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Biomedical subjects

D W Clapp

Publications and source records attributed to D W Clapp.

43 records · Page 3Linked to original sources
PubMed1986

Pasteurella multocida meningitis in infancy. An avoidable infection.

Pasteurella multocida is a common commensal in the upper respiratory tracts of cats and dogs. Infection with P multocida in humans usually follows infected bite wounds; however, infection in humans unrelated to animal bites is rare. We describe two infants with P multocida meningitis in whom infection was probably related to nontraumatic facial licking by household pet dogs. Both patients recovered fully. Although the risk is low, parents should be informed that mucous membrane exposure to household pets may expose an infant to the risk of systemic P multocida infection.

Ampicillin↗
PubMedDate not supplied

Targeted immunoglobulin therapy for the prevention of neonatal infections.

Premature infants demonstrate hypoglobulinemia and are at increased risk for serious infections. Although a cause-and-effect relation between low serum IgG levels and neonatal infections has not been established, prophylaxis of such severe infections may be possible by replacement of antibody with intravenous immunoglobulin (IVIG). For success, IVIG must provide specific antibodies to neonatal pathogens and reach therapeutic serum IgG target levels. Pilot investigations have demonstrated that IVIG reduces the incidence of bacterial sepsis among premature infants. Infants received IVIG every 2 weeks (or more frequently) until they weighed 2,000 g. Serum IgG levels were monitored after each dose so that the dose could be adjusted to achieve a target IgG level greater than 700 mg/dL. The observation that infection among placebo-treated patients occurred when the serum IgG level declined to less than 400 mg/dL suggests the importance of achieving a target level. In our preliminary analysis, the IVIG used did not reduce the incidence of infection with respiratory syncytial virus (RSV) and rotavirus or of necrotizing enterocolitis. That the lot of IVIG used did not contain significant antibody to RSV or rotavirus emphasizes the importance of pathogen-specific antibody. Because of the preliminary nature of these results and the potential for undetermined short-term and long-term sequelae, we do not recommend the indiscriminant use of IVIG for prevention or treatment of neonatal infections.

Humans↗
PubMedDate not supplied

CD34 stem/progenitor cells purified from cryopreserved normal cord blood can be transduced with high efficiency by a retroviral vector and expanded ex vivo with stable integration and expression of Fanconi anemia complementation C gene.

A future possibility for treatment of genetic diseases may be gene therapy using autologous cord blood (CB) stem/progenitor cells. This might require cryopreservation of CB stem/progenitor cells prior to purification, gene transduction, and ex vivo expansion of cells. To address this possibility, nonadherent low density T-lymphocyte depleted (NALT-) cells from fresh or cryopreserved cord blood were sorted for CD34 phenotype, transduced with a recombinant retroviral vector encoding Fanconi anemia complementation C (FACC) gene, and cells expanded ex vivo in suspension culture for 7 days with growth factors. The results demonstrate: 1) high recovery of viable cells after thawing; 2) high efficiency purification of CD34 cells from NALT- cells prior to and after cryopreservation; 3) high degree of expansion of nucleated cells and immature progenitors from CD34 cells before and after cryopreservation; 4) efficient transduction with stable integration and expression of newly introduced genes in cryopreserved and then sorted stem/progenitor cells, as detected prior to and after ex vivo expansion; and 5) high efficiency transduction of single isolated CD34 cells obtained from cryopreserved NALT- CB. This information should be of value for future studies evaluating the use of cryopreserved cord blood for gene transfer/gene therapy.

Antigens, CD34↗
PubMedDate not supplied

Correction of Fanconi anemia type C phenotypic abnormalities using a clinically suitable retroviral vector infection protocol.

Fanconi anemia (FA) is a complex autosomal recessive disease with hematologic manifestations characterized by a progressive hypoplastic anemia, hypersensitivity to clastogenic agents, and an increased incidence of acute myelogenous leukemia. The cDNA that corrects one of four FA complementation subtypes, named Fanconi anemia Type C (FAC) has recently been identified. We constructed a a simplified recombinant retrovirus (vMFGFAC) encoding only the FAC cDNA, and tested its ability to correct the FAC defect in a lymphocytic cell line and primary mobilized blood progenitor cells. In addition, the gene transfer efficiency using a clinically applicable gene transfer protocol into normal primitive hematopoietic progenitor cells, high proliferating potential colony forming cells (HPP-CFC), derived from CD34+ purified cord blood cells was examined. The gene transfer efficiency was significantly enhanced when cells were transduced with supernatant while adherent to a 30/35 KD fragment of fibronectin, FN30/35, and was similar to efficiency obtained by coculture with retrovirus packaging cells. Transduction of an FAC deficient lymphoid cell line with vMFGFAC supernatant resulted in an enhanced cell viability, and G-CSF mobilized peripheral blood cells from an FAC-deficient patient transduced with the vMFGFAC virus demonstrated enhanced progenitor cell colony formation. These data indicate that the vMFGFAC virus allows functional complementation of FAC in lymphoblasts and primary hematopoietic progenitors, and that primitive cord blood hematopoietic stem/progenitor cells can be transduced at an efficiency comparable to protocols using cocultivation if adherent to FN 30/35 fragment.

Base Sequence↗