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Biomedical subjects

S Peter

Publications and source records attributed to S Peter.

At least 19 recordsLinked to original sources

Multiple drug resistance gene expression in human renal cell cancer is associated with the histologic subtype.

Overexpression of p170 glycoprotein, the product of the multiple drug resistance (mdr) gene, has been associated with resistance to various cytotoxic drugs used in the treatment of human neoplasms. Normal renal epithelial cells express p170 as a function of their secretory capacity. Because renal cell carcinomas (RCC) respond poorly to chemotherapeutic regimens, p170 expression was studied in primary RCC. Such expression was measured in 40 human RCC and normal kidney tissues using immunohistochemical staining with the monoclonal antibody C-219. Staining intensities of the whole tumor and of different areas of the cryostat sections were transformed into digital numbers using an algorithm designed for this purpose. In most tumors, an inhomogeneous staining pattern and a correlation between grade of differentiation and C-219 immunoreactivity was observed. A comparison of the tumors according to their histopathologic subtypes showed clear differences. The means (range) of the staining intensities of the different types of RCC: clear cell carcinoma Grade 1 (n = 3), 2.0 (2.0 to 2.0); clear cell carcinoma Grade 2 (n = 19), 0.8 (0.0 to 2.9); clear cell carcinoma Grade 3 (n = 5), 0.1 (0.0 to 0.2); tubular carcinoma (n = 4), 2.0 (2.0 to 3.0); anaplastic carcinoma (n = 8), 0.05 (0.0 to 0.2); oncocytoma (n = 1), 0.0 (0.0 to 0.0); and normal kidney (n = 40), 0.5 (0.0 to 2.0). The differences between anaplastic, clear cell, and tubular carcinoma were significant (P less than 0.001 by Kruskal-Wallis test). In addition, the difference between the three subgroups of clear cell carcinoma was significant (P less than 0.01). It was concluded that the histopathologic subtypes of RCC correlate with the degree of mdr gene expression, as determined by staining with the C-219 monoclonal antibody.

ATP Binding Cassette Transporter, Subfamily B, Mem

Mutations in the ras protooncogenes are rare events in renal cell cancer.

Mutations in codon 12, 13 or 61 of one of the three ras genes, Ha-ras, Ki-ras, and N-ras, convert these genes into active oncogenes. To determine the role mutated ras genes play in the carcinogenesis of renal cell carcinoma, we analysed tumour DNA and unaffected renal tissue derived from 55 patients. The polymerase chain reaction technique was used to amplify DNA fragments containing Ki-, Ha-, and N-ras codons 12, 13, and 61. The amplified fragments were then probed on slot-blots with labeled mutation-specific oligomers. A single Ki-ras mutation (codon 12, gly- greater than val) was detected in a patient with a pT2N2M1 tumour. We concluded that ras oncogene mutations do not play an important role in the initiation of renal cell carcinoma.

Adult

[Significance of oncogenes and growth factors in hypernephroma].

In all cells there are a number of genes that regulate cell division and growth. In an "activated" form they are called oncogenes and play a role in the carcinogenesis. The activation results from such alterations as point mutation and translocation or alterations with increased synthesis of genes and gene product. There are different oncogene families. Up to now only a small number have been tested in renal cancer cells.

Carcinoma, Renal Cell

Expression of the hst-1 and c-kit protooncogenes in human testicular germ cell tumors.

Seventy testicular germ cell tumors were analyzed at the DNA and RNA levels for the c-kit, hst-1, and int-2 oncogenes using Northern and Southern blot analyses, respectively. There were significant differences in oncogene expression between seminomas and nonseminomas with c-kit being expressed in 24 of 30 (80%) seminomas but in only 3 of 40 (7%) nonseminomatous tumors (P = 0.0001, chi 2 test) and hst-1 being expressed in 24 of 38 (63%) nonseminomas but only 1 of 24 (4%) of seminomas (P = 0.0001, chi 2 test), demonstrating an inverse relationship in the expression pattern of these 2 oncogenes in human testicular germ cell tumors. A significant association between tumor stage and hst-1 expression in the nonseminoma group was found (P = 0.0002, chi 2 test). No gross alterations in the c-kit, hst-1, and int-2 loci were found at the DNA level and no int-2 mRNA expression was detected in any of the germ cell tumors examined.

Blotting, Southern

Oncogenes and growth factors in renal cell carcinoma.

Oncogenes and growth factors play a role in normal cellular processes such as growth and differentiation. In addition, considerable circumstantial evidence indicates that these genes may be responsible for the induction and/or maintenance of human malignancies. There are different oncogene families; up to now only a small number has been tested in renal cancer cells.

Carcinoma, Renal Cell

Inverse relationship of epidermal growth factor receptor and HER2/neu gene expression in human renal cell carcinoma.

Expression of the oncogenes, epidermal growth factor (EGF) receptor, HER2/neu, c-myc, and c-fos, in renal cell carcinoma and corresponding nonneoplastic kidney tissue of 30 patients has been analyzed by Northern blot analysis. In renal cell carcinoma an inverse relationship of EGF receptor and HER2/neu gene expression was detected, with high expression of the EGF receptor gene in 22 of 30 (73%) cases and low expression of the HER2/neu gene in 28 of 30 (93%) cases. Furthermore, altered expression of the oncogenes c-myc and c-fos was detected in renal cell carcinoma, which appears to be related to the tumor grade of malignancy. Additional Southern blot analysis of six renal cell carcinomas gave no indication of chromosomal rearrangement events or gene amplification.

Biomarkers, Tumor

The juxtaglomerular apparatus of rats with hereditary hypothalamic diabetes insipidus.

The juxtaglomerular apparatus (JGA) of rats with hereditary hypothalamic diabetes insipidus (DI) was studied. Plasma concentration of renin and angiotensin II, as well as serum sodium concentration and serum osmolality of DI rats are elevated. The morphological examination reveals no characteristic alteration of the epitheloid cells. The results show that the epitheloid cells are sufficiently adapted for the higher release of renin.

Angiotensin II

The junctional connections between the cells of the urinary bladder in the rat.

The junctional connections between the cells of the urinary bladder epithelium in rat have been studied by freeze-fracturing. Tight junctions and desmosomes are known as structural features of the epithelium. In addition, gap junctions (nexus) have been found to connect the epithelial cells in an irregular distribution pattern. The junction size ranges from few assembled particles up to plaques with irregular forms. This may indicate that the gap junctions are mobile structures. The functional significance of the junctions in comparison with electrophysiological data is discussed.

Animals

The transition of the thick ascending limb of Henle's loop into the distal convoluted tubule in the nephron of the rat kidney.

Examination of serial semithin sections of rat kidney cortex and a subsequent electron microscopic study of selected areas revealed that the characteristic epithelium of the cortical part of the thick ascending limb of Henle extends for a varying distance beyond the macula densa. The transition from the relatively thin epithelium of the thick ascending limb at this site to the three--or even four--fold thicker epithelium of the convoluted part of the distal tubule is sharply defined and occurs without the interposition of an intermediate cell type. The position of the macula densa at the end but still clearly within the ascending limb of Henle's loop is functionally interpreted to guarantee the separation of the sensor point macula densa from disturbing influences which might arise from the secretory activity of the subsequent tubular portion.

Animals

Amino acid transport in the rat exocrine pancreas. I. Transport of neutral amino acids and their utilization in protein synthesis.

The transport and utilization of three neutral amino acids in protein synthesis was studied using isolated pancreatic lobules in vitro. The significance of the extracellular and intracellular amino acid pool in this process was analyzed removing the extracellular pool (labeled by inulin) by a cold-wash procedure. This was especially useful in short-term experiments. Double-labeling experiments indicated a predominant utilization of the intracellular amino acid pool during protein synthesis. The advantage of isolated pancreatic lobule preparations compared to tissue fragments or slices was emphasized by fine structural studies. Using freeze-etching techniques on the same preparations, differences in the distribution of membrane particles between luminal and lateral plasma membranes described earlier were confirmed, as well as the abundant occurrence of gap junctions on both membrane faces.

Amino Acids

Amino acid transport in the rat exocrine pancreas. II. Inhibition by lanthanum and tetracaine.

The two calcium antagonistic agents lanthanum and tetracaine cause severe disturbances in the secretory process of the exocrine pancreas, including inhibition of the rate of protein synthesis and exocytosis. The former effect resulted mainly from the inhibition of amino acid transport. Lanthanum in a concentration up to 1 mM inhibited transport of different species of amino acids in an unspecific way whereas tetracaine interfered specifically with the Na+ -dependent transport system for neutral amino acids (14C-alpha-amino-isobutyric acid). Na+ -dependent transport of neutral amino acids (3H-leucine) was not affected. Transport inhibition was correlated to the acitvity of the Na+, K+ -ATPase system which was measured in isolated plasma membrane fractions. At higher concentrations (5-10 mM) some uptake of lanthanum into the cells by limited endocytosis was observed. At lower concentrations lanthanum seemed to bind exclusively to certain components of the plasms membrane, mainly at the lateral and basal cell surface. Even at a concentration of 5-10 mM no binding to the apical surface occurred. Similarly no binding of lanthanum was observed to the limiting membrane of isolated zymogen granules, while mitochondria, contained in the same fraction showed considerable binding affinity. The action of lanthanum and tetracaine on membrane carrier systems did not affect the interior organization of the plasma membrane. Particle density and distribution in freeze-fracture replicas as well as the submembrane microfilamentous=microtubular system and the junctional elements remained unaffected.

Adenosine Triphosphatases

Mutagenicity of polycyclic hydrocarbons. II. Monitoring genetical hazards of chrysene in vitro and vivo.

Mutagenicity tests were performed with chrysene in the Salmonella/microsome test, NMRI-mice oocytes, bone-marrow cells and spermatogonia of Chinese hamsters. Only in mice oocytes was a weak but significant increase of structural chromosome aberrations observed. Correlations were found between weak carcinogenic and observed weak mutagenic activities of chrysene in vitro and in vivo.

Animals

Ultrastructural studies on the secretory process in the epithelioid cells of the juxtaglomerular apparatus.

The epithelioid cells of the juxtaglomerular apparatus have been studied with respect to the release mechanism of the secretory granules. Invaginations of the plasma membrane into the interior of the epithelioid cells are interpreted as stages before or after an exocytotic process. Granules are sometimes observed in close contact with the plasma membrane, and material with electron density similar to that of the granules can also be observed in the invaginations. These morphological features suggest that the granular material of the epithelioid cells is extruded into the texture of the basal lamina. Furthermore, a dense network of microtubules and microfilaments is described and the functional role of this system in exocytosis is discussed.

Animals