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Biomedical subjects

M Torres

Publications and source records attributed to M Torres.

At least 253 records · Page 14Linked to original sources

The sisterless-b function of the Drosophila gene scute is restricted to the stage when the X:A ratio determines the activity of Sex-lethal.

The gene scute (sc) has a dual function: the scute function which is involved in neurogenesis and the sisterless-b function which is involved in generating the X:A signal that determines the state of activity of Sxl, a gene that controls sex determination and dosage compensation. We show here that the lethal phase of sc- females is embryonic and caused by the lack of Sxl function. We also analyze the time in development when sc and Sxl interact by means of (a) determining the thermosensitive phase (TSP) of the interaction between Sxl and sc and (b) a chimeric gene in which sc is under the control of a heat-shock promoter (HSSC-3). Pulses of sc expression from the HSSC-3 activate Sxl only at a very specific and early stage in development, which coincides with the TSP of the interaction between sc and Sxl. It corresponds to the syncytial blastoderm stage and coincides with the time when the X:A signal regulates Sxl. At this stage sc undergoes a homogeneous transient expression in wild-type flies. We conclude that the sc expression at the syncytial blastoderm is responsible for its sisterless-b function. Since sc expression from the HSSC-3 fully suppresses the sisterless-b phenotype, we further conclude that the sisterless-b function is exclusively provided by the sc protein. Finally, we have analyzed, by in situ hybridization, the effect of sc and sis-a mutations on the embryonic transcription of Sxl. Our results support the view that the control of Sxl by the X:A signal occurs at the transcriptional level.

Animals↗

Presence of ectonucleotidases in cultured chromaffin cells: hydrolysis of extracellular adenine nucleotides.

The granular ATP released from chromaffin cells during the secretory response can be hydrolyzed by ectonucleotidases that are present in the plasma membrane of these cells. The ecto-ATPase activity showed a Km for ATP of 250 +/- 18 microM and a VMAX value of 167 +/- 25 nmol/10(6) cells x min (1.67 mumol/mg protein x min) for cultured chromaffin cells, while the ecto-ADPase activity showed a Km value for ADP of 375 +/- 40 microM and a VMAX of 125 +/- 20 nmol/10(6) cells x min (1.25 mumol/mg protein x min). The ecto 5'-nucleotidase activity of cultured chromaffin cells was more specific for the purine nucleotides, AMP and IMP, than for the pirimidine nucleotides, CMP and TMP. The Km for AMP was 55 +/- 5 microM and the VMAX value was 4.3 +/- 0.8 nmol/10(6) cells x min (43 nmol/mg protein x min). The nonhydrolyzable analogs of ADP and ATP, alpha, beta-methylene-adenosine 5'-diphosphate and adenylyl-(beta, gamma-methylene)-diphosphonate were good inhibitors of ecto 5'-nucleotidase activity, the KI values being 73.3 +/- 3.5 nM and 193 +/- 29 nM, respectively. The phosphatidylinositol-specific phospholipase C released the ecto-5'-nucleotidase from the chromaffin cells in culture, thus suggesting an anchorage through phosphatidylinositol to plasma membranes. The presence of ectonucleotidases in chromaffin cells may permit the recycling of the extracellular ATP exocytotically released from these neural cells.

Adenine Nucleotides↗

All nucleoside transporters in bovine chromaffin cells are nitrobenzylthioinosine sensitive.

Nitrobenzylthioinosine is an effective inhibitor of adenosine transport in chromaffin cells. When adenosine transport was measured at a 0.15 microM adenosine concentration, in the presence of variable concentrations of nitrobenzylthioinosine, ranging from 10(-14) to 10(-6) M, a half-maximal inhibitory concentration value (IC50) of 1 +/- 0.3 nM was deduced. This compound has the capacity to inhibit the total adenosine transport at 10(-7) M concentration. Nitrobenzylthioinosine acts in a non-competitive manner in blocking adenosine transport, as deduced from a Dixon plot, with a constant inhibition value (K1) of 0.01 +/- 0.003 nM. The results suggest that all nucleoside transporters present in bovine chromaffin cells are sensitive to the nitrobenzylthioinosine inhibition.

Adenosine↗

Use of a piezoelectric film sensor for monitoring vascular grafts.

Detection of failing arterial reconstructions requires intensive surveillance by frequent physical examination and noninvasive laboratory testing. However, many grafts fail during the intervals between these examinations. For this reason, we have developed an implantable miniaturized piezoelectric flow detection device whose function can be monitored externally by radiotransmission across the skin. Sensors were constructed from ultrathin polyvinylidene fluoride (PVF2) with piezoelectric activity and attached with silicone fixative to 6-mm polytetrafluoroethylene grafts. Ten of these grafts were placed in mongrel dogs as iliofemoral bypasses. Real time data were acquired from the sensors at a rate of 200 Hz, using a DATAQ A/D data acquisition board and CODAS data acquisition software, while simultaneous blood flow (using an electromagnetic flowmeter) and intraluminal pressure were processed by using separate channels of the same data acquisition board. The data were stored on computer storage media and analyzed by the ASYST software, which allows simultaneous signal curves to be compared using regression analysis. In the resting state, the mean blood flow was 123 +/- 16 mL and the mean intraluminal pressure was 124/78 mm Hg, and there was perfect correlation between the PVF2 sensor and the flowmeter and between the sensor and the intraluminal pressure (correlation coefficient, r greater than or equal to 0.99 and r greater than or equal to 0.93, respectively). A tourniquet was applied to the iliac artery proximal to the graft to reduce the flow to approximately half of the resting state (mean flow after tourniquet: 66 +/- 6 mL/minute). Signal tracings from the three sources showed a remarkable similarity with a very high correlation coefficient (r greater than or equal to 0.99 between sensor and flowmeter and r greater than or equal to 0.92 between sensor and the pressure signal). These preliminary results show that the sensors made from low-profile and low-mass PVF2 material have the potential of being implanted around grafts for long-term, continuous monitoring of graft function. Further studies involving long-term implantation to assess the effect of tissue ingrowth and loss of compliance are necessary before this device can be used clinically.

Animals↗

Multiple endocrine neoplasia type II B with symptoms suggesting Hirschsprung's disease: a case report.

A 3-year-old child was referred with a tentative diagnosis of Hirschsprung's disease because of life-long constipation and "megacolon" demonstrated radiographically. Our rectal biopsy revealed hyperganglionosis suggestive of multiple endocrine neoplasia (MEN) type II B. This, in addition to an elevated serum calcitonin level, prompted surgical removal of her thyroid, which appeared grossly normal but on sectioning, contained a medullary carcinoma in each lobe. She remains disease-free 5 years later. Gastrointestinal symptoms are a significant component of the MEN type II B syndrome, and often antedate the full phenotypic expression of the syndrome and the development of potentially lethal endocrine neoplasms. On the basis of this experience, it is recommended that MEN II B be included in the differential diagnosis of chronic constipation.

Child, Preschool↗

Muscarinic control of gallbladder dynamics. A study using 99Tcm-HIDA and cholinergic agonists and antagonists.

We studied 12 normal subjects who underwent four 99Tcm-HIDA examinations. Imaging was performed with 111 MBq at 1 image/min for 60 min, and was registered on a computer on a 64 x 64 word matrix. Normalized and background corrected time-activity curves on the gallbladder were obtained from which total and cumulative 10 min interval emptying was calculated. During the first examination (control), 10 min after the beginning of acquisition, 1 ml saline solution was injected subcutaneously. The second examination was performed injecting 5 mg bethanechol subcutaneously instead of saline solution. During the third and fourth examinations 10 mg pirenzepine and 0.15 mg/10 kg atropine were injected i.v. respectively, 5 min before bethanechol injection. Wilcoxon's test was used to compare the first and second studies and the latter with the third and fourth studies. The median value of gallbladder emptying at 60 min was 2% with saline solution injection and 27.5% with bethanechol. This difference was significant from minute 30 onwards. Atropine administration inhibited gallbladder emptying completely in all cases, with significant differences (P less than 0.01) in relation to bethanechol values following the first 30 min of the examination. Gallbladder emptying was observed in the study with pirenzepine, but was significantly inferior to the bethanechol values after the first 30 min.

Adult↗

Effect of diadenosine polyphosphates on catecholamine secretion from isolated chromaffin cells.

1. The action of several diadenosine polyphosphates (AP3A, AP4A and AP5A) on basal, and on nicotine- and high K(+)-evoked, catecholamine (CA) release has been investigated. Each of the three diadenosine polyphosphates weakly but significantly increased basal CA secretion. This enhancement represented about 10% of the response evoked by 2 microM nicotine. 2. The evoked secretory response to diadenosine polyphosphates had an absolute requirement for extracellular Ca2+. 3. In contrast, these compounds had an inhibitory action on nicotine-evoked release. This response was concentration-dependent, EC50 values being 3.2 +/- 0.4 microM, 4.0 +/- 1.6 microM and 19.3 +/- 4.0 microM for AP3A, AP4A, and AP5A, respectively. The lower the concentration of nicotine used to evoke secretion, the higher the inhibitory power of these compounds. 4. The CA secretion evoked by K(+)-rich solutions was further enhanced by AP3A and AP5A, whereas AP4A inhibited it. The possible physiological role of these dual actions is discussed.

Adrenal Glands↗

Evaluation of lipoarabinomannan for the serological diagnosis of tuberculosis.

The availability of highly purified lipoarabinomannan from Mycobacterium tuberculosis in its native acylated, highly antigenic state allowed its application to the serodiagnosis of tuberculosis in patients from the Republic of Mexico. Antilipoarabinomannan immunoglobulin G antibodies in sera from 66 patients with pulmonary, miliary, and pleural tuberculosis and tuberculosis lymphadenities were measured by using the enzyme-linked immunosorbent assay against sera from a control population of healthy individuals, people with histoplasmosis, and people with lung diseases not caused by mycobacteria. The results pointed to an unexpectedly high degree of specificity of 91% and a sensitivity of 72%, comparable to figures from previous studies with other purified antigens; most of the false-positive results were for patients with histoplasmosis. Thus, lipoarabinomannan of M. tuberculosis is a potentially useful antigen for the serodiagnosis of tuberculosis.

Antibodies, Bacterial↗

Neutrophil chemotactic heterogeneity to N-formyl-methionyl-leucyl-phenylalanine detected by the under-agarose assay.

Human polymorphonuclear neutrophils (PMNs) are heterogeneous in their response to the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP). By using a computerized imaging method for analysis of agarose chemotaxis plates, the chemotactic sensitivity of the population of PMNs at the leading front to FMLP was greater than the mean sensitivity of all migrating PMNs. When PMNs were treated with the membrane-perturbing agent butanol at concentrations up to 0.25%, chemotaxis of the fastest PMN population in response to 10(-7) mmol/L FMLP was increased to 140% of control, whereas the mean of all populations was increased to only 110% of control. These data show that the PMN population at the leading front has a different chemotactic sensitivity to FMLP. Furthermore, the susceptibility to butanol treatment of the PMN population suggests that an alteration in membrane properties may partly account for this difference.

Butanols↗

The scute (T4) gene acts as a numerator element of the X:a signal that determines the state of activity of sex-lethal in Drosophila.

The ratio of X chromosomes to sets of autosomes (X:A) is the primary genetic signal that determines sex and dosage compensation in Drosophila. The gene Sex-lethal (Sxl) receives this signal and is responsible for the execution of the alternative developmental programmes of males and females. We have found that the scute (T4) gene, which is involved in neurogenesis, also plays a role in the activation of Sxl. The following results suggest that scute (T4) may be a numerator element of the X:A signal: scute (T4) mutations show female-specific lethality. There are female-specific lethal synergistic interactions between sis-a, a previously described numerator element, and mutants for T4. The female lethality is suppressed by SxlM1, a constitutive allele which expresses an active Sxl product independently of the X:A ratio. The Hw685 mutation, which overexpresses T4, is lethal to males with a duplication of sis-a. This lethality is suppressed by either Sxlf1, or the T4 point mutation sc10-1. There are female-specific lethal interactions between sc10-1 and daughter-less (da), a gene needed maternally for Sxl to become active. The sc10-1 mutation masculinizes triploid intersexes.

Alleles↗

Movement disorders and depression due to flunarizine and cinnarizine.

Over the last few years, cases of movement disorders induced by flunarizine and cinnarizine have been increasingly reported. We describe a series of 101 patients, whose ages ranged from 37 to 84 years (mean 69.1), developing abnormal movements frequently associated with depression, secondary to treatment with either or both drugs. Symptoms closely resembled those induced by neuroleptic drugs and remitted on drug discontinuance in all but five cases after 5-22 months' follow-up. Whether or not such undesirable side effects are attributable to calcium antagonism and/or dopamine receptor blockade, long-term treatment with flunarizine or cinnarizine should be discouraged, particularly in the elderly.

Adult↗

Evidence for a dopaminergic mechanism for the diuretic and natriuretic action of centrally administered atrial natriuretic factor.

1. Intracerebroventricular (IVT) administration of rat atrial natriuretic factor (ANF) (99-126) to conscious male hydrated rats induces a dose-dependent increase in urine and sodium excretion. The possible involvement of brain dopaminergic system in the IVT-ANF-induced diuresis and natriuresis was evaluated. 2. Central sympathectomy (6-OHDA, 250 micrograms/5 microliters, IVT; 72 and 48 hr before IVT-ANF) inhibited both the diuretic and the natriuretic action of centrally administered ANF, suggesting that in the brain ANF requires the integrity of central noradrenergic and/or dopaminergic systems function for its actions. 3. Intracerebroventricular injection of haloperidol and intragastric administration of domperidone prevent the diuretic and natriuretic response to centrally administered ANF. 4. Our data suggest a neuromodulatory action of ANF within the brain and demonstrate an interaction of the peptide with brain dopaminergic systems.

Animals↗