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Biomedical subjects

K Lapis

Publications and source records attributed to K Lapis.

At least 127 records · Page 7Linked to original sources

The effect of TP-3 (Arg-Lys-Asp), TP-4 (Arg-Lys-Asp-Val), and TP-5 on the metastatic capacity of intravenously injected Lewis lung tumor cells.

The oligopeptides Arg-Lys-Asp (TP-3), Arg-Lys-Asp-Val (TP-4), and Arg-Lys-Asp-Val-Tyr (TP-5) considered as the active short fragments of thymopoietin were administered (lo mg/kg) to C57B1 mice 24 hours before the intravenous inoculation of Lewis lung tumor (LLT) cells. A substantial decrease in lung metastasis number was observed as a result of treatment with all of the three oligopeptides. TP-3, TP-4, and TP-5 treatment decreased the immunosuppressive activity of Cyclophosphamid (240 mg/kg) given 96 hours before the inoculation of LLT cells. After thymectomy, performed eight days before the LLT inoculation, only TP-3 treatment resulted in the decrease of Cyclophosphamid immunotoxicity. A stimulating effect of TP-3 on T helper cell activity is assumed. The oligopeptides TP-3, TP-4, and TP-5 are recommended for clinical trial in case of malignant tumors and immunodeficiency.

Animals↗

Immunohistochemical localization of atrial natriuretic peptide in primary aldosteronism.

Using the immunoperoxidase method with specific antibody, we examined the presence of atrial natriuretic peptide (ANP) in adrenal tissues of a patient with primary aldosteronism and those derived from a patient with Cushing's syndrome. We found cells immunopositive for ANP in primary aldosteronism but not in Cushing's syndrome. In primary aldosteronism, we noted positively stained cells mainly but not exclusively in the adenomatous tissue. These results demonstrate for the first time the presence of immunoreactive ANP in adrenal tissues of a patient with primary aldosteronism and suggest that adrenal ANP may have potentially important impacts on aldosterone secretion in this disorder.

Adrenal Glands↗

Striated microfilament bundles (SMF) in the glomerular cells of human kidneys.

Rhizoplast or striated rootlet is a rarely described cytoplasmic organelle in non-ciliated mammalian cells. We observed the centrosome related rhizoplast like structures relatively often in the human renal glomerular cells. Of 226 kidney biopsies striated microfilament bundles (SMF) have been found in 41 cases in a total of 64 cells. More than half of these organelles were found in podocytes, about a quarter in endothelial cells, fewer in mesangial cells and they rarely occurred in the parietal epithelium. The majority of SMF are connected with the centrosome, but not in direct connection with the centriole. The longer bundles have often been located near the Golgi complex. The thickness of the SMF varies, their cross striation has a periodicity of 88 +/- 13.4 nm. The occurrence of SMF does not show any connection with the age of the patients, the type of disease, the morphological changes or therapy. It is difficult to say whether they are normal or pathological organelles. Their presence can be regarded as a metaplastic process in functionally overloaded cells.

Actin Cytoskeleton↗

Diethyl-nitrosamine hepatocarcinogenesis in cirrhotic rats.

The aim of this study was to clarify how the CCl4-induced cirrhosis modifies the process of diethylin-nitrosamine hepatocarcinogenesis. Two strains of rats (CFY and F-344) were used. CFY rats proved to be resistant toward both the cirrhogenic effect of CCl4 and carcinogenic effect of DEN. In the F-344 rats, on the other hand, a large number of foci, neoplastic nodules and hepatocellular carcinomas occurred following DEN treatment only and fullblown liver cirrhosis did develop in the CCl4-treated group. In F-344 rats with cirrhotic liver, foci and neoplastic nodules appeared in the usual number and at the usual time following DEN treatment, but--opposite to the expectations--much less carcinomas developed than in the rats receiving DEN only. When, however the CCl4-treatment was applied following the DEN administration, a promoting effect was seen. The mechanism of the inhibitory effect of the CCl4-induced liver cirrhosis upon hepatocarcinogenesis is not clarified, similarly to the mechanism of of the promoting effect of the CCl4-treatment applied following the DEN administration.

Animals↗

Therapeutic possibilities of thymopoietin fragments (TP3 and TP4) based on experimental animal models.

The effects of thymic hormones are focused on the induction of T-cell subpopulations and restoration of the reactivity of an impaired immune system. TP3 and TP4 (corresponding to thymopoietin 32-34 and 32-35) exert a thymic hormone substitution effect. These peptides elicit dissimilar quantitative and qualitative effects. The aim of the present experiments was to investigate: (a) the effect of thymopoietin fragments in mice with unbalanced immune systems caused by experimental manipulation; and (b) the ratio of target cells after treatment. The distribution of Thy1, Lyt1, Lyt2 positivity was determined in a direct complement mediated cytotoxicity test. Autoantibody production was measured by Coombs' test. A count of Lewis Lung Tumour (LLT) metastases was made after two weeks of inoculation. Groups of mice were thymectomized and/or injected with cyclophosphamide (CY) (240 mg/kg) 96 h before tumour cell inoculation. The number of LLT metastases was decreased by treatment with peptides (TP3 = 72, TP4 = 97, TP5[thymopoietin 32-36] = 83.1 in %) and immunosuppression produced by CY was partly restored. After thymectomy, however, only TP3 treatment caused a decreasing effect (97.4%) on CY immunotoxicity independently of thymectomy. Inhibition of autoantibody production was detected with TP3 (5-6 weeks earlier than in mice treated with TP5). The ratio of Thy1+ and Lyt2+ cells was increased by treatment with TP3 and TP4, but the ratio of Lyt1+ cells was decreased by application of TP5. After TP3 treatment of nude mice the Lyt1+/Lyt2+ ratio increased both in bone marrow and spleen. No effect of TP4 was observed on Lyt 1+ cells, but the number of Lyt2+ increased in bone marrow.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗

Antitumor action of N-(2-chloroethyl)-N-nitrosocarbamoyl derivatives of biologically active polypeptide hormone fragments.

The antitumor action of the 2-chloroethylnitrosocarbamoyl derivatives of peptides related to the 9-13 amino acid residues of alpha-MSH/ACTH and of the C-terminal tetrapeptide analogue of gastrin have been investigated. Series of 2-chloroethylnitrosoureas attached to amino acids, di-, tri-, tetra-, or pentapeptides were examined in a primary screening system. Among these compounds the Pro-Val-, Lys-Pro-Val-, and Trp-Gly-Lys-Pro-Val-containing 2-chloroethylnitrosocarbamoyl groups were the most effective in the L1210 system. The human melanoma xenograft line was also affected by these agents, while colorectal xenografts were insensitive. A combination of tripeptide-2-chloroethyl-nitrosourea with BCNU induced more than additive growth inhibition of L1210 leukemia.

Animals↗

Fatty degeneration in cultured hepatocytes. A new experimental model.

In co-cultures of adult rat hepatocytes and a neonatal rat liver cell line, severe fatty degeneration was induced by the addition of 50% rat serum. The light and electron microscopic patterns did not differ significantly from those of in vivo fatty degeneration and the changes were reversible on removal of the serum. The in vitro system is considered to simulate some forms of fatty degeneration of the liver and to be suitable for testing the effects of liver-protecting agents.

Animals↗

5-Ethyl-2'-deoxyuridine: an explanation for its lack of cytotoxic action in vivo.

The aim of this study was to explain why 5-ethyldeoxyuridine (EUdR) showed cytotoxic activity against Ehrlich ascites tumour (EAT) cells in vitro but not in vivo. In vitro studies showed that EUdR was phosphorylated to nucleotides which inhibit thymidylate synthetase and DNA polymerase. Toxicity in tissue culture appeared to be related to the inhibition of one or both of these enzymes; and could be prevented/reversed by thymidine (TdR). In vivo EAT cells also formed active EUdR nucleotides at levels which in vitro would have been associated with cytotoxicity but these levels were not maintained. EUdR has been shown to compete with TdR for catabolism by pyrimidine nucleoside phosphorylases from mouse liver and gut. In the ascitic fluid it was found that the level of EUdR fell rapidly while that of TdR and 5-ethyl-uracil increased. It is proposed that competition for catabolism in vivo resulted in the rise in TdR which then compromised the antitumour effect of EUdR.

Animals↗

Quantitative light microscopic study on the distribution of Kupffer cells during chemical hepatocarcinogenesis in the rat.

The quantitative distribution of Kupffer cells was measured in the liver of Fischer-344 male rats during the course of chemical hepatocarcinogenesis according to the Solt-Farber model, i.e. an initiating agent, a selective mitogenic inhibitor and a strong proliferation stimulus were applied subsequently. Pre-neoplastic and neoplastic lesions were followed up to 17 months. Kupffer cells were detected by the phagocyted carrageenan stained with toluidine blue and were counted using the ocular square in the light microscope. In the non-transformed areas of the liver of treated rats the number of Kupffer cells was generally different from the values of untreated controls. The altered cell foci contained fewer Kupffer cells than the normal untreated rats and the non-transformed liver areas, while in hepatocellular carcinomas there was a high reduction in the number of detectable Kupffer cells. The number of Kupffer cells was variable around and within neoplastic nodules. While Kupffer cells do not follow the neoplastic proliferation of hepatocytes during hepatocarcinogenesis, it is possible that humoral factors are produced by transformed hepatocytes against Kupffer cells.

Animals↗

Morphology and immunohistochemistry of experimental and human non-A, non-B hepatitis.

The diagnosis of non-A, non-B hepatitis (NANBH) presently depends on the exclusion of hepatitis A, B and other causes of hepatitis, because no specific tests are available for diagnosis. Different approaches were used in order to detect NANBH infection in human and chimpanzee tissue. Endogenous interferon production was not detected in the weekly serum samples of 6 chimpanzees inoculated with a human agent of NANBH in contrast to the 5 HBV-infected animals. An antibody raised against a glycoprotein (GP77) associated with NANBH reacted immunohistochemically with liver biopsies obtained from NANBH-infected chimpanzees and with 11 out of 14 human liver biopsies from patients with NANBH. Two out of 12 human biopsies taken from patients with other liver diseases were positive. Diffuse reaction was noted in the cytoplasm of hepatocytes in chimpanzees. Three reaction patterns--diffuse, submembranous and perinuclear--were observed in human liver biopsies. A 35S radiolabeled DNA-probe of 780 base pairs--specific activity 5.4 x 10(4) cmp/micrograms DNA--isolated from NANBH-infected chimpanzees has been shown to hybridize in situ with liver sections from NANBH-infected chimpanzees. Data suggest that immunohistochemical and in situ hybridization methods can be successfully used for detection of NANBH infection in the liver of humans and chimpanzees.

Animals↗

Morphologic and immunoelectronmicroscopic identification of human T-cell lymphotropic virus type III (HTLV-III).

The AIDS associated HTLV-III virus infected H9 cells were extensively studied using light, scanning and transmission electronmicroscopy. It was demonstrated that the morphological features of HTLV-III are different from the C-type particles and are similar to those of lentiviridae. For immunological identification high titer pre-AIDS patient sera served as the anti-HTLV-III envelope antibody source. The immunoelectronmicroscopic method was able to identify the viral envelope antigen on the surface of infected cells and in certain areas of the viral envelope. This is the first application of immunoelectronmicroscopy for the identification of the HTLV-III virus.

Cell Line↗

[Hepatoblastoma].

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Carcinoma, Hepatocellular↗

Comparison of biophysical parameters of primary low and high metastatic Lewis lung tumor cells.

Lewis lung tumor cells from tumors of both high and low metastatic potential were isolated from the leg muscle of C57-B1 mice and were purified by density gradient centrifugation. The purified cells retained most of their tumor-forming capacity; however, the difference in the metastatic capacity of the 2 cell lines increased with the purification process. The purified and viable cells were subjected to different biophysical studies. Electron spin resonance studies showed that the motional freedom of lipid and protein molecules of the cellular membrane is higher in the low metastatic cell population. Both cell types reduce penetrating and non-penetrating free radicals, but the reducing ability of the low metastatic cell population is 4 times greater than that of the high metastatic cell line. These findings argue for increased membrane dynamics in the low metastatic cell population.

Animals↗

Experimental studies on the effect of hepatoprotective compounds.

The hepatopharmacological actions of Prostacyclin, 1-phosphate-4-amino 5-carboxamido-imidazole (AICA-P), Catergen, Silymarin and a thiazolidine compound were investigated by applications in in vitro and in vivo model systems. The usefulness of the in vitro system to screen for potential hepatoprotective agents and to investigate the molecular mechanism of these substances is shown. It was concluded that different patterns of hepatoprotective action were elaborated by the same drug depending on the model system used for testing. PGI2 and the thiazolidine compound showed remarkable protection in acute liver damage. However PGI2 circumvented only the CCl4 induced cellular injury, and was inactive in the galactosamine model system. The induction of cirrhosis could be modified by the simultaneous treatment with PGI2 or by the thiazolidine compound but the fully developed cirrhosis was not affected. On the contrary AICA-P and Silymarin treatment resulted in reduction of the amount of collagen in cirrhotic liver.

Aminoimidazole Carboxamide↗

Flow cytometric measurements and electron microscopy of cell surface glycosaminoglycans using acridine orange.

Cell surface glycosaminoglycans (GAGs) were measured, after various treatments, by their binding to Acridine Orange using flow cytometry. Using a critical electrolyte concentration and combining it with specific degradation of individual GAG elements, it was found possible to differentiate between GAG components. The technique was adapted for electron microscopy level to reveal characteristics of membrane-associated GAG. By this means, the cell membrane of the human leukaemic cell line K562 was shown to contain a large amount of GAG; 75% of it was highly sulphated GAG, mostly heparan sulphate. This component was evenly distributed in the outer plasma membrane layer. In the presence of other GAGs, the appearance of complex proteoglycan granules was detected.

Acridine Orange↗

Distribution of fibronectin and laminin in human liver tumors.

Two extracellular matrix and basement-membrane components, fibronectin (Fn) and laminin, were studied by the indirect immunoperoxidase technique in ten primary human liver cancers. Similar distributions of both Fn and laminin were detected in the well differentiated hepatocellular carcinomas with trabecular and tubular pattern. Two moderately differentiated hepatomas contained Fn only. Neither Fn nor laminin were present, however, in the parenchyma of one poorly differentiated hepatoma. In three cases of cholangiocarcinoma, laminin surrounded the tumorous ducts, while Fn appeared mainly in the reactive connective tissue stroma. The present findings indicate that bile-duct cancers synthesize laminin, and not Fn while differentiated hepatocellular carcinomas produce both Fn and laminin in vivo. The presence of Fn even in moderately differentiated types of liver cancer is in contrast to the findings for carcinomas developing from other organs and it may serve as a marker for primary hepatocellular carcinomas in the differential diagnosis.

Adenoma, Bile Duct↗