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Biomedical subjects

F Martín

Publications and source records attributed to F Martín.

At least 109 records · Page 6Linked to original sources
PubMed1996

Glucose-induced [Ca2+]i oscillations in single human pancreatic islets.

Changes in cytosolic free calcium concentrations ([Ca2+]i) in response to stimulatory glucose concentrations were investigated in human pancreatic islets, using Fura-2 fluorescence imaging. Increasing glucose concentration from 3 to 11 mM caused a triphasic [Ca2+]i response in human islets: an initial decrease (phase 1), a rapid and transient increase (phase 2) and periodic oscillations with a frequency of 1 +/- 0.3 min-1 (phase 3). Raising the glucose concentration from 11 to 16.7 mM lowered the frequency of the glucose-induced [Ca2+]i oscillations to 0.15 +/- 0.2 min-1, without changes in their amplitude. Human islet [Ca2+]i response to stimulatory glucose concentrations is synchronous throughout the islet. Freshly isolated human islets responded to tolbutamide (50 microM) with a rise in [Ca2+]i. An increase in glucose concentration, from 3 to 16 mM, in the presence of 100 microM diazoxide, produced a decrease in [Ca2+]i. It is concluded that human islets respond to glucose with regular [Ca2+]i oscillations that are synchronous throughout the islet and whose duration is modulated by glucose.

Adenocarcinoma↗
PubMed1996

Diminished fraction of blockable ATP-sensitive K+ channels in islets transplanted into diabetic mice.

The reasons for the poor outcome of islet transplantation in diabetic patients are not well known; a better understanding of the pathophysiology of transplanted islets is needed. To study the mechanism coupling secretagogue stimuli with insulin release in transplanted islets, we determined the effects of glucose, tolbutamide, and carbamylcholine on the beta-cell membrane potential and cytosolic calcium concentrations ([Ca2+]i) of islets syngeneically transplanted into normal and streptozocin-induced diabetic mice. In both groups, normoglycemia was maintained after transplantation. Islets transplanted into normal recipients showed similar changes in beta-cell membrane potential and [Ca2+]i oscillations to those in control islets. In contrast, when islets were transplanted into diabetic mice, bursts of electrical activity were triggered at lower glucose concentrations (5.6 mmol/l) than in control islets (11 mmol/l), and maximal electrical activity was achieved at lower glucose concentrations (11 mmol/l) than in control islets (22 mmol/l). When membrane potential was plotted as a function of glucose concentration, the dose-response curve was shifted to the left. Compared with control islets, glucose-induced [Ca2+]i oscillations were broader in duration (22.3 +/- 0.6 s vs. 118.1 +/- 12.6 s; P < 0.01) and higher in amplitude (135 +/- 36 nmol/l vs. 352 +/- 36 nmol/l; P < 0.01). Glucose supersensitivity was attributed to a resting decrease in the fraction of blockable ATP-sensitive K+ (K+(ATP)) channels in transplanted islets that maintained normoglycemia with a limited beta-cell mass.

Adenosine Triphosphate↗
PubMed1996

[Lipoprotein(a) in children with hypercholesterolemia as a marker of the familial history of cardiovascular risk. The Working Group on Cardiovascular Risk Factors in Childhood and Adolescence].

OBJECTIVE: To evaluate the levels of lipoprotein (a) (Lp(a)) as a marker of familiar history of cardiovascular risk. MATERIAL AND METHODS: We have studied 176 children and adolescents between the ages of 3 and 18 years with hypercholesterolemia. In these children we determined Lp(a) levels and collected the family history concerning cardiovascular risk factors (hypercholesterolemia and cardiovascular disease under 55 years of age). RESULTS: Of the cases studied, 67.04% had a family history of cardiovascular risk. In this group, levels of Lp(a) were significantly higher than in the group without a family history of cardiovascular risk. Lp(a) levels higher than 30 mg/dl were found in 3.44% of the patients without a family history of cardiovascular risk in contrast to 28,43% and 37.5% of the cases with familiar history of hypercholesterolemia and cardiovascular disease, respectively. CONCLUSIONS: The levels of lipoprotein (a) in children and adolescents with hypercholesterolemia are a marker of family history of cardiovascular disease and hypercholesterolemia.

Adolescent↗
PubMed1996

[Preliminary studies on the design of retroviral vectors for substitutive gene therapy].

We have studied the effect that exerts on the Moloney murine leukemia virus (Mo-MLV) viral cycle the deletion of the 13 bases that constitute the inverted repeat (IR) present at the external U3 region of the pre-proviral DNA. Whereas supernatants of wild type- and modified virus-producing cells contained similar amounts of viral particles, the deleted viruses showed a 100 to 1000-fold decreased infectivity. To determine how the deletion interfered with the infective capacity of the virus, different steps of the viral cycle were studied using deleted viruses. The deletion affected neither reverse transcription nor the entry of the DNA into the cell nucleus; however, the integration of the pre-proviral DNA into the host genome was reduced to undetectable levels. These results open a pathway to the construction of Mo-MLV-derived retroviral vectors for gene targeting purposes.

3T3 Cells↗
PubMed1995

Characterization of a non-long terminal repeat retrotransposon cDNA (L1Tc) from Trypanosoma cruzi: homology of the first ORF with the ape family of DNA repair enzymes.

In the present paper we describe the characterization of a Trypanosoma cruzi cDNA (L1Tc) corresponding to a transcript from a new long terminal repeat (LTR) retrotransposon. This element is present in a high-copy number, and is found dispersed throughout the T. cruzi genome. Northern analysis shows an abundant expression of L1Tc-related sequences with a major band of about 5 kb. The transcript has at its 3' end a fragment of a highly repetitive DNA sequence (E12A), at its 5' end a ribosomal mobile element-like sequence and three putative open reading frames (ORF) in different frames. The ORF2 codes for a protein which has significant homology with the retrotranscriptase-related sequences from non-LTR retrotransposons containing the seven domains present in all the retrotranscriptase and retrotranscriptase-related proteins. The ORF3 codes for a gag-like protein showing unusual cysteine motifs present in all non-LTR trypanosomatid elements, similar to the C2H2 zinc finger family of transcription factors. Interestingly, ORF1 codes for a protein with significant homology to the major human AP endonuclease protein, and maintains in similar positions most of the amino acid domains described for all the Ape family of proteins. The presence of Ape-related sequences, described for the first time in a non-LTR retrotransposon (L1Tc), may have functional relevance for these types of elements.

Amino Acid Sequence↗
PubMed1995

Role of syntaxin in mouse pancreatic beta cells.

The role of syntaxin 1, a protein involved in the docking of synaptic vesicles at presynaptic active zones, has been investigated in pancreatic islet cells. Using two different monoclonal antibodies we have shown that syntaxin 1 is present in the pancreatic islet cell microsomal fraction. Furthermore, functional experiments demonstrate that anti-syntaxin antibodies inhibit CA(2+)-dependent insulin secretion in permeabilized islet cells. These data indicate that syntaxin 1 is present in the pancreatic beta cell and it is likely to play a functional role in the exocytosis of secretory granules.

Animals↗
PubMed1995

Expression of lymphoid-associated antigens in mast cells: report of a case of systemic mast cell disease.

In this study the expression of 'classically' considered lymphoid-associated antigens (CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD19, CD20, and CD22) was explored both in peripheral blood (PB) and bone marrow (BM) mast cells (MC) in a case of systemic mast cell disease (SMCD) by means of using multiple stainings and a direct immunofluorescence technique. CD2 and CD22 were expressed in both PB and BM MC, all the remaining lymphoid-associated markers were negative. Our results suggest that the reactivity for both CD2 and CD22 in PB and BM MC would be aberrant.

Aged↗
PubMed1995

Nonspecific bronchial hyperresponsiveness and development of asthma in children with hay fever.

It has been suggested that patients with allergic rhinitis who present nonspecific bronchial hyperresponsiveness (BHR) are those most likely to develop asthma. Therefore, a study was conducted in children with rhinoconjunctivitis to ascertain whether BHR to methacholine might predict the development of asthma in these patients. Fifteen patients with hay fever and no previous symptoms of asthma were selected. All underwent clinical symptom tests and methacholine tests, during the pollen season in the 4 consecutive years following the start of the study. At the end of this period, 5 patients had developed asthma. It may thus be affirmed that, in this group, neither the presence nor the degree of previous BHR was useful for predicting which patients would later develop asthma.

Asthma↗
PubMed1994

Naturally occurring cell death in the developing cerebral cortex of the rat. Evidence of apoptosis-associated internucleosomal DNA fragmentation.

Naturally occurring dead cells in the developing rat neocortex, subcortical white matter and hippocampus, which increase in number during the first postnatal week and decrease thereafter to disappear by the end of the first month, were examined by in situ labeling of nuclear DNA fragmentation. These cells showed peripheral chromatin condensation or extremely dark, often fragmented, nuclei. Southern hybridization following agarose gel electrophoresis of DNA extracted from the developing cortex, but not from adult brain, showed a 'ladder' pattern which is typical of internucleosomal DNA fragmentation. Taken together these results show that naturally occurring cell death (programmed cell death) in the developing cerebral cortex has the morphology of apoptosis and is associated with endonuclease activation.

Aging↗
PubMed1994

Characterization of a short interspersed reiterated DNA sequence of Trypanosoma cruzi located at the 3'-end of a poly(A)+ transcript.

We have carried out the molecular characterization of a highly repeated DNA element, called E12, from Trypanosoma cruzi, which has been found to be interspersed along its genome. The E12 element, repeated about 5.6 x 10(3) times, is found in most of the chromosomal bands of the parasite. Three subregions may be defined within the element on the basis of sequence similarities with other trypanosome genomic sequences. Northern blot analysis demonstrated that sequences of the E12 element are present in several polyadenylated RNA species of T. cruzi. The isolation and characterization of a cDNA clone, pSPFM55, which showed hybridization with the E12 probe, indicated that only one of the E12 subregions, E12A, is found in the cDNA and that it is located at the 3'-end providing the site of polyadenylation addition. The location and high degree of nucleotide conservation of E12A suggest a possible functional role of this sequence in gene expression.

Amino Acid Sequence↗
PubMed1994

Effects of chronic treatment with dexfenfluramine on serotonin in rat blood, brain and lung tissue.

We have examined the effects of continuous treatment (0.5, 1, 2.5 and 5 mg.kg-1.day-1 for 14 days, using minipumps) with dexfenfluramine (dF) on the concentration of serotonin (5-hydroxytryptamine, 5-HT) in blood, lungs and brain frontal cortex. 5-HT concentration was decreased in whole blood and tissues by the two higher doses (2.5 and 5 mg.kg-1.day-1). The concentration of dF in plasma was above detection limit only in these two treatment groups. The concentration of 5-HT in plasma (extracellular) was not modified dose-dependently, although values higher than controls were noted in the 2.5 mg.kg-1 group. Significant correlations were observed between the concentration of 5-HT in whole blood and that of 5-HT (and 5-HT + 5-HIAA) in frontal cortex. Both correlated inversely with the plasma concentration of dF. These results show that treatment with dF for two weeks reduces the concentration of intracellular 5-HT in peripheral stores (platelets, lung endothelial cells) without a concurrent increase of the extracellular 5-HT pool in blood. Correlation data suggest that whole blood 5-HT content may have a predictive value of dF-induced reductions of 5-HT in brain tissue after long-term treatment.

Animals↗