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Biomedical subjects

A Malik

Publications and source records attributed to A Malik.

At least 109 records · Page 6Linked to original sources
PubMed1994

Salmonella typhi vaccine strain CVD 908 expressing the circumsporozoite protein of Plasmodium falciparum: strain construction and safety and immunogenicity in humans.

rcsp, encoding amino acids 21-398 of Plasmodium falciparum circumsporozoite protein (CSP), under control of tacP was integrated into the chromosomal delta aroC locus of attenuated delta aroC, delta aroD Salmonella typhi CVD 908. By immunoblot and ELISA, rCSP expression was greater from a multicopy plasmid than from the single chromosomal gene. CVD 908 omega (delta aroC1019::tacP-rcsp) was well tolerated by 10 volunteers who were fed two doses of 5 x 10(7) organisms 8 days apart. Seven subjects excreted the vaccine strain for 1-3 days. All subjects developed serologic responses to O and H antigens of the live vector, whereas 3 vaccinees responded to the foreign antigen: 1 developed an 80-fold rise in serum anti-sporozoite antibody, another had a 4-fold rise in antibody to a recombinant portion of CSP (residues 309-345), while a third vaccinee developed CSP-specific CD8+ cytotoxic T lymphocyte activity. This is the first report of attenuated S. typhi eliciting a human serologic or a cytotoxic T lymphocyte response to a foreign protein. Improved foreign gene expression should enhance immunogenicity.

Administration, Oral↗
PubMed1994

[The immunological indices of diabetic patients following the transplantation of a pancreatic islet cell culture].

Some indices of cell-mediated and humoral immunity were studied in 35 patients with insulin-dependent diabetes mellitus before and 7, 14 days, 3, 6, and 12 months after transplantation of pancreatic islet cell culture obtained from newborn pigs into m. rectus abdominis. It was established that the transplantation does not affect number of T- and B-lymphocytes, T-helpers, T-suppressors and level of antibodies to insulin. Clinical effect depended on the base level of transplantation immunity. Favourable results, such as liquidation of hypoglycaemia and reduction of exogenic insulin at the background of improved general condition may be expected in cases with high of heterophilic haemagglutinins low cytotoxicity index and increased number of sensibilized leukocytes.

Adolescent↗
PubMed1993

Solute adsorption on polymer-coated fused-silica capillary electrophoresis columns using selected protein and peptide standards.

Three series of basic proteins and peptides were selected for use in studying the adsorption behavior of fused-silica capillary electrophoresis columns. A comparative study of untreated and treated fused-silica columns was done. The polymers used as coating materials ranged from very hydrophobic to very hydrophilic. The average efficiency of weakly hydrophilic Ucon-coated capillaries for basic proteins was over 1 million theoretical plates at a buffer pH of 4.8. For this coating, it was found that the maximum column efficiency was obtained at a film thickness of approximately 100 nm. It was easily seen that both ionic and hydrophobic interaction forces can play important roles in protein adsorption onto the capillary walls. Furthermore, strongly hydrophilic polymer coatings may possibly lead to hydrogen-bonding interactions, which decrease column efficiency. Studies have been conducted using two series of polypeptides with varying chain lengths. One series was used to study the effect of polypeptide chain length on retention behavior. Efficient separations of bioactive peptide drugs on Ucon-coated columns were achieved. The results indicate that high efficiency and resolution of basic peptides tested can be realized on columns modified with weakly hydrophilic polymers at a pH value of about 5.

Adsorption↗
PubMed1993

Rapid diagnosis of typhoid fever by co-agglutination in an Indian hospital.

Detection of Salmonella typhi infection by a co-agglutination assay for specific O, H and Vi antigens and by blood culture were compared for 110 patients with suspected typhoid fever. Blood cultures were positive for S. typhi in 25.5% of patients. Co-agglutination tests with patients' serum and with blood culture supernates gave positive results in 70.9% and 67.3% of cases respectively. S. typhi antigens Hd and O9 were detected in patients' serum by co-agglutination in 96.4% of blood culture-positive, and 62.2% of blood culture-negative patients. Co-agglutination results were uniformly negative with serum samples from a control group of 50 healthy individuals, 20 patients with febrile non-typhoid infectious disease and 20 patients with non-infectious febrile disease. Of the 25 patients with suspected typhoid fever who had not received prior antibiotic treatment, 88% yielded positive blood cultures and 96% gave positive results in serum co-agglutination tests. By contrast, of the 85 patients who had received prior antibiotics, only 7% yielded positive blood cultures, but 63.5% gave positive results in serum co-agglutination tests. Co-agglutination tests with serum offer a simple, rapid, sensitive, specific and economical method for the early diagnosis of typhoid fever.

Agglutination Tests↗
PubMed1993

Induction of cytotoxic T lymphocytes against the Plasmodium falciparum circumsporozoite protein by immunization with soluble recombinant protein without adjuvant.

Immunization of mice with irradiated malaria sporozoites induces protection that is dependent on CD8+ T cells, and adoptive transfer of CD8+ cytotoxic T lymphocyte (CTL) clones against rodent malaria circumsporozoite (CS) protein and sporozoite surface protein 2 completely protects against sporozoite challenge. Thus, there are now efforts to develop vaccines that induce CTL against the CS protein and sporozoite surface protein 2. Until recently, it was thought that induction of CTL required production of target proteins within cells, breakdown of the proteins to peptides in the cytoplasm, and transport of the peptides to the cell surface in combination with class I major histocompatibility complex molecules. It has now been shown that immunization with peptides in Freund's complete adjuvant and with soluble protein in liposomes can induce CTL. To determine whether we could induce CTL against the Plasmodium falciparum CS protein by immunization with soluble protein, B10.BR mice were immunized intravenously, intraperitoneally, or intramuscularly with a recombinant P. falciparum CS protein called RLF mixed with the adjuvant DETOX (monophosphoryl lipid A, cell wall skeleton of Mycobacteria phlei, and squalane). Two weeks after the last dose, spleen cells from mice immunized intravenously, but not intraperitoneally or intramuscularly, had peptide-specific, major histocompatibility complex-restricted, CD8+ T-cell-dependent cytolytic activity against peptide 368-390 from the 7G8 P. falciparum CS protein. To determine whether the adjuvant was required for induction of the cytolytic activity, mice were immunized with RLF without adjuvant, and similar cytolytic activity was demonstrated. The finding that we could induce CTL by administration of soluble protein without adjuvant markedly broadens the possibilities for vaccinologists working to develop methods of inducing CTL in humans.

Adjuvants, Immunologic↗
PubMed1993

Early childhood mortality--a rural study.

The present study was conducted in 9 villages of Rural Health Training Centre, Jawan, Aligarh, India, having 1792 registered families. The infant mortality rate was 79.3 per 1000 live births. Higher mortality in children between 1-2 years (29.6/1000) in comparison to 2-5 years (16.2/1000) reflected the higher vulnerability of children below 2 years. Diarrhoea (21.2%) and neonatal factors (21.2%) were the major cause of infant mortality followed by pneumonia (18.2%) and tetanus (15.1%). Diarrhoea (32.2%), pneumonia (22.6%) and malnutrition (12.9%) were the major killers in children between 1-5 years. Mortality in females was higher than males in infancy. Risk factors associated with infant mortality included extremes of maternal age (< 20+ > 35 years) primipara or multipara and illiterate mothers.

Cause of Death↗
PubMed1992

Characterization of Plasmodium falciparum sporozoite surface protein 2.

Immunization of mice with Plasmodium yoelii sporozoite surface protein 2 (PySSP2) and circumsporozoite protein protects completely against P. yoelii. The amino acid sequence of PySSP2 suggested that the thrombospondin-related anonymous protein (TRAP) [Robson, K. J. H., Hall, J. R. S., Jennings, M. W., Harris, T. J. R., Marsh, K., Newbold, C. I., Tate, V. E. & Weatherall, D. J. (1988) Nature (London) 335, 79-82] is the Plasmodium falciparum homolog of PySSP2. We report data confirming that TRAP is P. falciparum SSP2 (PfSSP2). Murine antibodies against recombinant PfSSP2 identify a 90-kDa protein in extracts of P. falciparum sporozoites, recognize sporozoites and infected hepatocytes by immunofluorescence, localize PfSSP2 to the sporozoite micronemes by immunoelectron microscopy and to the surface membrane by live immunofluorescence, and inhibit sporozoite invasion and development in hepatocytes in vitro. Human volunteers immunized with irradiated sporozoites and protected against malaria develop antibody and proliferative T-cell responses to PfSSP2, suggesting that, like PySSP2, PfSSP2 is a target of protective immunity, and supporting inclusion of PfSSP2 in a multicomponent malaria vaccine.

Amino Acid Sequence↗
PubMed1992

Naturally acquired CD8+ cytotoxic T lymphocytes against the Plasmodium falciparum circumsporozoite protein.

In rodent malaria model systems, protective immunity induced by immunization with irradiated sporozoites is eliminated by in vivo depletion of CD8+ T cells, and adoptive transfer of CTL clones against the circumsporozoite protein protects against malaria. We recently demonstrated that volunteers immunized with irradiated Plasmodium falciparum sporozoites produce CTL against peptide 368-390 of the P. falciparum circumsporozoite protein. To determine whether natural exposure to malaria induced similar CTL, we studied 11 adult, male, life-long residents of a highly malarious area of Kenya, who were selected because their lymphocytes had been shown to proliferate after stimulation with peptides 361-380, 371-390, or 368-390 and because nine had been resistant to malaria in previous studies. In four of the 11 individuals there was peptide-specific, genetically restricted, CTL activity. In all four individuals, this activity was unaffected by depletion of CD4+ T cells. In three volunteers the activity was eliminated or reduced by depletion of CD8+ T cells; in the fourth volunteer the CD8+ T cell depletion was uninterpretable. This first demonstration of CD8+ T cell, genetically restricted, Ag-specific CTL against a malaria protein among individuals exposed to endemic malaria provides a foundation for studying the relationship between circulating CTL and resistance to malaria infection.

Amino Acid Sequence↗
PubMed1992

A discordance between the human muscle NCAM sequence and those seen in other NCAM cDNA clones.

A cDNA clone, designated NC7, has been isolated from human foetal kidney that partially codes for the 140 kDa isoform of human NCAM. This clone contains a 6 bp insert that is not present in the human muscle cDNA clone lambda 4.4. This same sequence has also been found in both a cDNA clone obtained from a human Small Cell Lung Carcinoma (SCLC) line and in human genomic DNA. Furthermore, an equivalent sequence to the 6 bp region identified in the above samples is present in mouse, rat and chicken NCAM. The 6 bp insertion does not lie at a predicted intron/exon boundary as extrapolated by homology studies with the chicken and, therefore, the mechanism by which the sequence is deleted from the human muscle clone lambda 4.4 remains unclear.

Amino Acid Sequence↗
PubMed1992

Parathyroid hormone-related peptide: expression in fetal and neonatal development.

Hypercalcaemia frequently complicates the clinical management of cancer. Many factors have been implicated in the pathogenesis of this humoral hypercalcaemia of malignancy, the most recent candidate being parathyroid hormone-related peptide (PTHrP). Until now, this peptide has been detected only in some normal and transformed adult tissues. In recent years, it has become apparent that tumours are capable of expressing and secreting factors previously elaborated only during fetal life. Many of these factors act to stimulate the growth of both tumour and fetal cells in an autocrine manner. The data presented here demonstrate that PTHrP is expressed in the human and rat fetus throughout gestation. Immunocytochemistry reveals a gestationally related, changing pattern of expression which is paralleled by changes in mRNA transcription. These data support the hypothesis that PTHrP may function as a fetal growth factor.

Aging↗
PubMed1992

Operative risks and long-term results of operation for left ventricular aneurysm.

A review of 336 consecutive patients who underwent repair of left ventricular aneurysm from 1978 to 1989 disclosed that partial resection of the aneurysm and conventional closure of the ventriculotomy was performed in 281 patients, inverted T closure in 17, and endocardial patch in 38. These two latter techniques were developed in an attempt to restore normal left ventricular geometry. The operative mortality was 6.8% (23 patients). A stepwise logistic regression analysis of various preopeative clinical, hemodynamic, and angiographic variables revealed that left ventricular ejection fraction of 0.20 or less, age greater than 60 years, previous myocardial revascularization, lack of angina, and New York Heart Association functional class IV were independent predictors of operative mortality. The technique of repair was not a predictor of outcome, but when patients with poor left ventricular function were analyzed separately, the operative mortality was reduced from 12.5% to 6.5% when newer techniques were employed. Patients were followed up during a mean of 6.3 years. There have been 51 late deaths, 45 cardiac. Cox regression analysis indicated that poor left ventricular function and left main coronary artery stenosis were the only two predictors of late mortality. The actuarial survival at 10 years was 63% +/- 4%. Most patients (88%) are in New York Heart Association class I or II. These data indicate excellent long-term results after repair of left ventricular aneurysm. Newer techniques of repair are valuable in patients with poor left ventricular function.

Actuarial Analysis↗
PubMed1992

Asymptomatic Salmonella senftenberg carriage in a neonatal ward.

During a 23-day period in April 1991, nine infants in a neonatal ward were found to be colonized with Salmonella senftenberg. All were asymptomatic on detection and all except one (who developed septic ileus) remained asymptomatic on follow-up. The affected babies were isolated and subsequently discharged from the ward as soon as possible. These measures, along with emphasis on handwashing and intensification of cleaning and disinfection, were able to prevent spread to other babies. Despite extensive sampling of the environment, mothers and staff, the source of the organism could not be identified.

Carrier State↗
PubMed1992

Skin testing with recombinant Mycobacterium intracellulare antigens.

The immunoreactivity of four recombinant Mycobacterium intracellulare beta-galactosidase fusion proteins, which correspond to 22, 40, 43 and 85 kDa M. intracellulare antigens, was assessed. Lymphoproliferative assays demonstrated that Escherichia coli lysates containing each of the fusion proteins stimulated T cells in vitro. Purified preparations of three of these recombinant M. intracellulare antigens (22, 43 and 85 kDa) also induced delayed-type hypersensitivity (DTH) reactions in sensitized guinea pigs. However, the skin test responses evoked by each of these antigens was not species-specific. Given these results, the potential utility as skin test reagents of the purified antigens or peptides derived from these proteins is discussed.

Animals↗