Sodium-ion movement across intestinal mucosa in cholera patients.
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Biomedical subjects
Publications and source records attributed to R A Phillips.
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A cell transfer assay system was developed to study the precursors of bone marrow-associated (B) lymphocytes in the adult mouse. The rationale of the assay is to inject into irradiated mice a cell suspension depleted of B lymphocytes, to wait a period of time to let precursor cells differentiate to B lymphocytes, then to correlate the number of B cells present in the recipient mice with the number of precursor cells injected. The assay as described was shown to be linear in the range of 10(5)-3 x 10(6) fractionated bone marrow cells. Kinetic studies indicated that precursor cells start producing detectable numbers of B cells within 3 days after transplantation; B cell activity then increases with a doubling time of 24 hr. Physical characterization of that precursor cell has shown that it is lighter and sediments faster than small lymphocytes. Precursor cells were found in bone marrow and spleen but could not be detected in peripheral lymph nodes. Results of physical analysis also indicate that the precursors of B lymphocytes described here may not be pluripotent stem cells for the immune system.
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Experiments have been done to establish whether the radiation-resistant or A cell has a specific function in the initiation of an immune response in mice to sheep erythrocytes (SRBC). All previous demonstrations using accessory (A) cells have involved in vitro assays and are possibly explainable as tissue culture artifacts. If A cells are essential, it should be possible to demonstrate their requirement in vivo. Therefore we first established such conditions. Two methods were found for creating an A-cell deficiency in vivo: (a) A cells disappear gradually from the spleens of irradiated mice, presumably by migration since A-cell function was shown not to be decreased by irradiation. If 3 days elapse between irradiation and transplantation of mixtures of bone marrow and thymus cells (which provide B and T but few A cells), the usual synergistic response does not occur. Addition of large numbers of freshly irradiated spleen cells to the mixture of bone marrow and thymus completely restores the immune response. (b) Injection of 10(10) horse erythrocytes into mice suppresses A-cell activity in these mice 24 hr later; a much reduced response to SRBC is obtained when they are given at this time. The response can be partially restored if irradiated spleen cells are given with the SRBC. This observation formed the basis for a quantitative in vivo assay for A cells in which the magnitude of restoration by various suspensions of irradiated cells was used to estimate the A-cell activity of that suspension. A quantitative in vitro assay for A cells was also developed. It was essential for this assay that the total cell number, B-cell number, and T-cell number be kept constant and that only the number of A cells be allowed to vary. Only under these conditions was the response a linear function of the number of A cells added. If the in vivo and in vitro assays are detecting the same class of radiation-resistant cells, the physical properties of the cells active in each assay should be identical. Spleen cells were separated on the basis of both density and sedimentation velocity. Fractions from both separation methods were tested for their content of A cells using both the in vivo and in vitro assays. The density and sedimentation profiles of A cells were similar in both assays. The demonstration that a radiation-resistant cell is required in vivo and that this cell has properties identical to the radiation-resistant cell required in vitro indicates that this cell (the A cell) is directly involved in the initiation of an immune response to erythrocyte antigens.
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This study reports the use of bacteriophage prepared in the USSR in the treatment of cholera. Patients with acute cholera were rehydrated with a standard intravenous solution and were then given a bacteriophage preparation in addition to maintenance intravenous therapy. The titre of the phage preparations was between 10(8) and 10(9) pfu/ml. Bacteriophage was given by mouth (25 ml for adults and 20 ml for children) for 3 days; in addition, some patients were also given an intramuscular injection (20 ml) of phage on the first day in hospital. For comparison, other groups of patients were given a standard tetracycline regimen or a placebo preparation. Daily vibrio and phage counts were made on stool samples from all patients and the vibrio strains isolated from each patient were tested for sensitivity to the phage preparation.The criteria used to evaluate the various therapies were duration of diarrhoea, volume of stool, and duration of vibrio excretion.The results of the study demonstrate that, in the doses used, the therapeutic effect of bacteriophage, if any, was markedly inferior to that of tetracycline and that in the current state of our knowledge bacteriophage, as used in this study, has no place in the treatment of cholera.
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