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Biomedical subjects

S C Knight

Publications and source records attributed to S C Knight.

At least 145 records · Page 8Linked to original sources

Role of veiled cells in lymphocyte activation.

Peripheral blood lymphocytes from normal rabbits or from rabbits hyperimmunized with human immunoglobulin were cultured in 20-microliters hanging droplets. The cultures were stimulated with concanavalin A or, in the case of cells from sensitized animals, with human immunoglobulin. The addition to the cultures of small numbers of autologous or allogeneic veiled cells separated from afferent lymph increased the responses to low doses of the stimulants, particularly when the cells were cultured at low cell densities or for short periods of time. At high cell densities or at longer periods of culture, stimulation occurred in the absence of added veiled cells and was associated with clumping of the lymphoid cells and development of cells which morphologically resembled veiled cells found in afferent lymph. The enhanced responses upon addition of small numbers of veiled cells were also correlated with the formation of lymphoid aggregates which were frequently held together by the elongated processes of a single veiled cell. The observations support the view that the veiled cells are lymph-borne precursors of dendritic cells in the lymph nodes. This may provide an in vitro model for the cellular relationships which occur in paracortical cords of lymph nodes following antigenic stimulation.

Animals↗

The effect of veiled cells on lymphocyte function.

The response of lymphocytes to stimulation with Con A has been studied in the presence of veiled cells collected from the afferent lymph. In these enriched cultures the response occurred earlier with smaller numbers of lymphocytes and at lower concentrations of Con A. Veiled cells also caused clumping of lymphocytes in unstimulated cultures. In stimulated cultures small cells with veil-like projections appeared after 48 hr, but were not seen in unstimulated cultures.

Animals↗

HLA antigens in East African Black patients with Burkitt's lymphoma or nasopharyngeal carcinoma and in controls: a pilot study.

A pilot study is reported of HLA-A, B, and C antigens in 141 East African Blacks comprising patients with Burkitt's lymphoma or nasopharyngeal carcinoma, either with active disease or in long-term remission, together with comparable controls. This study forms part of a wider program investigating host factors in these diseases. A protocol was selected for optimal testing of cells processed and cryopreserved between 1972 and 1976, largely under field conditions, which employed a two-color fluorochromasia typing procedure. Antigen distribution and computed haplotype frequencies in the total unrelated population are given. New findings include an approximately equal frequency of Aw23 and Aw24, a high (18%) incidence of Bw21, and the gametic associations of Aw36 with Bw44, and Aw30 with Bw45. Of the major group of B15-related antigens reported earlier. SV is the most common, and there are strong linkages of SV with Cw2 and Bu with Cw3. The possible presence of further variants at the A- and B-loci is reported. The proportion of B-locus antigen "blanks" in this study is 5.9%. Relationships have been sought between the HLA antigens and diseases studied: the antigen A29, possibly in linkage with Bw42, shows a correlation with disease susceptibility, and associations are suggested between Bw44 (in possible combination with Aw36) and resistance to both BL and NPC, and between Bw45 and long-term remission in NPC.

Adolescent↗

Cell number requirements for lymphocyte stimulation in vitro: changes during the course of multiple sclerosis and the effects of immunosuppression.

Peripheral blood lymphocytes from 20 patients with clinically definite, relapsing and remitting multiple sclerosis (MS) were studied during their participation in a double-blind trial of immunosuppressive treatment. Proliferative responses occurring with different numbers of cells in culture and on different days of culture in the presence of phytohaemagglutinin (PHA) or with allogeneic cells from lymphoid cell lines (MLC) were assessed. Cells taken from patients before treatment showed similar responses to cells from laboratory personnel. However, when cells were taken from patients in relapse or from untreated patients as the disease progressed, there was an alteration in the pattern of response; higher number of cells were required in culture to produce responses. A change in the responsiveness to PHA or in MLC may therefore accompany the progression of the disease in MS (reflecting clinical relapses and possibly subclinical activity of the disease), perhaps resulting from a simple reduction in the proportion of cells able to respond. After intense immunosuppression followed by long-term maintenance on azathioprine, cells from patients gave similar responses to those found before treatment. Thus long-term immunosuppression prevented the progressive alteration in lymphocyte function. Shifts in the total cell number and time in culture required to allow proliferation with mitogens of cells from untreated MS patients could explain both the 'low' of PHA responses reported and the changes of in vitro 'suppressor' function of these cells.

Adult↗

Double-blind, controlled trial of immunosuppression in treatment of multiple sclerosis.

30 multiple sclerosis patients in a double-blind, controlled trial were given immunosuppressive treatment consisting of antilymphocyte globulin, prednisolone, and azathioprine, or placebo. After 15 months of treatment the immunosuppressed group had a reduction in the number of relapses and some retardation of the clinical course of the disease (p < 0.06). The beneficial effect was seen only in females.

Antilymphocyte Serum↗

Conditions for measuring DNA synthesis in PHA stimulated human lymphocytes in 20 microliters hanging drops with various cell concentrations and periods of culture.

We have studied conditions for measuring the uptake of [3H]thymidine ([3H]Tdr) by human lymphocytes in inverted microcultures, varying cell concentrations and periods in culture. Analysis of variance of the log values for [3H]Tdr uptake may be used to separate effects of variables and their interactions. A pulse time of 2 h, a total thymidine concentration of about 1 microgram/ml and a specific activity of [3H]Tdr of 2 Ci/mmole were optimal. Variables such as cell concentration, period of culture, type of serum and dose of PHA were shown to interact, suggesting that these variables should be examined together especially when comparing different samples of lymphocytes. Conditions for doing this simply in small volumes are now available for culturing, thymidine pulsing, harvesting and analysis of data.

Cell Division↗

B15 heterogeneity in East African Blacks.

One-hundred-forty-one Blacks (135 unrelated) from Kenya and Tanzania have been tissue-typed (HLA-A, B and C loci) as part of a study of host factors involved in Burkitt's lymphoma and naso-pharyngeal carcinoma. Evidence is presented for the existence in this population of several B15-related antigens which together occur with a relatively high frequency of 30% in unrelated individuals. It is likely that these variants may include the antigens SV and perhaps Bu recently defined with population frequencies of under 1% in Caucasians. In the absence of monospecific typing sera, identification of these variants may be helped by their apparently strong association with C-locus antigens in Blacks. Recognition of these B15 variants has been largely responsible for reducing the proportion of unidentified or "blank" B-locus antigens in this population to only 6%. These findings substantiate and amplify previous reports suspecting the presence of such antigens in Blacks, and should facilitate studies of possible associations of disease with HLA in these populations.

Africa, Eastern↗

Help and suppression by lymphoid cells as a function of cellular concentration.

The phytohemagglutinin-stimulated uptake of [3H]thymidine in mixtures of human lymphocytes from the same source was shown to depend on the cell concentration in vitro as well as on the period of cultivation. "Helper" and "suppressor" effects were obtained by varying the concentration of cells and the periods of cultivation. The possibility that helper and suppressor subpopulations were responsible was avoided by mixing lymphoid cell line cells with others of the same monoclonal origin. Even under these conditions, both the direction and the extent of activity depended on the same two variables. This weakens the case for postulating the existence of distinct subpopulations of lymphocytes with helper or suppressor properties. This case was based on the use of damaging treatments believed to separate cell populations which were then found to differ in their helper and suppressor properties. We propose instead that the effect of such treatments is mediated through changes in the concentrations of interacting cells. Our data make it clear that the function of lymphoid cells ascertained in one set of conditions need not apply within a different cellular environment.

Cell Count↗

Lone aortic regurgitation, sacroiliitis, and HLA B27. Case history and frequency of association.

An account of aortic regurgitation complicating ankylosing spondylitis is given. Twenty patients with lone aortic regurgitation and without overt spondylitis were examined clinically and radiologically and tissue typed. No evidence of sacroiliitis could be found in any patient. HLA B27 was absent from this group, and no significant disturbance in antigen frequency was noted.

Adolescent↗