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Biomedical subjects

S Ram

Publications and source records attributed to S Ram.

At least 55 records · Page 3Linked to original sources
PubMed1996

Synthesis of a new class of isothiocyanatopeptide bifunctional chelating agents for coupling to monoclonal antibodies.

The preparation of a new class of isothiocyanatopeptide bifunctional chelating agents, Boc-glycyl-L-(p-NCS)phenylalanylglycylglycine ethyl ester 1, N-(S-acetylmercaptoacetyl)-L-(p-NCS)phenylalanylglycylglycine ethyl ester 2, and N-(S-acetylmercaptoacetyl)glycyl-L-(p-NCS)phenylalanylglycine ethyl ester 3, starting from Boc-L-(p-nitro)phenylalanine 5 is described. The key intermediates, nitropeptides 7, 8 and 12, were prepared by standard DCC coupling and a deprotection procedure. The nitropeptides 7 and 12 on condensation with N-succinimidyl-S-acetylthioacetate provided a good yield of the corresponding S-(acetylmercaptoacetyl)nitropeptides 10 and 13, respectively. Catalytic hydrogenolysis of compounds 8, 10 and 13, followed by thiophosgenyation gave 28-95% yield of target products 1, 2 and 3, respectively. Compounds 1-3 were conjugated to the monoclonal antibody D612 reactive with human colon carcinoma using 12/1 to 60/1 ligand to antibody molar ratios, and the conjugates were labeled with 99mTc. The in vitro cell binding results of these immunoconjugates demonstrate that they retained their antibody binding specificity.

Antibodies, Monoclonal↗
PubMed1996

Microbiological quality & incidence of organisms of public health importance in food & water in Ludhiana.

Bacteriological analysis of 713 samples of various types of foods and related articles and potable water samples from different places in Ludhiana, Punjab was carried out. The highest counts ranging from 2.5 x 10(6)-7.5 x 10(8) organisms/g were observed in raw vegetables and fruits, followed by 3 x 10(6)-9.8 x 10(7)/ml, 8.3 x 10(4)-8.9 x 10(7)/g and 1 x 10(3)-6.7 x 10(7)/g in fruit juice, milk and its products, and salty/non milk snacks respectively. Fresh chapati, dal, rice, cooked vegetables and karhi etc., showed no microbial contamination. However, samples of these articles from road side cafes gave counts up to 1 x 10(7) organism/g. The most probable number of coliforms and Escherichia coli/100 ml of water ranged from < 1 to > 1100. Although 1332 isolates of 16 types of organisms of public health significance were obtained those of proven enteropathogenicity were enterotoxigenic Esch. coli (55), Esch. coli O157 (3), enteropathogenic Esch. coli (1), enterotoxigenic Klebsiella (23), Streptococcus faecalis (152), Bacillus cereus (133), Staphylococcus aureus (125), Aeromonas spp (47), Salmonella spp (10), Shigella spp (4) and Yersinia enterocolitica (2). Poor quality of potable water and widespread occurrence of enteropathogens in food consumed by the common man in Ludhiana was evident.

Food Microbiology↗
PubMed1996

Peritoneal dialysis solution attenuates microvascular leukocyte adhesion induced by nitric oxide synthesis inhibition.

In the mesenteric microcirculation, inhibition of nitric oxide (NO) synthesis results in an inflammatory response through increased leukocyte adherence to the microvascular postcapillary venular endothelium. Recent studies have demonstrated that elevated concentrations of endogenous NO synthesis inhibitors are present in renal failure. How peritoneal dialysis solutions may affect leukocyte-endothelial interactions during inflammation induced by NO synthesis inhibition has been previously unknown. Using in vivo intravital microscopy of the rat mesenteric postcapillary venules, microvascular leukocyte adherence was quantitated during baseline conditions in which the mesentery was superfused with a buffer solution, followed by the superfusion of a NO synthesis inhibitor NG-nitro-L-ARGININE methyl ester (L-NAME) added to the buffer, followed by 4.25% Dianeal (4.25% D). When compared to baseline, L-NAME increased the mean number of adherent leukocytes by fivefold (2.2 +/- 0.9 vs 11.6 +/- 3.6 leukocytes/100 microns venule/10 min, p < 0.05), while 4.25% D quickly reversed the L-NAME-induced inflammatory response, returning the number of adherent leukocytes back to baseline values (11.6 +/- 3.6 vs 2.4 +/- 1.3 leukocytes/100 microns venule/ 10 min, p < 0.05). These results confirm that NO synthesis inhibition induces inflammation in mesenteric postcapillary venules. Superfusion of 4.25% D reverses leukocyte adhesion induced by NO synthesis inhibition. Thus, a standard peritoneal dialysis solution (4.25% D) reverses the leukocyte-adhesive effects of NO synthesis inhibition in the mesenteric microcirculation.

Animals↗
PubMed1996

Bacteriological patterns of chronic suppurative otitis media in Ludhiana.

A series of 300 cases of chronic suppurative otitis media encountered in Dayanand Medical College and Hospital, Ludhiana was surveyed for type specificity to determine latest trends of bacterial prevalence in Ludhiana. Punjab Pseudomonas, staphylococcus and proteus head the list. The problem of resistance is discussed in the present context.

Bacteria↗
PubMed1995

Rapid classification of positive blood cultures: validation and modification of a prediction model.

OBJECTIVE: 1) To validate a previously developed prediction model to aid physicians in differentiating true positive blood cultures from contaminants when the laboratory first calls with a positive result, and 2) to determine whether it could be modified to make it more practical for clinical use without altering predictability. DESIGN: A prospective cohort study of hospitalized patients (validation set) who had blood cultures done over a two-month period. Data collected included the seven independent predictors in the rapid classification of positive blood cultures model. The model was modified by eliminating one of the predictors (which required clinical data) but maintaining the laboratory components (morphologic and Gram stain characteristics, number of bottles positive, and time to positivity). The "blood culture episode" was the unit of evaluation. A blood culture episode was defined as a 48-hour period beginning with the drawing of blood for the culture and included any blood cultures obtained during that time period. Receiver operating characteristic (ROC) curve analysis was used to compare the predictabilities of these models. SETTING: A 550-bed, university-affiliated county hospital that is a regional trauma center and has the only burn treatment unit in the region. PATIENTS: All adult (> or = 16 years old) patients who had blood cultures done during the study period were eligible. Only patients with positive blood cultures were included in the study. INTERVENTIONS: None. MAIN RESULTS: Of 559 blood culture episodes identified, 139 (25%) included the growth of one or more organisms; 62 (45%) of the 139 episodes represented true bacteremia. By ROC curve analysis, there was no significant difference in the mean areas under the curve (AUCs) (+/- SE) of the model in the derivation set (the previously developed model) (0.93 +/- 0.02) compared with the validation set (0.89 +/- 0.03; p = 0.29). In the validation set there was no significant difference in the mean AUCs when the model was modified (0.89 +/- 0.03) by removing the clinical component vs the unmodified model (0.89 +/- 0.03; p = 0.98). CONCLUSIONS: The rapid classification of blood cultures model was validated in a general hospital population. Predictability of the model was not altered significantly by eliminating one component that required clinical data. Because the modified model requires only laboratory information, this may allow reporting of the probability of true bacteremia at the time a positive blood culture is initially reported to physicians. This information may aid physicians in interpreting the positive blood culture.

Adult↗
PubMed1995

Hypertension and other cardiac risk factors among Asian Indians.

The pattern of cardiovascular disease among (Asian) Indians appears to be changing rapidly. Although we do not have large epidemiological studies, clinical observations and mortality data indicate that, in the last three decades, there has been an escalating incidence of hypertension and coronary artery disease in Indians. Clearly, the incidence of hypertension among the urban population is steadily increasing. Whether this is due to heightened awareness and expanding accessibility to health care providers is not known. An alarming number of deaths due to premature coronary disease is being reported. Compared to their Western counterparts, Indians experience the first coronary event at an earlier age. Studies performed in the UK, US, Trinidad, and South Africa have confirmed a high rate of cardiovascular disease among expatriate Indians. Although the precise cause is not known, hypertension and altered lipoprotein metabolism may be playing a participatory role in the genesis of cardiovascular disease.

Cardiovascular Diseases↗
PubMed1995

Peritoneal dialysis solutions reverse the hemodynamic effects of nitric oxide synthesis inhibitors.

Nitric oxide (NO) synthesis is inhibited by a variety of L-arginine analogs including NG-nitro-L-arginine methyl ester (L-NAME) and NG NG-dimethylarginine (ADMA). ADMA is present in elevated concentrations in renal failure and potentially could alter microcirculatory hemodynamics during peritoneal dialysis (PD). This investigation utilized the techniques of intravital microscopy to quantitate the mesenteric arteriolar hemodynamic effects of PD solutions during NO synthesis inhibition. L-NAME (100 microns) produced maximum arteriolar vasoconstriction to 74% of baseline diameter (19.9 +/- 2.2 vs. 26.9 +/- 1.4 microns, P < 0.001, N = 10) and ADMA (100 microns) to 68% (20.5 +/- 2.5 vs. 30.1 +/- 2.0 microns, P < 0.01, N = 6). L-NAME decreased red blood cell velocity to 44% of baseline velocity (3.8 +/- 0.8 vs. 8.5 +/- 1.1 mm/second, P < 0.001) and ADMA to 52% (5.1 +/- 1.1 vs. 9.8 +/- 0.9 mm/second, P < 0.01, N = 6). Despite NO synthesis inhibition, standard PD solutions reversed these hemodynamic effects with both 1.5% and 4.25% Dianeal (Baxter) rapidly reversing the vasoconstriction and restoring blood flow back to baseline values. When Dianeal and L-NAME were simultaneously superfused, no L-NAME induced vasoconstriction occurred and Dianeal maintained vasodilatory properties despite L-NAME (P < 0.01, N = 5). This investigation reaffirms that basal levels of NO are important in maintaining normal hemodynamics in the mesenteric microcirculation. Reversal of the L-NAME induced arteriolar hemodynamic effects by Dianeal suggests that the endogenous NO synthesis inhibitor ADMA has no significant effects in the regulation of the mesenteric microvascular arteriolar hemodynamics during PD. Since these PD solutions remain vasoactive despite NO synthesis inhibition, this suggests that these PD solutions possess vasoactive properties primarily through a NO independent mechanism.

Animals↗
PubMed1995

Validation of a bacteremia prediction model.

OBJECTIVE: To validate a previously published model for predicting bacteremia in hospitalized patients. DESIGN: Application of a published bacteremia prediction model to a prospective validation cohort of patients and comparison of its predictability to that found in the derivation cohort. SETTING: Urban, university-affiliated, 550-bed public hospital. PATIENTS: The validation cohort consisted of 342 patients with 559 blood culture episodes between October 14, 1992, and December 5, 1992. Each blood culture episode was scored based on the presence or absence of seven predictors of bacteremia and the findings compared with published results (derivation cohort). INTERVENTIONS: None. RESULTS: Application of the bacteremia prediction model to the validation cohort identified episodes with a low risk (3%) and a high risk (17%) for true bacteremia, similar to the findings in the derivation cohort (1% and 16%, respectively). Comparison of the predictions of the model in the two cohorts by receiver operator characteristic curve analysis revealed that the overall predictability of the model in the validation cohort was not as good as in the derivation cohort. CONCLUSIONS: Although the bacteremia prediction model did not perform as well overall in the validation cohort, the model still was able to clearly define two extreme groups: those with a low risk and those with a high risk for true bacteremia. This predictive capability may aid physicians in prescribing empiric antimicrobial therapy and also may be useful to hospital epidemiologists in assessing quality of care.

Adolescent↗
PubMed1995

Rapid identification of colonization factor antigens I & II of enterotoxigenic Escherichia coli by coagglutination test.

Specific antisera for colonization factor antigens (CFA/I and CFA/II) were adsorbed to Staphylococcus aureus Cowan I strain, ATCC 12598 to make coagglutination (CoA) reagents for detection of CFAs in enterotoxigenic Esch. coli (ETEC) isolates. Among 1782 strains of Esch. coli isolated from patients with acute diarrhoea, 238 (13.4%) strains exhibited CFA expression. Most prevalent CFA/I positive serogroups were 015, 0148, 0153, 020, 0128, 0114 and 078. CFA/II was detected among isolates of serogroup 080, 085, 06 and 08. Ten ETEC isolates each of serogroups 04, 07, 061, 068, 0117 and 0158 did not show presence of CFA/I or CFA/II. CoA technique proved an appropriate, rapid diagnostic tool which can be used for screening large number of Esch. coli isolates in epidemiological studies.

Agglutination Tests↗
PubMed1994

A peptide-based bifunctional chelating agent for 99mTc- and 186Re-labeling of monoclonal antibodies.

BACKGROUND: The development of new bifunctional chelating agents for the labeling of monoclonal antibodies with radiometals is a desirable goal in the area of radioimmunodetection and radioimmunotherapy of cancer. The authors have developed a new N3S-ligand, N-(S-acetylmercaptoacetyl) (p-NCS)phenylalanylglycylglycine ethyl ester (MAIPGG) for technetium-99m (99mTc) or rhenium-186 (186Re) labeling of monoclonal antibody D612 reactive with human colon cancer. The biodistribution of 99mTc/186Re-MAIPGG-D612 conjugates was studied in nude mice bearing human colon cancer xenografts. METHODS: MAIPGG was synthesized from Boc-p-nitrophenylalanine and was coupled to antibody D612, and the conjugate was labeled with 99mTc using a Glucoscan kit (DuPont, North Billerico, MA) as the reducing system. 186Re-MAIPGG-D612 was prepared by radiolabeling MAIPGG with 186Re, with sodium citrate/SnCl2 used as a reducing system, after which the raiolabeled MAIPGG was coupled to monoclonal antibody D612. The biodistribution of these radioimmunoconjugates in athymic nude mice bearing LS174T human colon cancer xenografts was studied. RESULTS: The cold precursor MAIPGG was prepared easily from Boc-p-nitro phenylalanine with an overall yield of 12-15%, which, when coupled to monoclonal antibody D612, did not affect its binding activity to LS174T cells in vitro. The biodistribution and imaging results demonstrated that these radioimmunoconjugates localized preferentially in tumor. CONCLUSIONS: These preliminary results suggest that MAIPGG may be useful for the radiolabeling of a variety of monoclonal antibodies with 99mTc or 186Re, which then can be used for radioimmunodetection and radioimmunotherapy of cancer.

Animals↗
PubMed1994

Radioiodination of monoclonal antibodies D612 and 17-1A with 3-iodophenylisothiocyanate and their biodistribution in tumor-bearing nude mice.

BACKGROUND: The development of a metabolically stable radioiodination reagent for coupling to monoclonal antibodies is a desirable goal. The radioiodination of monoclonal antibodies D612 and 17-1A reactive with human colon cancer with 3-iodophenylisothiocyanate has been investigated. This new ligand, on coupling with monoclonal antibodies, should form a stable thiourea linkage via a reaction of the isothiocyanate moiety with the epsilon-amino group of lysine. METHODS: The starting material, 125I- or 131I-labeled 3-iodophenylisothiocyanate, was synthesized in good radiochemical yield with a purity of > 99% via a reaction of electrophilic radioiodine with 3-tri-n-butylstannylphenylisothiocyanate. The coupling of radiolabeled 3-iodophenylisothiocyanate with monoclonal antibodies D612 and 17-1A in different buffers was investigated. Biodistribution of these radioimmunoconjugates in athymic nude mice bearing colon cancer xenografts was studied. RESULTS: The results demonstrated that monoclonal antibodies labeled with 3-iodophenylisothiocyanate retained specific binding activity and showed significantly less thyroid uptake than did directly radioiodinated antibodies prepared by the iodogen method. Radioimaging and biodistribution studies demonstrated that uptake of these new radioimmunoconjugates in LS174T colon cancer xenografts was similar to that of directly radioiodinated antibodies, while their uptake in other normal tissues was similar to or lower than that of directly radioiodinated antibodies. CONCLUSIONS: These results demonstrate that high specific activity can be achieved and pure 3-iodophenylisothiocyanate can be derived easily from 3-tri-n-butyl-phenylisothiocyanate. Biodistribution and imaging studies revealed that monoclonal antibodies conjugated with 3-iodophenylisothiocyanate are metabolically more stable in vivo in an animal model than directly radioiodinated antibodies, and that these new radioimmunoconjugates are localized selectively in tumors.

Animals↗
PubMed1994

Immunomodulators in clinical practice.

Immunomodulators have opened new vistas in the management of the immunocompromised patient. They have been shown to enhance the efficacy of vaccines in infections, head and neck malignancy, the immunosuppressed and recently in AIDS. The mechanism of their action is discussed. They hold promise of further advances in immunotherapy.

Adjuvants, Immunologic↗
PubMed1994

Platelet serotonin uptake in duodenal ulcer patients.

Platelet serotonin uptake was measured in 10 duodenal ulcer patients and 10 controls by determining the concentration of radioactivity in platelets after incubation with tritium-labelled serotonin binoxalate. Platelet 5-HT uptake in ulcer patients (312.0 +/- 125.0 CPM/10(7) platelets) was significantly higher than that in the control group (186.0 +/- 53.0 CPM/10(7) platelets; p < 0.01). Since the kinetics of 5-HT uptake by platelets may be a reflector of enhanced serotonergic activity, this finding may have implications in future therapeutic strategies for this disease.

Adult↗