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Biomedical subjects

R Biggar

Publications and source records attributed to R Biggar.

9 recordsLinked to original sources

Rapid telomere shortening in children.

Telomere shortening may reflect the total number of divisions experienced by a somatic cell and is associated with replicative senescence. We found that the average rate of telomere shortening in peripheral blood mononuclear cells (PBMCs) obtained longitudinally from nine different infants during the first 3 years of life (270 bp per year) is more than fourfold higher than in adults and does not correlate with telomerase activity. These results show that the rate of telomere loss changes during ontogeny, suggesting the existence of periods of accelerated cell division. Because human immunodeficiency virus (HIV) preferentially infects actively dividing cells, our observation suggesting accelerated cell division in children may provide an explanation for some of the distinctive pathogenic features of the HIV disease in infants, including higher viral loads and more rapid progression to acquired immunodeficiency syndrome (AIDS).

Adult

Intrathecal chemoprophylaxis in the prevention of central nervous system relapse in Burkitt's lymphoma.

A retrospective review of patients treated for endemic Burkitt's lymphoma in Ghana was undertaken to evaluate the efficacy of intrathecal (IT) chemoprophylaxis in preventing central nervous system (CNS) relapse. Patients treated before 1974 received no IT chemoprophylaxis and those treated between 1974 and 1979 received IT methotrexate in addition to systemic chemotherapy. In patients presenting with facial disease only (Stages I-II), there was no significant difference in the frequency of CNS relapse between those receiving IT chemoprophylaxis and those not receiving any. CNS relapse was, however, significantly reduced in patients presenting with abdominal disease (Stage III) who received IT chemoprophylaxis in addition to systemic combination therapy. This was associated with an improved survival.

Abdominal Neoplasms

Human T-cell leukemia virus (HTLV-I) antibodies in Africa.

Antibodies specific for human T-cell leukemia-lymphoma virus type I (HTLV-I) were demonstrated in serum samples from various groups of people in South Africa, Uganda, Ghana, Nigeria, Tunisia, and Egypt. The samples had been collected for other purposes and were presumably selected without bias toward clinical conditions associated with HTLV infections. Regional differences in antibody positivity were observed, indicating widely distributed loci of occurrence of HTLV on the African continent in people of both black and white ancestry. Two patients with high titers of antibody to HTLV-I had some signs of adult T-cell leukemia-lymphoma. In several groups a high frequency of false positive serum reactions was indicated when specific confirmation steps were included in the assay. Further characterization of these sera revealed highly elevated immunoglobulin levels, possibly due to polyclonal activation of immunoglobulin synthesis in these subjects. The possibility that related cross-reactive human retroviruses coexist in the same groups was not eliminated.

Adult

Pulmonary endothelial pavement patterns.

The appearance of the endothelial pavement pattern was studied in the pulmonary trunk, pulmonary veins, aorta, and inferior vena cava of the rat by means of silver staining of the cell borders. The endothelial cell in each of the four blood vessels was found to have its own distinctive shape, fusiform and pointed in the direction of blood flow in the case of the aorta and larger and more rectangular in the pulmonary trunk and pulmonary veins. Detailed quantitation of the dimensions and surface area of the endothelial cells in each blood vessel was carried out by a photographic technique. Pulmonary hypertension was induced in one group of rats by feeding them on Crotalaria spectabilis seeds. The endothelial pavement pattern in their pulmonary trunks became disrupted with many of the cells assuming a fusiform shape reminiscent of aortic endothelium. Many small, new endothelial cells formed in the pulmonary trunk suggesting division of cells to line the enlarging blood vessels. In contrast the endothelial cells of the inferior vena cava merely increased in size to cope with the dilatation of this vein.

Animals

Endothelial cell pavement pattern in the pulmonary trunk in rats in chronic hypoxia.

Right ventricular hypertrophy, and by inference pulmonary arterial hypertension, were induced in female Wistar Albino rats by subjecting them to a barometric pressure of 380 mmHg for four weeks. A control group was kept at normal barometric pressure for a similar period of time. The cell boundaries of the endothelial lining of the aorta, pulmonary trunk and inferior vena cava were stained in situ by a modified silver method of Poole et al. (1958). Photomicrographs of the intimal surfaces of these blood vessels at a standard magnification were used to determine the length, breadth and area of the cells. In the control rats the endothelial cells were found to have a characteristic shape and size in each of the three vessels studied. Those of the aorta were small and elongated in the direction of blood flow with tapering ends. The endothelial cells of the inferior vena cava were rectangular. Those of the pulmonary trunk were polygonal and had tessellated borders. In the test rats with right ventricular hypertrophy induced by chronic hypoxia the endothelial cell pavement pattern of the pulmonary trunk changed to resemble that of the aorta. It is considered that this was an expression of the acquired pulmonary hypertension, the fusiform shape appearing appropriate for an elevated pressure.

Animals

Sequential evaluation of cutaneous delayed hypersensitivity responses to recall and to lymphoid cell line antigens in Burkitt's lymphoma.

Delayed cutaneous hypersensitivity reactions to standard recall antigens (candidin, mumps and PPD), to crude membrane extracts of a cell line derived from Burkitt's lymphoma (Raji) and to cell line derived from normal lymphocytes (F265) were sequentially evaluated in 44 patients with Burkitt's lymphoma. Sixteen patients (36%) manifested delayed hypersensitivity responses to the standard antigens and seven (16%) to the Raji membrane extract at presentation. Following successful chemotherapy, there was prompt and significant improvement of reactivity to both the standard and Raji antigens (p greater than 0.001), suggesting that the initial impairment of delayed hypersensitivity was most likely related to tumor burden. By 9 months after treatment, all patients in sustained remission expressed reactivity to Raji and 21 of 22 to the standard antigens. None of the patients skin-tested with the F265 extract at presentation gave a positive response and only one subsequently expressed reactivity after remission was induced. On relapse, reactivity to the standard antigens was more readily lost (4 of 11) then reactivity to the Raji extract (1 of 7). Pretreatment delayed hypersensitivity to the standard antigens also correlated better with long-term survival than to pretreatment responses to Raji. It remains to be determined whether the antigens expressed in the Raji extract are indeed tumor-specific or related to Epstein-Barr virus.

Adolescent

Respiratory syncytial virus infections within families.

To examine intrafamily spread of respiratory syncytial virus infections and their associated illnesses, 36 families with 188 members were studied during an outbreak of such infections. Nurses visited every three to four days to obtain specimens for viral isolation and interview household members. The virus infected 44.4 per cent of families, and 21.9 per cent of all members. All age groups had appreciable attack rates (with a range of 16.8 per cent in adults to 29.4 per cent in infants). In infected families, 45.9 per cent of members became infected, including 10 of 16 infants. Secondary attack rate for all ages was 27 per cent, and that for infants 45.4 per cent. An infant's older sibling appeared most likely to introduce the virus into the family. Associated acute respiratory illnesses occurred in 94.9 per cent of cases, and appeared more severe than those not associated with respiratory syncytial virus. When the virus was introduced into a family the high attack rate produced an illness of age-related severity.

Adolescent