Factor VIII and antithrombin III in atherosclerosis obliterans of the lower limbs.
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Biomedical subjects
Publications and source records attributed to A Pinto.
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Adult female rats (N = 26) were prepared with either sham lesions or electrolytic lesions of the dorsolateral tegmentum (DLT). Body weight gain, adiposity, 72-hour food intake and day/night food intake, serum glucose and serum insulin levels were measured 15 and 17 days post-operatively. Dorsolateral tegmental lesions produced moderate weight gains and enhanced adiposity as assessed by the Lee Index. Although dorsolateral tegmental rats were hyperphagic only at night, hyperinsulinemia was observed during the day and the night. Hyperinsulinemia may contribute to the obesifying action of tegmental lesions in rats fed high-fat diets.
A systematic study has been performed using a series of differentiated rat thyroid epithelial cell lines either uninfected or infected with Kirsten murine sarcoma virus (KiMSV), to determine the levels of the p21 product of the v-ras-Ki oncogene in transformed and normal cell lines. The p21 levels have been assayed by SDS-polyacrylamide gel electrophoresis of immunoprecipitates of 35S-labelled cell extracts and by a GDP binding assay. All cell lines analysed showed a significant increase in the levels of p21 after transformation with KiMSV compared to the p21 levels of uninfected and untransformed differentiated thyroid cells. The results reported here confirm the potential ability of the v-ras-Ki oncogene product to transform epithelial cells. They show, furthermore, that not only is p21 present in some epithelial cells transformed by KiMSV, but also that it is functionally active, as has been shown for fibroblasts transformed by the same virus, and that its functioning is maintained after passaging in vivo of the transformed cells.
The effect of a 3 month daily administration of 800 mg pentoxifylline (Trental 400 bds) or placebo was assessed under double blind crossover design in 18 patients (12 males and 6 females) with peripheral occlusive arterial disease in respect of painfree walking distance and various hemorheological and hemostasiological variables, platelet aggregation, serum cholesterol and triglycerides. In first treatment period walking distance significantly increased with pentoxifylline by 46% from baseline 121 +/- 15 m and by 4% with placebo from baseline 134 +/- 18 m. Pentoxifylline administration furthermore yielded significant decrease in whole blood and plasma viscosity and significant increase in erythrocyte deformability. This was paralleled by distinct reduction of fibrinogen, platelet aggregation and euglobulin lysis time, also plethysmographic variables showed positive changes pointing to improvement of limb perfusion. The results of the study suggest that treatment of peripheral occlusive vascular disease by a drug improving blood fluidity through correction of hemorheological and hemostasiological factors turns especially promising and beneficial since the action centers finally on the languishing microcirculation in the ischemic tissue.
A prospective study of the effects of cytomegalovirus (CMV) infection on 145 recipients of 155 renal allografts is reported. Immunosuppression was either with azathioprine and low-dose prednisolone (103 transplants) or with Cyclosporin A (52 transplants). Sixty-one cases of CMV infection were diagnosed; of those 21 were primary (i.e. in CMV sero-negative recipients) and 40 were secondary (i.e. in previously sero-positive recipients). The infection rate in patients treated with azathioprine and low-dose prednisolone did not differ from the rate in those treated with Cyclosporin A. Eighteen of the 21 primary CMV infections were clinically overt; several of these patients became seriously ill, and one of them died. Only four of the 40 secondary infections were overt, and these were all mild. Graft and patient survival were not adversely affected by CMV infection. Indeed the group with secondary CMV had significantly better survival rates than the uninfected sero-positive or sero-negative patient groups. Recommendations to minimise the effects of primary CMV infections are given.
In this study, the effects of 5-aza-2'-deoxycytidine on differentiation of human leukemic cells in primary suspension culture are reported for the first time. Morphological and functional differentiation was induced in cells from two acute monoblastic leukemias and two of three acute myeloid leukemias following repeated exposures to 1 mumol/L 5-aza-2'-deoxycytidine. The observation that nontoxic concentrations of the drug are able to induce the in vitro differentiation of both monoblastic and myeloblastic leukemic cells into mature elements may encourage the exploitation of the differentiating properties of 5-aza-2'-deoxycytidine in chemotherapy protocols for acute non-lymphoblastic leukemias.
5'-Methylthioadenosine is a sulfur-containing nucleoside derived from the metabolism of polyamines which is known to exert an antiproliferative effect on several cell systems in vitro, including the Friend leukemia cell system. We have investigated the role of 5'-methylthioadenosine on the dimethyl sulfoxide-induced differentiation of this system. At a concentration of 400 microM, the drug strongly inhibited (80%) the induced differentiation of Friend cells, and this effect was already observable at a concentration as low as 10 microM (36% inhibition), as evidenced by the benzidine staining procedure and by the dot-blot hybridization of globin mRNA with a human beta-globin probe. Similar results have been obtained by using 5'-S-isobutylthioadenosine, which is a synthetic structural analogue of 5'-methylthioadenosine. The block of differentiation produced by these nucleosides was not mediated by adenine (a catabolite of both molecules) and was not reverted by spermine or spermidine, the two polyamines whose synthesis is inhibited by 5'-methylthioadenosine. We report a decrease of the aminopropyltransferases activities (the enzymes responsible for 5'-methylthioadenosine biosynthesis) in dimethyl sulfoxide-treated Friend cells, which could lead to a decrease of the intracellular content of 5'-methylthioadenosine during the erythroid maturation of Friend cells. The results obtained are consistent with the hypothesis that 5'-methylthioadenosine may act as an endogenous regulator of Friend cell differentiation.
Adrenalin (5.0 X 10(-5) M) increases gill vascular resistance up to 23.2 +/- 6.8% in the isolated and perfused head of the european eel (Anguilla anguilla L.). This vasoactive response is nearly abolished by the alpha-adrenergic blocking agent phentolamine mesylate (5.0 X 10(-5) M), while it is increased by the beta-blocker propranolol (5.0 X 10(-4) M). From these results it may be inferred that, in our experimental conditions, the major response to the catecholamine is a vasoconstriction mediated via alpha-adrenoceptors.
In 12 patients with arterial hypertension (stages I and II according to WHO), adrenergic stimulation was induced by the immersion of a hand in ice water for 2 min. Blood samples were withdrawn before, at the end of, and 15 min after the cold application: the experiment was repeated 2 h after the ingestion of 200 mg acebutolol, a selective betablocking agent. The following assays were performed: serum nonesterified fatty acid (NEFA), plasma beta-thromboglobulin (BTG) and PF4 with specific radioimmunoassays; thromboxane B2 (TXB2) in plasma was also estimated with radioimmunoassay, platelet sensitivity to exogenous prostacyclin; furthermore, the thrombin-induced thromboxane production before and after acebutolol ingestion as well as serum TXB2-levels were measured. The blood pressure and the heart rate were also monitored. After cold stimulation, a significant increase of NEFA, BTG, and plasma TXB2 was observed, which was still discernible 15 min after the application of cold. After acebutolol, the cold treatment led to a lower increase of blood pressure with a reduction of the heart rate, as well as to a diminished release of BTG, PF4 and TXB2 no changes in the reduced platelet sensitivity to prostacyclin were noticed.
Differentiated rat thyroid epithelial cells, infected in vitro with a temperature-sensitive mutant of the Kirsten murine sarcoma virus, expressed at the permissive temperature (33 degrees C) some phenotypic properties typical of transformed cells, including morphological features, colony formation in agar, and induction of tumors in newborn animals. Specific functional markers of these differentiated cells, i.e., synthesis/secretion of thyroglobulin, synthesis of thyroglobulin mRNA and iodide uptake, were blocked during growth at 33 degrees C. Normal morphology, failure to grow in agar, and the requirement of hormones for optimal growth were all restored after shifting to the temperature nonpermissive for transformation (39 degrees C), though the typical differentiated functions remained blocked. Infection with a leukemia helper virus clone (Moloney or Kirsten murine leukemia virus) did not lead to the loss of the differentiated phenotype of rat epithelial thyroid cells, thus demonstrating that the loss of the differentiated phenotype is caused by the sarcoma virus component. These results indicate that the expression of some of the phenotypic properties of transformed differentiated rat thyroid epithelial cells is under the direct control of the p21 thermosensitive activity, whereas the block in the expression of two typical differentiation markers of thyroid epithelial cells is irreversible and probably controlled by different mechanisms.
Red blood cell filterability was compared with some blood coagulation parameters in 50 patients suffering from atherosclerosis obliterans of lower limbs at stages II, III and IV. The reduced red blood cell filterability correlated positively with the stage of the arterial disease (r = 0.8185), with levels of plasma fibrinogen (r = 0.8366) and with the euglobulin lysis time (r = 0.8124), while negative correlations with platelet reactivity threshold (r = 0.6928) and with antithrombin III activity (r = 0.6557) were found. The authors believe that in the therapy of these vascular diseases it is necessary to modify the reduced red blood cell filterability together with the blood coagulation order.
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TxB2 formation in PRP after thrombin stimulus, serum TxB2 and platelet sensitivity to prostacyclin and the correlation with ambient fasting plasma glucose and lipoproteins were determined in 20 insulin-independent diabetics (IID) with macroangiopathy, 10 insulin-dependent diabetics (IDD) with microangiopathy and 30 matched controls. Platelets obtained from insulin-independent diabetics synthetize significantly higher amounts of TxB2 than those of insulin-dependent diabetics and matched controls. IDD and IID patients required significantly higher concentrations of prostacyclin (p less than 0.001) for a similar degree of platelet aggregation inhibition. The amount of prostacyclin required for 50% platelet aggregation inhibition was correlated with fasting plasma glucose (r = 0.64, p less than 0.001) and HbA1% (r = 0.48, p less than 0.01) in all diabetic subjects. We conclude that: 1) only PRP, obtained from some insulin-independent diabetics with a concomitant macroangiopathy, shows an increased synthesis of TxB2; 2) platelet sensitivity to prostacyclin is highly dependent on the fasting ambient plasma glucose.
Sera from Somalis of both sexes between the ages of 16 and 60 were examined for leptospiral agglutinins. 37% of 105 apparently healthy individuals living in the arid Mogadishu area were positive, as were 64% of 107 schistosomiasis patients living in two villages on the Shabeele River (50.5% over-all). Pools of sera from similar subjects, as well as leprosy patients living on the Juba River and patients in Mogadishu hospitals with suspected viral hepatitis showed a similar prevalence rate of 56%. These figures are higher than prevelance rates for leptospiral antibodies generally found in other parts of the world, and in part may be related to the nomadic, cattle-driving existence common in Somalia. The titres of 11.2% of the positive sera examined singly indicated recent infection. Approximately twice as many subjects from the river villages as from the Mogadishu area were positive for more than one serovar, and a greater number of serovars were recorded from the villages. Antibodies to bratislava serovar, not previously recorded in Africa, were found in 57% of positive subjects, showing the highest prevalence rate among the investigated serovars. Co-antibodies to saprophytic Leptospira biflexa serovars were found in many of the sera.
Well-differentiated epithelial cells, derived from primary cultures of normal rat thyroid glands (T-79 cells), as well as a cloned cell line also derived from normal rat thyroid glands (FRT-L cells) were infected with Kirsten murine sarcoma virus carrying outer coat of the helper Kirsten murine leukemia virus. Infected T-79 and FRT-L cells changed morphologically and began to proliferate rapidly, suggesting malignant transformation by the virus. Both cell lines can support the replication of both transformation-competent and transformation-incompetent viruses such as murine or rat leukemia viruses. Infected T-79 and FRT-L cells had a high colony-forming efficiency (68 and 64%, respectively) when grown in agar and formed tumors when transplanted s.c. into syngeneic rats. These tumors morphologically resemble undifferentiated adenocarcinomas, thus showing that Kirsten sarcoma virus carrying the outer coat of the helper Kirsten murine leukemia virus is able to transform differentiated epithelial cells. Transformed T-79 and FRT-L cells, in contrast to uninfected cells, neither secrete thyroglobulin concentrate iodide, two biochemical markers of differentiated thyroid function. Thus, expression of the differentiated phenotype is blocked as a consequence of cell transformation. The system described may be useful in studying epithelial cell carcinogenesis in terms of regulated expression of differentiated functions.
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