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Biomedical subjects

M Howard

Publications and source records attributed to M Howard.

At least 217 records · Page 12Linked to original sources
PubMed1981

Long-term culture of normal mouse B lymphocytes.

A procedure is described for the preparation of long-term lines of normal mouse B lymphocytes. Surface immunoglobulin-bearing splenic B lymphocytes were purified with the fluorescence-activated cell sorter and then cultured with lipopolysaccharide for 1-4 wk. The cells were then transferred into medium supplemented with a T-hybridoma-derived supernatant containing interleukin 2 (IL2). Continuous feeding with this supernatant led to the establishment of cell lines that also could be propagated to IL 2-free medium containing interleukin 1 but not in culture medium alone. Cell lines have been propagated in this manner for as long as 10 mo. The cells in these lines have the appearance for small, dense lymphocytes, which all bear surface IgM detectable by immunofluorescence, rosetting, and surface radiolabeling and immunoprecipitation. The cells express Ia and lack Thy 1. These cultured B lymphocytes are unresponsive to lipopolysaccharide but can be activated to become more rapidly dividing, immunoglobulin-secreting cells by exposure to culture supernatants containing both T-cell-replacing factor and IL 2.

Animals↗
PubMed1980

Analgesic nephropathy induced by common proprietary mixtures.

Renal papillary necrosis has been induced in 36.4% to 75% of rats which were gavage-fed with analgesic mixtures containing proprietary combinations of aspirin, paracetamol, phenacetin, phenazone, salicylamide and caffeine. These findings support the recent recommendations of the National Health and Medical Research Council which suggest that the free availability of analgesic mixtures be restricted.

Acetaminophen↗
PubMed1980

Antigen-initiated B-lymphocyte differentiation. XVII. The inhibitory effects of recent antigen prepriming on the subsequent responsiveness of 'pre-progenitor' B cells.

We have analysed the transient unresponsiveness of B cells following specific antigen prepriming. The effect is restricted to adoptive-transfer antibody-forming cell (AFC) progenitors (that is, 'pre-progenitors') and does not occur with the separate subset of cell culture AFC progenitors ('direct progenitors'). The transient unresponsiveness is displayed by both primary and secondary 'pre-progenitor' B cells. Mixing experiments and experiments with athymic mice indicate that the effect is not due to suppressor T cells or other inhibitory cells. Nor is the effect due to an impaired seeding ability of the activated or antigen-binding cells, since after adoptive transfer the preprimed cells can be activated by an appropriate non-specific stimulus. The most likely explanation involves direct interaction of specific antigen with the antigen receptors on 'pre-progenitor' B cells, rendering these cells more prone to temporary or permanent 'tolerance' on further antigen contact or, alternatively, directing their differentiation away from IgM AFC production on day 8 after transfer.

Adoptive Transfer↗
PubMed1979

Some limits to post-antigen generation of diversity: failure to detect variants in clones of hapten-specific antibody-forming cells (AFC) developing in culture from direct AFC-progenitor B cells.

A search was made for variants in clones of hapten-specific antibody-forming cells (AFC) arising by stimulation of mature B cells with either thymus-independent hapten-POL (polymerized bacterial flagellin) conjugates, or the polyclonal activator lipopolysaccharides. Enriched, hapten-binding B cells or unfractionated spleen cells were cultivated for 3-4 days at limiting dilution in the presence of thymus filler cells, and the AFC in each microculture well were then assayed for plaque formation on various hapten-sheep red cell monolayers. No variants were found from (4-hydroxy-3-iodo-5-nitrophenyl) acetyl (NIP) to 2,4-dinitrophenyl specificity, nor from fluorescein (FLU) to NIP specificity. No variants were found in avidity for FLU hapten. All 374 clones examined, including clones of up to 300 AFC, appeared to be homogeneous in antibody specificity and plaque morphology under our conditions. These results differ from published findings using erythrocytes as antigens. Reasons for this discrepancy are discussed, including differences in sensitivity differences in immunological similarity between the test antigens, and in the particular B cell subsets involved.

Animals↗
PubMed1978

A follow-up of the career preferences of Manchester and Sheffield graduates of 1972 and 1973.

Pre-registration house officers who answered enquiries in 1973 and 1974 about career preferences were written to again in 1976. This yielded 205 comparisons, in which 134 (65.5%) doctors retained their original first choice of career, thirty-five (17%) opted for their previous second or third choice and thirty-six (17.5%) gave a completely new choice. The most common reasons for a change in career choice were reappraisal of aptitudes and abilities, altered domestic circumstances, additional knowledge of promotion and career prospects and additional experience of the new choice of career.

Career Choice↗
PubMed1978

Bleeding vascular malformations of the intestine.

Thirty-nine patients with bleeding vascular malformations were evaluated. The age range was from 3 to 78 years, with a bimodal age distribution. The younger patients had no associated diseases, while those in the older category invariably had an associated cardiac lesion (aortic stenosis in 12 patients and severe atherosclerotic disease in 11 patients). With experience, colonoscopy has become a valuable adjunct to arteriography with the lesion visualized in 12 patients. Arteriography is the most useful study being diagnostic in 35 of 38 cases. Exploration alone was diagnostic in only one of 39 patients. The most common site of bleeding was the cecum (21 patients) followed by the proximal small intestine (eight patients), terminal ileum (seven patients), and ascending colon (five patients). The lesions in the proximal small bowel were much more common in the younger patients and were believed to be congenital. Resection controlled the bleeding in the majority of patients, although four recurrences have been noted. All have been documented angiographically to have been from a new lesion and two were controlled with reoperation. The key elements to control of these patient's bleeding include: (1) systematic work-up with a team approach emphasizing careful visceral angiography, and (2) the avoidance of a premature laparotomy prior to complete evaluation.

Adolescent↗
PubMed1977

Antigen-initiated B lymphocyte differentiation. IX. Characterization of memory AFC progenitors by buoyant density and sedimentation velocity separation.

The characteristics of memory B cell antibody-forming cell (AFC) progenitors from long-term hapten-primed CBA mice were investigated by using sedimentation velocity and buoyant density separation to isolate physically distinct B cell sub-sets. The isolated fractions were assayed by the adoptive immune response to NIP-POL antigen, under conditions where neither T cells nor other accessory cells were limiting the IgM or IgG AFC responses. The results were compared to previous studies on the IgM AFC-progenitors of unprimed adult mice. Splenic IgM and IgG memory AFC-progenitor activity was largely found among the typical B cells of slow to medium sedimentation rate, in contrast to the fastre sedimenting IgM AFC-progenitor activity of unprimed animals. Splenic IgM and IgG memory AFC-progenitor activity was found among the medium to light density cells, and so resembled by this parameter the IgM AFC-progenitor activity in unprimed animals. Thoracic duct lymphocytes from hapten-primed mice also exhibited memory IgM and IgG AFC-progenitor activity in the slow-medium sedimentation range. However, in contrast to spleen, the IgM and IgG memory AFC-progenitor activity in lymph was found among very dense B cells. Two physically distinct sub-populations of memory B cells have thus been identified, namely: i) small, medium-light density, presumably tissue-resident B lymphocytes found in spleen; and ii) small, dense, presumably recirculating B lymphocytes found in lymph. Both physical forms include IgM and IgG progenitors. Both forms are distinct from the larger, medium-light density "virgin" AFC-progenitors in the spleen of unprimed adult mice.

Animals↗
PubMed1977

Development of a highly sensitive radioimmunoassay for digoxin and its application in pediatric practice.

The sensitivity of two established routine digoxin radioimmunoassay methods has been increased to enable the provision of a rapid and relatively atraumatic inpatient and outpatient service for neonates and small children, using capillary blood samples obtained by heel-prick. The methods employ 125I- or 3H-labelled digoxin, a rabbit antiserum raised against a digoxin: bovine serum albumin conjugate and only 10 or 25 microliter of plasma as the sample. The results obtained using these highly sensitive assays correlate closely with those found using conventional assays, requiring larger sample volumes. An apparent difference in sensitivity to digoxin has been demonstrated between infants and children more than 1 yr old. Thus infants appear to tolerate plateau phase plasma levels (mean value for non toxic infants 2.6 +/- 1.8 ng/ml) that in older children or adults would be associated with digoxin toxicity.

Binding Sites, Antibody↗
PubMed1975

Antigen-initiated B-lymphocyte differentiation. VII. Quantification of AFC progenitor levels in adoptive and culture responses to NIP-POL antigen.

Quantitative studies on B cells require a direct assay for antibody-forming cell (AFC) progenitor function, in which the number of AFC produced bears a simple, linear arithmetic relationship to the number of progenitors present. This might be expected under conditions where helper T-cell and accessory cell requirements are by-passed, or provided in excess. This possibility has been tested using as antigen the hapten NIP (4-hydroxy-3-iodo-5-nitrophenylacetic acid) on the carrier POL (polymerized bacterial flagellin), in adoptive transfer of normal and nude mouse spleen cells to irradiated recipients, and in cell culture. Primary and secondary IgM responses to this antigen are "T cell-independent'. The secondard IgG response is T cell-dependent but this function can be provided by 'carrier-primed' irradiated recipients. However in no case did the cell dose response curve show a linear, arithmetic relationship between cells transferred or cultured, and AFC produced. If less than 10 X 10(6) cells were adoptively transferred or cultured, a sigmoid curve was obtained, approximately linear with a slope of around 1-6 on a log-log scale. In adoptive transfer, a plateau was then seen above 10 X 10(6) cells, followed by a second sharp rise beginning around 15 X 10(6) cells. Addition of irradiated spleen cells as 'fillers' to maintain cell numbers constant produced a linear (arithmetic scale) dose response curve for the primary IgM responses, both adoptive and in culture. Lipopolysaccharide injection of recipients also produced linear regions in the adoptive transfer system. These techniques provide more direct, quantitative assay systems for the primary IgM responses to this antigen. However, arithmetic linear cell dose response curves were still not obtained for the secondary IgG responses, using irradiated filler cells.

Animals↗