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Biomedical subjects

M Ray

Publications and source records attributed to M Ray.

At least 19 recordsLinked to original sources
PubMed1992

Allosteric modulation of Leishmania donovani plasma membrane Ca(2+)-ATPase by endogenous calmodulin.

The plasma membrane of the human pathogen Leishmania donovani possesses a high-affinity transmembrane Ca(2+)-ATPase that has its catalytic site oriented toward the cytoplasmic milieu (Ghosh, J., Ray, M., Sarkar, S., and Bhaduri, A. (1990) J. Biol. Chem. 265, 11345-11351). When the enzyme is studied in its more authentic, physiologically relevant, membrane-associated form, it exhibits pronounced sigmoidal kinetics with Ca2+ (K0.5 approximately 700 nM) in a trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid buffering system that effectively complexes all available Mg2+. Addition of exogenous Mg2+ (60 microM) completely abolishes sigmoidicity and establishes strictly hyperbolic kinetics, and the Km for Ca2+ reduces to 100 nM. Mg2+ can be replaced by heterologous calmodulin. The exclusive dependence of the enzyme on only Ca2+ for its activity and its positive allosteric modulation by Mg2+ distinguish this enzyme from other well-characterized plasma membrane Ca(2+)-ATPases. Employing this Ca(2+)-ATPase as the assay system, a soluble endogenous activating protein factor was purified that, by several criteria, corresponds to authentic calmodulin. The parasite calmodulin shifts the kinetics to hyperbolic kinetics, increases the Vmax 2-fold, and most important lowers the Km (approximately 100 nM) to a physiological level. The interaction with endogenous calmodulin thus converts the enzyme from a totally inactive to a fully active state.

Adenosine Triphosphate↗
PubMed1992

Postinjury scopolamine administration in experimental traumatic brain injury.

A single bolus dose of scopolamine (1.0 mg/kg) or saline (equal volume) was injected (i.p.) at 15, 30 or 60 min after fluid percussion traumatic brain injury in the rat. Scopolamine administered at 15 min postinjury significantly reduced beam walking deficits and body weight loss assessed for 5 days after injury. Scopolamine treatment at 30 or 60 min postinjury had no effect on behavioral outcome assessed for 5 days after injury. Plasma concentrations of scopolamine were measured with a radioreceptor assay. The plasma half-life for scopolamine was 21.6 min in injured rats and 17.3 min in normal rats (P less than 0.05). These results, along with evidence from previous studies, suggest that a brief period of excessive neuronal excitation can produce relatively long-lasting behavioral deficits. The temporal effectiveness of receptor antagonist intervention in this process appears to be brief.

Animals↗
PubMed1992

Canadian multicenter randomized clinical trial of chorion villus sampling and amniocentesis. chromosome mosaicism in CVS and amniocentesis samples.

Data on 1040 chorionic villus and 969 amniotic fluid samples were collected from women studied in the Canadian Multicentre Randomized Clinical Trial of Chorion Villus Sampling and Amniocentesis. Cytogenetic results were obtained from 98.0 per cent of chorionic villus samples and from 99.9 per cent of amniotic fluid samples. Level I mosaicism (a single cell with an abnormal karyotype) occurred frequently in both chorionic villus and amniotic fluid samples and appeared to have no clinical significance. Level II mosaicism occurred in 0.9 per cent of CVS mesenchyme and 1.5 per cent of amniotic fluid cultures and in general was not perceived to be of sufficient concern to warrant cytogenetic follow-up studies. Level III mosaicism was reported in 18 CVS cases (15 cytotrophoblast, 1 mesenchyme, and 2 with both cell methods) and in one amniotic fluid case. In all cases but one (fetus with trisomy 18), level III mosaicism was confined to the placenta. Maternal cell contamination occurring with a frequency of 6.4 per cent in the mesenchyme analyses was a concern. This study supports the final report of the Canadian Multicentre Randomized Clinical Trial of Chorion Villus Sampling and Amniocentesis. Cytogenetic analysis of chorionic villus samples appears to be an acceptable alternative to the analysis of amniotic fluid samples. However, because of mosaicism and maternal cell contamination concerns, the examination of both cytotrophoblast preparations and mesenchyme cultures from chorionic villus samples is recommended.

Adult↗
PubMed1992

An attempt to standardize APTT reagents used to monitor heparin therapy.

Citrated samples from 100 patients on i.v. heparin and 20 normal patients were tested with three batches each of three activated partial thromboplastin time (APTT) reagents: Thrombosil I (Ortho); Automated APTT (Organon Teknika) and Actin FSL (Baxter). The ratio of APTT over the geometric mean normal APTT for each heparinized sample was calculated. One batch of reagent arbitrarily chosen as a reference gave the ratios APTRREF (y). The remaining reagents to be standardized against the reference system gave the ratios APTRTEST (x). The best correlation between systems was given by log vs log x. Standard curves were prepared from the APTT ratios of the 20 normal patients and 65 of the heparinized samples. On plotting log APTRTEST vs log APTRREF the y intercept was close to zero so x was expressed in terms of y using; log x = HSI. log y, where HSI (Heparin Sensitivity Index) = slope. The APTRTEST results of the remaining 35 heparinized samples were transformed using; APTRTRANS = (APTRTEST)HSI.APTRTRANS was then compared to APTRREF to determine whether the transformation brought the results closer to the reference. We conclude that although some improvement was found by using the transform, it was not possible to mathematically relate APTT results due to a high degree of variation between results using different reagents. A standard APTT reagent for the monitoring of heparin therapy is recommended. A separate APTT reagent may be required for the screening of factor deficiencies and lupus anticoagulants.

Animals↗
PubMed1992

Preoperative systemic chemotherapy followed by adjuvant postoperative intraperitoneal therapy for gastric cancer: a University of Southern California pilot program.

PURPOSE: A clinical trial for patients with gastric cancer amenable to curative resection was undertaken to determine feasibility and response to preoperative systemic chemotherapy followed by postoperative intraperitoneal (IP) chemotherapy. METHODS AND MATERIALS: Thirty-eight patients with resectable gastric tumor received two cycles of protracted intravenous (IV)-infusion fluorouracil (5FU), 200 mg/m2/d, for 3 weeks with weekly IV leucovorin 20 mg/m2 and IV cisplatin 100 mg/m2 days 1 and 29. Resection of the gastric tumor followed within 3 weeks of completion of systemic chemotherapy. Those who had all visible tumor removed with clear margins received two cycles of IP floxuridine 3,000 mg (total dose) per day for 3 days and IP cisplatin 200 mg/m2 with IV sodium thiosulfate on the fourth day of IP therapy. RESULTS: Thirty-seven of 38 patients (97%) received two cycles of systemic chemotherapy. Thirty-five of 38 patients (92%) underwent laparotomy for gastric tumor resection. Thirty-three patients (87%) had gastric resections performed; 29 (76%) had all visible tumor removed with microscopically negative margins. No operative mortality was encountered. Twenty-six patients (68%) received IP treatment. IV neoadjuvant treatment was well tolerated and resulted in 68% of the patients reporting improvement in abdominal pain, 45% objective remissions by computed tomography (CT), 38% objective remissions by gastroscopy and biopsy, and 8% had complete surgical pathologic response. Neutropenic sepsis during the IP treatment phase contributed to the only treatment-related death. Four of 29 completely resected patients (14%) have had tumor recurrence. The median follow-up time of patients remaining alive is now 19 months. The median survival for 38 patients entered onto this protocol has not been reached at 17+ months. CONCLUSION: This novel approach to the treatment of adenocarcinoma of the stomach is feasible. The neoadjuvant systemic therapy results in significant primary tumor regression. The determination of whether systemic or IP components of the program contribute to decreased recurrence or increased survival awaits a prospectively randomized clinical trial.

Adenocarcinoma↗
PubMed1979

Nucleolar organizing regions of human chromosomes.

Silver-stained cells from 49 parents with a history of several abortions were compared with cells from 35 parents with normal liveborn children. The modal and mean number of silver-stained NORs (Ag-NORs) observed on D- or G-group chromosomes was similar in both groups and between males and females. Ag-NORs were randomly distributed on all five acrocentric pairs. The distribution and size of Ag-NORs within an individual was not random and was fairly consistent from cell to cell. The mean number of associations per cell was similar in both males and females of the abortion group and was less than the number of associations in controls. The probability of D- or G-group chromosomes being associated was near the expected probability of 0.6 for D-association and 0.4 for G-association. The frequency of association of any chromosome combination did not differ statistically from the expected values, though the number of associations, 15/22, was higher than expected.

Abortion, Spontaneous↗
PubMed1979

Paroxysmal atrioventricular tachycardia involving an anomalous pathway with antegrade unidirectional block.

37 consecutive patients with frequent episodes of palpitation and/or dizziness underwent electrophysiological study. They had no signs of ventricular preexcitation during either sinus rhythm or atrial pacing. In 17 (46%), the supraventricular tachycardia was sustained by a reentry mechanism involving an anomalous AV pathway with unidirectional antegrade block (AV tachycardia). Some findings were accepted to demonstrate the existence of the anomalous pathway (AP) and others, its participation in the reentry circuit. The possible location of the AP was established in 15 cases at the following sites: left lateral in 5 cases, left posterior in 5 cases, left posteromedial in 1 case, right posterior in 1 case, right anterior in 1 case, posterior septal in 1 case, and anterior septal in 1 case. The rate of the AV tachycardia can be influenced not only by the ventriculoatrial interval but also by the other pathways included in the reentry circuit. It may change conspicuously in cases with dual AV pathway and anomalous AV pathway in relation to the modality of antegrade conduction by the AV node.

Adolescent↗
PubMed1979

Nucleolar organizing regions of normal Chinese hamster and CHW cell line chromosomes.

The chromosome preparations from fibroblasts of normal male and female Chinese hamsters and the cell line CHW were stained with AgNO3. The silver stain was usually localized at the telomeres of autosomes. The marker chromosome M1 in the CHW cell line has Ag-NOR near the centre of the long arm, which indicates that either the long arms of two number 5 chromosomes fused at the telomeres or the intact telomeric region of one chromosome fused with one with a deleted telomere. The variation of Ag-NORs' number per cell and Ag-heteromorphism in chromosome number 4 were observed. The Ag-NORs of chromosome number 4 and 5 are in approximately the same position as the positive C-bands and these may play a role in the preservation of heterochromatin.

Animals↗
PubMed1978

UDP-glucose 4-epimerase from Saccharomyces fragilis. Involvement of sulfhydryl group(s) at the active site.

UDPglucose-4-epimerase (EC 5.1.3.2) from Saccharomyces fragilis is inactivated by 0.1 mM 5,5'-dithiobis-(2-nitrobenzoate) in 6 min. Unlike p-chloromercuribenzoate-inactivated or heat-inactivated enzymes, the dithiobisnitrobenzoate-inactivated enzyme retains the dimeric structure and NAD is not dissociated from the protein moiety. Inactivation of the enzyme by dithiobisnitrobenzoate can not therefore be attributed to any subsequent loss of structural integrity or to the detachment of the cofactor from the apoenzyme. The inactivated enzyme can be almost fully reactivated in the presence of mercaptoethanol and characteristic properties of native enzyme are regained. The inactivation by dithiobisnitrobenzoate can be substantially protected by UDPglucose or UDPgalactose indicating a possible critical involvement of one or more sulfhydryl groups at the active site.

Binding Sites↗