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Biomedical subjects

R K Gupta

Publications and source records attributed to R K Gupta.

At least 325 records · Page 18Linked to original sources
PubMed1994

Removal of endotoxin from antibody preparations for clinical use. Assessment of polymyxin-sepharose CNBr affinity chromatography.

Despite attempts to maintain asepsis, good manufacturing practices, and the use of terminal sterilization by millipore filtration, the nuclear practitioner is always worried about the possibility of endotoxin contamination. Methods, such as ion-exchange chromatography, have been tried for removing endotoxins during the preparation of radiolabeled antibodies, and so on. As suggested by Stevenson (1990), we evaluated the Issekutz technique (1) of endotoxin removal by affinity chromatography using a polymyxin cyanogen bromide (CNBr) Sepharose column. The endotoxin content of millipore filtrates of heat killed/sonicated suspensions of Pseudomonas pyocyaneus, E. coli were measured using a Sigma (St. Louis, MO) Endotoxin Assay Kit before and after filtration through such columns and compared with the results obtained using gel exclusion and ion-exchange columns of the same length and diameter. Reduction of endotoxin content to undetectable levels by the polymyxin column was observed. The use of such columns for terminal endotoxin removal analogous to terminal sterilization is advocated especially when developing a radiopharmaceutical such as radiolabeled antibodies for in house use.

Antibodies, Monoclonal↗
PubMed1994

The role of early flap coverage in the management of open fractures of both bones of the leg.

Sixty patients with type III injuries (open fractures) of the tibia were treated in a prospective fashion by combined orthopaedic and plastic surgical schemes based on the principles of early radical cleaning, a second-look operation, and early coverage of soft tissue defects with an appropriate local or distant flap. Stabilization of fractures was achieved by external fixation in most cases and patients were allowed to walk within 4-8 weeks (partial weight bearing). Bony union was achieved in 23.4 weeks. The mean hospital stay was 3.5 weeks. Limb salvage was achieved in all cases and there were no major complications.

Adolescent↗
PubMed1994

Biodegradable microspheres as controlled-release tetanus toxoid delivery systems.

Purified tetanus toxoid, a high-molecular-weight protein, was entrapped within poly(L-lactic acid) (PLA) and poly(D,L-lactic/glycolic acid) (PLGA) microspheres prepared by either a solvent extraction or a solvent evaporation method carried out in a multiple emulsion system (water-in-oil-in-water). The physical integrity and antigenicity of the protein treated under different processing conditions were investigated. A reduction of antigenicity that was related to the percentage of aggregated protein was noticed under some experimental conditions. This partial loss of antigenicity was associated with the lyophilization process and affected by the nature of the organic solvent. All types of microspheres prepared with different molecular weight PLA and PLGA displayed a high protein-loading efficiency (> 80%) but their size was strongly influenced by polymer molecular weight (3000 versus 100,000). Protein release pattern was influenced by both polymer molecular weight and composition (PLA versus PLGA). A constant release pattern after an induction period of 10 days was observed for microspheres composed of high-molecular-weight polymers (PLA and PLGA). The release rate was lower from PLA microspheres than from PLGA microspheres. In contrast, a continuously increasing release rate preceded by a burst was observed for low-molecular-weight (3000) PLGA microspheres. Microencapsulated tetanus toxoid was significantly more immunogenic in mice than fluid toxoid as determined by IgG anti-tetanus antibody levels and neutralizing antibodies. However, the magnitude and duration of the antibody response did not differ significantly from a similar dose of aluminium phosphate-adsorbed toxoid. We conclude that microencapsulated tetanus toxoid shows significant adjuvant activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Nuclear magnetic resonance measurement of intracellular sodium in the perfused normotensive and spontaneously hypertensive rat heart.

We have used 23Na nuclear magnetic resonance spectroscopy to examine the relationship between intracellular sodium and cardiac muscle alterations in genetic hypertension. In the spontaneously hypertensive rat (SHR) compared with the normotensive Wistar-Kyoto rat (WKY) (aged 15 to 19 weeks), mean systolic blood pressures (measured using the tail-cuff method) were significantly (P < .05) different (WKY: 118 +/- 8 mm Hg, n = 5; SHR: 185 +/- 9 mm Hg, n = 5). Heart weights were also increased significantly (P < .05) in SHR (grams dry heart to kilograms body weight ratio was 0.73 +/- 0.04, n = 5, for SHR and 0.55 +/- 0.02, n = 5, for WKY). Intracellular sodium levels, measured using shift-reagent-aided and triple quantum filtered (TQF) nuclear magnetic resonance techniques, were significantly increased (P < .05) in the isolated Langendorff perfused hypertensive rat hearts (17.3 +/- 3.6 mmol/L, n = 5) compared with normotensive rat hearts (8.4 +/- 2.3 mmol/L, n = 5). These data demonstrate increased sodium in cardiac muscle in essential hypertension. We also investigated the effect of pacing on cardiac TQF 23Na nuclear magnetic resonance and found an increase in TQF Na+ content in both WKY and SHR hearts on stepped up pacing. These results support the existence of sodium pump lag in the rat heart perfused at physiologic Ca2+ concentration and suggest that the hypertensive rat heart has adapted to compensate for increased basal intracellular Na+ and maintain a normal response to increased heart rate. Our data appear to suggest an ionic contribution to the cardiac hypertrophy of genetic hypertension in the rat.

Animals↗
PubMed1994

Proliferation of Reed-Sternberg cells and variants in Hodgkin's disease.

The proliferative activity and the origin of multinucleated Reed-Sternberg cells and mononuclear variants in Hodgkin's disease have been studied in the past using several techniques. The presence of both proliferating-cell nuclear antigen and the cell-proliferation-associated antigen Ki-67 have also been reported in Hodgkin's disease. P34cdc2 is the protein product of the cell-cycle-control cdc-2 gene. Using a monoclonal antibody against the protein p34, cases of three different histological subtypes of Hodgkin's disease have been studied along with normal tonsil and follicular lymphoma as controls. In all these cases of Hodgkin's disease, positive p34 staining was seen in the majority of Reed-Sternberg cells and mononuclear variants (> 80%), along with a proportion of small lymphocytes, mainly T cells. Staining was predominantly cytoplasmic and occasionally additional nuclear signals were apparent. In two cases, double immunostaining with the anti-p34 antibody and CM-1 for p53 demonstrated positive signals for both proteins within the same neoplastic cells. Although the presence of p34 in Reed-Sternberg or variant cells reflects mitosis and hence suggests proliferation, the possibility of endomitosis remains and may explain the multinucleated appearance of Reed-Sternberg cells.

CDC2 Protein Kinase↗
PubMed1994

Tuberculous radiculomyelitis (arachnoiditis): myelographic (and CT myelographic) appearances.

Tuberculous radiculomyelitis (arachnoiditis) remains one of the important causes of paraplegia in India. The diagnosis usually rests on clinical history and examination, and on laboratory findings in the cerebro-spinal fluid (CSF). Few descriptive reports are available of the myelographic appearance, with water-soluble contrast media, in tuberculous radioculomyelitis (arachnoiditis). A retrospective review of 21 myelograms and 10 computed tomographic (CT) myelograms, in 14 patients with tuberculous radiculomyelitis, was carried out, with a view to describing, in detail, the radiographic features. An attempt was made to assess the use of the radiologic procedures in diagnosis and follow up in these patients. Conventional myelographic findings included block (8/14), irregular subarachnoid space (9/14), filling defects (8/14), sluggish contrast flow (2/14), root thickening (3/14) and atrophic cord (2/14). Computed tomographic myelography showed reduced contrast density in portions of the opacified CSF ring around the cord in affected region (6/7) and, in addition, demonstrated septa and adhesions. Intravenous contrast CT was not found to be useful (2/2). Follow-up studies showed partial resolution (3/6), deterioration (1/6) and status quo of radiological findings (2/6). Although these changes can be seen in chronic radiculomyelitis (arachnoiditis) from other causes, such as leukaemic infiltration/lymphoma, other chronic central nervous system infections and iatrogenic causes, including repeated intrathecal injections, conventional myelography appeared to be useful for diagnosis and follow up in tuberculous radiculomyelitis (arachnoiditis).

Adult↗
PubMed1994

Muscular sufficiency, serum protein, enzymes and bioenergetic studies (31-phosphorus magnetic resonance spectroscopy) in chronic malnutrition.

Muscle sufficiency was significantly lower in 1336 children with chronic malnutrition of moderate to severe degree. Eighteen children with a chronic moderate degree of malnutrition and 8 well-nourished, age-matched controls were selected for biochemical and 31-phosphorus magnetic resonance spectroscopy (31-P MRS) studies. The results showed that: (a) serum total protein, albumin, iron, calcium and inorganic phosphate were similar in both groups; (b) serum enzyme levels were significantly increased in the malnourished group; (c) 31-P MRS showed significantly higher means for total ATP, beta-ATP, alpha-ATP and inorganic phosphate for the malnourished compared to the control group. In chronic malnutrition, proteins are maintained by degradation in muscle resulting in release of amino acids and enzymes. 31-P MRS studies showing increases in total ATP, beta-ATP and inorganic phosphate and a decrease in phosphocreatine suggest that ATP is maintained at the cost of phosphocreatine.

Adenosine Triphosphate↗
PubMed1994

Prognostic value of a 90kD subunit containing glycoprotein tumor-associated antigen specific immune complexes in lung cancer patients.

An ELISA to detect a glycoprotein TAA-specific immune complexe (IC) has been developed utilizing a murine monoclonal antibody, AD1-40F4, that recognizes a 90kD subunit of the antigen. In this study we determined the applicability of the assay to assess the presence of the glycoprotein TAA-IC in lung cancer patients. The incidence of glycoprotein TAA-IC was 63% (33/89), significantly higher (p < 0.05) than normal controls (3.2%; 8/250). Comparative analyses of pre- and post-operative sera of non-small cell lung cancer patients revealed that in 30% (20/66) of patients, the ELISA value for the marker did not become negative, i.e., decrease below the cut-off level (0.410 ODnm) after surgical resection of the tumor. It is postulated that these patients either had extensive disease or microscopic metastases that were not resectable. Evaluation of post-operative glycoprotein TAA-IC results in relation to disease recurrence revealed a significant association between the presence of the antigen in serum and disease recurrence. There did not appear to be any association between the glycoprotein TAA-IC and the other conventional marker, CEA; however, using more than one marker increases the incidence of detection of the disease.

Adolescent↗
PubMed1994

Intracellular ionic consequences of dietary salt loading in essential hypertension. Relation to blood pressure and effects of calcium channel blockade.

To study the ionic basis of salt sensitivity in hypertension, 19F-, 13P-, and 23Na-nuclear magnetic resonance techniques were used to measure cytosolic free calcium (Cai), pH (pHi), free magnesium (Mgi), and sodium (Nai) in erythrocytes of essential hypertensive subjects (n = 19). Individuals were studied for 2 mo each on low- (UNaV < 50 meq/d) and high- (UNaV > 200 meq/d) salt diets, with the concomitant administration of nifedipine (10 mg t.i.d.) or placebo tablets for 1 mo of each diet. Salt loading elevated Cai and Nai while suppressing Mgi and pHi; these changes occurred predominantly in salt-sensitive subjects (n = 9). Nifedipine blunted the pressor response to salt loading > 50% (delta diastolic BP [high-low salt vs placebo] = 5 +/- 2 vs 14 +/- 2 mmHg, P < 0.05) and reversed salt-induced ionic changes, lowering Cai and elevating Mgi and pHi. Regardless of the definition of salt sensitivity, continuous relationships were observed between the pressure response to salt loading, the levels of Cai (r = 0.726, P < 0.001), Nai (r = 0.747, P < 0.001), and pHi (r = -0.754, P < 0.001), and the salt-induced change in Mgi (r = -0.757, P < 0.001). Altogether, these results emphasize the reciprocal and coordinate nature of intracellular ionic changes in response to dietary salt loading and calcium channel blockade in essential hypertension. They suggest that salt sensitivity is mediated by cellular calcium accumulation from the extracellular space, in association with magnesium depletion and acidification. Lastly, interpretation of intracellular ion measurements in the future will require concurrent assessment of dietary salt intake.

Analysis of Variance↗
PubMed1994

Role of repellents in vector control and disease prevention.

Repellents are an inexpensive and practical means of protection against nuisance and disease vector arthropods in conjunction with or when other control measures are not feasible. Appropriate selection of skin and/or clothing repellents along with proper wear of clothing can provide adequate protection from biting arthropods, and are available in a wide variety of forms including lotions, creams, foams, soaps, aerosols, sticks, and towellettes. A coordinated effort among different research groups associated with advances in the science of insect repellents such as mode of action information, doses of repellents to generate threshold level responses and controlled release delivery mechanisms, may help in understanding the mechanisms by which repellents work. This in turn may revolutionize the development of repellents for personal protection and their use in vector control.

Animals↗
PubMed1994

Serum-mediated intracellular calcium changes in normotensive and hypertensive red blood cells: role of parathyroid hypertensive factor.

To study cellular calcium metabolism in hypertension, we investigated the effects of human serum, and of the circulating pressor substance, parathyroid hypertensive factor (PHF), on the cytosolic free calcium (Cai-f) content of erythrocytes from normotensive and essential hypertensive subjects. In their own serum, basal Cai-f was higher in hypertensive than in normotensive and essential hypertensive subjects. In their own serum, basal Cai-f was higher in hypertensive than in normotensive subjects (mean +/- SEM; 39.4 +/- 4.0 vs. 23.4 +/- 2.7 nM; p < 0.05). Without serum, Cai-f was lower and not significantly different (23.0 +/- 3.1 vs. 18.2 +/- 2.7 nM; p = not significant). Addition of serum to serum-free erythrocytes increased Cai-f, and reestablished the Cai-f gradient in hypertensive cells (31.4 +/- 0.8 vs 23.0 +/- 2.3 nM; p < 0.05). PHF levels were directly related to basal Cai-f (r = -0.648; p < 0.05) and to the serum-induced rise in Cai-f (r = 0.600; p < 0.05). Furthermore, semipurified PHF, but not similarly prepared normotensive serum, increased Cai-f in normal human erythrocytes (PHF: +83.9 +/- 37.3% vs. +14.5 +/- 27.5%; p < 0.05). We conclude that circulating factors in general, and PHF in particular, may account for the increased basal Cai-f of hypertension, and thus at least partially contribute to te pathophysiology of the hypertensive process.

Aged↗
PubMed1994

Needle aspiration cytology in the diagnosis of mucinous cystadenocarcinoma of pancreas. A study of five cases with an emphasis on utility and differential diagnosis.

In this study, our experience with five cases of mucinous cystadenocarcinoma of the pancreas is described, which was seen over a 13-yr period. The diagnosis in four of the cases was made from aspirated material that was obtained under computed tomography (CT) guidance and, in one case, following an intraoperative aspirate. In four cases, the tumor was found to be in the head of pancreas, whereas in one case, the neoplasm was located in the tail. All the cases were elderly male patients. As a result of our study, it is believed that aspiration cytodiagnosis of mucinous cystadenocarcinoma (a rare subtype of pancreatic carcinoma) can be made with confidence when performed intraoperatively or with imaging assistance. Also, aspiration cytology is a sensitive, specific, and relatively simple procedure that provides adequate material on which a confident diagnostic interpretation can be made of this uncommon neoplasm.

Adenocarcinoma↗
PubMed1994

Evaluation of the laboratory mouse model for screening topical mosquito repellents.

Eight commercial repellents were tested against Aedes aegypti 0 and 4 h after application in serial dilution to volunteers and laboratory mice. Results were analyzed by multiple regression of percentage of biting (probit scale) on dose (logarithmic scale) and time. Empirical correction terms for conversion of values obtained in tests on mice to values expected in tests on human volunteers were calculated from data obtained on 4 repellents and evaluated with data obtained on 4 others. Corrected values from tests on mice did not differ significantly from values obtained in tests on volunteers. Test materials used in the study were dimethyl phthalate, butopyronoxyl, butoxy polypropylene glycol, MGK Repellent 11, deet, ethyl hexanediol, Citronyl, and dibutyl phthalate.

Aedes↗
PubMed1994

Studies on the inheritance of repellent tolerances in Aedes aegypti.

Two laboratory strains and 6 inbred strains of Aedes aegypti were tested against deet, ethyl hexanediol, dimethyl phthalate, and Indalone. Reciprocal crosses and backcrosses of 2 inbred strains were tested against deet only. Results obtained were compatible with a quantitative genetic model in which the effects of the factors involved were multiplicative. Certain inbred strains differed significantly from cognate laboratory and/or inbred strains in tolerance to one or more test materials. Heritability in the broad sense (H2) was estimated at 0.05 for deet, 0.22 for ethyl hexanediol, 0.48 for dimethyl phthalate, and 0.51 for Indalone. Partial dominance was observed in the inheritance of tolerance to deet.

Aedes↗