaneous insulin infusion (CSII) in pregnant diabetic women
Authors: Mancuso S. , Caruso A. , Lanzone A. , Bianchi V. , Massidda M. , Codipietro F. , Fulghesu A. M.
Published: October 2009

Abstract. Insulin infusion pump treatment (CSII) in pregnancy was compared with conventional therapy (IIT) in 12 pregnant diabetic women. In patients poorly controlled on IIT a plasma glucose equilibrium was achieved with CSII (mean of: glucose levels = 84 vs 137 mg/dl; SD = 36 vs 63 mg/dl; MAGE = 65 vs 112 mg/dl). In patients well controlled on IIT, CSII led to a reduction in the variation of glucose excursions (SD = 29 vs 36 mg/dl; MAGE = 48 vs 76 mg/dl). CSII generally led to a reduction of 20–37% of daily insulin dose but in 3 cases there was an increase of dose with the achievement of glycaemic control. A significant relation between bolus/basal ratio of insulin daily dose and the quality of glycaemic control was also found during CSII. All infants were born at or near to term and none were macrosomic or had neonatal complications. It is concluded that CSII is highly efficient in pregnancy not only in type I but also in type II or gestational diabetes.
Growth hormone deficiency due to GH-N gene deletion in an Austrian family
Authors: FRISCH HERWIG , PHILLIPS JOHN A.
Published: October 2009

An 11 year old Austrian boy with isolated growth hormone deficiency type I A is described. On institution of GH therapy at the age of 2 2/12 years there was only a short growth response and anti-GH-antibodies with high binding capacity were detected, and growth was inhibited. Examination of the nuclear DNA by restriction endonuclease analysis demonstrated a defect of the GH-N gene in the patient. The results suggest the deletion in this Austrian family is different from that seen in other patients. The parents were heterozygous for the deletion and had a subnormal GH response to stimulation with arginine, but their somatomedin-C concentrations and their heights were normal. The patients' sister was of normal height, hormone analyses were normal, and the GH-N gene was not affected.
The physical, psychological, educational and professional conditions of young adults given growth hormone for childhood growth hormone deficit
Authors: PIERSON M. , LEHEUP B. , SCHWEITZER Cl. , MANGIN E.
Published: October 2009

Twenty five of the 75 patients having been given human growth hormone in the Pediatric Nancy Endocrinological Division have reach final adult heigh All have been treated the same way, 10 boys and 4 girls were diagnosed as isolated deficit, 7 boys and 4 girls as combined deficit. The physical, sexual, radiological, intellectual, professional and psychological characteristics have been defined either during the treatment follow-up or at a final interview. All results have been compared to the familial conditions if possible. Final adult statures are in the low range of the normal (−2 DS). The sexual development, normal for patients with isolated deficit, has not been achieved completely by regular protocole for patients with combined deficit. The intellectual and professional achievements are rather low but this has to be matched with below the normal familial conditions. Psychological determination is quite satisfactory but the personality is dominated by shyness and lack of responsability. It is likely that an earlier onset of treatment and a better psychological guidance may lead to a better final results judged both on physical grounds but also on psychological and professional conditions.
The McCune-Albright syndrome
Authors: MAURAS NELLY , BLIZZARD ROBERT M.
Published: October 2009

Abstract. The presence of polyostotic fibrous dysplasia of bone, hyperpigmented skin macules, and precocious sexual development in children is known as the McCune-Albright syndrome. To date, a complex combination of multiple endocrinopathies including goiter, hyperthyroidism, acromegaly, Cushing syndrome, hyperprolactenemia, sexual precocity, hyperparathyroidism, and hypophosphatemic hyperphosphaturic rickets have been described in association with this syndrome. Even though the pathogenetic mechanisms involved in the development of the endocrinopathies is unknown, it was assumed for many years that hypothalamic dysfunction was the cause in most cases. The overwhelming amount of data now permits the development of an alternate hypothesis; one of hyperfunctioning endocrine organs working with relative autonomy from hypothalamic control.
Adrenarche is dissociated from gonadarche – studies in patients with Turner's syndrome
Authors: TELLER W.M. , HOMOKI J. , WUDY S. , SCHLICKENRIEDER J.H.M.
Published: October 2009

Twenty-two patients with gonadal dysgenesis (14 45,XO; median age 13.6 years; 8 mosaics, median age 12.3 years) were studied regarding their clinical onset of adrenarche (pubarche) and breast development. The latter was considered evidence of gonadarche. 1/22 showed breast development, stage 2; 9/22 had pubarche, stage 2-4. The 24 -urinary excretion of androsterone, etiocholanolone, dehydroepiandrosterone, 16α- and 16β-dehydroepiandrosterone was studied in these patients by urinary capillary column gas chromatography profiling. The urinary steroid profiles of twenty-one healthy, normal girls (median age 10.4 years) served as controls. Dehydroepiandrosterone and its 16-hydroxylated derivatives were excreted in significantly greater amounts by the patients with Turner's syndrome as compared to normal girls. These findings support the hypothesis, that adrenarche is independent of gonadarche and proceeds even in instances of gonadal dysgenesis.
Patterns of growth from birth to maturity in infants and children with congenital adrenal hyperplasia
Authors: Clayton George W.
Published: October 2009

Patterns of growth of 30 children with Congenital Adrenal Hyperplasia of the 21-hydroxylase type were studied from infancy to maturity. These children were compliant as to therapy. Intramuscular (I.M.) Cortisone (40mg/M2) given every three days resulted in growth failure after the first year of life. A marked increase in height velocity occurred when oral Cortisone (20-25mg/M2) was given at approximate] 3 years. Growth was relatively normal during childhood in both boys and girls but there was a marked increase in mean weight in both sexes.

Pubertal growth spurt occurred normally in males but was delayed in females. Weight decreased in both sexes at puberty but not to normal. Better methods of monitoring this condition should result in therapeutic regimes which allow normal growth patterns as well as normal mature height.
Thyroid function in prematures with respiratory distress syndrome (RDS)
Authors: STAHNKE N. , STENZEL E. , HELLWEGE H.
Published: October 2009

Reports on thyroid function in newborns with respiratory distress syndrome (RDS) are controversial, the significance of obtained results is not clear. Therefore we conducted a longitudinal study of thyroid function in 35 infants with RDS (gestational age 24-36 weeks, birth weights 65o-277o g). 43 well prematures, matched for gestational age, served as controls. No significant differences were observed in cord blood TSH, T3, T4, TBG values and T4:TBG ratios between infants with and without RDS. Prematures with RDS showed lower levels of T3, T4, TBG and T4:TBG at 24 hours of age and increases of TSH values at 72 hours. Subsequently these prematures exhibited a spontaneous rise in thyroid hormone levels. Even non-surviving RDS-infants had initial T3, T4, T4:TBG and TSH values within the normal range. Thyroid hormone concentrations correlated significantly with the severity of pulmonary disease. Depressed thyroid hormone levels were found to be the result and not the cause of RDS. T4 or T3 therapy is not warranted in this condition.
Generalized unresponsiveness to mineralocorticoid hormones: familial recessive pseudohypoaldosteronism due to aldosterone-receptor deficiency
Authors: BOSSON Danièle , KUHNLE Ursula , MEES Nicole , RAMET Joseph , VAMOS Esther , VERTONGEN Françoise , WOLTER Renée , ARMANINI Decio
Published: October 2009

The present report describes two sibs - born from consanguineous parents - presenting with severe salt wasting. Generalized pseudohypoaldosteronism (PHA) was diagnosed on the basis of markedly elevated sodium concentration in urine (84 & 63 mmol/L respectively), sweat (181 & 196), saliva (- & 120) and stool (- & 189), hyponatremia (112 & 132) and hyperkalemia (10.7 & 7.3) in the presence of increased plasma aldosterone (> 8.5 & 5.4 ng/ml), plasma renin activity (40 & 18.9 ng/ml/hr) and urinary aldosterone (> 32 & 11.6 μg/day). Both parents investigated under basal conditions (sodium ad libitum) and under sodium restricted diet appeared to be normal. Aldosterone binding studies performed on mononuclear leukocytes showed no type I receptors in the investigated child whereas low amounts were found in both parents (90 sites/cell and 63 sites/cell in the mother and the father, respectively). Isolated renal unresponsiveness to mineralocorticoid hormones is thought to be an autosomal dominant inherited disease. In contrast, the results obtained in these two new cases of generalized PHA, as well as the fact that four of five yet reported cases were born from consanguineous parents,suggest an autosomal recessive mode of inheritance for generalized PHA.
Some aspects of androgen insensitivity
Authors: HUGHES I.A. , EVANS B.A.J.
Published: October 2009

Abstract. The clinical and endocrine features of the syndromes of androgen insensitivity which display a wide phenotypic spectrum are reviewed. A simple, dispersed whole cell assay to study androgen receptor binding in genital skin fibroblasts has been used to determine the pathogenesis of androgen insensitivity. Classification of the disorders based on in vitro studies does not show absolute concordance with the clinical sub-groups. Androgen-induced augmentation of basal specific binding is proposed as a possible functional test of androgen responsiveness in disorders such as partial androgen insensitivity, isolated hypospadias and micropenis. Understanding the cause of androgen insensitivity in many receptor-positive patients awaits identification and isolation of DNA probes for the X-linked gene locus for the androgen receptor.
Feminization in a galactosemic girl in the presence of hypergonadotropic hypogonadism
Authors: Schwarz Hans P. , Zimmermann Andreas , Carasso Arnaud , Zuppinger Klaus
Published: October 2009

A galactosemic girl has been followed in our clinic since her 8th day of life when the diagnosis of transferase-deficiency galactosemia was made until her present age of 21 years. Although she presented with direct hyperbilirubinemia and severe liver dysfunction, her subsequent somatic and intellectual development under a strict galactose-free diet was normal. Liver function normalized. Her pubertal stage was Tanner B II and PH II at age 11.7 years and progressed normally to B V and PH V, but menarche did not occur. At age 16.8 years, low estradiol (51 pmol/L) and high gonadotropin levels (LH 44 U/L; FSH 43 U/L) were measured. Severely hypoplastic ovaries with a streak-like aspect were seen on laparoscopy. Sex chromatin was positive. Follow-up studies over the next 4 years confirmed elevated LH and FSH levels with an excessive response to stimulation with LHRH and persistently low estradiol levels (41 to 117 pmol/L). After an intravenous load of 200 mg DHEA-S, plasma estrone levels rose 1.8-fold and estradiol 11.4-fold above basal, demonstrating prompt conversion of androgens to estrogens. For over one year, the patient has been treated with the synthetic progestin norethisterone (15 mg per day for 10 days in a row every month) which has resulted in regular menstrual bleedings.
Molecular cloning of antigens to thyroid autoantibodies using the expression vector lambda gt 11
Authors: Rapoport Basil , Hirayu Hideshi , Seto Pui , Magnusson Ronald P.
Published: October 2009

Abstract. The molecular cloning of certain antigens to thyroid autoantibodies present in patients with autoimmune thyroid disease would be of great value in further understanding the pathogenesis of these diseases, and in devising new approaches for their treatment. The ideal method for molecular cloning is to first obtain a partial amino acid sequence of a purified protein and to construct an oligonucleotide probe for screening an appropriate cDNA library. Unfortunately in the case if thyroid autoimmunity, important antigens such as the TSH receptor and the microsomal antigen have not been purified. An alternate approach devised by Young & Davis (1983) is to construct a cDNA library in a vector that expresses the encoded proteins. The library can then be screened with an antibody as a probe. We have constructed cDNA libraries in gt11 using mRNA purified from human, pig and rat thyroid cells. Our experiences in constructing and screening these libraries will be described. The advantages of this system are 1) the protein does not have to be purified, 2) previously unknown antigens may be identified. The disadvantages are 1) lack of specificity with antibody selection, 2) because the cDNA is inserted in the β-galactosidase gene in the vector the antigen is expressed as a fusion protein. This may disturb the tertiary structure of the antigen and alter its antigenicity, 3) cDNA inserts frequently only contain part of the antigen molecule, and may therefore lack important epitopes; polyclonal antibody may therefore be preferable to monoclonal, 4) only 1 in 6 cDNA inserts will be in the correct reading frame for antigen expression, 5) the expressed protein is not glycosylated, 6) antibody absorption or purification is necessary to reduce the high background of antibody binding to bacterial host protein products. Despite these disadvantages the system has been used to clone numerous proteins. Thus far we have been successful in cloning 3 newly recognized autoimmune thyroid disease-related antigens that are of potential importance in further understanding the nature of these diseases.
Effects of high and low doses of methimazole in patients with Graves' thyrotoxicosis
Authors: Benker G. , Reinwein D. , Creutzig H. , Hirche H. , Alexander W. D. , McCruden D. , Galvan G. , Kahály G. , Beyer J. , Lazarus J. H. , Schatz H. , Schleusener H. , Schneider H.-G. , Ziegler R. , Tegler L. , Nilson O. R.
Published: October 2009

Abstract. In spite of the long-established use of antithyroid drugs, there are many unsettled questions connected with this treatment of Graves' disease. There is a lack of controlled prospective trials studying the results of antithyroid drug therapy while considering the many variables such as disease heterogeneity, regional differences, drug dosage and duration of treatment. Therefore, a multicenter study has been set up in order to compare the effects of two fixed doses of methimazole (10 vs 40 mg) with thyroid hormone supplementation on the clinical, biochemical and immunological course of Graves' disease and on remission rates. Experience accumulated so far suggests that treatment is safe using either 10 or 40 mg of methimazole. While there is a tendency for an advantage of the higher dose within the first weeks (higher effectiveness in controlling hyperthyroidism), this difference is not significant. The impact of dosage on remission rates remains to be shown.
Pathophysiological and clinical implications of thyroid growth-stimulating immunoglobulins: Evidence for their intrathyroidal production
Authors: Schatz H. , Ludwig I. , Wiss F. , Goretzki P. E.
Published: October 2009

Abstract. Thyroid growth-stimulating immunoglobulins are responsible for goitre formation not only in Graves' and Hashimoto's disease but also (partly) in simple goitre, especially in recurrent cases. TGI are antibodies, the TSH receptor, however, appears not to be the antigenic site in simple goitre. In our own studies two TGI assay systems ([3H]thymidine incorporation into isolated porcine thyroid follicles and into FRTL-5 cells) gave comparable results. TGI was found in 20 out of 72 patients with simple goitre (27%) coming from an endemic goitre area (biased by selection, i.e. certainly including sporadic forms) and in 10 out of 26 patients (38%) with recurrent goitre. TGI levels were higher in thyroidal venous blood compared to cubital blood (simultaneously drawn during surgery) indicating an intrathyroidal production of TGI. Thyroid growth-blocking antibodies as estimated in the FRTL-5 cell assay in one of our patients might be of significance not only in primary myxoedema but also for congenital hypothyroidism.
CLINICAL EVALUATION OF THE PROGESTATIONAL EFFECT OF ALLYLESTRENOL
Authors: BORGLIN N. E.
Published: October 2009

Allylestrenol, a new oral progestational steroid, was studied for its effect on primary and secondary amenorrhoea, anovulation, irregular shedding of the endometrium, premenstrual tension, and threatened or habitual abortion. The progestational effect was good in all of the groups. Allylestrenol is not excreted as pregnanediol in the urine. In the doses used the preparation had no inhibitory effect on the adrenal cortex, the plasma histaminase activity did not increase, and it had no demonstrable androgenic or other side effects.
Theoretical Modeling of Reinfiltration Process in Naturally Fractured Reservoirs: A Comparative Study on Traveling Liquid Bridges and Continuum Film Flow Approaches
Authors: Dejam Morteza , Ghazanfari Mohammad Hossein , Masihi Mohsen
Published: October 2009

Most of the Iranian oil reservoirs are naturally fractured. Reinfiltration is a key process which controls oil flow from the upper to the lower matrix block. However, theoretical modeling of fracture aperture as well as fracture dip angle effects on flow rate of drained oil during reinfilteration process remains a topic of debate in the literature. Moreover, there is no reported experience in the literature that compared the oil velocity predicted by traveling oil bridges and continuum film flow approaches. In this work reinfiltration process is modeled through two different approaches: discrete traveling liquid elements and continuum film flow along inclined fractures. For a case study reported in the literature, the oil velocity at various fracture aperture as well as fracture dip angle was predicted and compared using both approaches. The results of this work confirmed that the geometry of fractures between matrix blocks plays a crucial role on drained oil during reinfiltration process. By decreasing fracture aperture or fracture dip angle the oil velocity modeled by liquid film flow approach decreases, it might be due to more time available, for the droplets and film to be adsorbed on lower block; therefore reinfiltration effect increases. It has been observed that the velocity of traveling liquid bridges is maximized for fracture aperture close to 0.5 mm. A surprising result, for the case studied here, is that there are critical values for fracture aperture and fracture dip angle, close to 1 mm and 15 degree respectively, in which after those the velocity of traveling liquid elements is higher than that predicted by liquid film flow approach. The results of this work might help to obtain an independent transfer function for dual permeability model incorporating the interaction between matrix blocks which might improve the reliability of simulators for evaluation of naturally fractured reservoirs.
Changes in Near Wellbore Stress and Fracture Gradient Due to Cold Water Injection in a Sirte Basin Field, Libya
Authors: Abdalkadeer K. M. , Senturk E. , Dunn-Norman S. , Goodman H. E. , Prada M. , Rivera N.
Published: October 2009

It is important to understand the effects of introducing thermal changes in the subsurface because such changes alter the state of stress and, ultimately, the behavior of the formation. Inducing fractures in the formation may cause injection fluids to advance at different rates through the reservoir, thereby reducing the areal sweep through the reservoir and the overall efficiency of a flooding operation. To avoid induced fractures, it is necessary to maintain water flooding operations below the fracturing (breakdown) pressure of the formation. For these reasons, it is extremely important to model the cold water injection response and to predict whether it is possible to inject without creating fractures in the formation.

In late 2006 a reservoir simulation study using ECLIPSE was performed for 103N Field in Sirte Basin to evaluate the reservoir response to water flooding in an attempt to understand the potential for improving oil and gas recovery with water flooding. This study showed that the main effect of cold water injection on the recovery of N- Field was reduced injectivity due to high water viscosity. Another effect of cold water injection was that bypassed oil was cooled down and its mobility was reduced due to the increase in the oil viscosity, thus reducing ultimate recovery.

This paper provides an extension of the reservoir simulation done by Wintershall to examine the effect of cold water injection on formation fracturing gradients. The work includes a review of the rock mechanics and stress analysis of the subsurface formations and provides an estimation of fracture penetration within the reservoir for a range of water injection rates and water surface temperatures. The conclusions of this study provide important insights into applying water flooding operations in the N-field.