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Biomedical subjects

M Polak

Publications and source records attributed to M Polak.

At least 109 records · Page 6Linked to original sources

Expression of functional nerve growth factor receptors in pancreatic beta-cell lines and fetal rat islets in primary culture.

Previous data demonstrated that one rat insulinoma cell line, RINm5F cells, which is a rat beta-cell line derived from a pancreatic tumor, express mRNA coding for both the low- and the high-affinity nerve growth factor receptors. Goals of this study were to extend our data to other beta-cell lines and fetal islets in primary culture and to study further the binding characteristics of nerve growth factor receptors on beta-cells. Northern blot analysis revealed that not only a panel of endocrine beta-cell lines (RINm5F, INS-1, beta-TC3) but also fetal rat islets in primary culture express mRNA coding for trk-A, which has been proposed to be the neuronal high-affinity nerve growth factor receptors. Reverse polymerase chain reaction followed by sequencing revealed that the sequence of trk-A receptor in RINm5F cells is identical to that of trk-A expressed in PC12 cells. The expression of the low-affinity nerve growth factor receptor was examined by Northern blot analysis that showed low-affinity nerve growth factor receptor to be expressed in RINm5F and INS-1 cell lines, in fetal rat islets in primary culture, but not in beta-TC3-cells. Binding experiments revealed the presence of low- and high-affinity nerve growth factor binding sites, identical to those described for PC12 cells, on RINm5F and INS-1 cells and only high-affinity binding sites on beta-TC3 cells. Exposure of all three beta-cell lines to nerve growth factor increased NGFI-A and c-fos mRNA steady-state levels, showing that these receptors are functional.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Subacute necrotizing encephalopathy: oxidative phosphorylation defects and the ATPase 6 point mutation.

Subacute necrotizing encephalopathy (SNE) or Leigh's disease is associated with various defects in oxidative phosphorylation (OXPHOS). However, the relationships between these OXPHOS defects and nuclear DNA or mitochondrial DNA (mtDNA) mutations is still unclear. We evaluated three SNE pedigrees (two singleton cases and a pedigree) biochemically for OXPHOS abnormalities and genetically for four mtDNA point mutations. There was a complex I defect in all three pedigrees that was associated with a complex III defect in two individuals. An mtDNA mutation in the ATPase, subunit 6 gene (np 8993) was present in one SNE pedigree. This mutation was maternally inherited, heteroplasmic, produced marked clinical and biochemical heterogeneity between pedigree members, and varied along the maternal lineage at levels ranging from 0% to > 95% of the total mtDNAs. These mtDNA mutations were not present in the other two pedigrees. These observations emphasize the importance of screening for OXPHOS defects and mtDNA mutations in SNE cases.

Adenosine Triphosphatases↗

A human TSH-secreting adenoma: endocrine, biochemical and morphological studies. Evidence of somatostatin receptors by using quantitative autoradiography. Clinical and biological improvement by SMS 201-995 treatment.

An invasive TSH-secreting adenoma inducing mild hyperthyroidism was diagnosed in a 16-year-old male. Initial surgical treatment led to a temporary clinical and biological improvement. Recurrence of the thyrotoxicosis was treated with the somatostatin analogue, SMS 201-995 (octreotide) with normalization of the serum thyroid hormone levels with a dose of 200 micrograms per day. With immunoelectron microscopy, the tumour cells appeared poorly granulated with small secretory granules located at the periphery of the cells; only part of those were immunoreactive with an anti-TSH beta monoclonal antibody. No specific TRH binding site was found in a tumour membrane preparation. By quantitative autoradiography, somatostatin specific binding sites were as numerous in the TSH-secreting tumour as in control GH-secreting tumours. Binding kinetics and guanosine triphosphate dependency of the binding were equivalent in the TSH and GH tumours tested. Although all of the tumour cells displayed the same ultrastructural features, some were non-immunoreactive, suggesting that they could secrete an altered form of TSH. The absence of TRH receptors in the tumour cells is in accordance with previous reports on this type of tumour. We confirm the efficiency of octreotide treatment in this case of neoplastic TSH inappropriate secretion. The therapeutic effect of octreotide goes along with the presence of a high density of guanine nucleotide-dependent somatostatin binding sites in the tumour cells.

Adenoma↗

Demonstration of lactogenic receptors in rat endocrine pancreases by quantitative autoradiography.

A direct effect of growth hormone and/or prolactin on the growth of the pancreatic beta-cell has been proposed. This study assessed the presence of human growth hormone (hGH)-binding sites in male adult rat endocrine pancreas via quantitative autoradiography. The binding of 125I-labeled hGH was evaluated by receptor autoradiography on frozen-pancreas cryostat cut sections. The sections were incubated with 125I-hGH (10(-10) M) for 75 min at room temperature, and nonspecific binding was determined in the presence of excess native hGH (5 X 10(-7) M). The specificity of the binding was assessed in competition experiments with bovine GH and ovine prolactin. The autoradiograms were quantified with a computer-assisted image-processing system. The sections were then stained to visualize the endocrine islets. Nondiabetic control and streptozocin (STZ)-injected rats were used. Our results show that 1) there is specific binding of iodinated hGH in small areas of the pancreas, which appear as the Langerhans islets when the autoradiogram and the stained sections are superimposed; 2) the specificity of hGH binding in rat islets is lactogenic; 3) the density of the hGH-binding sites in the endocrine pancreas is estimated at 4.8 fmol/mg protein, with IC50 ranging from 0.98 to 2.50 nM; and 4) binding sites may be present on the beta-cell, because specific binding disappears in STZ-injected rats. In conclusion, by use of a quantitative autoradiographic technique, we provide evidence for the presence of lactogenic receptors on rat beta-cells.

Animals↗

Representativity of human mammary tumor cell cultures: DNA-cytophotometry as a method for checking tumour cell characteristics.

Short term cultures (3-6 days) of 40 primary human mammary carcinomas were prepared and compared with the original tumours from which they were derived. As a criterion the nuclear DNA Frequency Distribution Pattern (FDP), cytophotometrically measured, was used. Comparisons were made between the FDPs of smears of freshly-cut tumour surfaces and their cultures. Twenty-nine (73%) cultures showed FDPs identical with the smears. Eleven cultures (27%) showed gross shifts in ratios between different peaks or showed a complete loss of one or more peaks in the FDP and were classified as not representative. Our results show that it is necessary to check primary mammary tumour cultures to determine whether or not they are representative of the original tumour. This is especially so if conclusions are to be drawn from the cultures about the original tumour. Analysis of FDPs in the cell islands of the cultures (migration of cells from attached clumps) resulted in a better understanding of the FDPs found in the smears. We showed that cultures of human mammary tumours either can be composed of cell islands with identical FDPs (diploid or aneuploid) or may show heterogeneity between different cell islands within one tumour.

Breast Neoplasms↗

In situ localization of human papilloma virus type 16 DNA in a metastasis of an endocervical adenocarcinoma.

Metastatic tissue from an endocervical adenocarcinoma was examined for human papilloma virus (HPV) DNA sequences. Southern blot analysis with 32P-labeled viral probes revealed the presence of about 150 copies of HPV-16 DNA per cellular genome. DNA in situ hybridization of frozen sections with biotinylated probes showed that HPV-16 DNA was exclusively detectable in the nuclei of the malignant epithelial cells and not in the stroma.

Adenocarcinoma↗

Preoperative radiotherapy in the management of posterior fossa choroid plexus papillomas.

Although primary radical removal is the procedure of choice in the treatment of choroid plexus papillomas, the age of the child, the size and/or location of the tumor and an above average surgical risk can make advisable the use of a first stage shunt operation, with section of the tentorium if there are signs of upwards tentorial herniation. The present two observations clearly demonstrate that radiotherapy shrinks the vascular stroma of these tumors, thus reducing its size and vascularity making possible the postponement of radical surgery and greatly simplifying the final radical removal of the lesion. Preoperative radiotherapy as well as shunt operations and tentorial section can be considered as first stage procedures for the surgical management of choroid plexus neoplasms in certain cases.

Cerebral Ventricle Neoplasms↗

Azathioprine hepatotoxicity, direct complication or secondary effect in rat liver transplantation.

The risk of azathioprine-induced hepatocellular damage was investigated using the auxiliary liver transplantation model in rats. This model permits to study the effect of the drug on both graft and the recipient's liver vascularized in different ways. Neither histopathological changes were observed, nor could any deaths be directly attributed to toxic effects of the drug on hepatocytes. Morphological lesions were absent in treated and untreated, subtotally hepatectomized rats with normal bile flow. However, lesions did become manifest after reimplantation (grafts) and/or ligation of the common bile duct (hosts). We concluded that in rats azathioprine is toxic for hepatocytes only when the normal bile flow is impeded, independent of the way of the liver vascularization.

Animals↗

Microglioma and/or reticulosarcoma of the nervous system.

49 microgliomas of nervous parenchyma were studied, all of them with aniline techniques in part of the material embedded in paraffin, and the rest with Del Rio Hortega-Polak's technique in frozen sections. It is considered that the microglia is the representative of the R.E.S. in the nervous tissue, and is characterised by its cytoplasmic argentophilia. The existence of a non-argentophilic primitive reticular cell is denied, and it is maintained that microglioma and reticulosarcoma are synonymous thus refuting the concept of the existence of a reticulosarcoma consisting of non-argentophilic cells and a microglioma consisting of argentophilic cells, as different neoplasms.

Brain Neoplasms↗

[Laparoscopic photography on infra-red sensitive film].

Photographs taken on Ektachrome infrared IE 135-20 film during laparoscopy are distinguished by improved contrast. Details that can be recognized indistinctly or not at all on regular color film can be brought out. This film has proved to be particularly useful for the visualization of lymph vessels and close-ups of the surface.

Humans↗