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K Junker

Publications and source records attributed to K Junker.

107 records · Page 6Linked to original sources
PubMed1984

Glucocorticoid receptor number and intracellular water space.

In order to elucidate the relationship between cell water content and number of glucocorticoid receptors, eleven normal and malignant lymphoid or myelomonocytic cell types originating from mouse, rat and man were investigated. The cellular water space was measured with 3H2O, and glucocorticoid receptor number was measured in a whole-cell binding assay with [3H]dexamethasone at 30 and 37 degrees C. The intracellular water phase concentration of glucocorticoid receptors (around 40 nmol/l cell water), and the dependence of receptor affinity on temperature were similar in normal and malignant rodent and human cells. It is concluded that comparisons of glucocorticoid receptor levels are best made on the basis of intracellular receptor concentrations.

Animals↗
PubMed1983

Glucocorticoid receptors of human mononuclear leukocytes in vitro.

The present study was performed to analyze glucocorticoid receptor binding in peripheral blood mononuclear leukocytes from normal adult humans. In addition, the potential regulatory effect of excess amounts of glucocorticoids and thyroid hormones on glucocorticoid receptor binding was investigated. A whole cell binding assay with [3H]dexamethasone (3H-labeled 9 alpha-fluoro-11 beta, 17 alpha, 21-trihydroxy-16 alpha-methyl-pregna-1,4-diene-3,20-dione) was used. Binding parameters were estimated by means of unweighted nonlinear regression analysis, using the free ligand concentration as the independent variable and the ratio of bound to free ligand at steady state as the dependent variable. The dissociation constant (Kd) at 30 C was 5.5 +/- 1.4 nM (mean +/- SD; n = 57) compared to 10.5 +/- 4.8 nM (n = 16) at 37 C. The numbers of receptors per cell were not affected by temperature and were 7400 +/- 1560 and 7180 +/- 2710, respectively. The number and affinity of glucocorticoid receptors did not differ between women and men. Receptor binding did not change in subjects ranging in age from 18-63 yr. Moreover, no diurnal or seasonal variations were recorded. Cells from five pregnant women in the last trimester showed decreased receptor affinity (Kd at 30 C = 7.7 +/- 1.4 nM; P less than 0.01) and increased receptor number (8950 +/- 870; P less than 0.05). Six patients with untreated thyrotoxicosis had normal receptor binding. No change in receptor number or affinity (30 C) was found in cells from three patients with Cushing's disease and four prednisone (17 alpha,21-dihydroxy-pregna-1,4-diene-3,11,20-trione)-treated asthmatics. These data indicate a widespread invariability of glucocorticoid receptors of human mononuclear leukocytes and do not support the theory of a regulatory role of excess glucocorticoids on their own receptor number or affinity.

Adolescent↗
PubMed1981

Binding of dexamethasone and inhibition of transport of 3-O-methylglucose in rat thymocytes.

The effect of temperature (21-37 degrees C) on binding of [3H]dexamethasone in intact rat thymocytes was investigated. Receptor binding was correlated with inhibition by dexamethasone of in vitro transport of 3-O-[14C]methyl-D-glucose at 37 degrees C. Receptor binding of dexamethasone was dependent on temperature. The number of receptors per cell was about 3000 at all temperatures studied. However, an increase of temperature from 21 to 37 degrees C changed the rate constant of dissociation from 6.0 . 10(-3) min-1 to 55.0 . 10(-3) min-1, and the dissociation constant from 1.1 to 5.9 nM. The effect of dexamethasone (0.8-790 nM) on transport of 3-O-[14C]-methyl-D-glucose (10-50 muM) was investigated during the initial 30 s of uptake at 37 degrees C. A dose-dependent inhibition of transport was found at 60 and 120 min after the addition of hormone. Correlation between effect and receptor occupancy was linear. Maximal inhibition was achieved at concentrations of dexamethasone resulting in 95-97% receptor occupancy, and 50% of the maximal effect was obtained at a concentration of dexamethasone corresponding to 50% receptor occupancy. Inhibition of transport differed in latency between cell preparations. However, this could not be ascribed to change of either amount of affinity of dexamethasone receptors.

Animals↗
PubMed1981

Simultaneous small-intestinal reconstruction and gastric partitioning as treatment for complications after jejunoileal bypass for morbid obesity.

Three female patients aged 34-35 years, who underwent jejunoileal bypass 11, 5, and 3 years ago, respectively, developed renal tubular acidosis. Furthermore, one of the patients needed prednisone for seronegative polyarthritis that developed 2 years after a revision of her jejunoileal bypass. Because of the possible risk of renal damage from renal tubular acidosis and to avoid recurrent obesity, the patients were offered a simultaneous intestinal reconstruction and gastric partitioning. This combined procedure promptly cured the renal tubular acidosis and the arthritis and simultaneously produced a maintained weight loss.

Adult↗
PubMed1980

Inhibition by dexamethasone of the in vitro transport of 3-O-methylglucose into rat thymocytes.

Reduced glucose transport across the plasma membrane and reduced phosphorylation may both be responsible for the early inhibitory effect of physiological concentrations of glucocorticoids on glucose uptake by rat thymocytes. The early inhibitory effects of glucocorticoids (5 . 10(-7) M dexamethasone) on glucose consumption and 14CO2 formation from D-[U-14C]glucose were reproduced. The total uptake curve of 4.8 microM 3-O-[14C]methyl-D-glucose was biexponential with t 1/2 of 1.1 min and 36 min, respectively, the rapid part comprising about 50% of the equilibrated intracellular water space. The latency of the effect of 5 . 10(-7) M dexamethasone on 3-O-[14C]methyl-D-glucose uptake ranged from 15 to 100 min and the inhibition varied from 15 to 55% independently of the lag period. The effect of 3-O-methylglucose concentration on the initial uptake by steroid-responsive cell preparations was tested after 45 min of preincubation with or without 5 . 10(-7) M dexamethaone. In 12 experiments dexamethasone reduced V from 1.36 +/- 0.16 mmol . min-1 . l-1 cell water to 0.81 +/- 0.10 mmol . min-1 . l-1 cell water with insignificant change of Km (6.0 mM versus 5.9 mM). Dexamethasone had similar effect after 90 or 120 min. The variabilities of control cell transport capacity, the lag period and the magnitude of the dexamethasone effect could not be accounted for by changes in pH, effects of cell density, concentrations of albumin, ethanol, nucleosides, pyruvate or correlated to age and sex of the rats. In conclusion the inhibition of glucocorticoids on glucose consumption by thymocytes appears to be an inhibited plasma membrane transport capacity.

Adrenalectomy↗
PubMed1976

Autoimmune insulitis. Pathological findings in experimental animal models and juvenile diabetes mellitus.

Organ-specific, species non-specific anti-pancreatic cellular immunity has been reported as a feature associated with juvenile diabetes of short duration. In order to further elucidate a possible causal relation between autoimmunity and juvenile diabetes morphological studies were made on an autopsy material from 12 juvenile onset diabetics, dying within 1 year after the onset of the disease. Each patient was compared with 2 age and sex matched controls. In the group of patients the islets of Langerhans showed the following characteristics: 1. The B cells were degranulated and present in reduced number, 2. The A cells appeared normal, 3. A lymphocytic, non-cicatricial insulitis was detected in 50% of the patients. Those findings were correlated with animal experiments, in which rats and mice were immunized with A: heterologous and homologous preparations of endocrine pancreas, in complete Freunds' adjuvant, B: heterologous and homologous insulin in complete Freunds' adjuvant, and C: complete Freunds' adjuvant. Only animals of group A developed spleen cell migration tests positive to the pancreatic preparations, lymphocytic infiltrations of the islets and degranulation of the B cells. In addition, the B cells showed ultrastructural signs of degeneration. The morphological changes were reversible and were accompanied by a transient reduction in glucose tolerance.

Adolescent↗
PubMed1972

Abnormal glomerular filtration rate, renal plasma flow, and renal protein excretion in recent and short-term diabetics.

Glomerular filtration rate and renal plasma flow were simultaneously determined in comparable groups of 43 diabetics less than 40 years of age and with a duration of diabetes less than 10 years and 32 control subjects. The average glomerular filtration rate in the diabetic group was significantly higher than that in the control group (P <0.01). The average renal plasma flow in the diabetic group was found to be significantly lower than that in the control group (P <0.05). The filtration fraction in both male and female diabetics was significantly higher than in the male and female control groups (P <0.001). These changes were found to be present even in recent juvenile diabetics with disease of a duration of less than one year. No correlation was apparent between the average levels of serum growth hormone and glomerular filtration rate.The urinary protein excretion was determined in 36 diabetic and 38 healthy subjects comparable with regard to glomerular filtration rate. In the diabetic group there was a greater frequency of cases with higher protein excretion rates (P <0.02). The average protein excretion rate was increased even in diabetics with less than one year's duration of the disease.The results of the changes in renal haemodynamics in subjects with recent and short-term diabetes are compatible with the presence of a constrictive state of the vas efferens leading to an increase in the filtration pressure. The increase in protein excretion rate may similarly be a consequence of this process or of an increase in the glomerular permeability with augmented molecular sieving of proteins or both.

Adolescent↗
PubMedDate not supplied

Computed tomography of cholesterinic granulomas in the choroid plexus of horses.

Cholesterinic granulomas are tumor-like masses in the choroid plexuses of horses. This report describes the computed tomographic findings in four horses with cholesterinic granulomas, including the clinical and the pathologic features. All four horses had bilateral cholesterinic granulomas in the lateral ventricles. Computed tomographic images clearly delineated the masses, the opacity of the granulomas, and the enhancement pattern after intravenous bolus injection of contrast medium; these factors varied considerably. Additional CT findings were symmetric or asymmetric widening of the lateral ventricles.

Animals↗
PubMedDate not supplied

Meizothrombin, an intermediate of prothrombin cleavage potently activates renal carcinoma cells by interaction with PAR-type thrombin receptors.

Recently, meizothrombin (MT), an intermediate enzyme in the prothrombin cleavage cascade has been shown to activate cells of a brain tumor cell line by interaction with PAR-1-type thrombin receptors with a potency comparable to that of thrombin. In this study, we investigated the effect of recombinant human MT (rMT) on calcium mobilization in primary cultures established from surgically resected human renal cell carcinomas. Meizothrombin induced very rapidly transient calcium mobilization in RCC cells comparable to that observed with thrombin. RCC cells stimulated with thrombin after rMT challenge were unable to elicit a new calcium response and vice versa. Therefore, rMT and thrombin seem to activate calcium signaling in primary RCC cultures by similar mechanisms including PAR-1- and PAR-3-type thrombin receptors as shown by using PAR-type specific antibodies. Our results demonstrate rMT as a potent activator of human RCC cells suggesting a function of not only thrombin but also of this catalytically active thrombin precursor enzyme in human renal cell carcinoma.

Calcium↗
PubMedDate not supplied

Prognostic significance of mutations in the p53 gene in superficial bladder cancer.

Bladder tumors as the most common urologic malignancy present mostly as superficial transitional cell carcinoma. Many patients with superficial bladder cancer have a good prognosis, however, may develop recurrences or progress to muscle invasive or metastatic disease. It is therefore important to find new markers associated with the biological behaviour of an individual tumor for identifying patients at risk for disease progression. Previous reports on the prognostic significance of p53 alterations in bladder tumors revealed conflicting results. The aim of our study was to evaluate p53 mutation analysis as an effective concept for the characterization of subsets of superficial bladder tumors differing in biological aggressiveness. Screening 66 amplified DNA from micro-dissected tumor cells by direct genomic sequencing p53 alterations were detected in 12%. We found no association between p53 status and tumor stage but a tendency to a higher mutation rate in more malignant tumors (G2 and G3) compared to G1 tumors and a higher recurrence rate in patients with a p53 mutation in the primary tumor after 24 months follow-up. We conclude a general low incidence of p53 mutations in superficial bladder cancer. Detectable p53 damage might be related to a more aggressive phenotype and a higher recurrence risk. Our results are discussed in the context of other studies reviewed from 1995-2000.

DNA Mutational Analysis↗
PubMedDate not supplied

Differentiation of multifocal renal cell carcinoma by comparative genomic hybridization.

Multifocality occurs in 12-22% of all renal cell carcinoma (RCC) cases. In order to differentiate multifocal RCC, we performed comparative genomic hybridization (CGH) and correlated the results with histopathological and clinical data. After histopathological examination of multifocal tumors, tumor areas were dissected from histopathological sections. Isolated DNA was amplified by DOP-PCR. CGH was performed according to standard protocols. Twenty cases were analyzed. In eight cases, at least one identical aberration was detected in the related tumors. Another eight cases showed different chromosomal changes in tumors of the same kidney. In the small additional clear cell tumors typical genetic alterations of clear cell carcinomas were detected whereas in the chromophilic tumors aberrations characterizing both adenomas and carcinomas were found. From these results we conclude that multifocal RCC represents a heterogeneous group of tumors. The malignant potential of small additional tumors in multifocal RCC cannot be excluded.

Carcinoma, Renal Cell↗
PubMedDate not supplied

Differentiation of positive autofluorescence bronchoscopy findings by comparative genomic hybridization.

Up to 50% of the results of autofluorescence bronchoscopy (AF) of histologically benign lesions are false-positive. For better differentiation of such lesions we have used comparative genomic hybridization (CGH). We studied biopsy material from 47 patients by CGH. For a comparison of findings, the patients were grouped as follows: Group 1, patients with manifest malignant lesions (n=10); group 2, patients with positive autofluorescence and negative (benign) histology (n=16); group 3, patients with negative autofluorescence and negative histology, who belong to a typical high-risk group for lung cancer (n=21). The biopsy specimens of 21/47 patients (45%) showed chromosome aberrations. In 8/10 cases (80%) in group 1, one or several chromosome lesions were detected. Chromosome aberrations were found in 13/16 specimens (81%) taken in group 2. None of the 21 biopsy specimens from the patients of group 3 showed any chromosome lesions. The chromosome aberrations detected in groups 1 and 2 show nearly identical distribution patterns. Lesions of chromosome 3 are the most frequent ones in both groups. The results of the CGH investigation show that regions of the bronchial mucosa with positive AF finding and benign histology frequently are seriously damaged and may develop into potentially malignant lesions.

Biopsy↗