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Biomedical subjects

S Reddy

Publications and source records attributed to S Reddy.

318 records · Page 18Linked to original sources
PubMed1969

Glucose-6-phosphate dehydrogenase deficient red cells: resistance to infection by malarial parasites.

Erythrocyte mosaicism occurs in females heterozygous for glucose-6-phosphate dehydrogenase deficiency. In blood from female children with acute Plasmodium falciparum malaria the parasite rate was 2 to 80 times higher in normal than in deficient erythrocytes. This may be the mechanism whereby the gene for glucose-6-phosphate dehydrogenase deficiency confers selective advantage against malaria to heterozygous females, and thus may have attained the polymorphic frequency occurring in populations living in areas with endemic malaria.

Child, Preschool↗
PubMedDate not supplied

Large-scale manufacturing of safe and efficient retrovirus packaging lines for use in immunotherapy protocols.

BACKGROUND: The use of gene modified T lymphocytes for immunotherapy in a cancer or AIDS clinical trial requires an efficient, safe ex vivo method for modification of these cells at manufacturing scale. Since retroviruses have been shown to be a moderately effective means of stably integrating therapeutic genes into T lymphocytes, we wanted to create packaging and producer cell lines that would produce replication competent retrovirus (RCR)-free supernatants, at large scale (> 200 l), and transduce with high efficiency. METHODS: cDNA expression plasmids containing only coding sequences for gagpol or env were built and sequentially transfected into human 293 cells. Packaging and producer clones were characterized for stability, titer and RCR. A producer clone delivering chimeric immune receptors was scaled-up and supernatants used to transduce patient T lymphocytes for clinical studies. PCR and RT-PCR assays were utilized to evaluate the transmission of HERV-H sequences. Relative infectivity of producer clones pseudotyped with different envelopes was determined by transduction and RT assays. RESULTS: RCR-free, human 293 split-genome packaging lines, pseudotyped with amphotropic, xenotropic, or 10A1 envelopes, were created. A CC49 zeta producer clone was scaled-up to 5 x 54 l lots and supernatants used to safely and efficiently transduce patient T lymphocytes with minimal ex vivo manipulation. While 293 cells express HERV-H mRNA, the transmission frequency in our packaging clones was less than 1 HERV-H sequence per 5 x 10(5) proviral integrations. Additionally, 10A1 and xenotropic packaging lines had higher infectivities than the amphotropic clone. CONCLUSION: These packaging lines represent the safest configuration for the large-scale production of retroviral vectors, and are capable of producing high titer, RCR-free retroviral vector for large scale clinical use. While all three clones efficiently transduce human T lymphocytes, the 10A1 clone has the highest infectivity. These packaging cell lines will be valuable for use in human gene therapy protocols.

Animals↗
PubMedDate not supplied

Effects of abrupt and gradual osmotic stress on antibody production and content in hybridoma cells that differ in production kinetics.

AB2-143.2 cells exhibit non-growth-associated antibody production (constant specific antibody production rate (qAb) throughout batch culture), while IND1 cells exhibit growth-associated production (decrease in qAb during stationary phase). AB2-143.2 cells increase qAb following abrupt batch osmotic stress. Enhanced antibody production in IND1 cells after batch osmotic shock is evidenced as maintenance of the higher exponential phase qAb into the stationary phase. AB2-143.2 cells also increase qAb in response to gradual osmotic stress in continuous culture. In contrast, IND1 cells decrease qAb during gradual osmotic stress. Although the two cell lines differ in antibody production, they have very similar intracellular antibody content profiles. Both show (1) constant antibody content during the exponential phase in control culture with a decrease as cells enter stationary phase; (2) maintenance of exponential-phase antibody content into the stationary phase after batch osmotic shock; and (3) no change in antibody content in response to gradual osmotic stress.

Animals↗
PubMedDate not supplied

Magnetic flow sorting using a model system of human lymphocytes and a colloidal magnetic label.

Cells of identical physical properties that differ in the expression of surface proteins can be sorted conveniently using immunospecific stains conjugated to fluorescent, or magnetic, labels. Immunomagnetic cell sorting using commercial batch sorters offers advantages of high sorting capacity, high viability of sorted fractions, and high depletion rates; its disadvantages are low enrichment rate and batch processing. The authors developed and tested a continuous, flow-through magnetic cell sorter for small volume, experimental cell enrichment. Freshly isolated human peripheral lymphocytes were labeled using an immunofluoromagnetic sandwich consisting of mouse anti human CD8 monoclonal antibody-fluorescein conjugate and rat anti mouse polyclonal antibody-colloidal iron-dextran conjugate. A total of 2-3 min lymphocytes were sorted per hour using a saturation magnetic field of 1.334 T and a five channel sorter. The fluorescent cells were distributed among the channels in relation to their fluorescence intensity and magnetic susceptibility. The purity (68-85%) and enrichment rates (16-34x) were comparable to those of commercial batch magnetic separators; sorting capacity and recovery of the enriched fractions (up to 32%) were limited by the small scale of the sorter. Future direction is focused on increasing the resolution, recovery, and sorting capacity of the enriched fractions, and testing the sorter on other cell systems.

Animals↗
PubMedDate not supplied

Gorlin syndrome. A case report.

Gorlin's syndrome is a genetic disorder of autosomal dominant inheritance with high penetrance and variable expression. It embraces a constellation of many organs principally affects the skin, skeleton, and endocrine and nervous system. A rare case is reported to illustrate the features of Gorlin's syndrome without the features of basal cell carcinoma and to emphasize the need for early recognition and careful follow up by the dentist prevent severe sequelae.

Adult↗
PubMedDate not supplied

Studies of immunoglobulin M and malarial antibodies in Nigerians.

Measurements of immunoglobulin M, in 111 healthy adult Nigerians have been presented. IgM values ranged between 10 and 518 mg per 100 ml with a mean of 213.2 mg per 100 ml. Using the indirect immunofluorescent antibody test, 53.7 per cent of the 111 symptomless subjects in the study had demonstrable malarial antibodies of titres greater than 10,000. The implications of the observations in a holoendemic malarial zone are briefly discussed.

Adolescent↗
PubMedDate not supplied

The health effects of ionizing radiation: a survey of local health officials in New England and New York.

The purpose of the study is to determine the educational needs of public health officials concerning their knowledge, attitude, beliefs, and practices with specific reference to ionizing radiation. The public health directors or designates, working in health departments whose jurisdictions fall within a 60-mile radius of the 14 operating nuclear power plants in the New York-New England region, were studied. A review of the literature indicates that historically there appears to have been a limited effort to conduct such a needs assessment in the United States. A questionnaire was developed to measure the public health directors' knowledge, attitudes, and practice. The instrument was mailed in the summer of 1992 to all public officials listed in the National Directory of Local Health Departments. Knowledge, attitude, and practice questions were analyzed in terms of frequency of correct, incorrect, and don't know responses. The data presented convey the message that there should be public input into the risk assessment of nuclear plants and that local health departments should inform the public about the health risks posed by nuclear plants in their locality. The authors recommend that an appropriate Federal agency sponsor a national survey and that States should establish a training program on the health effects of ionizing radiation for local public health officials.

Government Agencies↗