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Biomedical subjects

J C Torres

Publications and source records attributed to J C Torres.

At least 19 recordsLinked to original sources

Regions of allelic imbalance in the distal portion of chromosome 12q in gastric cancer.

AIMS: To define regions of loss on the distal portion of chromosome 12q in gastric adenocarcinoma. METHODS: Microsatellite analysis on chromosome 12 was performed on 19 human gastric cancer cell lines using 77 markers, 71 of which were within or distal to 12q21; some portions of this region showed extended regions of homozygosity (ERHs) in 10 of 19 gastric cancer cell lines. In addition, microdissected tumour cells from 76 primary gastric adenocarcinomas were examined using 13 markers of interest implicated by the cell line data; 70% of these showed allelic imbalance (AI) at one or more markers in or distal to 12q21. RESULTS: Mapping ERHs in the cell lines and sites of AI in the tumours identified three regions that contain putative tumour suppressor genes: region A is located within 2.8 Mb between markers D12S1667 and D12S88; region B, within 1.9 Mb between markers D12S1607 and D12S78; and region C, in 0.74 Mb between markers D12S342 and D12S324. Fluorescence in situ hybridisation (FISH) analysis in two cell lines confirmed that two of the ERHs reflected deletions, not amplifications, of D12S81 in region A and D12S340 in region C. FISH analysis of marker D12S1075 within an ERH containing region B in one cell line showed neither amplification nor deletion. AI on 12q was not associated with prognosis, but was associated with ethnicity of the patient. CONCLUSIONS: These results identify regions on chromosome 12 that appear to contain tumour suppressor genes important in the development of gastric cancer.

Adenocarcinoma↗

Triclinic and orthorhombic polymorphs of 2-iodo-4-nitroaniline: interplay of hydrogen bonds, nitro...I interactions and aromatic pi-pi-stacking interactions.

In the triclinic polymorph of 2-iodo-4-nitroaniline, C(6)H(5)IN(2)O(2), space group P-1, the molecules are linked by paired N-H...O hydrogen bonds into C(8)[R(2)(2)(6)] chains of rings. These chains are linked into sheets by nitro...I interactions, and the sheets are pairwise linked by aromatic pi-pi-stacking interactions. In the orthorhombic polymorph, space group Pbca, the molecules are linked by single N-H...O hydrogen bonds into spiral C(8) chains; the chains are linked by nitro...O interactions into sheets, each of which is linked to its two immediate neighbours by aromatic pi-pi-stacking interactions, so producing a continuous three-dimensional structure.

Aniline Compounds↗

A program evaluation study of a nursing home operated as a modified therapeutic community for chemically dependent persons with AIDS. Project Samaritan AIDS Services, Inc.'s Residential Health Care Facility, Highbridge Section, Bronx, NY.

An interagency evaluation of the treatment effectiveness of a speciality nursing home (NH) run as a therapeutic community (TC) for residents diagnosed with acquired immunodeficiency syndrome (AIDS) and substance abuse/dependence (SA/D) was conducted. A total of 79 chemically dependent men and women with AIDS were: (a) administered the Tennessee Self-Concept Scale (TSCS; Roid & Fitts, 1991) at initial testing (T(1)) and 8 months after their initial testing (T(2)); and (b) assessed on specific physical health indicators (i.e. , weight, CD-4 count, and viral load) and other treatment outcomes (e.g., abstinence) over the same two time periods. The TSCS results identified a valid and invalid TSCS test group and further distinguished among three subgroups of invalid responders. Significant improvements were observed from T(1) testing to T(2) testing on the TSCS, on the physical health indicators, and on other treatment outcomes. The need for additional and continued mental health services for this population was noted.

Acquired Immunodeficiency Syndrome↗

A cluster of pediatric metallic mercury exposure cases treated with meso-2,3-dimercaptosuccinic acid (DMSA)

Nine children and their mother were exposed to vapors of metallic mercury. The source of the exposure appears to have been a 6-oz vial of mercury taken from a neighbor's home. The neighbor reportedly operated a business preparing mercury-filled amulets for practitioners of the Afro-Caribbean religion Santeria. At diagnosis, urinary mercury levels in the children ranged from 61 to 1,213 microg/g creatinine, with a geometric mean of 214.3 microg/m creatinine. All of the children were asymptomatic. To prevent development of neurotoxicity, we treated the children with oral meso-2,3-dimercaptosuccinic acid (DMSA). During chelation, the geometric mean urine level rose initially by 268% to 573.2 microg mercury/g creatinine (p<0.0005). At the 6-week follow-up examination after treatment, the geometric mean urine mercury level had fallen to 102.1 microg/g creatinine, which was 17.8% of the geometric mean level observed during treatment (p<0.0005) and 47.6% of the original baseline level (p<0.001). Thus, oral chelation with DMSA produced a significant mercury diuresis in these children. We observed no adverse side effects of treatment. DMSA appears to be an effective and safe chelating agent for treatment of pediatric overexposure to metallic mercury.

Administration, Oral↗

A mutant phosphofructokinase produces a futile cycle during gluconeogenesis in Escherichia coli.

Strains of Escherichia coli bearing different forms of phosphofructokinase were used to assess the occurrence of futile cycling in cell resuspensions supplied with glycerol as gluconeogenic carbon source. A model was used to simulate results of different kinds of experiments for different levels of futile cycle. The main predictions of the model were experimentally confirmed in a strain with a mutant phosphofructokinase-2 (phosphofructokinase-2*) which is not inhibited by MgATP. The intracellular fructose 1, 6-bisphosphate concentration reaches significantly higher levels in the mutant-bearing strain than in strains with either phosphofructokinase-1 or -2. Also, this strain showed a higher rate and level of in vivo radioactive labelling of fructose 1, 6-bisphosphate, from a trace of [U-14C]glucose supplied during gluconeogenesis, indicating higher kinase activity in these conditions. Cell resuspensions of the mutant-bearing strain produced higher levels of radioactively labelled CO2 when supplied with [U-14C]glycerol as the only carbon source. Simultaneously, fewer glycerol carbons were incorporated into HClO4-insoluble macromolecules. Finally, radioactive CO2 output was measured in resuspensions supplied with glycerol as the major carbon source with traces of either [1-14C]glucose or [6-14C]glucose. It was found that, whereas in the strains with either of the wild-type phosphofructokinase isoenzymes, radioactive CO2 output from [1-14C]glucose was higher than with [6-14C]glucose, the reverse is found for the strain with phosphofructokinase-2*. This result also agrees with the corresponding prediction of the model. Using the radioactivity flux rates predicted by the model, an explanation linking the futile cycle to the differential labelling of CO2 is advanced. Finally, on the basis of these results it is proposed that strains bearing phosphofructokinase-2* sustain higher rates of futile cycling during gluconeogenesis than strains bearing either of the wild-type isoforms of phosphofructokinase. The kinetic equations and parameter values used for the model simulations are given in Supplementary Publication SUP 50183 (8 pages), which has been deposited at the British Library Document Supply Centre, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1997) 321, 8.

Carbon Dioxide↗

A new method of assessing rates of the futile cycle during glycolytic and gluconeogenic metabolism.

A method for assessing rates of the futile cycle is presented, and it is illustrated in vitro. Glycolytic- and gluconeogenic-type futile cycles are simulated for the reactions catalyzed by phosphofructokinase (EC 2.7.1.11) and fructose-1,6-bisphosphatase (EC 3.1.3.11) in assays systems in which the cycle rates in either direction can be varied and determined. While either system is sustaining a net flux of carbons in a given direction, the flux of radioactively labeled carbons in the opposite direction is determined. Different cycle rates are obtained by varying phosphofructokinase activity while keeping fructose-1,6-bisphosphatase activity constant in the "gluconeogenic" simulation and varying fructose-1,6-bisphosphatase while keeping phosphofructokinase activity constant in the "glycolytic" simulation. A direct, linear relationship was found between the cycle rate and the radioactive labeling of fructose 1,6-bisphosphate from [U-14C]glucose 6-phosphate during net gluconeogenic carbon flux. Also, a direct, linear relationship was found between cycle rate and radioactive labeling of fructose-6-P from [U-14C]fructose-1,6-bisP during net glycolytic carbon flux. The applicability, advantages, and problems of the method are discussed.

Animals↗

The separation and identification of picomole amounts of intermediates of glucose metabolism by high performance liquid chromatography on pellicular resins.

A column (CarboPac PA1, Dionex) containing an anion-exchange pellicular resin was used for the separation of phosphoryl-hexoses derived from labeled glucose microinjected into individual frog oocytes or from cultures of Escherichia coli. Intermediates were identified by: a) comparison of retention times with those of authentic commercial compounds; b) the use of internal labeled standards; c) incubation of samples with specific enzymes and noting the disappearance of one radioactive peak and appearance of another at a new retention time.

Animals↗

An in vitro model showing different rates of substrate cycle for phosphofructokinases of Escherichia coli with different kinetic properties.

An in vitro assay model is introduced for the coupled assay of phosphofructokinase (PFK) and fructose-bisphosphatase. The model is applied to the study of three PFK of Escherichia coli: two isoenzymes, phosphofructokinase-1 (PFK-1) and phosphofructokinase-2 (PFK-2), and a mutant form of phosphofructokinase-2 (PFK-2*). Results show that for a variety of conditions the PFK-1/fructose-bisphosphatase pair gives the lowest and the PFK-2*/fructose-bisphosphatase pair the highest rates of substrate cycle, with the PFK-2/fructose-bisphosphatase pair in an intermediate position. The effects of variables such as maximum activity ratios and MgATP concentration were explored. The possible role of MgATP in decreasing the futile cycle of the PFK-2/fructose-bisphosphatase pair is described. The results are discussed in terms of possible metabolic consequences of PFK-2* and of predictions of the model to be tested in vivo.

Adenosine Triphosphate↗

A behavioral role for enkephalins in regulating locomotor activity in the insect Leucophaea maderae: evidence for high affinity kappa-like opioid binding sites.

D'-Ala-2 met-5-enkephalinamide application to the cerebral ganglia of Leucophaea maderae results in a decrease in locomotor activity. The opiate antagonist, naloxone, can block this effect as well as the depressant effect of morphine on locomotor activity. D-Ala-2,leu-5-enkephalinamide and dynorphin enhance locomotor activity following their topical application to the cerebral ganglia. This effect also can be antagonized by concomitant naloxone treatment. Benzomorphans were the most potent ligands tested in their ability to displace [3H]D'-ala-2,met-5-enkephalinamide whereas mu and delta ligands were by comparison less potent. These results suggest the presence of kappa-like opioid receptors in Leucophaea cerebral ganglia. The kappa ligands also are potent in enhancing locomotor activity in addition to being weakly antagonized by naloxone. Again, these results indicate the presence of multiple-opiate receptor types in invertebrates.

Animals↗

Slow axoplasmic transport: a fiction?

Ribosomes have not been observed in axoplasm. This had led to the notions that the perikaryon is the only source of neuronal proteins and that the axoplasm is supplied by a (slow) transport mechanism. However, we question these two notions because they are unable to give an account of real neurones in accordance with the body of biological knowledge. We point out, for example, that the synthetic rate of perikarya or the life span of axoplasmic proteins should be beyond known ranges for animal cells and that a uniform axon is unlikely to result if it is fed from one end. We propose an alternative view for the maintenance of the axon which accepts the controversial idea of axoplasmic synthesis of proteins; as a result, the slow transport becomes unnecessary. Our view gives a qualitative account of the observations dealing with the maintenance of the axoplasm. To account for the phenomenology in a more quantitative fashion, a computer simulation was carried out where the equations of the program provided only for axoplasmic synthesis of proteins; the set of curves retrieved were in good agreement with experimental findings believed so far to support the notion of slow transport. In conclusion, we think that the notion of "slow axoplasmic transport" has been a misinterpretation of good observations because the frame of reference was incomplete in not providing for axoplasmic synthesis of proteins.

Animals↗

Interaction of heparin with multimolecular aggregates of acetylcholinesterase.

It has been reported previously that heparin, a sulfated glycosaminoglycan, releases the asymmetric 16 S form of acetylcholinesterase (AChE) from cholinergic synapses. Here it is shown that heparin releases the synaptic AChE not as individual 16 S species but as multimolecular aggregates (30 S) of such molecules. Heparin is able to convert low-ionic strength AChE aggregates into a heparin type of AChE aggregates. Our results suggest that the AChE aggregates detached by heparin are likely to be the physiologically important state of aggregation of the 16 S AChE form in the synaptic basal lamina.

Acetylcholinesterase↗

Salutary effects of moderate hypothermia on the circulatory and myocardial consequences of acute coronary occlusion in dogs.

The efficacy of moderate hypothermia with rewarming in attenuating the myocardial and circulatory consequences of acute coronary ligation was studied in open-chest, anesthetized dogs. Thirty minutes after ligation of the proximal left anterior descending coronary artery, 14 dogs were surface-cooled to 27 degrees C, maintained at this temperature for 2 hr, rewarmed to normothermic levels, and monitored for an additional hour. Fifteen dogs were maintained for a corresponding time period after coronary ligation at normothermic levels. Dogs maintained normothermic demonstrated significant depression (from preligation values) of dP/dt, cardiac output (CO), stroke volume (SV), and left ventricular stroke work and power (LVSW, LVSP) at elevated levels of left ventricular end-diastolic pressure (LVEDP). Dogs subjected to the hypothermic procedure demonstrated decreased inotropic status during hypothermia, but with rewarming, exhibited significantly greater values of left ventricular pressure, dP/dt, CO, SV, LVSW, and LVSP at lower values of LVEDP than observed in dogs maintained normothermic. Increased dysrhythmic activity was not observed during hypothermia. Hearts from dogs subjected to the hypothermic protocol demonstrated qualitatively greater dehydrogenase activity both at the periphery and in the center of the nonperfused region. The results suggest that moderate hypothermia during evolving myocardial infarction may preserve left ventricular cardio- and hemodynamics and thus may be useful in delaying morphological and functional deterioration until definitive treatment can be instituted.

Animals↗

Gastroplasty conversion to Roux-en-Y gastric bypass at the lesser curvature due to weight loss failure.

From January 1982 to April 1984, 20 patients with lesser curvature gastroplasty had conversion to Roux-en-Y gastric bypass at the lesser curvature for failure to lose more than 50 per cent of excess body weight within 12 months of the original gastroplasty. The average excess weight of these patients before gastroplasty was 103 lb, and the average excess weight before conversion to gastric bypass was 73 lb. The average weight loss after gastric bypass was doubled within 6 to 15 months. Only one patient failed to lose weight after conversion to gastric bypass, and this patient had endocrine problems. Late surgical complications occurred in two patients (10%); one had cholecystectomy and the other had vagotomy and hiatus hernia repair. There were no mortalities in this series.

Adult↗

Neural 16S acetylcholinesterase is solubilized by heparin.

The effect of heparin, a sulphated glycosaminoglycan, on the solubilization of rat sciatic-nerve acetylcholinesterase (acetylcholine acetylhydrolase; AChE; EC 3.1.1.7) was studied. It was found that heparin solubilized esterase activity from ligated nerves. Sedimentation analysis revealed this activity to be mainly the 16S form. Chondroitin sulphate did not solubilize AChE activity, and protamine eliminated the solubilizing effect. Our results suggest the involvement of sulphated glycosaminoglycans in the intra-axonal localization and transport of 16S AChE.

Acetylcholinesterase↗

Heparin solubilizes asymmetric acetylcholinesterase from rat neuromuscular junction.

We are interested in the factors involved in the anchorage of acetylcholinesterase (AChE) to the synaptic basal lamina. Here, we report studies showing that heparin, a sulfated glycosaminoglycan, specifically solubilized AChE from endplate regions of rat diaphragm muscle. Of the several molecular forms of AChE present in that region, heparin only released the asymmetric A12 and A8 forms of the enzyme. Our results strongly support the involvement of heparin-like macromolecules in the in vivo immobilization of the collagen-tailed forms of AChE to the basal lamina of the neuromuscular junction.

Acetylcholinesterase↗

Gastric bypass: Roux-en-Y gastrojejunostomy from the lesser curvature.

We describe a new technique for the surgical treatment of exogenous morbid obesity. The stomach is partitioned from the angle of His toward the lesser curvature, and a Roux-en-Y proximal jejunal limb drains the proximal gastric pouch, which is 25 to 35 ml in capacity. By use of the enteroanastomosis (EEA) or the intraluminal (ILS) stapling instrument for the gastrojejunostomy from the lesser curvature of the stomach, the functional reliability, vascular integrity, and ease of construction of the stoma have been improved. We performed the gastric bypass operation on 300 consecutive patients, 268 women and 32 men, over a two-year period beginning in June 1979. The patients' average admission weight was 126 kg. Diseases associated with obesity were observed in 57% of the patients, and concomitant operations were performed in 29%. The average weight loss at 6, 12, 18, and 24 months was 37.0, 48.5, 51.5, and 52.0 kg, respectively. Early and late complications occurred in 37 patients (12%), requiring 40 reoperations. Two deaths (0.6%) occurred within the 30 months' of observation.

Adolescent↗