Biomedical subjects

A Martinotti

Publications and source records attributed to A Martinotti.

At least 19 recordsLinked to original sources

PubMed1996

Slow coronary flow: clinical and histopathological features in patients with otherwise normal epicardial coronary arteries.

Slow flow of dye in epicardial coronary arteries is not an infrequent finding in patients during routine coronary angiography. Whether this pattern of flow can be reversed by nitroglycerin or dipyridamole and whether this angiographic finding is associated with histopathological abnormalities is unknown. We hypothesized that this abnormality could be associated with small vessel disease of the heart, since the epicardial arteries are usually widely patent. Thus, out of the patients undergoing heart catheterization at our institution during the past 5 years, 10 (7%) presented with chest pain, normal epicardial coronary arteries, and abnormal coronary progression of dye. Rest electrocardiogram (ECG), exercise test, echocardiographic examination, and left ventricular angiogram were normal. Coronary angiography showed slow flow of dye on a total of 20 main coronary vessels, that was not reversed by intracoronary nitroglycerin administration. Six of them underwent dipyridamole intravenous infusion that normalized dye run-off in all affected vessels, for a total of 9 main coronary vessels. Histopathological examination (light and electron microscope) of left ventricular endomyocardial biopsies showed thickening of vessel walls with luminal size reduction, mitochondrial abnormalities, and glycogen content reduction. Normal and pathological zones often coexisted in the same specimen. Thus. In some patients with slow coronary flow and patent coronary arteries, functional obstruction of microvessels seems to be implicated, as it is relieved by dipyridamole infusion. Patchy histopathological abnormalities suggestive of small vessel disease are also detectable and could contribute to increase flow resistance.

Adult↗

PubMed1995

CD4 T cells inhibit in vivo the CD8-mediated immune response against murine colon carcinoma cells transduced with interleukin-12 genes.

Retroviral-mediated cytokine gene transfer into tumor cells is a highly effective way of inducing tumor inhibition and immunity. We analyzed the tumorigenicity of C-26 murine colon carcinoma cells transduced with genes encoding the two subunits of murine interleukin-12 (IL-12) in a polycistronic retroviral vector and selected for resistance to G418 and for IL-12 production (30-80 pg/ml). BALB/c mice injected s.c., i.v. and intrasplenically with C-26/IL-12 cells from three different IL-12-producing clones showed delayed tumor onset as compared with mice injected with control NeoR-transduced or parental tumor cells. Although C-26/IL-12 tumor-bearing mice eventually died of lung metastasis, their survival time was twice as long as that of mice injected with control cells. In experiments with mice selectively depleted of natural killer (NK) cells before tumor cell injection, the time of tumor onset and survival of mice injected with C-26/IL-12 s.c. and i.v., respectively, was reduced. CD8+ T cell depletion had no effect on latency or survival, whereas removal of CD4+ T cells led to C-26/IL-12 tumor regression in about 40% of mice. Histological and immunocytochemical characterization of leukocytes infiltrating C-26/IL-12 tumors showed only slight infiltration with few T cells in non-depleted mice but abundant infiltration by CD8+ T cells and asialo-GM1+ NK cells in tumors of mice depleted of CD4+ T cells. The lack of CD8+ T cell infiltration is not due to a CD4-mediated suppression of their activation because irradiated C-26/IL-12 cells primed for the induction of a strong cytotoxic T lymphocyte response against C-26 parental cells and induced CD8+ effector cells that protected against C-26/IL-12 in a Winn assay. Rather, the results suggest that, although C-26/IL-12 cells injected in vivo stimulate both NK and CD8+ T cells, tumor infiltration by the latter is inhibited by CD4+ T cells.

Animals↗

PubMed1994

Expression of a growth arrest specific gene (gas-6) during liver regeneration: molecular mechanisms and signalling pathways.

A set of growth arrest-specific (gas) genes negatively regulated by serum has been identified. To define the role of gas genes in a model of cell proliferation in vivo we analyzed the expression of one of these genes (gas-6) during liver regeneration after partial hepatectomy (PH). We found that gas-6 mRNA was down-regulated 4 hours after PH, within the G0 to G1 transition. Later on, gas-6 mRNA increased over the level found in normal liver with a peak at 16 hours, before the onset of DNA synthesis. This surge was probably triggered by an inflammatory response caused by the surgical trauma, because an increase of similar extent occurring with the same time course was present in livers of sham-operated and turpentine-treated rats. Comparison of mRNA steady state levels with nuclear transcription rates indicated that gas-6 expression is post-transcriptionally regulated. As we found that down-regulation of gas-6 expression was prevented by treatment with Actinomycin D, a labile protein might be involved in the determination of gas-6 mRNA stability. To investigate the mitogenic signals controlling gas-6 expression during liver regeneration we treated hepatectomized rats with a specific alpha-1-adrenoceptor blocker (prazosin) as well as with drugs which modify intracellular calcium levels. The decrease of gas-6 mRNA 4 hours after PH was prevented by prazosin and by neomycin, an inhibitor of calcium release from endogenous stores. These findings suggest that down-regulation of gas-6 expression during hepatic regeneration is triggered by catecholamines interaction with alpha-1-adrenergic receptors and by subsequent calcium release. In addition we found that the rise of gas-6 gene expression occurring at 16 hours after PH was not affected by prazosin but was inhibited by trifluoperazine. Therefore, we suggest that up-regulation of gas-6 gene expression is mediated by the interaction of calcium with calmodulin, independently of catecholamines.

Animals↗

PubMed1993

Sequence of human GAS3/PMP22 full-length cDNA.

We have cloned the human growth arrest-specific gene GAS3 cDNA that encodes a transmembrane glycoprotein, the peripheral myelin protein 22 (PMP22). GAS3/PMP22 is implicated in Charcot-Marie-Tooth disease type 1A, an inherited peripheral neuropathy.

Amino Acid Sequence↗

PubMed1992

Localization of growth arrest-specific genes on mouse chromosomes 1, 7, 8, 11, 13, and 16.

Growth arrest in NIH3T3 cells is associated with increased expression of a variety of mRNAs, several of which have been isolated as cDNA clones. Six of these growth arrest-specific (Gas) genes were mapped by following the inheritance of DNA restriction fragment length variants (RFLVs) associated with them in panels of recombinant inbred (RI) strains of mice and in the progeny of backcrosses both between laboratory mouse strains and between a laboratory strain and Mus spretus. The six genes are unlinked. Gas-1 maps to Chromosome (Chr) 13, Gas-2 to Chr 7, Gas-3 to Chr 11, Gas-4 to Chr 16, Gas-6 to Chr 8, and Gas-10 to Chr 1.

3T3 Cells↗

PubMed1992

Isolation and mapping to 17p12-13 of the human homologous of the murine growth arrest specific Gas-3 gene.

A family of growth arrest specific (Gas) genes was operationally defined on the basis of the strategy utilized to isolate them e.g. differential expression in quiescent and growing cells. Our interest in the Gas-3 gene was prompted by our previously reported localization of the gene on the mouse chromosome 11.44 +/- 1.9 cM proximal to the Trp53 locus and by the finding, by others, that it codes for a myelin protein and that a point mutation in its fourth putative transmembrane region is associated with the trembler mutation. We have isolated the human homologous of the mouse Gas-3 gene and utilized the cloned sequences as a probe to localize the gene on human chromosomes both by analysis of human-rodent somatic cell hybrids and in situ hybridization of human metaphases. We have now localized the human Gas-3 gene on chromosome 17p12-13. Its possible role in both the development of neoplasia in neurofibromatosis patients and in the myelin degenerative disease as the Charcot-Marie-Tooth is discussed.

Amino Acid Sequence↗

PubMed1992

Subcellular structure of the atrial myocardium of children in cases of atrial septal defect.

In order to study the initial development of myocardial ultrastructural changes owing to right atrium volume overload, myocytes have been studied in specimens taken from the right atrial wall and auricle of four children aged 1 to 6 years with ostium secundum atrial septal defect undergoing cardiac surgery. The younger patients (1 to 4-year-old children) we observed did not show diffuse and significant myocardial ultrastructural damages. The most significant myocardial changes were observed in the 2 older patients (six years old) as we found subcellular signs of myocardial hypertrophy such as an increased number of mitochondria, increased glycogen inclusions, areas of new sarcomerogenesis and nuclei lobulated and variably shaped. Focal degenerative changes, such as rupture of mitochondrial cristae and intercellular fibrosis were also noted. These changes may be considered as the initial features of myocardial hypertrophy because they were not as severe and diffuse as those usually seen in a marked functional failure.

Cardiomegaly↗

PubMed1991

Scanning electron microscopy of stellate cells of mammalian adrenal cortex as revealed by NaOH maceration.

After removal of connective tissues by the NaOH maceration method, adrenal gland stellate cells of monkeys, rats and rabbits were studied by scanning electron microscopy. The stellate cells were situated in the perivascular and interstitial spaces and showed an ovoid cell body with numerous round or flat processes. Through these processes they were in contact with other adjacent stellate cells and thus formed a continuous cellular net around capillaries and parenchymal cells. This net, which probably provides a cellular scaffolding for the gland, may also play additional roles such as capillary contraction and nutrition for adjacent parenchymal cells.

Adrenal Cortex↗

PubMed1990

[Effect of diazepam on mitochondrial respiration].

Our hypothesis that the strong effects of neutropic drugs on nervous system have hidden more widespread effects on all tissues and cells, is collecting evidences in our laboratory. We have essayed in vitro benzodiazepines on liver rat mitochondria. The present work deals with experiments on diazepam: it depresses the respiration coupled to phorphorylation in mitochondria having a good respiratory control; so respiratory control too is depressed. Also P/O ratio is lowered.

Animals↗

PubMed1988

Magnesium plus nifedipine: potentiation of hypotensive effect in preeclampsia?

Two women with preeclampsia treated unsuccessfully with alpha-methyldopa and magnesium sulfate became profoundly hypotensive when oral nifedipine was added. Blood pressure returned to previous levels without changes in fetal vitality. Awareness of this potentiation is important because nifedipine is being used increasingly in the treatment of pregnancy-related hypertension.

Adult↗

PubMed1981

Effect of vincristine on bone marrow cells of patients with multiple myeloma. A cytokinetic study.

The cytokinetic changes induced by Vincristine (VCR) on bone marrow erythroblasts, myeloid cells and neoplastic plasma cells have been studied in four patients with plasma cell malignancies using combined DNA cytofluorometry and in vitro tritiated thymidine cytoautoradiography. The changes observed 9 h after the administration of the drug were in accordance with its S-phase specificity. The magnitude of the stathmokinetic effect was in fact roughly proportional to the proliferative activity of the different cell lines, i.e., marked on the erythroblasts, less evident on the myeloid cells and still lower on the plasma cells. In this last cell population VCR has also blocked or partially impaired the DNA synthesis. Nine days after VCR, the plasma cells were recruited into the proliferative cycle while the regeneration of the hemopoietic cells was already exhausted. Repeated administrations of VCR spaced at about 9 day intervals are more and more effective on the plasma cell population, since the S place specificity of the drug against the recruited plasma cells is potentiated. On the contrary, the regeneration of the hemopoietic cells is protected by this time interval.

Autoradiography↗

PubMed1978