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Biomedical subjects

S Werner

Publications and source records attributed to S Werner.

At least 235 records · Page 13Linked to original sources
PubMed1989

DNA evaluation in growth hormone producing pituitary adenomas: flow cytometry versus single cell analysis.

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 frequency 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 clinical significance can so far be drawn from these results.

Acromegaly↗
PubMed1989

Effect of congenital renal disease and neonatal thyroid status on urinary human epidermal growth factor concentrations.

We have previously demonstrated that changes in urinary epidermal growth factor/creatinine ratios relate to gestational age and gender. It is unclear what controls this developmental pattern although chronic renal disease and thyroid aberrations have significant effects on epidermal growth factor and creatinine excretion in childhood and in adults. Therefore, we chose to explore the effects of these disease states on epidermal growth factor excretion during the perinatal time period. We collected urine samples from 8 infants with congenital renal disease and 45 infants with low T4 and normal TSH values who 'failed' the newborn screen. In addition, 2 infants with hypothyroidism and 2 infants with neonatal Grave's disease had urine samples examined. Values were compared with the epidermal growth factor and creatinine excretion from 190 infants. We demonstrated that epidermal growth factor excretion increased earlier in gestation than does creatinine excretion. In infants with renal disease or hypothyroidism, epidermal growth factor excretion was decreased while hyperthyroidism enhanced excretion. Epidermal growth factor excretion increased with relief of an obstruction but still remained low and creatinine excretion was unchanged. We confirm that in preterm infants as in childhood there are similar effects of thyroid and renal diseases on epidermal growth factor excretion.

Congenital Hypothyroidism↗
PubMed1989

Depletion of PDGF from serum inhibits growth of AIDS-related and sporadic Kaposi's sarcoma cells in culture.

We have examined the mitogenic potential of platelet-derived growth factor (PDGF) on AIDS (acquired immune deficiency syndrome)-related and sporadic Kaposi's sarcoma cells in comparison to fibroblasts at physiological and subphysiological calcium concentrations of the culture medium. At low calcium concentrations in the presence of 3% human serum the growth rate of fibroblasts and Kaposi's sarcoma (KS) cells is similarly reduced to less than half of the growth rate at physiological Ca2+ concentrations. In the presence of 3% PDGF depleted, platelet poor plasma-derived serum (PPPS) growth of KS cells ceased completely, whereas fibroblasts made 1-2 cell divisions within 15 days. At physiological Ca2+ concentrations, the reduced PDGF content in 3% PPPS had no effect on human embryonal fibroblasts and little effect on adult skin fibroblasts. In contrast, KS cells became growth-arrested after one to two doublings. This is consistent with the observation that PDGF B-chain mRNA could not be detected in our KS cells whereas PDGF receptor mRNA was expressed.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Quality of life after bilateral adrenalectomy in MEN 2.

Pheochromocytoma is a major cause of morbidity and mortality in the multiple endocrine neoplasia type 2 (MEN 2) syndrome. For the physician, surgical treatment seems well justified even though bilateral adrenalectomy will induce iatrogenically complete loss of adrenocortical function. For the patient this treatment may be a cause of medical problems as well as worry. We have evaluated quality of life after bilateral adrenalectomy in 27 MEN 2 patients through a combined oral and written approach. Mortality was low (one of 27), as was serious morbidity. Most patients had adapted well to the postadrenalectomy state. However, fatigue, worry, and noncompliance with daily medication often caused problems.

Adaptation, Psychological↗
PubMed1988

Cultured, AIDS-related Kaposi's sarcoma cells express endothelial cell markers and are weakly malignant in vitro.

Up to 30% of patients with acquired immunodeficiency syndrome (AIDS) suffer from Kaposi's sarcoma (AIDS-KS). The histogenesis and neoplastic nature of this tumor is still controversial. We have established cell cultures of KS biopsies from 7 patients with AIDS. All donors were seropositive for the human immunodeficiency virus I (HIV-I), cytomegalovirus (CMV) and hepatitis B virus (HBV). The tumors were histologically shown to be KS. Cell cultures derived from these tumors all expressed the endothelial cell marker BMA 120 antigen. Most of these cultures were positive for acetylated low-density lipoprotein (acLDL) uptake and alkaline phosphatase (AP) expression, and negative for factor-VIII-related antigen (FVIII-RAg). The staining pattern was heterogeneous with respect to number of endothelial cell markers expressed in each culture. We conclude from subcloning experiments that the cultured cells cease to express acLDL receptor and AP, but not the antigen detected by the monoclonal antibody (MAb) BMA 120. The cells grew well in culture up to 50 passages and showed a fibroblast-like morphology. Assays performed to investigate their degree of malignancy revealed a significantly increased passage number under reduced serum conditions as compared to normal fibroblasts but no tumor formation in nude mice. Neither HIV, HBV nor CMV sequences were found in any of the cell lines tested. We conclude that AIDS-KS is an endothelial-cell-derived neoplasm of low malignancy and that HIV, HBV and CMV are not directly involved in its genesis.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Pethidine analogues, a novel class of potent inhibitors of mitochondrial NADH: ubiquinone reductase.

Analogues of the analgetic drug pethidine were synthesized. Two N-aralkylen derivatives displayed a superior inhibitory effect on the activity of NADH:ubiquinone reductase in beef heart mitochondrial membranes. Dose-response curves revealed that the potency of these compounds is very comparable to that of the standard probe rotenone. The inhibitors were characterized by (a) their action on the reductase activity in various (eukaryotic and prokaryotic) organisms, (b) their influence on the enzyme kinetics, (c) their effects on the NADH dependent reduction of different electron acceptors, (d) their interference with the activities of other mitochondrial oxido-reductases. With regard to many of these aspects a close analogy between pethidine derivatives and rotenone was observed. A computer simulation of the steric structures of these molecules indicates that both classes of the chemically rather unrelated inhibitors may imitate very similar conformations. The potential advantages of the pethidine derivatives for the investigation of structure - function relationships within complex I of the respiratory chain is discussed.

Animals↗
PubMed1988

Chromophobe cell renal carcinoma and its variants--a report on 32 cases.

This paper reports on 32 chromophobe cell renal carcinomas observed in 697 renal cell cancers (RCC) of adults (peak in the sixth decade of life). The chromophobe cell-type differs from other types of RCC macroscopically, the cut-surface being predominantly of grey-beige colour. Histologically, there are two variants: one is the typical (light) variant (n = 22) and the other is eosinophilic (n = 10). Both variants have in common (a) reaction of the cytoplasm with Hale's acid iron colloid; (b) electron microscopic detection of cytoplasmic microvesicles (150-300 nm), frequently with 'inner vesicles', and (c) low glycogen content in comparison with the clear cell carcinoma. Immunocytochemical investigations on the intermediate filaments show a positive reaction for cytokeratins No. 18 (uniformly) and Nos. 7 and 19 (to varying extents) for both variants, whereas vimentin was not found in any of these carcinomas, in contrast to the clear-cell type. The cytomorphological grading revealed predominantly G II tumours. A lymph node metastasis was found in one patient. On the basis of the mortality curves determined, the prognosis for patients with chromophobe cell carcinomas is more favourable than that of the clear-cell type. In terms of differential diagnosis, on the one hand, the typical (light) variant of the chromophobe cell RCC must be delimited from the clear-cell RCC, and on the other hand, the eosinophilic variant must be distinguished from the chromophilic or 'granular' RCC. Microscopic, histological, histochemical, electron microscopic, and intermediate filament analysis results document that the chromophobe cell type of RCC is a distinct entity. The implications for the nomenclature of RCC, especially with regard to the 'granular' type, are discussed.

Adult↗
PubMed1988

Insulin regulates the 35 kDa IGF binding protein in patients with diabetes mellitus.

The serum levels of the low molecular form of insulin-like growth factor binding protein (IGFBP) was determined in 56 outpatients with diabetes mellitus by a radioimmunoassay developed for amniotic 35 kDa IGFBP. The mean level of 35 kDa IGFBP was found to be threefold higher in insulin dependent diabetes mellitus (IDDM), 112 +/- 13 ng/ml, than in age matched controls, 37 +/- 2 ng/ml, while the mean level in non-insulin dependent diabetes mellitus (NIDDM), 16 +/- 2 ng/ml, was decreased. In hospitalized IDDM patients there was a significant correlation (r = 0.91, p less than 0.01) between fasting blood-glucose and 35 kDa IGFBP levels, not found in NIDDM patients. During insulin infusion the 35 kDa IGFBP levels declined with a half-life of 60-120 min. The decline in IGFBP continued even after the establishment of steady state B-glucose at 4.7 mmol/l. In conclusion, the elevated 35 kDa IGFBP levels in IDDM can be attributed to insulin deficiency and may reflect a reduced bioavailability of the IGFs at the target cells.

Adult↗
PubMed1988

Breast feeding-induced effects on plasma gastrin and somatostatin levels and their correlation with milk yield in lactating females.

Maternal gastrin and somatostatin levels have been shown to be influenced during suckling in dogs and pigs. The present study was performed to investigate whether the levels of gastrin and somatostatin are influenced by breast feeding in lactating women. Repeated blood samples were drawn in connection with nursing in 15 females and plasma levels of gastrin and somatostatin were measured by radioimmunoassay. Gastrin levels rose significantly (P = 0.01) within two minutes after onset of suckling. Somatostatin levels either decreased or increased as an effect of breast feeding. The direction of the change was correlated to the pre-suckling somatostatin levels (P less than 0.01). The somatostatin level recorded 60 min after start of breast feeding was significantly lower than basal levels (P less than 0.01) indicating a long-term inhibitory effect on somatostatin secretion. The suckling-induced effect on somatostatin levels was correlated with the amount of milk ejected (Rs - 0.52, P less than 0.05). The mechanism by which suckling influences circulating gastrin and somatostatin levels is unknown, but we suggest that suckling leads to a reflex activation of the vagal nerves, which influence the release of these hormones from the stomach. The size of the gastrointestinal tract is increased during pregnancy and lactation, illustrating that the maternal digestive capacity is adapted to the high demand for energy intake occurring during lactation. We speculate that the suckling stimulus enhances gastric functions by influencing the release of gastrin and somatostatin, which stimulate and inhibit gastric functions and growth, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Expression of coxsackievirus B3 capsid proteins in Escherichia coli and generation of virus-specific antisera.

Subgenomic fragments of cloned infectious coxsackievirus B3 (CVB3) cDNA up to the size of the complete coding sequence of the viral polyprotein were inserted into the prokaryotic expression vector pPLc24 and expressed in Escherichia coli. Fusion proteins, containing 54 amino acids of MS2 replicase at their amino terminus followed by different parts of the CVB3 structural proteins, were expressed from several constructs. The expression product of a plasmid encoding the capsid proteins VP4, VP2, and the amino-terminal part of VP3 was obtained in high amounts. However, primary expression products containing the complete viral capsid precursor VP4-VP1 were completely degraded, indicating the presence of domains downstream from VP3 that are accessible to E. coli proteases. This finding is consistent with the observation that the structural intact expression product of the separately subcloned VP1 gene is also extremely unstable and consequently obtained only in low amounts. Two fusion proteins of non-overlapping parts of the viral structural proteins containing VP4, VP2, and VP3 or VP1, respectively, were isolated and used for the generation of antisera in rabbits. The antisera obtained recognize distinct CVB3 structural proteins in infected cell cultures as well as from purified CVB3 preparations. In addition, significant cross-reactivity of the described antisera with the corresponding structural proteins of other enteroviruses was observed, indicating that these antisera provide a valuable tool for an improved broad spectrum diagnosis of enteroviral infections.

Capsid↗
PubMed1988

Characteristic changes in psychiatric symptoms, cortisol and melatonin but not prolactin in primary hyperparathyroidism.

Psychiatric symptoms in primary hyperparathyroidism (PHPT) are usually characterized as depressive. In this study 13 patients with PHPT and six control patients with atoxic nodular goiter underwent psychiatric ratings with the comprehensive psychopathological rating scale (CPRS) the day before surgery. The 21 items in this scale were grouped into clusters. The ratings were repeated after successful removal of a parathyroid adenoma. Diurnal serum concentrations of cortisol, melatonin and prolactin were studied pre- and postoperatively in eight of the patients. Patients with PHPT had significantly higher CPRS total scores, 8.5 +/- 1.3, compared with goiter controls, 1.9 +/- 0.8, and showed a significant improvement of psychiatric symptoms after excision of the parathyroid adenoma, to 3.3 +/- 0.9. The preoperative diurnal and peak levels of cortisol and melatonin were higher (P less than 0.05) than after surgery. Serum melatonin fell to levels lower than those in healthy controls. Correlations were found between some clusters or items and cortisol or melatonin. Serum prolactin levels were normal and unaltered by parathyroid surgery. It is concluded that patients with PHPT show well defined psychiatric symptoms many of which are correlated to alterations in serum cortisol and melatonin accompanying PHPT. The improvement of symptoms seen after successful surgery further suggests that PHPT is associated with a specific psychiatric disorder similar to but distinguishable from major depressive disorder.

Adenoma↗
PubMed1988

Cardiac output determinations in the newborn. Reproducibility of the pulsed Doppler velocity measurement.

Cardiac output (QAo) can be estimated noninvasively by pulsed Doppler (PD) ultrasonographic determination of mean ascending aortic blood flow velocity (VAo) combined with M-mode echocardiographic determination of ascending aortic cross sectional area (AAo). Cardiac output is calculated from the volumetric flow equation (QAo) = (VAo) X (AAo). Pulsed Doppler measurements are known to correlate well with Fick and thermodilution methods; however, inter- and intraoperator variability of the velocity component of the PD method has not been determined in newborns. We did three repeated PD measures of mean aortic flow velocity in ten term infants (using four trained operators) to determine inter- and intraoperator reproducibility. The coefficient of variation for intraoperator variability (random error) for a single measurement of VAo was 11.7%. If three repeated measures by a single operator were averaged, the random error was 7.0%. There was little interoperator variability found.

Aorta↗
PubMed1987

Melatonin, cortisol, prolactin, and calcitonin secretion in primary hyperparathyroidism before and after surgery.

The aim of the present study was to determine the diurnal secretion of melatonin, cortisol, prolactin, and calcitonin during chronic parathyroid hormone-dependent hypercalcemia. Eight women, aged 40-76 years, with primary hyperparathyroidism (PHPT) were studied before and after surgical removal of a parathyroid adenoma. The hormone concentrations in blood were determined at 08, 12, 16, 22, 02, 04, and 06 h. Concomitantly, the excretion of melatonin and cortisol in urine between 07-19 h and 19-07 h, and the clearance of calcium and creatinine were measured. Nyctohemeral serum prolactin and calcitonin were unaffected by moderate parathyroid hormone-dependent hypercalcemia. In contrast, serum cortisol and melatonin were significantly higher during active disease than after surgical cure. Mean 24-h variation of serum cortisol was 349 +/- 34 nmol/liter vs. 223 +/- 17 nmol/liter and mean serum melatonin was 0.13 +/- 0.04 nmol/liter vs. 0.06 +/- 0.02 nmol/liter. Endogenous creatinine clearance was similar before and after surgery, while the clearance of melatonin and cortisol significantly increased after surgery, indicating an increased tubular reabsorption of both hormones during active disease. Fasting morning glucose concentrations were also significantly decreased after successful surgery, 6.1 +/- 0.6 vs. 5.2 +/- 0.5 mmol/liter. It is suggested that the relative hypercortisolism may be the cause of the glucose intolerance in primary hyperparathyroidism. Three to 4 months after surgical cure the serum melatonin levels were significantly lower than those seen in age-matched controls, indicating a melatonin insufficiency in patients successfully treated for PHPT. The meaning of this finding is not yet understood but might be of importance in the development of primary hyperparathyroidism.

Adenoma↗
PubMed1987

Longitudinal trends in left ventricular cardiac output in healthy infants in the first year of life.

We studied left ventricular (LV) cardiac output as estimated by ascending aorta blood flow (QAo) longitudinally in 31 healthy infants from birth through the first year of life using noninvasive pulsed Doppler ultrasound technique. The temporal mean ascending aortic blood flow velocity (VAo) was measured with a 5-MHz pulsed Doppler velocimeter and on line integration system. Ascending aortic cross-sectional area (AAo) was determined using M-mode echography. Ascending aortic blood flow was calculated as QAo = VAo X AAo and was corrected to body weight (BW) in kilograms or body surface area (BSA) in meters squared. Mean ascending aortic flow velocity (VAo) remained relatively constant over the first year, averaging 20.5 +/- 3.4 cm/sec (+/- SD). Changes in AAo over time correlated strongly with changes in BW or BSA (r = 0.99). Therefore, changes in QAo correlated strongly with changes in AAo, BW, and BSA (r = 0.99). LV cardiac output corrected for body weight or BSA remained relatively constant throughout the first year, mean values ranging from 180-226 ml/min/kg or 3.06-3.76 L/min/m2 and averaging 204 +/- 45 ml/min/kg or 3.48 +/- 0.74 L/min/m2. A similar strong correlation was seen between serial changes in LV stroke volume and changes in BW or BSA (r = 0.99).

Aging↗