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Biomedical subjects

A Pinto

Publications and source records attributed to A Pinto.

At least 307 records · Page 17Linked to original sources
PubMed1987

Expression of major histocompatibility complex class I antigens in normal and transformed rat thyroid epithelial cell lines.

Recent evidence suggests that the expression of abnormally high amounts of major histocompatibility complex (MHC) class I molecules may be a feature of at least some kinds of transformed cells. To investigate this aspect of neoplastic transformation we studied the expression of MHC class I antigens in an experimental model of normal, tumor-derived, and virus-transformed thyroid epithelial cell lines. The expression of MHC class I antigens has been studied by means of several monoclonal antibodies directed against either monomorphic or polymorphic epitopes and quantified by flow cytometry. Class I specific mRNA transcripts have been also analyzed by Northern blot hybridization, using a mouse genomic H-2 DNA probe. Our results indicate a modulation of MHC class I expression associated with loss of the differentiated phenotype and with transformation of thyroid epithelial cell lines. Undifferentiated cells in fact show a small quantity of these antigens, because acquisition of a fully differentiated phenotype is associated with an increase in their expression. Cell lines derived from thyroid tumors show reduced expression of MHC class I antigens, as compared to differentiated cells. Conversely, cells transformed in vitro by a retrovirus carrying the v-raski oncogene exhibit an increase in these antigens in comparison to their normal differentiated counterparts. Cells infected with a mutant virus able to transform cells only at the permissive temperature of 33 degrees C show a similar increased expression. After a shift to the nonpermissive temperature of 39 degrees C, infected cells, even those losing the transformed phenotype retain the same increased amount of MHC class I antigens. Our data suggest that the modulation of MHC class I antigen expression is strongly associated with transformation in thyroid epithelial cells.

Adenocarcinoma↗
PubMed1987

Characterization of a novel neuroglandular antigen (NGA) expressed on abnormal human melanocytes.

Murine monoclonal antibodies (MAbs) were produced with reactivity to human malignant melanoma. Six MAbs, 3 of the IgGI (LS113, LS140, LS152) and 3 of the IgG2a (LS59, LS62, LS76) subclasses, were selected for their binding, with an identical pattern of reactivity, to a novel melanoma-associated antigen. As characterized by the enzyme-linked immunosorbent assay (ELISA), these MAbs were found to be positive on n-octyl-beta-D-glucopyranoside extracts of all 10 melanoma cell lines tested and on extracts of 22 metastatic melanoma tumors. The antibodies had minimal reaction with a panel of 14 normal adult tissue extracts. A degree of cross-reactivity was observed with 50% of 39 non-melanoma tumor extracts. The results obtained with the ELISA on cell line and tissue extracts were duplicated using the ABC method of peroxidase staining. The pattern of cross-reactivity, as demonstrated by the intense staining of paraffin-embedded and frozen tissue sections of normal, benign and malignant tissues, defines the recognized protein as a neuroglandular antigen (NGA). Immunoadsorbents made with the antibodies were used to purify the antigen shed from cultured melanomas. All 6 MAbs recognized this purified antigen while 5 other antimelanoma antibodies did not react with it. On gel electrophoresis this antigen is a highly glycosylated glycoprotein with a protein core of 21 kDa.

Animals↗
PubMed1987

Prevalence of leptospirosis in man. Pilot survey.

A survey on the prevalence of leptospirosis was performed on the population living in an area of central Italy. The size of the sample was calculated in order to provide significant results in the case of a prevalence of infection in not less than 1% of the population. Results demonstrated an unexpectedly wide circulation of leptospirosis in the surveyed area, showing a prevalence rate of infection of 11.34% for people living in rural areas and 3.08% for people living in the main town. The highest prevalence of infection (17.44%) was found in people between 30 and 44 years of age, living in rural areas. Such a wide circulation of undiagnosed past leptospiral infections was attributed both to the prevalence of mild clinical cases of leptospirosis in humans and the lack of microbiological tests performed to differentiate current leptospirosis from other infectious illnesses. An unexpected persistence in sera of co-agglutinins towards non-pathogenic serovars of L. biflexa was also noticed in healthy people. Criteria were established for the extension of the survey on the prevalence of leptospirosis to cover larger areas by limiting sampling to the more exposed age groups and to areas representative of a larger land belt.

Adolescent↗
PubMed1987

Argininosuccinic aciduria: long-term treatment with arginine.

The presentation and 2 year treatment of a patient with argininosuccinic aciduria is reported. Erythrocyte argininosuccinate lyase activity was less than 2% of normal. Long-term management included protein restriction and arginine dietary supplementation. The child experienced three episodes of hyperammonaemia (greater than 100 microns), the first at birth, the second at 6.5 months and the third at 16 months. Neurological development deteriorated between 14 and 24 months. Hepatomegaly and biochemical hepatitis, a feature of this condition, was accompanied by enlarged mitochondria with tubular paracrystalline inclusions not previously recognized in this disorder.

Amino Acid Metabolism, Inborn Errors↗
PubMed1987

Antagonistic actions of prostaglandins E2 and F2 alpha on the isolated lungs of the frog, Rana esculenta L.

Isolated lungs of the frog, Rana esculenta L., when incubated in amphibian Ringer solution for 30 min, produced a prostaglandin E2-like substance (27.1 +/- 3.8 ng/g w.w.), as determined by bioassay on the isolated rat stomach strip. The release of PGE2-like substance from skin, heart and bowel is also reported. The activity of synthetic prostaglandins E2 (PGE2) and F2 alpha (PGF2 alpha) on the muscular contractility of frog isolated lungs was investigated: PGE2 and PGF2 alpha relaxed and contracted respectively in a dose-dependent manner this preparation, a result similar to that obtained in mammals.

Animals↗
PubMed1987

Identification of heme oxygenase and cytochrome P-450 in the rabbit heart.

The regulation of cardiac heme oxygenase and cytochrome P-450 mixed function oxidase was studied in the rabbit heart. Heme oxygenase activity is found in ventricular and atrial microsomal fractions. This activity is NADPH dependent, and is inhibited by tin and zinc protoporphyrin, but not by either SKF 525A or 7,8-benzoflavone. Immunologic studies of cardiac heme oxygenase demonstrate that antibodies prepared against human purified hepatic heme oxygenase recognize rabbit atrial heme oxygenase and inhibit the enzyme activity by 92%. In contrast, control immunoglobulin does not inhibit heme oxygenase activity. Further, the western blotting technique demonstrates that a similar band of protein with a molecular weight of 32,000 exists in cardiac microsomes and that no protein cross-reacts with purified hepatocyte heme oxygenase. Marked induction of atrial heme oxygenase is observed in microsomal fractions prepared from rabbits treated with cobalt chloride. Atrial microsomes possess 0.24 nmol of cytochrome P-450 as compared to 0.68 nmol/mg protein in microsomes from the liver. The levels of aryl hydrocarbon hydroxylase (AHH) activity, a cytochrome P-450-dependent enzyme, in ventricle and atrium are stimulated by a NADPH-generating system and are sensitive to 7,8-benzoflavone, and SKF 525A, known inhibitors of cytochrome P-450 mixed function oxidase. AHH activity in ventricular and atrial microsomes is 2-3% of that seen in liver microsomes whereas the P-450 content/mg protein is about 20% of that observed in the liver. AHH activity is mediated by a form of cytochrome P-450 that is inducible by 3-methylcholanthrene/beta-naphthoflavone. A possible new role of the heart cytochrome P-450 system in cardiac function is proposed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Impaired endothelium-dependent relaxations in rabbits subjected to aortic coarctation hypertension.

Rabbits were rendered hypertensive by suprarenal coarctation of the abdominal aorta. Seven days later, endothelium-dependent and endothelium-independent vascular relaxations were examined in vascular rings taken from hypertensive (thoracic aorta, carotid artery) and normotensive (abdominal aorta) regions. Relaxation of phenylephrine-contracted rings in response to endothelium-dependent agonists (acetylcholine, A23187) was impaired, compared with that in sham-operated and intact controls, in regions exposed to the elevated blood pressure (i.e., above the coarctation). Responses to acetylcholine and A23187 in the abdominal aorta, below the coarctation, were not altered. The diminished endothelium-dependent responses in the thoracic aorta were not affected by pretreatment with the cyclooxygenase inhibitor indomethacin. In contrast to acetylcholine and A23187, responses to the endothelium-independent agonist nitroprusside were not attenuated in vessels from hypertensive regions, indicating that the defect occurred in the endothelium. The EC50 for acetylcholine-induced relaxations of thoracic aorta correlated significantly with mean arterial pressure above the coarctation, indicating that the extent to which endothelium-dependent relaxation is impaired is in proportion to the degree of blood pressure elevation. This study suggests that the diminished relaxations by endothelium-dependent agonists is a local response to the elevation of blood pressure and is not due to a circulating factor.

Acetylcholine↗
PubMed1987

Endothelium, arachidonic acid, and coronary vascular tone.

Vasoactive mediators play an important role in the control of coronary vascular tone. Arachidonic acid (AA) metabolites and endothelium-derived vasoactive factors have been implicated in coronary vasoregulation. AA can be metabolized via three separate routes in blood vessels, mediated by cyclooxygenase, lipoxygenase, and cytochrome P-450-dependent monooxygenase enzymes. AA can evoke endothelium-dependent relaxations that are due in part to the formation of cytochrome P-450-dependent metabolites, inasmuch as drugs that modify cytochrome P-450 activity produce parallel changes in endothelium-dependent relaxations to AA. Moreover, some cytochrome P-450-derived metabolites formed biologically cause relaxations of isolated blood vessels. A cytochrome P-450-dependent pathway does not appear to contribute to endothelium-dependent relaxations induced by acetylcholine, which suggests that there may be a number of endothelium-derived relaxing factors (EDRFs). In addition, two endothelium-derived contractile factors have been described, including an unidentified cyclooxygenase metabolite of AA and a polypeptide isolated from cultured cells. As both prostaglandin I2 and acetylcholine-induced EDRF also inhibit platelet aggregation, endothelial injury and loss of these factors may predispose to vasospasm precipitated by release of platelet-derived mediators such as thromboxane A2 (TXA2) and 5-hydroxytryptamine. Unstable angina may be a clinical syndrome in which these events occur, which can be alleviated by inhibition of platelet activation and TXA2 formation with aspirin. Attenuation of endothelium-dependent relaxations can also occur without loss of endothelial cells. Neutrophil-endothelium interactions, precipitated by an ischemic episode, may initiate endothelial dysfunction and underlie the development of vasospasm in some conditions. Whether increased production of endothelium-derived contractile factors also occurs in vasospastic conditions remains to be determined.

Animals↗
PubMed1987

Arachidonic acid-induced endothelial-dependent relaxations of canine coronary arteries: contribution of a cytochrome P-450-dependent pathway.

Arachidonic acid (AA, 10(-8)-5 X 10(-6) M) induced dose-dependent relaxations of canine coronary arterial rings precontracted with dinoprost that were significantly greater (P less than .001) if the endothelium was intact. Cyclooxygenase inhibition with indomethacin displaced the dose-response curve to AA to the right but did not prevent the relaxant effects of the fatty acid. SKF-525A, an inhibitor of cytochrome P-450-dependent enzymes, also attenuated the response to AA although the combination of SKF-525A and indomethacin prevented any relaxant effect. Induction of cytochrome P-450-dependent enzymes in the coronary artery with 3-methylcholanthrene and beta-naphthoflavone given in vivo (40 mg/kg/day for 3 days) or depletion of these enzymes with cobalt chloride (24 mg/kg/day for 2 days) resulted in an enhancement or diminution, respectively, of AA-induced endothelial-dependent relaxations. These results implicate a cytochrome P-450-dependent mixed function oxidase in the endothelial-dependent relaxations to AA in the canine coronary artery. Precontraction of coronary arteries with U46619 in contrast to dinoprost failed to display endothelial-dependent relaxations to AA, whereas the responses to bradykinin and acetylcholine were also partially attenuated. Pharmacologic manipulations of AA metabolism via cyclooxygenase and cytochrome P-450-dependent monooxygenases indicate that the endothelial-dependent relaxations induced by bradykinin are partially dependent upon metabolites of AA, whereas the relaxations produced by acetylcholine are independent of AA metabolites, suggesting that a number of potential relaxing factors may be released from the endothelium.

Animals↗
PubMed1987

c-fos oncogene expression in human hematopoietic malignancies is restricted to acute leukemias with monocytic phenotype and to subsets of B cell leukemias.

To evaluate relationships between c-fos proto-oncogene expression and specific lineages of hematopoietic differentiation we analyzed the constitutive and TPA-induced expression of the c-fos gene in a wide variety of fresh human leukemic cells. High constitutive c-fos expression was detected in acute leukemias with monocytic phenotype (FAB M4/M5) and in subsets of B lymphoid leukemias, some of which coexpressed B lymphocytic and monocytic markers. Conversely, low basal levels of c-fos transcripts were found in pure acute granulocytic leukemias (FAB M1/M2/M3), in erythroleukemias (FAB M6), in the great majority of B, and in all T lymphoid leukemias. TPA-induced c-fos expression seems to correlate with monocytoid differentiation only when sustained levels of transcripts (ie, detectable for at least 24 hours) were detected. Sustained c-fos expression was in fact observed only in those myeloid or lymphoid cells that acquired a stable monocyte-like phenotype in response to the phorbol ester. These results indicate that high constitutive c-fos expression may identify myelomonocytic-oriented forms of leukemia, specific subsets of B lymphoid malignancies, and at least some cells terminally differentiated in vitro to a monocyte-like phenotype. c-fos oncogene expression can therefore be regarded as an additional marker for the subclassification of human leukemias.

Acute Disease↗
PubMed1986

Calf blood flow and vascular resistance in borderline hypertensives in comparison with control subjects.

A significant reduction of maximal vasodilation capacity at the calf in relation to the severity of the hypertensive state has been demonstrated in essential hypertension. The aim of this study was to evaluate the behavior of calf blood flow and vascular resistance in borderline hypertensives (BH) in comparison with normotensive control subjects (CS). We studied 32 BH, with average age of 47.31 +/- 16.78 years and blood pressure 140-160/90-95 mm/Hg, in comparison with 20 CS, with average age of 47.24 +/- 11.75 years and blood pressure values below 140/85 mm Hg. Calf rest flow (RF) and peak flow (PF) were evaluated by strain-gauge plethysmography, and basal vascular resistance (BVR) and minimal vascular resistance (MVR) were calculated by the ratio between mean blood pressure and RF and PF, respectively. Mean blood pressure was significantly higher in BH in comparison with CS. RF and PF did not differ significantly in BH in comparison with CS. BVR did not differ in BHs in comparison with CS. In contrast, MVR were significantly higher in BH in comparison with CS. These results show that in BH, arterial flow at the calf is normal, whereas MVR are higher, indicating an impairment of maximal vasodilation capacity despite the modest blood pressure elevation.

Adult↗