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Biomedical subjects

A Kumar

Publications and source records attributed to A Kumar.

At least 1,315 records · Page 73Linked to original sources
PubMed1992

Design and synthesis of a self-assembling peptide derived from the envelope proteins of HIV type 1. An approach to heterovalent immunogens.

A chimeric peptide that included sequences from gp120 and gp41 of HIV type 1 was synthesized. Cleavage from solid support yielded a composite of self-oligomerized products with molecular masses ranging from 5 to about 9 kDa. The oligomer but not its reduced, monomeric form was recognized by human anti-HIV sera and at least one of the two lysines in the sequence was involved in antibody binding. The oligomeric peptide was immunogenic, yielding a conformation-specific antibody response. Co-oligomerization of a hepatitis B surface Ag-derived peptide and the HIV type 1-derived peptide yielded a bivalent product in which conformational integrity of the individual components was maintained. Immunization with this hybrid peptide resulted in conformation-specific antibodies to both epitopes in all four murine strains tested. Lymphocyte proliferation assays revealed that the T epitopes resident in both peptide sequences remained active in the hybrid peptide. These results demonstrate the potential of this approach in generating multi- and heterovalent immunogens which may eventually find application as vaccines.

Amino Acid Sequence↗
PubMed1992

"Universal" T helper cell determinants enhance immunogenicity of a Plasmodium falciparum merozoite surface antigen peptide.

Synthetic peptide constructs containing a limited number of epitopes are being currently investigated as subunit vaccines against a variety of pathogens. However, because of widespread nonresponsiveness to most such constructs, possibly attributable to MHC restriction, the choice of appropriate carrier molecules to enhance immunogenicity of peptides constitutes an important and essential aspect of designing synthetic immunogens for human use. Widely used vaccines such as tetanus toxoid (TT) have not been uniformly effective as carrier proteins because of the phenomenon of epitope-specific suppression in which induction of an immune response against a synthetic peptide conjugated to TT is prevented by preexisting immunity to TT. Recently, T cell determinants that can be recognized in the context of several class II MHC molecules have been identified in tetanus toxin as well as in the circumsporozoite protein of a human malarial parasite, Plasmodium falciparum. Such determinants can be potentially used to circumvent the problem of epitope-specific suppression. In the present study we evaluated two such T cell determinants, viz., tt830-844 from tetanus toxin and CST3 from the malarial parasite, for their ability to help induce a boostable antibody response and to overcome genetic nonresponsiveness to a synthetic 20-residue construct containing a B cell and an overlapping T cell epitope from a major merozoite surface protein of P. falciparum. Our data provide support for the view that widely recognized T cell determinants may be used as universal carrier molecules for general vaccination.

Adolescent↗
PubMed1992

Low-molecular weight B cell growth factor (BCGF-12KD) as an autocrine growth factor in B cell chronic lymphocytic leukemia.

The role of cytokines in the growth and spreading of human hematologic malignancies has been underlined in recent years. Here we report evidence that a human 12-kDa B cell growth factor (BCGF-12KD) may function as a growth stimulatory factor in B cell chronic lymphocytic leukemia (B-CLL). First, recombinant BCGF-12KD induced dose-dependent DNA synthesis in neoplastic B cells of four B-CLL patients tested. Second, seven different B-CLL clones secreted a BCGF-12KD-like product that accounted for their proliferation. A neutralizing monoclonal antibody (mAb; Ac8) directed against a BCGF-12KD synthetic peptide inhibited the spontaneous growth of the leukemic B cells. The same mAb blocked DNA synthesis in normal tonsillar B lymphocytes induced by the culture supernatant of spontaneously proliferating B-CLL cells. Finally, BCGF-12KD mRNA was expressed in freshly isolated (two of three patients) as well as in vitro proliferating B-CLL cells (three of three patients). These findings strongly suggest that BCGF-12KD can modulate the growth of B-CLL cells in vivo as well as in vitro. They may offer significant insights into the biology of this frequent B lymphoproliferative disorder.

Adult↗
PubMed1992

Hypersymmetry in a transcriptional terminator of Escherichia coli confers increased efficiency as well as bidirectionality.

Rho-independent transcriptional terminators in Escherichia coli usually consist of a GC-rich region encoding a sequence which allows the nascent transcript to form a stem-loop structure, and thereby apparently causes the RNA polymerase to pause; followed by an A-rich region on the DNA template strand, whose weak pairing to the consequently U-rich 3'-tail of the transcript is believed to aid release of the RNA. Quite commonly there is additional symmetry encoding, in the RNA, an A-rich sequence complementary to the 'tail', just upstream of the GC-rich motif. It has been pointed out by others that this should allow the termination of transcription in both directions. We hypothesized that it might also increase the efficiency of termination, for example by competing with the template DNA strand so as to help 'unzip' the 3'-end of the RNA from its complementary DNA. We have tested this hypothesis by deletion analysis of the hypersymmetric alpha-operon terminator, tL17. The results show that efficiency as well as bidirectionality is indeed adversely affected by deletion of the upstream A-rich sequence.

Base Sequence↗
PubMed1992

Infection with hepatitis A, B, delta, and human immunodeficiency viruses in children receiving cycled cancer chemotherapy.

Serological markers of hepatitis A, B, and Delta and human immunodeficiency viruses were studied in 25 children receiving cancer chemotherapy. Eighty-eight percent had pre-existing HAV immunity which was unaltered by chemotherapy. HDV infection was observed in 8% while HIV was conspicuous by its absence. Active HBV infection, observed in 76% of the children, was asymptomatic in the majority and was accompanied by a high incidence of HBe antigenaemia (57.9%) and its persistence. Pre-existing anti-HBs failed to prevent HBV infection recurrence, which was, however, transient and self-limiting. Multiple blood transfusions and repeated parenteral exposures appeared to be the possible sources of HBV acquisition. Transmission to close contacts was also observed. The study suggests that although HBV vaccine might not be protective against HBV infection in patients receiving cancer chemotherapy, it may prevent its persistence and thereby help in reducing chronic liver disease-related morbidity and a highly infectious reservoir. Strict HBV screening of blood donors, exclusive use of disposable equipment, and vaccination of close contacts of cancer patients is recommended, particularly in HBV endemic third-world countries.

Antineoplastic Agents↗
PubMed1992

Primary oesophageal carcinoma in teens.

Seven teenaged patients with primary oesophageal carcinoma, treated at our hospital in the last 6 years are presented and their management discussed. Five patients had localised disease. Three of them underwent total oesophagectomy, one was given radical radiotherapy, and one was lost to follow-up. Two patients had metastatic disease at presentation. The primary oesophageal carcinoma in this age group may not be so rare as reported in the literature and must be considered in the differential diagnosis of dysphagia. Like their older counterparts, the outcome depends on the stage of the disease and is not influenced by age per se.

Adenocarcinoma↗
PubMed1992

Expression and sequence analysis of cDNAs induced during the early stages of tuberisation in different organs of the potato plant (Solanum tuberosum L.).

cDNA clones of two genes (TUB8 and TUB13) which show a 25-30-fold increase in transcript in the stolon tip during the early stages of tuberisation, have been isolated by differential screening. These genes are also expressed in leaves, stems and roots and the expression pattern in these organs changes on tuberisation. Southern analysis shows homologous sequences in the non-tuberising wild type potato species Solanum brevidens and in Lycopersicon esculentum (tomato). Sequence analysis reveals a high degree of similarity between the TUB13 cDNA, and a human S-adenosylmethionine decarboxylase gene. The predicted TUB8 peptide sequence shows several repeats of alanine, glutamate and proline which suggests a structural role for the encoded protein.

Adenosylmethionine Decarboxylase↗
PubMed1992

Extreme heterogeneity of Ty1-copia group retrotransposons in plants.

We have used the polymerase chain reaction to analyse Ty1-copia group retrotransposons of flowering plants. All eight species studied contain reverse transcriptase fragments from Ty1-copia group retrotransposons. Sequence analysis of 31 subcloned fragments from potato reveals that each is different from the others, with predicted amino acid diversities between individual fragments varying between 5% and 75%. Such sequence heterogeneity within a single species contrasts strongly with the limited diversity seen in such retrotransposons in yeast and Drosophila. The fragments from the other seven plant species examined are also heterogeneous, both within and between species, showing that this is a general property of this transposon group in plants. Phylogenetic analysis of all these sequences reveals that many of them fall into subgroups which span species boundaries, such that the closest homologue of one sequence is often from a different species. We suggest that both vertical transmission of Ty1-copia group retrotransposons within plant lineages and horizontal transmission between different species have played roles in the evolution of Ty1-copia group retrotransposons in flowering plants.

Amino Acid Sequence↗
PubMed1992

Survival in patients with systemic lupus erythematosus in India.

Survival in patients with systemic lupus erythematosus (SLE) in developed countries has improved considerably over the last 2 decades. In India, however, survival in patients with SLE reported 5 years ago from this tertiary referral centre was very poor. The present study was conducted to examine trends, if any, towards improvement in the survival of patients with SLE attending the same centre during the period 1981-1990. No statistically significant change in survival was noted. It appears that improvement in the survival of SLE patients would require an overall improvement in the standard of medical care in India.

Adult↗
PubMed1992

Spinal anaesthesia with lidocaine 2% for caesarean section.

Spinal anaesthesia with 2, 2.5 or 3 ml of glucose-free lidocaine 2% was studied in 50 patients undergoing Caesarean section. Onset time, cephalad spread of analgesia, quality of analgesia, muscle relaxation, the cardiovascular effects and duration of analgesia and motor block were assessed. Reliable anaesthesia was provided with 2.5 and 3 ml while 2 ml of 2% lidocaine was insufficient. Onset time varied between 5.5 to 6 min and maximum cephalad spread was achieved in 10-15 min. The mean maximum extent of sensory analgesia was higher after 2.5 ml (T4.1) and 3 ml (T3.6) than after 2 ml (T7) (P < 0.001). Complete motor block was achieved in all the patients. The mean duration of sensory block was 123 +/- 6.23 min (2 ml) to 126 +/- 7.53 min (2.5 and 3 ml). The mean duration of motor block in 2.5 and 3 ml groups was higher (P < 0.001) than in the 2 ml group and was correlated with the dose of lidocaine (P < 0.05). Hypotension (SBP < 100 mmHg) was noted in 10% (n = 5) of patients in whom the cephalad spread of analgesia was also higher. All the neonates had an apgar score of 7 or more at 1 min. These results suggest that 2.5 to 3 ml of 2% lidocaine provides satisfactory anaesthesia for Caesarean section.

Adult↗
PubMed1992

Arterial blood nicotine concentration and coronary vasoconstrictive effect of low-nicotine cigarette smoking.

Low-nicotine cigarettes have been advertised to the public as less harmful to the cardiovascular system. We studied the effects of smoking two low-nicotine cigarettes on arterial and venous blood nicotine levels, hemodynamics, and coronary vascular tone in 12 patients referred for diagnostic coronary arteriography. All were chronic smokers as evidenced by their elevated baseline arterial and venous cotinine blood levels (139 +/- 30 ng/ml and 155 +/- 34 ng/ml, respectively). High-resolution coronary angiograms were evaluated "blindly" before and after smoking. An electronic caliper was used to measure the diameter of disease-free coronary segments of the left anterior descending and circumflex arteries. Arterial nicotine levels rose from 5 +/- 1 ng/ml at baseline to 37 +/- 7 ng/ml (p less than 0.01) after the first cigarette was smoked and to 45 +/- 8 ng/ml (p less than 0.01) after the second cigarette. Venous nicotine levels rose from 8 +/- 2 ng at baseline to 15 +/- 3 ng/ml (p less than 0.05) after the first cigarette and to 20 +/- 3 ng/ml (p less than 0.01) after the second cigarette. After the first cigarette heart rate increased 8 +/- 2 beats/min (p less than 0.003) and double product 1229 +/- 400 beats/min x mm Hg (p less than 0.02). Compared to baseline values, after the second cigarette heart rate increased 9 +/- 1 beats/min (p less than 0.001) and double product 1767 +/- 486 beats/min x mm Hg (p less than 0.01). Systolic, diastolic, and mean blood pressure did not change significantly after either the first or second cigarette.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Catheterization↗
PubMed1992

Prevalence and predictors of rhabdomyolysis in patients with hypophosphatemia.

PURPOSE: We undertook this study to determine the prevalence and predictors of rhabdomyolysis in the hypophosphatemic state. PATIENTS AND METHODS: To identify patients with hypophosphatemia, we reviewed medical admissions for the period of January through December 1989. The hypophosphatemic state was considered whenever the serum phosphate was less than or equal to 2.0 mg/dL. Rhabdomyolysis secondary to hypophosphatemia was defined when serum creatine kinase levels were greater than or equal to 224 IU/L; it occurred within 72 hours of the hypophosphatemic episode; and it subsequently normalized. Patients who had any other independent etiology for rhabdomyolysis were excluded. Clinical and biochemical characteristics of patients with rhabdomyolysis (Group I) and patients without rhabdomyolysis (Group II) were compared. Variables that predicted rhabdomyolysis in hypophosphatemia were identified by stepwise logistic regression using a backward elimination procedure. RESULTS: One hundred twenty-nine patients were found to have hypophosphatemia. Forty-six (Group I) of 129 patients (36%) showed biochemical evidence of rhabdomyolysis. There was no difference in serum phosphate and potassium concentrations between Group I and Group II patients. Patients in Group I showed higher values for serum osmolality (p less than 0.05), serum glutamic oxaloacetic transaminase (p less than 0.001), chloride (p less than 0.01), and blood urea nitrogen (less than 0.05) when compared with Group II patients. When biochemical profiles of patients with rhabdomyolysis were evaluated on the day of their peak creatine kinase level, only 16 patients were hypophosphatemic, and the majority of patients showed a transient increase in serum phosphate levels because of ongoing muscle cell injury. Of 17 potential predictors, six variables emerged including sodium, chloride, glucose, blood urea nitrogen, uric acid, and osmolality. These variables provided high sensitivity (0.88) as well as moderate specificity (0.79) for predicting the occurrence of rhabdomyolysis in hypophosphatemia. CONCLUSION: We conclude that rhabdomyolysis commonly occurs in the hypophosphatemic state and that at times severe hypophosphatemia as an etiology may be masked because of ongoing rhabdomyolysis. Serum sodium, chloride, glucose, blood urea nitrogen, uric acid, and osmolality have a predictive role for the occurrence of rhabdomyolysis in the hypophosphatemic state that shows a high specificity and a moderate sensitivity.

Adult↗
PubMed1992

Resolution of dihydroxyeicosanoates and of dihydroxyeicosatrienoates by chiral phase chromatography.

A chromatographic method is described for the direct enantiomeric characterization of 5,6-, 8,9-, 11,12-, and 14,15-vic-dihydroxyeicosatrienoic acids (DHETs), metabolites of the cytochrome P-450 arachidonate epoxygenase pathway, and of their corresponding saturated vic-dihydroxyeicosanoic acids. Following esterification, the individual methyl or pentafluorobenzyl esters are resolved by chiral-phase chromatography utilizing a Chiralcel OC or OD column. This methodology will find analytical and preparative applications since it is simple and efficient and preserves, intact, the diol functionality.

8,11,14-Eicosatrienoic Acid↗
PubMed1992

The effect of cimetidine on lymphocyte subpopulations in vivo in experimental mice.

The effects of cimetidine, an H2 receptor antagonist, on subpopulation of splenic lymphocytes were studied in mice. Cimetidine (50 mg/kg) was given to groups of mice by intraperitoneal injection. The splenic mononuclear cells from treated and control animals were evaluated for relative number of lymphocyte subpopulations (i.e. LYT1, LYT2, L3T4 and GAM cells) by flow cytometry. The percentages of LYT2 cells (suppressor equivalent) were significantly lower (5.5 vs 12.0%) in mice who were treated with cimetidine vs control animals. The percentages of L3T4 (helper equivalent) were not statistically different in any of the experimental groups.

Animals↗
PubMed1992

Influenza B virus infection associated with non-bacterial septic shock-like illness.

We report the details of four children aged between 6 months and 5.5 years who had underlying chronic disease and who developed life-threatening illness in association with influenza virus B infection. Influenza has received relatively little attention, yet its morbidity and mortality in children can be considerable. This report emphasises the need to vaccinate the population groups at high risk, such as children with cardiovascular disorders, chronic bronchopulmonary, metabolic and renal disease and chronic neurological disorders.

Child, Preschool↗
PubMed1992

Comparison of immune responses to a native viral antigen and a synthetic peptide derived from it: implications for vaccine development.

Murine immune responses to the hepatitis B surface antigen (HBsAg) and a synthetic peptide derived from it were compared at the humoral level. Six of nine strains used responded to either peptide or HBsAg, though restriction profiles were not superimposable. Two of three strains non-responsive to HBsAg produced an antibody response on immunization with peptide which was cross-reactive with both peptide and HBsAg. In in vitro lymphocyte stimulation assays, lymphocyte from all six peptide-immunized mouse strains could be induced to proliferate on challenge with HBsAg. However, of the HBsAg-immunized groups, lymphocytes from only three of six responder strains proliferated on in vitro HBsAg challenge. Cumulatively, these results suggest that a vaccine formulation that includes both protein antigens and synthetic peptides derived from these proteins may be more effective at eliciting an immune response in a broader cross-section of target population.

Animals↗