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Biomedical subjects

R Nath

Publications and source records attributed to R Nath.

At least 127 records · Page 7Linked to original sources

Allogeneic bone marrow transplantation for refractory and recurrent low-grade lymphoma: the case for aggressive management.

PURPOSE: To evaluate the role of allogeneic bone marrow transplantation (BMT) in recurrent low-grade lymphoma. PATIENTS AND METHODS: Between 1989 and 1994, 10 patients with chemotherapy-refractory and recurrent low-grade lymphoma were treated with myeloablative therapy and allogeneic BMT. All patients had poor prognostic features and had been extensively pretreated. RESULTS: Eight patients achieved a complete remission and none have relapsed at a median follow-up time of 816 days (range, 346 to 1,865). Two patients died of early complications. The actuarial survival and failure-free survival rates are both 80% +/- 12.6%. For surviving patients, the duration of the current remission exceeds that of any previous remission achieved. CONCLUSION: These results compare favorably with those for autologous BMT. Allogeneic BMT offers considerable promise for the treatment of patients with poor-prognosis low-grade lymphoma. Its role should be further defined in prospective studies.

Adult↗

A phase I-II study of high-dose thiotepa, busulfan and cyclophosphamide as a preparative regimen for autologous transplantation for malignant lymphoma.

Thirty-four adults with malignant lymphoma at high-risk for relapse were treated on a Phase I-II study of high-dose thiotepa (THIO), busulfan (BU) and cyclophosphamide (CYC) with autologous marrow or peripheral blood stem cell support. Four patients were in untreated relapse, 7 had stable or progressive disease, 12 were in partial remission, and 11 were in complete remission after reinduction chemotherapy before proceeding to the preparative regimen. Median follow-up time is 22 months. Grades 3-4 regimen-related toxicity occurred in 3 (14%) of 22 patients treated with THIO 250 mg/m2 x 3, BU 1 mg/kg x 10 and CYC 50 mg/kg x 3, and this was considered the maximal tolerated dose-schedule. Of the 23 patients with active disease at the time of transplantation, 52% (95% CI 31-73%) achieved a complete response, and 26% (95% CI 10-48%) achieved a partial response. For all patients, median time to progression was 13 months, median survival was 16 months, and disease-free survival at 18 months was 34% (95% CI 18-51%). The combination of THIO, BU and CYC is tolerable as a preparative regimen for lymphoma and has a high response rate, but further measures are needed to reduce the relapse rate for patients with advanced disease.

Adult↗

Vitamin B6 deficiency and galactose induced alterations in morphology and osmotic fragility of rat erythrocytes.

Recently, red blood cells have been investigated mainly for alterations in ion transporting capacity, membrane bound enzymes or modifications in the structure of its individual constituents in clinical and experimental urolithiasis. However, the implication of such modifications on the physical state or morphology of cells has not been investigated. Scanning electron microscopic studies performed in vitamin B6 deficient and/or galactose fed rat (established hyperoxaluric models) erythrocytes, showed the presence of large number of stomatocytes, spherocytes and other variously deformed cells as compared to discocytic cells seen in normal control group. These changes in shape were in concurrence with red cell osmotic fragility, which decreased both in vitamin B6 deficient and vitamin B6 deficient + galactose fed group (19 % and 33 % hemolysis at 4 g/l NaCl, respectively) while it increased in galactose control group (73 % hemolysis at 4 g/l NaCl) as compared to normal control group (55 % hemolysis at 4 g/l NaCl). These morphological and physical state alterations could be correlated with red blood cells' membrane cholesterol and phospholipid sub-class distribution. These findings suggest that some structural membrane changes occur due to vitamin B6 deficiency and/or galactose feeding, which may be responsible for the altered membrane functions known to be associated with pathogenesis of urolithiasis.

Animals↗

Purification and characterization of a low molecular weight zinc binding protein from human placenta.

A low molecular weight, native zinc binding, cytosolic protein (LMZP) has been isolated, purified and characterized from human normal term placenta. Gel filtration of heat treated placental cytosol after sequential acetone precipitation (80% ppt) revealed a major zinc binding protein in the range of low molecular weight. This partially purified zinc binding fraction was further fractionated on DEAE-Sephadex A-25. The zinc was eluted in one of the three peak fractions. Further, the purity of zinc binding protein was confirmed on fast protein liquid chromatography (FPLC). The purified placental LMZP was homogenous on SDS-polyacrylamide gel electrophoresis with a single band. Ultraviolet (UV) spectrum of LMZP showed an absorption maximum at 257 nm which disappeared at pH 2. Molecular weight of LMZP as determined by gel chromatography, SDS-polyacrylamide gel electrophoresis and amino acid analysis was 6 kDa. It was calculated that 1 g atom of zinc was bound to 1 mole of the LMZP. Unlike in classical metallothionein, the amino acid composition of placental LMZP revealed the presence of aromatic amino acids, lower content of cysteine and higher content of histidine, glutamic acid and aspartic acid (10, 9 and 5 residues/mole, respectively).

Amino Acids↗

Effect of combined supplementation of magnesium oxide and pyridoxine in calcium-oxalate stone formers.

A combined supplement of magnesium oxide (300 mg/day) and pyridoxine.HCl (10 mg/day) was given p.o. to 16 recurrent calcium oxalate (CaOx) stone formers, and its therapeutic efficacy was biochemically evaluated by measuring various parameters of blood (Na, K, Mg, urea, creatinine, calcium, phosphate, uric acid, alanine transaminase, aspartate transaminase and alkaline phosphatase) and urine (volume, pH, creatinine, Na, K, Mg, uric acid, calcium, phosphate, oxalate and citrate) at 0, 30, 60, 90 and 120 days of treatment. Serum Mg significantly (P < 0.01) increased after 30 days of treatment and remained constant thereafter while other blood parameters were unaltered. Combined treatment led to a significant increase in the urinary excretion of Mg and citrate over pretreatment values while oxalate excretion showed a gradual and significant decline during the therapy. The results confirmed the efficacy of MgO-pyridoxine supplementation in terms of changes in urinary excretion of lithogenic and inhibitory components, leading to a significant (P < 0.01) decrease in CaOx risk index from 0.09 +/- 0.04 at 0 day to 0.05 +/- 0.02 after 120 days of treatment.

Adult↗

Effect of Tribulus terrestris on oxalate metabolism in rats.

This study concerns the effect of an aqueous extract of Tribulus terrestris on the metabolism of oxalate in male rats fed sodium glycolate. Glycolate feeding resulted in hyperoxaluria as well as increased activities of oxalate synthesizing enzymes of the liver i.e. glycolate oxidase (GAO), glycolate dehydrogenase (GAD) and lactate dehydrogenase (LDH), and decreased kidney LDH activity. T. terrestris administration to sodium glycolate fed rats produced a significant decrease in urinary oxalate excretion, and a significant increase in urinary glyoxylate excretion, as compared to sodium glycolate fed animals. The supplementation of T. terrestris with sodium glycolate also caused a reduction in liver GAO and GAD activities, whereas liver LDH activity remained unaltered. The isoenzyme pattern of kidney LDH revealed that normalization of kidney LDH by T. terrestris feeding was mainly due to an increase in the LDH 5 fraction. The LDH 1 isoenzyme remained unchanged in all the groups.

Animals↗

The calibration and use of plane-parallel ionization chambers for dosimetry of electron beams: an extension of the 1983 AAPM protocol report of AAPM Radiation Therapy Committee Task Group No. 39.

This report is an extension of the 1983 AAPM protocol, popularly known as the TG-21 Protocol. It deals with the calibration of plane-parallel ionization chambers and their use in calibrating therapy electron beams. A hierarchy of methods is presented. The first is to calibrate the plane-parallel chamber in a high energy electron beam against a cylindrical chamber which has an Ncylgas value that has been obtained from a NIST traceable 60Co beam calibration. The second method, which is recommended for implementation by the ADCLs is an in-air calibration against a NIST-traceable calibrated cylindrical chamber in a Cobalt-60 beam to obtain a plane-parallel-chamber calibration factor in terms of exposure or air kerma. The third method places the two chambers in a phantom in a Cobalt-60 beam, and leads to an Nppgas value for the plane-parallel chamber. This report also gives Nppgas/NxAion)pp and Nppgas/(NkAion)pp values for five commonly used commercially available plane-parallel chambers: the Capintec PS-033, the Exradin P-11, the Holt, the NACP and the PTW-Markus. The calculation of these Ngas ratios introduces a Kcomp factor which is also calculated for the five parallel plate chambers. The use of the plane-parallel chambers follows the 1983 AAPM protocol for absorbed dose calibrations of electrons, except that new energy-dependent Prepl values are given for the Capintec PS-033 and PTW-Markus chambers consistent with the consensus of reports in the literature. For all the chambers, however, Prepl is unity for 20 MeV electrons. This report does not address the issue of the use of plane-parallel chambers in calibrating photon beams.

Cobalt Radioisotopes↗

Study of urinary calcium excretion after oral calcium load in stone formers, their spouses and first-degree blood relatives.

Hypercalciuria has long been considered a common abnormality in stone formers, and familial predisposition to renal stone formation has also been reported. Renal stone formers, their spouses and first-degree blood relatives (the latter two groups of subjects had no previous or present history of stone disease) were investigated for their response to an oral load of 2 g calcium (as di-calcium phosphate). Serum calcium, phosphorus, uric acid, creatinine and urea were within the normal range in all the subjects initially as well as 4 h after the load. After the oral calcium load, 66.6% of the stone formers, 25% of the first-degree relatives and none of the spouses were hypercalciuric. Administration of 2 g calcium produced a significantly greater urinary excretion of calcium in stone formers (123.8 +/- 43 mg/8 h, p < 0.001) and their first-degree blood relatives (89.8 +/- 26 mg/8 h, p < 0.01) as compared to the spouses of stone formers (65.5 +/- 12.8 mg/8 h). A significant increase in urinary calcium excretion after calcium loading was also found among the stone formers (p < 0.01) as compared to their first-degree blood relatives. A significantly higher mean rise in calcium excretion (over the basal excretion) in calcium stone formers (p < 0.001) and their first-degree blood relatives (p < 0.01), as compared to the spouses of stone formers suggests a greater predisposition to renal stone disease in first-degree blood relatives than the spouses of the stone patients.

Administration, Oral↗

Calcium and oxalate uptake by the renal brush border membrane vesicles in magnesium-deficient rats.

Calcium and oxalate uptake by renal brush border membrane vesicles (BBMV) was examined in magnesium-deficient and pair-fed control rats. Uptake studies were carried out by rapid filtration technique and rate of influx of calcium and oxalate as a function of extravesicular concentration (0.1 nM--1.0 mM) examined. Calcium uptake by renal BBMV exhibited saturable kinetics while oxalate uptake followed a biphasic transport mechanism showing saturable kinetics at low oxalate concentrations and passive diffusion at higher concentrations. In magnesium deficiency the kinetics of calcium and oxalate uptake by renal BBMV remained unaltered but the rate of uptake was significantly enhanced at all the extravesicular concentrations studied. Double reciprocal plot for calcium uptake showed no change in Vmax but a decrease in Km (2.08 mM) in magnesium--deficient rats as compared to pair-fed controls (Km = 5.00 mM). Similar plot for oxalate uptake showed an increase in Vmax (7.69 nmoles/8 min/mg protein) in magnesium deficient group as compared to pair-fed controls (5.55 nmoles/8 min/mg protein), while Km remained unchanged. The results of the present study indicate high risk of calcium oxalate stone formation in magnesium--deficient rats due to hyperabsorption and retention of calcium and oxalate by the renal tubular brush border membrane.

Animals↗

Visible-light and X irradiations of Chinese hamster lung cells treated with hematoporphyrin derivative.

Single cell suspensions of Chinese hamster lung cells were treated with hematoporphyrin derivative (HPD) and were exposed under aerobic conditions to visible light alone, X rays alone or light and X rays concurrently. Cytotoxicity was assayed using the colony formation ability of cells as the end point. The drug toxicity, phototoxicity, radiosensitization and photoradiosensitization of HPD were examined for a drug concentration of 1 microgram/ml and incubation time of 24 h. In these experiments, the X-ray dose was 3 Gy and the energy fluence of visible light was 0.35 kJ/m2, and both irradiations lasted for 10 min. A significant enhancement in cytotoxicity was observed when the HPD-treated cells were irradiated concurrently with light and X rays. However, no significant enhancement was observed when visible-light and X irradiations were performed sequentially with a 15-min waiting time between the two irradiations.

Animals↗

Effect of chronic cadmium exposure on glutathione S-transferase and glutathione peroxidase activities in rhesus monkey: the role of selenium.

The effect of cadmium (Cd) on the activity of glutathione S-transferase (GST) and glutathione peroxidase (GSH-Px) which play an important role in the detoxification of xenobiotics, was studied in the liver, kidney, heart and lung of Rhesus monkeys. Furthermore, the role of selenium (Se) in the modulation of Cd toxicity with respect to GST and GSH-Px was also evaluated. Cadmium exposure (5 mg Cd/kg body wt./day as CdCl2 for 10 weeks) to monkeys resulted in decreased GSH-Px activity in all four organs present in the order liver > kidney > heart > lung. Cadmium administration also resulted in a significant decrease in total GST activity present in the order liver > heart > kidney > lung, whereas a significant increase in the pi class GST activity was observed greatest in the heart followed by lung, kidney and liver. Oral administration of Se (0.5 mg Se/kg body wt./day as Na2SeO3 for 10 weeks) caused a significant increase in GSH-Px activity in the order liver > heart > kidney > lung. Selenium administration caused an increase in total GST activity in liver and lung but a decrease in kidney and heart. Simultaneous administration of Cd and Se resulted in an increase in total GST activity (except in lung) including the pi class activity as well as GSH-Px activity in all four tissues under study. Thus, the mechanism by which selenium decreases Cd toxicity in Rhesus monkeys, seems to rely on the protection of the enzyme systems GST and GSH-Px in the four organs, possibly by forming non-toxic cadmium selenide.

Animals↗

Prothymosin alpha gene expression correlates with proliferation, not differentiation, of HL-60 cells.

Accumulating evidence suggests that prothymosin alpha has an as yet undefined intracellular, perhaps intranuclear, function related to cell proliferation. Prothymosin alpha mRNA and/or peptide levels increase when cells are stimulated to proliferate. Because proliferation and differentiation events are often inversely correlated, we examined prothymosin alpha gene expression during proliferation and differentiation of HL-60 myeloid leukemia cells. Steady-state levels of prothymosin alpha mRNA, which are high in exponentially growing HL-60, decrease within hours after induction of HL-60 to differentiate along the neutrophil pathway with dimethylsulfoxide (DMSO) or along the macrophage lineage with either tetradecanoylphorbol acetate (TPA) or bryostatin 1. The decline in prothymosin alpha mRNA in response to these differentiation signals parallels that of c-myc mRNA under the same conditions. We then determined whether the downregulation of prothymosin alpha and c-myc mRNA were due to differentiation or cessation or proliferation. Recombinant human gamma-interferon induces monocytic differentiation of HL-60, but permits continued proliferation, and, under these conditions, expression of prothymosin alpha, as well as of c-myc, mRNA remains elevated. We conclude that prothymosin alpha and c-myc expression are coregulated in differentiating HL-60 and that their expression correlates with the proliferative state of HL-60 cells, rather than with the differentiated state.

Cell Differentiation↗

Local anesthesia by peribulbar block for cataract extraction in an eye relief camp. A double-masked, randomized controlled trial.

OBJECTIVE: To test the hypothesis that the median scores for globe anesthesia are not significantly different for patients receiving local anesthesia (LA) by peribulbar block (PB) than for those receiving retrobulbar block (RB) for cataract surgery. DESIGN: Double-masked, randomized controlled trial. SETTING: An eye camp in Bhetwa, India, base hospital was King George's Medical College, Lucknow. (Eye camps are temporary set-ups used for cataract surgery throughout rural India.) Study carried out over a 2-day period. PATIENTS: Out of 125 patients eligible for intracapsular cataract extract on under LA, 122 agreed to enter the trial, and were randomly allocated to 2 groups just before the operation. The groups were equal in size and similar in composition in terms of patient age and sex. INTERVENTION: PB or RB infiltrated with 5 mL of the same anesthetic at the same site but with a different needle size and direction. MAIN OUTCOME MEASURES: Globe anesthesia (primary outcome), globe akinesia, lid akinesia, pupillary dilatation, and hypotony were scored separately on a 4-point scale during surgery by a masked surgeon. During infiltration, surgery, and the 1st 30 minutes after surgery, pain was scored by patients and recorded by an interviewer. RESULTS: Median scores for globe anesthesia were 4.0 in both groups, and the Mann-Whitney test revealed no difference in the medians of these scores (P = 0.6). There was no difference in scores on other outcomes measured, except lid akinesia, which was better with PB. Subjective pain scores were significantly higher with RB. The surgeon's guess about the type of LA administered was correct only for 58% of patients. CONCLUSION: PB is no different from RB in terms of producing globe anesthesia when used for cataract surgery at eye camps.

Aged↗

Influence of ethanol on cadmium accumulation and its impact on lipid peroxidation and membrane bound functional enzymes (Na+, K(+)-ATPase and acetylcholinesterase) in various regions of adult rat brain.

Influence of ethanol on cadmium accumulation and its effect on metallothionein induction, binding of cadmium to metallothionein, lipid peroxidation and membrane bound functional enzymes such as (Na(+)-K+)-ATPase and acetylcholinesterase in various regions of adult rat brain was investigated. Ethanol (2 g/kg body wt) and cadmium (1 mg/kg body wt) were administered alone as well as in combination to different groups of rats, i.p., for a period of 1 week. It was observed that cadmium when co-administered with ethanol led to pronounced increase in cadmium accumulation in various regions of the brain. This ethanol induced accumulation of cadmium did not induce the synthesis of metallothionein and also did not bind to this protein in brain and mainly was present as non-metallothionein bound cadmium. It lead to a significant increase in lipid peroxidation and inhibition of membrane bound functional enzymes; (Na(+)-K+)-ATPase and acetylcholinesterase in various regions of the brain indicating functional impairment. The results of the present study imply that ethanol renders the adult brain more susceptible to cadmium neurotoxicity. Corpus striatum and cerebral cortex are more vulnerable regions than other areas of the brain.

Acetylcholinesterase↗

Properties of Barrier, a novel Saccharomyces cerevisiae acid protease.

We have studied the specificity of Barrier, a protease secreted by Saccharomyces cerevisiae, towards its natural substrate alpha-factor, a tridecapeptide mating pheromone. Sub-fragments of alpha-factor synthesized or prepared by cyanogen bromide cleavage and a related pheromone from Saccharomyces kluveri were studied as potential substrates or competitive inhibitors. None of the tested peptides was a potent inhibitor or substrate for Barrier. Barrier shares extensive sequence similarity to the active site residues of aspartyl proteases but universal irreversible inhibitors of this class of enzymes failed to inactivate Barrier, suggesting that it is a novel fungal aspartyl protease.

Amino Acid Sequence↗

How safe is 1% alum irrigation in controlling intractable vesical hemorrhage?

A prospective study was done to evaluate the efficacy and safety of intravesical instillation of 1% alum solution in 12 cases of hematuria of vesical origin, uncontrolled by saline irrigation for 24 hours via a 3-way Foley catheter. There were 10 cases of transitional cell carcinoma and 2 of radiation cystitis. Complete response was noted in 6 patients and a partial response in 4. Local side effects included suprapubic pain and vesical tenesmus, which were controlled by antispasmodic and/or analgesic drugs. Transient low grade pyrexia (maximum up to 38.2C) was noted in 4 patients. Among the other various clinical and biochemical parameters, serum aluminum level and prothrombin time showed statistically highly significant changes. Serum aluminum increased from an average baseline value of 1.68 to 3.36 mumol./l. without clinical evidence of aluminum toxicity and with levels well below the recommended safe limit. Prothrombin time increased parallel with the increase in serum aluminum level to a maximum of 1 1/2 times the control. Prothrombin values, therefore, can be used clinically, since they are readily obtainable whereas serum aluminum levels are not. Vesical irrigation with 1% alum solution is a safe method to control hematuria of vesical origin in properly selected cases.

Administration, Intravesical↗