bluuebunny/crossref_metadata_2025 huggingface dataset:
A sensitive enzyme immunoassay system of rat epidermal growth factor in biological fluids and tissue extracts
Authors: Joh Takashi , Itoh Makoto , Yasue Naoji , Miyamoto Tadahisa , Iwai Akira , Matsusako Kei , Endoh Kazuo , Takeuchi Toshihiko , Moriyama Akihiko , Kato Taiji , Tanaka Ryo
Published: December 2008

Abstract. Rat epidermal growth factor was purified from rat submandibular glands to obtain specific antiserum for the establishment of an immunoassay system. Purified rat epidermal growth factor showed a single peak on reverse phase HPLC and a single band on sodium dodecyl sulphate polyacrylamide gel electrophoresis at mol wt 5100 in the presence of 2-mercaptoethanol and at mol wt 41000 in the absence of 2-mercaptoethanol. Antibody against rat epidermal growth factor showed crossreactivities with mouse and human epidermal growth factors on soft agar-double immunodiffusion test. The established sandwich enzyme immunoassay for rat epidermal growth factor had a high sensitivity (500 fg/tube), which made it possible to measure minute amounts of endogenous rat epidermal growth factor without pretreatment. Physiological concentrations of rat epidermal growth factor in rat biological fluids and tissues were determined. Species differences in physiological distributions of epidermal growth factor are discussed.
In vitro effect of human growth hormone on lymphocyte transformation and lymphocyte growth factors secretion
Authors: Schimpff R. M. , Repellin A. M.
Published: December 2008

Abstract. Cultures of human blood peripheral lymphocytes were performed in the presence or absence of human growth hormone, and also of phytohemagglutinin and normal human serum 10%. After incubation for 48 h, the supernatants were tested for their ability to promote the uptake of [3H]thymidine into lectin-activated lymphocytes. Supernatants from lymphocyte-free control samples, treated in the same manner, were assayed under the same experimental conditions. Variance analysis of the different dose-response relationships was performed. The results of these in vitro experiments confirm that physiological levels of GH inhibit the lectin-induced lymphoproliferation and that lymphocytes secrete an 'activity' able to stimulate the incorporation of [3H]thymidine into lectin activated lymphocytes. Furthermore we show that: 1) Secretion of this lymphocyte-stimulating activity is increased by physiological levels of GH; 2) This lymphocytic secretion is not radioimmunoassayable IGF-I; 3) Using fast protein liquid chromatography (FPLC), this activity appears in fractions with various molecular weights.
A weight-related intravenous dexamethasone suppression test distinguishes obese controls from patients with Cushing's syndrome
Authors: Atkinson A. B. , McAteer E.J. , Hadden D. R. , Kennedy L. , Sheridan B. , Traub A. I.
Published: December 2008

Abstract. To establish a rapid test for Cushing's syndrome we measured serum cortisol during and following iv dexamethasone infusion (5 μg · kg−1 · h−1 for 5 h from 10.00 h) in simple obesity (N = 19) and in Cushing's syndrome (N = 12). We had first established that 5 μg · kg−1 · h−1 was the lowest dose which consistently lowered serum cortisol in simple obesity. In obesity, serum cortisols ranged from undetectable (<30) to 48 nmol/l at 17.00, < 30 to 37 at 19.00 and < 30 to 38 at 08.00 h the following day. Serum cortisol at these three times did not show any overlap between simple obesity and Cushing's syndrome. Having established these findings we proceeded to study a group of patients with polycystic ovarian disease. These patients behaved differently. Their values at 17.00 and 19.00 h did not overlap those of Cushing's syndrome. However, at 08.00 h, 5 of the 7 had values within the range seen in Cushing's syndrome with a mean of 290 ± 99 nmol/l. In conclusion, 17.00 and 19.00 h serum cortisol levels distinguish between Cushing's syndrome and both simple obesity and polycystic ovarian disease. However, in the latter, cortisol suppression is less prolonged than in simple obesity. This finding may be important for our understanding of the pathogenesis of the disease.
Growth hormone influences collagen deposition and mechanical strength of intact rat skin. A dose-response study
Authors: Jørgensen Peter Holmberg , Andreassen Troels Torp , Jørgensen Karin Damm
Published: December 2008

Abstract. The influence of biosynthetic human growth hormone on biomechanical properties (strain at maximum load, maximum load, relative failure energy, maximum stiffness) and collagen content of intact rat skin was measured after injection of biosynthetic human growth hormone for 90 days at doses of 0.16, 1.10 and 8.33 mg· kg−1 · day−1. The mechanical test showed that strain at maximum load, maximum load and relative failure energy increased with increasing doses of biosynthetic hGH. In the group receiving 8.33 mg · kg−1 · day−1, skin collagen content per surface area and skin collagen concentration in per cent of dry weight were increased, whereas the fat concentration in per cent of dry weight was decreased. Also when correcting the mechanical data for cross-sectional area, a positive correlation between dose and relative failure energy was found. When dividing the mechanical data by collagen content per surface area of the skin, the maximum stress and relative failure energy reached the highest value at a dose of 1.10 mg · kg−1 · day−1. The study shows that biosynthetic hGH can induce an increase in collagen content and mechanical strength of intact rat skin which is dependent on the dose of biosynthetic hGH, and that the increase in mechanical strength cannot be explained only by an increased collagen content.
Timed interruption of insulin therapy in diabetic BB/E rat pregnancy: effect on maternal metabolism and fetal outcome
Authors: Eriksson U. J. , Bone A. J. , Turnbull D. M. , Baird J. D.
Published: December 2008

Abstract. Experimental and clinical studies have suggested that periods of poor metabolic control in early diabetic pregnancy have an adverse effect on the developing embryo, but the precise nature and mechanism of this damaging influence have not been defined. In this study the effect of withdrawing treatment with insulin for 2 days at various times during early gestation on maternal metabolism and fetal outcome has been investigated in the spontaneously diabetic BB/E rat. Nondiabetic BB/E rats and diabetic BB/E rats treated continuously with insulin throughout pregnancy served as controls. Continuously treated diabetic rats had a higher rate of fetal resorption and bigger placentae and their offspring had fewer ossification centres, lower extractable pancreatic insulin content, larger hearts, and smaller kidneys and lungs than the offpring of non-diabetic rats. Interruption of treatment with insulin further aggravated the adverse effect of diabetes on the outcome of pregnancy by resulting in a further increase in the rate of fetal resorption, a rise in the neonatal death rate, a reduction in fetal body weight, and retardation of skeletal development. These effects were more apparent when interruption of treatment with insulin occurred during the period of organogenesis, i.e. during gestational days 8 and 9, and 10 and 11. Two severe malformations were seen, both in litters originating from mothers whose treatment with insulin was interrupted during and immediately before fetal organogenesis. We conclude that a period of disturbed maternal metabolism during fetal organogenesis is capable of affecting the survival, growth, and organ development of the fetus and that the spontaneously diabetic insulin-dependent BB rat appears to be a good model for studies of the effect of diabetes and its treatment on the outcome of pregnancy.
Skeletal muscle potassium increases after diet and weight reduction in obese subjects with normal and impaired glucose tolerance
Authors: Landin Kerstin , Lindgärde Folke , Saltin Bengt
Published: December 2008

Body composition calculated from total body potassium and skeletal muscle potassium were studied in middle-aged obese men and women with normal and impaired glucose tolerance as well as Type II diabetes before and after advice on calorie reduction during twelve months. The subjects were compared with healthy lean men and women. Mean weight loss was 6.6 kg (P< 0.05). Lean body mass and body fat decreased 2.0 kg (P< 0.05) and 4.6 kg (P< 0.05), respectively. Total body potassium decreased by a mean of 146 ± 49 mmol (P< 0.01). Obese men with Type II diabetes and impaired glucose tolerance had lower total body potassium and muscle potassium levels than obese healthy men. After dieting, the obese men and women increased their muscle potassium levels with a mean of 2.8 mmol/100 g fat-free dry weight to 42.6 ± 2.6 mmol/100 g fat-free dry weight (P< 0.05), but they were still below the levels of the lean controls, 44.4 ± 1.3 mmol/100 g fat-free dry weight, (P< 0.01). Increase in skeletal muscle potassium was correlated to decrease in body weight, r = 0.55 (P< 0.01) and to decrease in fasting blood glucose, r = 0.42 (P< 0.05).
Evidence for reversible and irreversible biochemical defects in accessory sex organs and kidney of neonatally androgenized male mice
Authors: Veyssiere G. , Jean-Faucher Ch. , Berger M. , Jean Cl.
Published: December 2008

Studies were conducted to evaluate the effects of neonatal administration of supraphysiological doses of testosterone on the growth, hormone responsiveness, DNA and protein content, and protein profiles of the epididymis, vas deferens and seminal vesicles in adult mice. Results indicate that in androgenized males, testicular growth (DNA and protein content), circulating and organ androgen levels, and fertility were significantly depressed. The weights of the epididymis, vas deferens, seminal vesicle and kidney, but not that of the spleen, were significantly diminished subsequently to a reduction of protein (all organs) and DNA (epididymis, vas deferens) content. The efficacy of testosterone in promoting accessory sex organs and kidney growth, in adult castrated males, was persistently reduced in neonatally androgenized males. When assessed by DNA content, the response of all organs (except the seminal vesicle) was similar to that of controls, but it was significantly reduced from 16 to 43% when measured in terms of protein content. The protein profiles from seminal vesicles and vas deferens analysed by polyacrylamide gel electrophoresis, showed reproducible persistent alterations which could be reversed by adult androgen therapy.
Ultrasonography related to clinical and laboratory findings in lymphocytic thyroiditis
Authors: Gutekunst Rainer , Hafermann Wiard , Mansky Thomas , Scriba Peter C
Published: December 2008

The value of ultrasonography compared with established diagnostic procedures was investigated by reviewing medical records of 92 patients (88 women and 4 men, age 11–81 years, mean age 47) with lymphocytic thyroiditis. Clinical manifestations of the disease and serum antimicrosomal antibodies and TSH were determined in all patients. The thyroid was examined by ultrasound. Both lobes were aspirated by a fine needle under sonographic control and smears examined cytologically. A total of 27 (29.3%) patients had no clinical symptoms. Antimicrocosmal antibodies were undetectable in 12 (13%) patients, 16 (17.4%) had low titres 1:32–1:100, and 64 (69.6%) ≥ 1:320. TSH (reference values 0.3–3.9 mU/l) was < 0.3 in 4 (4.3%) 0.3–3.9 in 41 (44.6%), 4–20 in 26 (28.3%), and > 20 in 21 (22.8%) patients. Ultrasound revealed a scattered sonolucent echo in 87 (94.6%) patients, and in 45 (48.9%) a normal thyroid volume (women < 18, men < 25 ml). Cytology alone was diagnostic in 84 (91.3%) patients. In conclusion, ultrasound can suggest lymphocytic thyroiditis. If antimicrosomal antibodies are undetectable or titres are not significant and/or clinical symptoms are uncertain, fine-needle aspiration can confirm the sonographic finding. Epidemiological studies including ultrasonography are necessary to obtain reliable data on the prevalence of lymphocytic thyroiditis.
Serum gonadotropins levels in childhood. Critical comparison between immunoradiometric assays and radioimmunoassays
Authors: De Hertogh R. , Wolter R. , Van Vliet G. , Vankrieken L.
Published: December 2008

The complex changes in serum LH and FSH levels from infancy to adulthood are diversely evaluated by radioimmunoassays or bioassays. The relative lack of sensitivity and specificity of radioimmunoassay, using polyclonal antibodies, could possibly be overcome by new immunoradiometric assays, using specific antibodies to LH and FSH. Significant differences were indeed observed between radioimmunoassays and immunoradiometric assays. During the prepubertal period, LH levels, measured by the immunoradiometric assays, were below the sensitivity of the method in the majority of the samples. LH levels were, however, well detectable when measured with radioimmunoassay, showing the heterogeneity of circulating LH structures. At the onset of puberty, LH levels increased at least 3 to 4 times in both sexes, when measured with immunoradiometric assays, whereas their increase was only 20 to 60% with the radioimmunoassays. FSH levels remained well detectable in the prepubertal period whether measured by immunoradiometric or radioimmunoassays. At pubertal onset, FSH increase in both sexes was more important in the immunoradiometric assays. The results obtained with immunoradiometric assays give a better insight into the quantitative and qualitative function of the gonadotropes during childhood. The almost complete absence of LH during the prepubertal period and the steep increase at the onset of puberty better reflects the reported data obtained with bioassays. The persistance of significant levels of FSH in the prepubertal ages, and the lesser increase at the onset of puberty, when compared with LH, illustrates that the individual regulation of LH and FSH secretion vary over time and is influenced by developmental factors.
Changes in basal and stimulated TSH and other parameters of thyroid function in acromegaly after transsphenoidal surgery
Authors: Geelhoed-Duijvestijn P. H. L. M. , Bussemaker J. K. , Roelfsema F.
Published: December 2008

T4 and T3 levels, TSH response to TRH and somatomedin-C levels in 63 patients with acromegaly, were measured before transsphenoidal surgery and during a 4-year follow-up period. Criteria for cure were: mean GH level <5 mU/l, suppression of GH by oral glucose tolerance test below 2.5 mU/l and normalization of paradoxical GH reaction to TRH. Nine patients underwent radioiodine studies to assess the renal and thyroid clearance of iodide, plasma inorganic iodine level and absolute iodine uptake. Among the patients 40% had goitre, with a male preponderance. T4 and T3 levels were in the normal range both before and after surgery. A transient decrease in T3 levels was found in the immediate postoperative period. Before treatment a diminished or absent TSH response to TRH was exhibited by 64% of the goitre patients and 34% of the non-goitre groups (p < 0.05). Despite normalization of GH and somatomedin-C levels and normal T4 and T3 levels no improvement of the TSH response was found during followup. No correlation between the incremental response of TSH to TRH and circulating T4 or T3 levels, basal TSH, GH or tumour size was found. There was, however, a negative correlation (r = −0.765, p < 0.05) between the incremental TSH response to TRH and somatomedin-C levels for females with goitre. Somatomedin-C levels were higher in patients with goitre than in those without goitre (95 ± 26 vs 75 ± 30 nmol/l; mean ± sd, p = 0.05). Radioiodine studies showed an increased renal clearance of iodide which was related to the increase in creatinine clearance. The absolute iodine uptake was significantly higher for male acromegalic patients than for controls (7.2 ± 2.2 vs 3.9 ± 2.3, p < 0.05) and decreased significantly postoperatively. From this study we conclude that the increased incidence of goitre in acromegaly is not caused by iodine deficiency, but is probably related to a stimulatory effect of GH or somatomedin-C on thyroid growth and function. In contrast to patients with other pituitary tumours, the impaired TSH response in acromegalic patients is not associated with hypothyroidism, and the TSH response to TRH does not normalize postoperatively, despite normalization of GH levels.
Renal iodide clearance in rabbits
Authors: Vadstrup Steen
Published: December 2008

The purpose of the study was to compare indirect clearance methods based on plasma values and external detection of activity using small skin attached radioactivity detectors with a direct clearance method based on constant infusion and urine collection. The experiments were performed in anesthetized rabbits. The plasma iodide concentration was increased 100 times to prevent thyroid organification of radioactive iodide. [131I]iodide was infused at a constant rate and [125I]iodide was administered iv as a bolus for indirect clearance determination. The ratio between plasma values and external values 125I-activity was constant in all experiments from 15 min after administration of [125I]iodide and throughout the experiment. The results of 7 experiments in 3 rabbits showed a highly significant correlation (r = 0.98) between direct and indirect values within the range of direct clearance values obtained (0.002–0.6 ml · min−1 · kg−1· The direct and indirect clearances were measured simultaneously during a 2-h period of steady state. The 95% confidence interval of the mean ratio between direct and indirect clearances was ± 20% for plasma activity and ± 26% for externally measured activity. It is concluded that both methods of indirect clearance determination can be applied to rabbits to estimate absolute values of the renal iodide clearance.
Effects of physiologic and supraphysiologic hyperglycemia on early and late-phase insulin secretion in chronically dialyzed uremic patients
Authors: Schmitz Ole
Published: December 2008

To test secretory capacity of the beta-cell to a glucose stimulus in uremic patients on chronic dialysis, three hyperglycemic clamps (plasma glucose increments: 1, 4.5 and 11 mmol/l) were performed in 8 uremic and 8 healthy subjects. Early-phase insulin and C-peptide responses (ΔI and ΔC) during the initial 6 min were consistently exaggerated at all three steps in uremic patients compared with controls (ΔI. 16 ± 4 vs 4 ± 2, 41 ± 11 vs 15 ± 4 and 60 ± 12 vs 24 ± 5 mU/l; ΔC. 0.39 ± 0.13 vs 0.07 ± 0.02, 0.40 ± 0.13 vs 0.16 ± 0.02 and 0.73 ± 0.15 vs 0.29 ± 0.04 nmol/l, p < 0.05 in all cases). Similarly, late-phase insulin secretion defined as the insulin increment between 90 and 120 min after initiation of the glucose challenge was enhanced in uremic patients at the two highest glycemic steps (44 ± 10 vs 16 ± 2 and 123 ± 29 vs 44 ± 5 mU/l, both p < 0.01). The raised late-phase insulin response allowed comparable glucose disposal in the two groups (uremic patients: 9.2 ± 1.0 and 15.5 ± 1.6 mg · kg−1 · min−1· Controls: 9.0 ± 1.3 and 19.9 ± 2.4 mg · kg−1 · min−1). The slopes of potentiation, i.e. the slopes of the regression lines expressing the relationship between changes in insulin increments and changes in glucose, were markedly steeper in uremic patients (0.45 ± 0.09 and 0.66 ± 0.20, early and late-phase respectively) than in controls (0.20 ± 0.06 and 0.25 ± 0.03). No relationship between serum insulin responses and electrolytes or PTH was demonstrated. In conclusion, despite several factors which may inhibit the ability of the beta-cell to respond to a glucose stimulus, acute hyperglycemia elicits in insulin-resistant uremic subjects an exaggerated early and late-phase insulin secretion which is able to compensate for insulin resistance, thereby maintaining normal glucose disposal.
Estrogen biosynthesis in human uterine adenomyosis
Authors: Urabe Mamoru , Yamamoto Takara , Kitawaki Jo , Honjo Hideo , Okada Hiroji
Published: December 2008

Estrogen biosynthesis (aromatase activity) was investigated in human adenomyosis tissue and compared with that of the normal myometrium, endometrium, and endometrial cancer tissues. Homogenates were incubated with [1,2,6,7-3H]androstenedione and NADPH at 37° C for 1 h. After stopping the enzymatic reaction with ethyl acetate, [4-14C]estrone and [4-14C]estradiol-17β were added to the incubated sample. Estrone and estradiol were purified and identified by Bio-Rad AG1-X2 column chromatography, thin-layer chromatography and co-crystallization. Estrogen formed in the incubated sample was calculated from the 3H/14C ratio of the final crystal. The value for estrone formed from androstenedione was 52–132 fmol· h −1 · g−1 wet weight. Aromatase activity in the adenomyosis tissues was higher than that in normal endometrial or myometrial tissues, but lower than that found in myometrial or endometrial tumour tissue. Furthermore, we investigated the effect of danazol, progesterone, and medroxyprogesterone acetate on adenomyosis cells in primary cultures. Aromatase activity in adenomyosis was blocked by danazol, but stimulated by progesterone and MPA. These results indicate that aromatase activity in adenomyosis may contribute to the growth of the ectopic endometrial tissue which occurs in this disease.
Familial acromegaly
Authors: Pestell Richard G. , Alford Frank P. , Best James D.
Published: December 2008

Five family members over 3 generations had isolated functional pituitary adenomas diagnosed. In four cases acromegaly was diagnosed, and in the fifth galactorrhoea from prolactin excess was the presenting feature. A prominent feature of the affected members tumours were histological finding of either atypical mixed cell or undifferentiated cell type. Given the low incidence of acromegaly and the demonstration of vertical transmission over 3 generations it is suggested this family represents an inherited pituitary syndrome, distinct from Multiple Endocrine Neoplasia (MEN) type 1.
Erratum
Authors: Schleusener H. , Schwander J. , Fischer C. , Holle R. , Holl G. , Badenhoop K. , Hensen J. , Finke R. , Bogner U. , Mayr W. R. , Schernthaner G. , Schatz H. , Pickardt C. R. , Kotulla P.
Published: December 2008

Graves' disease is an autoimmune disease characterized by a course of remission and relapse. Since the introduction of antithyroid drug treatment, various parameters have been tested for their ability to predict the clinical course of a patient with Graves' disease after drug withdrawal. Nearly all these studies were retrospective and often yielded conflicting results. In a prospective multicentre study with a total of 451 patients, we investigated the significance of a variety of routine laboratory and clinical parameters for predicting a patient's clinical course. Patients who had positive TSH receptor antibodies activity at the end of therapy showed a significantly higher relapse rate than those without (P < 0.001). However, the individual clinical course cannot be predicted exactly (sensitivity 0.49, specificity 0.73, N = 391). The measurement of microsomal (P = 0.99, sensitivity 0.37, specificity 0.63, N = 275) or thyroglobulin antibodies (P = 0.76, sensitivity 0.18, specificity 0.84, N = 304) at the end of antithyroid drug therapy did not show a statistically significant difference in the antibody titre between the patients of the relapse and those of the remission group. Additionally, HLA-DR typing (HLA-DR3: P = 0.37, sensitivity 0.36, specificity 0.58, N = 253) was proven to be unsuitable for predicting a patient's clinical course. Patients with abnormal suppression or an abnormal TRH test at the end of antithyroid drug therapy relapse significantly more often (P< 0.001) than patients with normal suppression or normal TRH test. Patients with a large goitre also have a significantly (P< 0.001) higher relapse rate than those with only a small enlargement. The sensitivity and specificity values of all these parameters, however, were too low to be useful for daily clinical decisions in the treatment of an individual patient. This is also true for the combinations of different parameters. Though the highest sensitivity value (0.94) was found for a combination of the suppression and the TRH test at the end of therapy, the very low specificity value (0.13) for this combination reduced its clinical usefulness.
DNA evaluation in growth hormone producing pituitary adenomas: flow cytometry versus single cell analysis
Authors: Hulting A. L. , Askensten U. , Tribukait B. , Wersäll J. , Auer G. , Grimelius L. , Falkmer S. , Werner S.
Published: December 2008

DNA patterns were analysed in 26 GH-producing pituitary adenomas by flow cytometry as well as by microspectrophotometry. Twelve tumours (46%) were diploid according to both methods, whereas 5 tumours (19%) showed aneuploid DNA patterns. Nine tumours were classified differently by the two methods: flow cytometry resulted in diploidy in 2 and aneuploidy in 7 patients, whereas microspectrophotometry showed diploidy in 5 tumours, tetraploidy in 3 and aneuploidy in 1. Methodological limitations may explain the discrepancy in the results obtained by the two methods. However, both the flow cytometry and the microspectrophotometry method show the presence of aneuploid DNA patterns in GH-producing pituitary adenomas despite their benign growth characteristics and the clinically benign course of the disease. This comparative study with two methods measuring DNA content, shows that depending on the criteria used for diploidy-aneuploidy, the freqency of aneuploidy will vary. In this material of 26 GH-producing adenomas, 46% were aneuploid according to flow cytometry and 23% according to microspectrophotometric. However, no correlation to tumour size or GH levels was found with either method when patients with aneuploid and diploid tumours were compared. Therefore, no clinial significance can so far be drawn from these results.
Impaired somatostatin response to orally administered glucose in Type II diabetes entails both somatostatin-28 and -14 and is associated with deranged metabolic control
Authors: Gutniak Mark , Grill Valdemar , Roovete Arved , Efendic Suad
Published: December 2008

We have investigated the effects of hyperglycemia in Type II diabetic patients on the somatostatin response to oral glucose. In these patients hyperglycemia prevailed (11.8 ± 1.4 mmol/l) and was markedly increased to a maximum of 18.9 ±1.0 mmol/l following the ingestion of 75 g of glucose. The rise in blood glucose following glucose ingestion failed to induce a rise in plasma levels of somatostatin-like immunoreactivity. Biostator-regulated insulin infusion normalized fasting levels of blood glucose and reduced the hyperglycemia following glucose ingestion, i.e. blood glucose now rose from 4.6 ± 0.1 to a maximum of 7.3 ±0.8 mmol/l. This moderate rise in blood glucose was accompanied by a significant (p <0.05) rise in somatostatin-like immunoreactivity. Somatostatin-28 and somatostatin-14 were separated using a Sephadex G-50 fine column. Biostator treatment suppressed plasma levels of both peptides during fasting conditions. Treatment was also accompanied by a rise in both peptides during the first hour following glucose ingestion; this rise did not occur in the untreated state. In conclusion: lack of somatostatin response to glucose in non-insulin-dependent diabetes mellitus is associated with deranged metabolic control. Unresponsiveness to glucose entails the secretion of both somatostatin-28 and -14.
Study on clinical and endocrine characteristics of dexamethasone-suppressible hyperaldosteronism compared with those in primary aldosteronism owing to aldosterone-producing adenoma
Authors: Yamakita Noriyoshi , Yasuda Keigo , Noritake Nobuyasu , Mercado-Asis Leilani B. , Murase Hiroshi , Mune Tomoatsu , Morita Hiroyuki , Miura Kiyoshi
Published: December 2008

The clinical and endocrine characteristics of 12 Japanese patients with dexamethasone-suppressible hyperaldosteronism were compared with those in 49 Japanese patients with primary aldosteronism due to aldosteronoma. The results were as follows: 1. Most of the laboratory data in the two groups were almost the same. 2. The grade of vascular damage in both uncontrolled (3) and well-controlled (9) patients with dexamethasonesuppressible hyperaldosteronism did not correlate with blood pressure response. 3. The responsiveness of plasma aldosterone to exogenous ACTH in 6 patients with dexamethasone-suppressible hyperaldosteronism was not different from that in 9 patients with aldosteronoma. Even in 3 well-controlled patients in the former group, the plasma aldosterone response was as low as in all the 3 patients with small aldosteronomas. 4. In 4 patients with small aldosteronomas, plasma aldosterone was continuously suppressed with daily dexamethasone to the same degree as in dexamethasone-suppressible hyperaldosteronism. 5. The blood pressure, however, did not improve even in the patients with small aldosteronomas. The possible indistinguishable mechanism in dexamethasone-suppressible hyperaldosteronism and primary aldosteronism with small adenomas and the role of unknown hypertensinogenic steroid(s) other than aldosterone in inducing hypertension in dexamethasone-suppressible hyperaldosteronism are discussed.
Changes in plasma renin activity and aldosterone concentration in response to endothelin injection in dogs
Authors: Otsuka Atsuhiro , Mikami Hiroshi , Katahira Katsutoshi , Tsunetoshi Takeshi , Minamitani Kaori , Ogihara Toshio
Published: December 2008

The effects of endothelin on the renin-aldosterone system were examined by injecting it intravenously at low (40 pmol/kg) and high (400 pmol/kg) doses into pentobarbital-anesthetized dogs. Plasma renin activity and aldosterone concentration together with hemodynamic parameters were measured before and 60 min after endothelin injection. The lower dose of endothelin induced no significant increase in mean blood pressure or total peripheral resistance. It caused a slight decrease of plasma renin activity from 10.3 ± 1.6 to 5.9 ± 1.3 μg · l−1 · h−1 (p <0.1) and a decrease of aldosterone concentration from 364 ± 68 to 231 ± 58 ng/l (p <0.05) with an increase in total peripheral resistance (p <0.05), but it did not cause any clear change in the plasma renin activity or aldosterone concentration. Thus, endothelin increases the blood pressure mainly by vasoconstriction. The finding of a slight decrease in the plasma renin activity after the lower dose of endothelin, together with our previous finding that endothelin inhibits renin release from isolated rat glomeruli, suggests that endothelin inhibits renin release in vivo. With the higher dose of endothelin, stimulation of renin release secondary to renal vasoconstriction might have counteracted the direct inhibitory action of endothelin. The decrease in aldosterone concentration may have been due to the direct inhibitory action of endothelin on aldosterone release or it may be a secondary effect induced by suppression of plasma renin activity.
Effect of hypothyroidism and thyroid hormone treatment of the rat on hepatic Spot 14 and thyroxine binding prealbumin mRNAs
Authors: Franklyn J. A. , King S. , Ahlquist J. A. , Sheppard M. C.
Published: December 2008

We have examined the influence of hypothyroidism and thyroid hormone replacement on hepatic levels of Spot 14 and thyroxine binding prealbumin mRNAs determined by dot hybridization and by Northern blot hybridization to specific complementary DNA probes. A marked reduction in Spot 14 mRNA was demonstrated in hypothyroidism, compared with the euthyroid state. T3 replacement of hypothyroid rats, using a wide dose range of T3 (1–20 μg) and 6 and 72 h time points, demonstrated no sustained effect at 6 h, but a dose-dependent stimulation of Spot 14 mRNA at 72 h after daily treatment with T3 was commenced. In contrast, no effect of hypothyroidism or T3 replacement on hepatic levels of thyoxine binding prealbumin mRNA was demonstrated, indicating the specificity of thyroid hormone action. T3 treatment of euthyroid rats was also associated with a dose-related stimulation of Spot 14 mRNA levels. The effect of hypothyroidism and T3 treatment of the rat on hepatic Spot 14 mRNA contrasts with divergent regulatory influences of thyroid status in the anterior pituitary and ventricular myocardium demonstrated using identical animal models, indicating the tissue specific influences of thyroid status.
Slow growth but intense hypertrophy of thyrocytes in long-standing Graves' goitres
Authors: Derwahl Michael , Huber Gerold , Studer Hugo
Published: December 2008

In order to evaluate the relative contribution of true cell replication, in comparison to mere cell hypertrophy, to the notoriously slow growth of toxic Graves' goitres persistently exposed to TSH receptor antibodies and requiring continuous thyrostatic treatment for more than one year, we have determined the fraction of dividing cells in 8 such goitres, using the monoclonal antibody Ki-67. This antibody identifies cells in late Gl-, S-, G2- and M-phase. The fraction of Ki-67 positive cells ranged from 0.1 to 4.1% with a mean of 2.3 ± 1.6. The apparently low absolute number of dividing cells is in full accordance with growth rates observed in multinodular goitres and in benign tumours of thyroidal and non-thyroidal origin. It is compatible with continuous, intense growth stimulation of the gland, particularly since thyrocytes may down-regulate their growth response when exposed to chronic stimulation. The observations account for the the clinical observation that goitres, and in parti ular Graves' goitres, may take years to double their total mass of thyrocytes, whereas cell hyperplasia and functional overactivity (if untreated) continue unabated.
The effect of tamoxifen on the function and lifespan of the corpus luteum and on subsequent ovarian function
Authors: Swahn M. L. , Bygdeman M. , Matlin S. A. , Wu Z. Y.
Published: December 2008

The aim of the present study was to investigate the effects of tamoxifen on pituitary and luteal function and on the bleeding pattern when administered continuously in the secretory phase. The study included 16 women with regular menstrual cycles followed during one control, one treatment and one follow-up cycle. Each volunteer received 20 mg tamoxifen twice daily from cycle day 18 to menstruation in the treatment cycle. The luteal phase was slightly, but significantly prolonged during treatment, and FSH, progesterone, 17-hydroxyprogesterone, 20α-dihydro progesterone, estrone, estrone sulphate and estradiol significantly elevated in comparison with corresponding data during the control cycle. The results indicate that estrogen may be of some importance for the regulation of the life span of the corpus luteum in the human. The significantly elevated levels of pregnanediol glucuronide and estrone glucuronide during the follow-up cycle are most likely a result of either a direct effect of remaining circulating tamoxifen levels on the ovary, or mediated through the increased release of FSH. If estrogens are of importance for the process of implantation, which has recently been suggested in subhuman primates, also in the human remains unclear. Studies on the effect of anti-estrogens on the endometrium during the secretory phase of the cycle are ongoing.
Testosterone and its binding in hyperthyroid women before and under antithyroid drug therapy
Authors: Loric Sylvain , Duron Françoise , Guéchot Jérôme , Aubert Pierre , Giboudeau Jacqueline
Published: December 2008

The serum concentrations of the different forms of circulating testosterone, total testosterone, free testosterone and non-sex-hormone binding globulin bound testosterone (albumin bound + free fractions) which is considered as the biovailable hormone, were measured in 15 hyperthyroid women before and after anti-thyroid drug therapy and in 15 age-matched healthy women. Sex-hormone binding globulin and albumin were quantified. Total testosterone was significantly higher in hyperthyroid women before treatment, whereas free testosterone and non sex-hormone binding globulin bound testosterone were significantly decreased. After recovery, all the parameters returned to the normal range. In hyperthyroid patients, the variations in the different fractions of testosterone can be related to the rise of sex-hormone binding globulin. These variations could be explained by the displacement of the equilibrium defined by the binding equation.
Small stature and insulin-like growth factors: prolonged treatment of mini-poodles with recombinant human insulin-like growth factor I
Authors: Guler Hans-Peter , Binz Katharina , Eigenmann Eugen , Jäggi Silvia , Zimmermann Daniel , Zapf Jürgen , Froesch E. Rudolf
Published: December 2008

The short stature of mini-poodles is associated with low serum levels of IGF-I. Standard poodles are taller and have considerably higher serum levels of IGF-I. Low IGF-I serum levels may be a symptom or the cause of small stature. We, therefore, undertook a study in which serum IGF-I levels of mini-poodles were elevated over a prolonged period of time by a constant infusion of rhIGF-I and the growth rate of the mini-poodles was followed. We infused four mini-poodles from day 91 to day 221 of age with 6 mg/day of recombinant human insulin-like growth factor I (rhIGF-I). Serum levels of IGF-I rose from about 160 to about 500 μg/l. Blood glucose remained within normal limits. Stimulation tests with clonidine and with GHRH revealed suppression of endogenous GH secretion during the IGF-I infusion. Serum levels of IGF-II and of creatinine were lower in the IGF-I-infused animals. Radial length and body weight did not increase to a greater extent in the IGF-I infused dogs than in controls. However, 'adapted body mass index' (aBMI = gram body weight/(mm radial length)2) decreased in each of the IGF-I infused animals, whereas it increased in each of the control dogs (p <0.05). We conclude that long-term infusion of IGF-I does not stimulate growth in young minipoodles, but may change body composition.
Maturational changes in steroidogenic enzyme activities metabolizing testosterone and dihydrotestosterone in two populations of testicular interstitial cells
Authors: Murono Eisuke P.
Published: December 2008

The present study examined changes in steroidogenic enzyme activities which metabolize testosterone or dihydrotestosterone between days 21–73 of maturation in Band 2 and Band 3 cells isolated by centrifugation of rat testicular interstitial cells on metrizamide density gradients. 5α-reductase and 17β-hydroxysteroid dehydrogenase activities increased progressively in Band 2 and Band 3 cells between days 21–35 of maturation, then both enzyme activities declined to reach low levels in adult Band 2 and Band 3 cells. The significantly higher activities of both enzymes in Band 3, which contains a greater concentration of Leydig cells at each age, suggest their localization in Leydig cells. 5α-androstane-3α- and 3β-hydroxysteroid dehydrogenase activities increased in both Band 2 and Band 3 cells between days 21–50 of maturation and remained elevated; however, dihydrotestosterone was metabolized primarily to 5α-androstane-3α,17β-diol in Band 2 cells, while 5α-androstane-3β,17β-diol was the major metabolite of dihydrotestosterone in Band 3 cells. These studies suggest that testosterone accumulation during sexual maturation can be influenced by changing patterns of 5α-reductase and 17β-hydroxysteroid dehydrogenase activities which metabolize testosterone, and of 5α-androstane-3α- and 3β-hydroxysteroid dehydrogenase activities which metabolize dihydrotestosterone in both Band 2 and Band 3 cells.
Impaired ACTH and β-endorphin response to sauna-induced hyperthermia in heroin addicts
Authors: Vescovi Pier P. , Pedrazzoni Mario , Gerra Gilberto , Pioli Giulio , Maninetti Letizia , Michelini Massimo , Passeri Mario
Published: December 2008

To evaluate the responses of circulating β-endorphin, met-enkephalin and ACTH to sauna-induced hyperthermia, 8 male heroin addicts recently admitted to a therapeutic community and 8 age-matched normal subjects were examined. Compared with control subjects, heroin addicts showed 1. A decrease of the basal levels of β-endorphin; 2. Absence of the normal increase of β-endorphin and ACTH after sauna; 3. A lower increase in systolic blood pressure. It is concluded that an impairment of the adaptive response to stress may be present in heroin addicts, even after a relatively short drug-free period (14 days).
Normal visual fields as assessed by computerized static threshold perimetry in patients with untreated primary hypothyroidism
Authors: Hallengren Bengt , Manhem Per , Bramnert Margareta , Redlund-Johnell Inga , Heijl Anders
Published: December 2008

In this prospective study, 25 consecutive patients with untreated primary hypothyroidism were tested with a highly sensitive perimetric technique, since a high prevalence of visual field defects has been described in this condition. All patients had clinical hypothyroidism, a serum TSH value > 20 mU/l (reference range 0.4–4.0) and decreased/low normal serum total T4 concentration. Visual fields were tested with fully automated threshold-measuring computerized perimetry of the central 30 degrees field. Interpretation of fields included computer-assisted analysis provided by a perimetric statistical programme package. In 23 patients, conventional inspection and computer-assisted analysis showed no visual field defects. Two patients were excluded from the latter analysis: one patient who did not respond adequately at computerized perimetry and in whom manual field tests were entirely normal; one patient who had low sensitivity values in the uppermost parts of both visual fields owing to markedly swollen upper eye lids. In conclusion, although pituitary hyperplasia has been well documented in primary hypothyroidism, the present prospective study clearly indicates that visual field defects are not a common finding in patients with this disease.
IgE antibodies to human growth hormone prior to and during treatment
Authors: Petersen Karl-Georg , Khalaf Abdulnasser , Zeisel Hans-Joachim , Stryjek-Kaminska Danuta , Kerp Lothar
Published: December 2008

Clinical manifestations of allergy to biosynthetic hGH were not reported in 245 patients treated for one year. A sensitive radioallergosorbent test showed, however, the presence of anti-hGH IgE antibodies in the sera of 13%. All patients with anti-hGH IgE had also elevated concentrations of total serum IgE, similar to atopic persons (2459 ± 147 μg/l, normal 70 ± 8, 2p < 0.0001); 83% of all patients who had specific IgE antibodies to hGH had specific antibodies prior to treatment. Administration of hGH did not consistently change concentrations (up to 8 μg/l or affinities (< 107 to 1.3 × 109 l/mol) of the specific reagins. Anti-hGH IgE antibodies were related to atopy. Treatment with biosynthetic hGH did not significantly stimulate specific IgE.
Biological activity of 26,26,26,27,27,27-hexafluoro- 1,25-dihydroxyvitamin D3 in the chick
Authors: Kiriyama Takeshi , Okamoto Sumiaki , Suzuki Hiroyuki , Nagata Akihiko , Izumi Motomori , Morii Hirotoshi , Nagataki Shigenobu
Published: December 2008

A newly synthesized fluorinated analogue of 1,25-dihydroxyvatimin D3 (1,25(OH)2D3), 26,26,26,27,27, 27-hexafluoro-1,25-dihydroxyvitamin D3 (26,27-F6-1,25-(OH)2D3) has been compared with 1,25(OH)2D3 as to its biological activity in vitamin D-deficient chicks. One day old, white Leghorn cockerels were fed a rachitogenic diet for 5 weeks. They were then given vehicle or 32.5, 130 or 325 pmol of 26,27-F6-1,25(OH)2D3 or 1,25(OH)2D3 in a solution of propylenglycol:ethanol (95:5 v/v) sc every day for 2 weeks. Twenty-four hours after the last dose, the animals were sacrificed and their femurs were removed. 26,27-F6-1,25(OH)2D3 was more active than 1,25(OH)2D3 in stimulating growth, healing of rachitic cartilage visualized by soft X-ray radiography, elevation of serum inorganic phosphorus, and mineralization of rachitic bone. These biological differences between two compounds were observed only for the dose of 130 pmol. However, this fluorinated compound has less binding ability than 1,25(OH)2D3 to fetal chick intestinal cytosol receptors. The mechanism of the higher potency of this analogue is still unknown, but its affinity to the 1,25(OH)2D3 receptor does not account for the higher activity. Since 26-hydroxylation can be postulated as the inactivation step in vitamin D metabolism, these results suggest that the reason for increased activity of this fluorinated analogue is most likely its slower metabolism.
Characterization of α2-adrenoceptors in a plasma membrane enriched fraction from the insulin-secreting cell line RINm5F
Authors: Ullrich Susanne , Wollheim Claes B.
Published: December 2008

A plasma membrane enriched fraction from the insulin-secreting cell line RINm5F was used to characterize [3H]clonidine binding. After a single self-generating Percoll gradient, the specific activity of 5'-nucleotidase (a plasma membrane marker) of the membrane fraction was enriched about 8-fold over that of the homogenate and nearly 30% of the total amount was recovered. The fraction was essentially free of mitochondria and secretory granules. [3H]clonidine binding to this membrane fraction revealed a single, high affinity binding site with a Kd of 2.3 nmol/l. The binding was competitively inhibited by adrenergic agonists in the following order of potency: clonidine > epinephrine > phenylephrine > isoproterenol, and by antagonists in the order of potency: idazoxan > yohimbine > propranolol > prazosin. Pertussis toxin pretreatment of the cells did not alter the inhibition of [3H]clonidine binding by epinephrine and clonidine nor the estimated receptor number for [3H]clonidine. In conclusion, the pharmacologic characteristics of [3H]clonidine binding sites on a plasma membrane enriched fraction from insulin-secreting RINm5F cells demonstrate that the receptor is of the α2-adrenergic subtype.
Urinary excretion of human growth hormone: daily variation and relationship with albumin and α1-microglobulin in urine
Authors: Hattori Naoki , Shimatsu Akira , Kato Yuzuru , Koshiyama Hiroyuki , Ishikawa Yasuhiro , Tanoh Tsutomu , Assadian Hossein , Imura Hiroo
Published: December 2008

Urinary excretion of growth hormone during night-time was measured by a highly sensitive enzyme immunoassay in 6 normal men for 18–24 days. Urinary GH excretion distributed widely from 0.12 to 4.7 pg/μmol creatinine and the coefficient of variation in each subject ranged from 37 to 57% (mean 49%). Urinary excretion of albumin and α1-microglobulin also showed moderate day-to-day variations (mean coefficients of variation: 37 and 42%, respectively). No correlation was found among urinary excretion of GH, albumin and α1-microglobulin. Plasma and urinary GH levels were determined every 5 min and 2 h, respectively, from 09.00 h to 17.00 h in 4 normal men. Urinary GH excretion every 2 h during daytime closely reflected the change of plasma GH levels in each subject, suggesting that physiological GH secretory dynamics are reflected on the urinary GH excretion. Repeated measurements of urinary GH excretion are required to evaluate GH secretory capacity.
Thyroid-infiltrating lymphocytes, thyroid function, and HLA-DR in juvenile autoimmune thyroiditis
Authors: Mäenpää Jorma , Lautenschlager Irmeli , Nyberg Marcus , Koskimies Saija , Kontiainen Sirkka
Published: December 2008

Eighteen patients with juvenile autoimmune thyroiditis were studied. At diagnosis 8 (44%) of the patients were euthyroid and 10 hypothyroid, whereas at the end of 6 to 12 months follow-up, 12 (66%) were euthyroid and 6 hypothyroid. All the patients were HLA-typed. The frequency of HLA-DR4 was increased in the patients when compared with the normal population, 63 vs 28% (p < 0.01). An analysis of thyroid-infiltrating mononuclear cells revealed that the majority of the thyroid-infiltrating lymphocytes were T cells. More T lymphocytes and fewer B lymphocytes and HLA class II positive lymphocytes were found among the thyroid-infiltrating mononuclear cells in euthyroid than hypothyroid patients. The numbers of thyroid-infiltrating B lymphocytes correlated with the levels of thyroid microsomal antibodies. No correlation was found between thyroid function and thyroid antibodies.