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W A Scherbaum

Publications and source records attributed to W A Scherbaum.

At least 217 records · Page 12Linked to original sources
PubMed1991

Gonadotropin secretion during aging in postmenopausal women.

Although chronological aging is known to result in reduced gonadotropin secretion in women, the precise mechanisms to account for this neuroendocrine manifestation are yet obscure. To evaluate the extent to which the pituitary and/or hypothalamus are involved in the process of aging, we aimed at characterizing the unstimulated and GnRH-stimulated gonadotropin secretion in postmenopausal women (PMW) of different ages. Accordingly, 9 younger PMW (mean age: 53.8 years) in their first and 9 older PMW (mean age: 80.3 years) in their 4th decade of life after natural onset of menopause were studied. In both groups, blood was collected at 10-min intervals for 10 h, while GnRH (25 micrograms i.v.) was administered 8 h after initiation of blood samplings. Compared to younger PMW, basal serum concentrations of dehydroepiandrosterone-sulfate were lower (p less than 0.05) in older PMW, while estrogen (estradiol, estrone), androgen (testosterone, androstendione) and sex hormone binding globulin levels were similar. Lower (p less than 0.01) mean LH levels composed of attenuated (p less than 0.05) LH pulse amplitudes and pulse frequencies (as determined by the cluster pulse algorithm) were found in the 8-hour LH secretory profiles of older PMW. Furthermore, the FSH secretion of older PMW was characterized by lower (p less than 0.01) mean FSH levels with lower (p less than 0.05) FSH pulse amplitudes, but not pulse frequencies. The absolute peak concentrations attained and the total amount of LH and FSH released in response to GnRH stimulations were blunted (p less than 0.001) in older PMW.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1991

Role of the vasoactive intestinal peptide in a neuroendocrine regulation of the adrenal cortex.

Using a method for isolation and perfusion of pig adrenal glands with preserved nerve supply, we measured the release of cortisol and aldosterone and of the vasoactive intestinal peptide (VIP) after electrical stimulation of the splanchnic nerves. Additionally, the effect of VIP (at final concentrations of 10(-10)-10(-7) M) in the perfusion medium on the release of cortisol and aldosterone was investigated. The amount of VIP contained within the adrenal was measured by chromatography, and the localization of VIP in the adrenal gland was investigated immunohistochemically. Stimulation of the splanchnic nerves provoked a significant release of VIP (2.7- to 17-fold) and of the corticosteroids cortisol (2.5- to 6.7-fold) and aldosterone (1.6- to 2.8-fold). VIP added to the perfusion medium stimulated secretion of both corticosteroids with a maximal effect at 10(-8) M. Cortisol release increased 20- to 58.5-fold over basal, aldosterone release increased 2.9- to 4.9-fold over basal. This VIP-stimulated release had the same range of magnitude as the release stimulated by adrenocorticotropic hormone in physiological concentrations (10(-10) M). The mean concentration of VIP-like immunoreactivity in the adrenal glands was 8.9 +/- 2.1 pmol/g wet weight. Immunohistochemical investigations showed immunoreactive cells within the adrenal medulla as well as VIP-ergic nerve fibers in the cortex of the adrenal gland. These data show that the adrenal cortex can be stimulated independent of the hypothalamus-pituitary-adrenal axis via a neuroadrenocortical axis. In this regulatory pathway, the VIP-ergic innervation of the adrenal cortex may be a potent stimulatory element.

Adrenal Cortex↗
PubMed1991

Ultrastructural evidence for cortico-chromaffin hybrid cells in rat adrenals?

The adrenals of perfusion fixed rats were investigated by electron microscopy. In 2 out of 12 animals studied, chromaffin cells were detected that contained organelles identical to adrenocortical mitochondria and smooth endoplasmic reticulum. The mitochondria were round-shaped with the vesicular cristae typical for steroid hormone producing cells. They were located within the cytoplasm of adrenomedullary cells neighbouring chromaffin vesicles, rough endoplasmic reticulum and the characteristic elongated mitochondria of chromaffin cells with laminar cristae. The mitochondria-like structures could be clearly differentiated from the extracellularly located synaptic endings. It can therefore be concluded that some rare cortico-chromaffin hybrid cells or chromaffin cells that present a mitochondrial-endoplasmic system of adrenocortical cells exist within the adrenal medulla. This surprising finding may offer an explanation for the long line of inconsistencies in clinico-pathological reports of adrenal morphology.

Adrenal Cortex↗
PubMed1991

Adrenaline stimulates cholesterol side-chain cleavage cytochrome P450 mRNA accumulation in bovine adrenocortical cells.

The effect of adrenaline on the accumulation of mRNA encoding cholesterol side-chain cleavage cytochrome P450 (P450scc) and cortisol secretion was studied in bovine adrenocortical cells in primary culture. Treatment of cultured cells with adrenaline resulted in a 2-fold increase in mRNA encoding P-450scc, as revealed by Northern blot analysis. Under these conditions the maximal stimulation with ACTH resulted in a 6-fold accumulation of mRNA encoding P450scc. The effect of adrenaline on the expression of P450scc was abolished by the beta-blocker propranolol, while propranolol had no effect on ACTH-induced P450scc mRNA accumulation. Adrenaline stimulated the secretion of cortisol in a dose-dependent manner with a median effective dose of 0.5 mumol/l. The adrenaline-stimulated cortisol secretion amounted to 42% of the effect of ACTH (0.1 nmol/l). Upon adrenaline treatment, cAMP concentration in the culture medium increased about 50-fold over the basal value. It is concluded that the stimulatory action of adrenaline upon cortisol formation requires beta-adrenergic receptors and is due, at least in part, to a cAMP-mediated increases in the accumulation of mRNA encoding P450scc.

Adrenal Cortex↗
PubMed1991

Epidemiology and immunogenetic background of islet cell antibody--positive nondiabetic schoolchildren. Ulm-Frankfurt population study.

Islet cell antibodies (ICAs) were determined in a large cohort of white nondiabetic schoolchildren (n = 4287) from a homogenous population in southern Germany. The prevalence of ICA levels greater than or equal to 5 Juvenile Diabetes Foundation (JDF) U was 1.05% (95% confidence interval 0.8-1.4%). Analysis of HLA-DR beta and -DQ beta alleles revealed that the specificities found to be increased in insulin-dependent (type I) diabetic subjects with the same ethnic background were also associated with ICA positivity in the nondiabetic schoolchildren. HLA-DR3 (P less than 0.01) and -DR4 (P less than 0.01) phenotypes and absence of Asp residue (P less than 0.01) at codon 57 of the HLA-DQ beta-chain were significantly increased in ICA+ compared with control subjects. High levels of ICAs, which were categorized as either greater than or equal to 17 or greater than or equal to 30 JDF U, were found to be associated with amino acids other than Asp at position 57 of the HLA-DQ beta-chain. No association of ICA level was found for HLA-DR phenotypes.

Adolescent↗
PubMed1990

[Epidemiologic studies of the recognition of the preclinical phase of type I diabetes in school children].

Sera of 4208 schoolchildren in Ulm and surrounding areas (1916 boys, 2292 girls; mean age 13.9 [7-21] years) were analysed for the presence of cytoplasmatic islet-cell antibodies (ICA). ICA were demonstrated in 44 children (1.05%). Complement-fixing ICA (CF-ICA) were found in six of them, insulin autoantibodies (IAA) in seven. The early phase of insulin response in the intravenous glucose tolerance test was below the 1st percentile of normal controls in two of the ICA-positive children. In the course of the subsequent 6-9 months the ICA disappeared in half of the previously positive children. In the two with abnormal glucose tolerance tests ICA, CF-ICA and abnormal insulin secretion persisted during the observation period of 9 months. In another CF-ICA-positive schoolchild insulin response to the glucose tolerance test fell below the 1st percentile after 6 months. These results indicate that, even in an unselected group of children, persisting ICA and CF-ICA are high-risk markers for abnormal insulin secretion, which precedes the onset of type I diabetes.

Adolescent↗
PubMed1990

Adrenocortical atrophy of hypophysectomized rats can be reduced by corticotropin-releasing hormone (CRH).

The effects of high dose injections of corticotropin-releasing hormone (CRH) on the adrenal cortex of hypophysectomized rats were studied at the light- and electron-microscopical levels. Adrenocortical atrophy induced by hypophysectomy could be reduced by daily i.p. injection of 10 micrograms (3 nmol) CRH given for 3 days starting at day 5 after the operation. The cortex broadened, mostly because of hypertrophy of the zona fasciculata. Blood vessels were enlarged. Although the adrenocortical cells of hypophysectomized rats showed features of a functionally suppressed state, such as tubular mitochondria, the cells of CRH-treated animals showed characteristics of stimulated cells. The inner membrane of the mitochondria formed the typical densely packed vesicles of adrenocortical cells that are active in steroidogenesis. Lipid droplets were found to be reduced, and the cells developed filopodia at their surface. These morphological observations indicate that CRH influences the adrenal cortex via extrapituitary mechanisms.

Adrenal Cortex↗
PubMed1990

Substrate specificity for the detection of autoantibodies to anterior pituitary cells in human sera.

Using the indirect immunofluorescence test for the detection of pituitary autoantibodies in human serum, the results obtained with human fetal and non-human pituitary antigens were compared. Of the sera that were positive on human fetal substrate, 4% were recovered with adult baboon, 0% with fetal cymologous, 20% with porcine, 11% with bovine, 11% with ovine, and 7% with rat tissue. The rate of heterophilic antibodies to the above animal substrates was 5% to 14%. In contrast to human adult pituitaries, normal human sera did not bind to Fc receptors on ACTH-cells of human fetal pituitaries. This allowed the demonstration of ACTH-cell antibodies. The specificity of the reaction was proven by absorption studies with purified Fc fragments. These results suggest that human fetal tissue is the best source of antigen for the detection of pituitary autoantibodies. The use of animal tissue including non-human primate pituitary yields results that bear no clinical significance.

Animals↗
PubMed1990

Effect of cytokines on proliferation of Epstein Barr virus-transformed B lymphocytes.

Plating efficiencies of EBV transformed human B cells seeded in single cell cultures are far lower (less than 1%) than observed in T cell cloning experiments. This report describes the stimulatory effect of several crude as well as recombinant growth factors on proliferation of EBV transformed B cells measured by [3H]thymidine uptake. Supernatant of LPS activated monocytes (HSF) and recombinant interleukin 4 (rIL-4), but not recombinant IL-1 beta, IL-2, IL-6, TNF alpha, GM-CSF, and interferon gamma increased [3H]thymidine incorporation. The combination of HSF and rIL-4 was found to be synergistic on B cell proliferation. Plating efficiency of EBV transformed B cells at limiting dilution was improved by HSF, but not by the combination of HSF and rIL-4.

B-Lymphocytes↗
PubMed1990

Effects of splanchnic nerve stimulation on the adrenal cortex may be mediated by chromaffin cells in a paracrine manner.

The effects of nerve activation and of the catecholamines epinephrine and norepinephrine on adrenal corticosteroid release were investigated in intact isolated perfused pig adrenals with preserved nerve supply. To study the contact zones of medullary and cortical tissues, porcine adrenals were examined on the histological and ultrastructural levels. Splanchnic nerve activation stimulated in parallel the release of epinephrine (from a basal value of 0.31 +/- 0.11 to 8.13 +/- 0.60 microgram/min) and norepinephrine (from 0.76 +/- 0.68 to 12.94 +/- 3.58 micrograms/min) and the release of the corticosteroids cortisol (from 0.62 +/- 0.19 to 2.00 +/- 0.35 micrograms/min) and aldosterone (from 3.34 +/- 0.59 to 7.53 +/- 1.63 ng sigma in). Also, perfusion of the isolated adrenals with catecholamines provoked a significant release of the corticosteroids. Epinephrine (10(-6) M) stimulated the release of cortisol (from 0.59 +/- 0.31 to 2.66 +/- 0.34 micrograms/min) and aldosterone (from 2.12 +/- 0.42 to 4.68 +/- 0.92 ng/min). Norepinephrine (10(-6) M) stimulated the release of cortisol (from 0.26 +/- 0.07 to 1.28 +/- 0.10 micrograms/min) and aldosterone (from 1.28 +/- 0.37 to 3.57 +/- 0.80 ng/min). Using an immunostaining for synaptophysin, which is specific for neuroendocrine cells, chromaffin cells could be detected within all three zones of the adrenal cortex. The two endocrine tissues appear to be closely interwoven. On the ultrastructural level, medullary cells are in apposition to cortical cells, with close cellular contacts. These results show that the release of corticosteroids cortisol and aldosterone can be stimulated through the sympatho-adrenal system. Taking into consideration the close colocalization of cortical and medullary tissues, this stimulation may be mediated by chromaffin cells in a paracrine manner.

Adrenal Cortex↗
PubMed1990

[Effect of pancreatin on diabetes mellitus in chronic pancreatitis].

The effect of pancreatin on insulinopenic diabetes was studied in 10 patients with chronic pancreatitis and exocrine function impairment. All patients were treated for 4 days in a randomized crossover trial with either pancreatin (6 x 2 capsules, 6 x 300 mg/d) or placebo. Blood glucose levels were determined 7 times every day and night. On day 5, the patients were studied by a glucose sensor with adjustment of blood glucose to 120 mg/dl until 8.00 in the morning. A test meal was applied with 2 capsules pancreatin or placebo. Blood glucose and plasma levels of C-peptide, glucagon and pancreatic polypeptide (PP) were determined in regular intervals for 4 hours. Blood glucose levels were not significantly altered by pancreatin. As shown by M-value according to Schlichtkrull (21.6 +/- 2.9 versus 32.4 +/- 7.4), there was a tendency towards smaller oscillations of blood glucose with pancreatin treatment. C-peptide levels (basal 0.081 +/- 0.008 ng/ml; postprandial 0.119 +/- 0.013 ng/ml) were not significantly altered by the administration of pancreatin. Basal and postprandial glucagon and PP plasma levels were not influenced by pancreatin. From these results, we conclude that pancreatic enzyme supplementation does not significantly alter the requirement of insulin in patients with diabetes mellitus secondary to chronic pancreatitis. Possible disturbances of the enteroinsular axis are discussed in this paper.

Blood Glucose↗
PubMed1989

Non-human primate pancreas as a substrate for the detection of islet-cell antibodies in human sera.

In an effort to find out if the use of non-human primate pancreas may improve the sensitivity of the islet cell antibody (ICA) test, the sera from patients with type 1 diabetes (insulin-dependent IDDM) and controls were investigated by indirect immunofluorescence (IFL) on both human and baboon substrates. The mean titers of positives were insignificantly higher (1:24.9) on baboon as compared to human tissue (1:22.3). Of 50 sera from IDDM patients positive for ICA on human tissue, 47 were also positive on baboon pancreas. Of 40 ICA-negative IDDM sera two were judged positive on baboon substrate. ICA were positive on human/baboon pancreas in 3/4 out of 50 first-degree relatives of IDDM patients, 2/2 of 50 sera from patients with autoimmune diseases, 0/0 of 50 sera from type 2 diabetics and 2/1 of 100 mixed hospital controls. A disadvantage of baboon pancreas for ICA testing by IFL is the high background fluorescence given by the exocrine pancreas. With baboon tissue, three highly positive results would have been missed with undiluted sera which are usually used in this assay. It is therefore suggested that human pancreas should still be preferentially used for ICA determination, but baboon tissue may be a valuable substitute.

Animals↗
PubMed1989

[Clinical and laboratory chemical studies of the incidence and extent of diabetic cheiropathy in childhood and adolescence].

Diabetic cheiropathy is often not diagnosed because of a paucity of symptoms. In the present study, 100 type I diabetic patients and 20 controls were investigated. The age of patients ranged from seven to 26 years, the duration of diabetes was one to 23 years. Extension of hands by "prayer position", a hand-print and angle determinations of joints were considered for the determination of diabetic cheiropathy. The presence of cheiropathy was unrelated to the duration of diabetes. However, it was well correlated with the quality of blood sugar control and it was often associated with diabetic retinopathy: Diabetic cheiropathy was detected in 53 (53%) of the diabetic patients, and in 26 (49%) of them diabetic retinopathy was also diagnosed. Only three patients had a retinopathy without cheiropathy. On the basis of our results, diabetic cheiropathy is a surprisingly common feature in young type I-diabetics. It is not to be considered as a late complication but rather a sequel of badly controlled diabetes mellitus.

Adolescent↗
PubMed1989

Re-evaluation of eye muscle autoantibody determination in Graves' ophthalmopathy: failure to detect a specific antigen by use of enzyme-linked immunosorbent assay, indirect immunofluorescence, and immunoblotting techniques.

Sera from 41 patients with Graves' ophthalmopathy were investigated for presence of autoantibodies directed against eye muscle preparations using different methods: 1. ELISA with pork eye muscle membrane preparations; 2. Immunoblotting with glycoprotein preparations from human eye muscle; 3. Indirect immunofluorescence with human eye muscle sections. The ELISA was not suitable for detection of specific immunoglobulin binding with sera from patients suffering from endocrine ophthalmopathy. Immunoblotting exhibited only nonspecific binding to some muscle proteins; it could be prevented by pre-adsorption procedures and was not different from the pattern observed with skeletal muscle as antigen. The indirect immunofluorescence technique revealed no binding of Graves' sera to human muscle sections, whereas sera containing antibodies against skeletal muscle bound to eye muscle as well. Thus far, an antigenic structure of eye muscle specific for Graves' ophthalmopathy is not detectable with the methodology used here. The possibility that retroorbital connective tissue may be the main target of the autoimmune process must be considered.

Animals↗
PubMed1989

Determination of islet cell antibodies using an ELISA system with a preparation of rat insulinoma (RIN A2) cells.

An enzyme-linked immunosorbent assay (ELISA) was established for the detection of islet cell antibodies in human sera. The antigen was prepared from rat insulinoma (RIN A2) cells. Cells were dissociated in lysis buffer and the lysate was centrifuged at 100,000 x g. The supernatant was used to coat microtiter ELISA plates (10 micrograms protein/ml in PBS pH 7.2). Non-specific binding sites on the plates were blocked with 2% PBS-BSA. Human test sera were preabsorbed on separate plates using 2% PBS-BSA and incubated on precoated plates at an optimal dilution of 1/10 in 60 mM PBS for 60 min at 37 degrees C. Phosphatase-labeled anti-human IgG serum and phosphatase substrate were applied and the reaction was stopped by adding 3 M NaOH. Out of 90 sera from type I diabetic patients, 47 (52.2%) reacted in the new ELISA whereas none of 15 type II diabetics, 50 sera containing non-islet specific antibodies or 100 normal controls were positive. In the same group of patients, ICA were positive in 63.3%. When both, the ELISA and conventional ICA testing were applied, the number of positives was increased to 83%. The ICA-ELISA with the above described antigen preparation provides a well standardized and reproducible test method which is highly specific for type I diabetes. It may therefore be useful for large screening procedures.

Adult↗
PubMed1989

Interferon-alpha antibodies in autoimmune diseases.

Circulating autoantibodies constitute a prominent feature of many autoimmune diseases. Recently, antibodies to interferon (IFN) have been recognized as an additional variant occurring spontaneously in about 10% of patients with autoimmune disorders. The reactivity of these antibodies appears to be restricted to IFN-alpha, with antibodies of individual patients recognizing unique epitope patterns. IFN antibodies are preferentially of the IgG type, and they likely constitute part of the normal B-cell repertoire. Whereas antibody titers differ largely among patients, the affinity of IFN binding has not been determined. Likewise, the mechanisms involved in IFN antibody synthesis as well as the clinical impact of these antibodies in autoimmune disorders remain elusive. Based on recent reports and our own observations, this article reviews current knowledge regarding occurrence and properties of IFN antibodies associated with autoimmune conditions. From clinical and experimental evidence, mechanisms possibly involved in IFN antibody production are derived and the significance of antibody-mediated sequelae is evaluated.

Aged↗
PubMed1988

Tietze's syndrome--a chameleon under the thoracic abdominal pain syndrome.

Tietze's syndrome is characterized by pain due to a self-limiting, localized, non-suppurative swelling of the costochondral or sternoclavicular junction of unknown etiology. The case of a woman is presented here who was submitted to the hospital under the suspicion of a pathological fracture. After extensive investigations the diagnosis of Tietze's syndrome was made by exclusion, and the patient was successfully treated with local injection of an anaesthetic. Possible differential diagnoses of Tietze's syndrome include myocardial infarction, pneumonia, and others. This report emphasizes the importance of a thorough clinical investigation and the need for the exclusion of severe and lifethreatening diseases.

Adult↗