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Biomedical subjects

J Slack

Publications and source records attributed to J Slack.

At least 73 records · Page 4Linked to original sources

Subclass restriction of murine antibodies. III. Antigens that stimulate IgG3 in mice stimulate IgG2c in rats.

The IgG subclass distribution of rat antibodies to 13 different antigens was measured. Antibodies to protein and hapten-protein conjugates were predominantly IgG2a. Antigens labeled thymus-independent type 1, based upon responses in mice, stimulated both IgG2b and IgG2c antibodies, but little IgG2a. Polysaccharide and hapten-polysaccharide antigens (thymus-independent type 2) as well as phosphocholine-keyhole limpet hemocyanin, stimulated predominantly IgG2c antibodies. A division of antigens into essentially the same categories has been made on the basis of subclass restriction in mice. Antigens that stimulate IgG2c in rats stimulate IgG3 in mice. Thus, by comparing subclass preference with a variety of antigens, functional analogues among subclasses in different species can be identified.

Animals

Subclass restriction of murine antibodies. II. The IgG plaque-forming cell response to thymus-independent type 1 and type 2 antigens in normal mice and mice expressing an X-linked immunodeficiency.

Antigens have been classified previously into three categories, thymus-dependent (TD), thymus-independent type (TI) 1, and TI-2, based upon thymic dependence and ability to stimulate an immunodeficient strain of mouse, CBA/N. Here we demonstrate that the different antigen classes elicit IgG antibodies of different subclasses. TD antigens stimulate predominantly IgG1 antibodies, with smaller amounts of IgG2 and IgG3 being expressed. TI-1 antigens stimulate almost no IgG1 antibodies and equal amounts of IgG2 and IgG3. TI-2 antigens elicit predominantly IgG3 antibodies. Mice expressing the CBA/N phenotype are known to be nonresponsive to TI-2 antigens. This was confirmed in this study. In addition, we demonstrate that the IgG3 component of the response to TI-1 antigens is virtually absent in mice expressing the CBA/N phenotype, which supports our previous finding that the CBA/N defect may be restricted to a B-lymphocyte subpopulation containing most of the precursors of IgG3-secreting cells.

Animals

Family study of lipid and purine levels in gout patients and analysis of mortality.

A family study was performed to determine whether the hypertriglyceridaemia associated with gout is present in families of gout patients or simply due to their life-style. The study revealed hypertriglyceridaemia in gout patients, reflected by hyperprebetalipoproteinaemia and with reciprocal reduction in the proportion of beta-lipoprotein. These abnormalities were not seen in first-degree relatives. No definite increase in mortality was found from coronary or cerebrovascular disease in male gout patients after presentation to hospital or in their relatives. Families of hyperlipidaemic gout patients did reveal a slight increase in male coronary deaths although the significance of this finding was doubtful since some hypercholesterolaemia was found in these hyperlipidaemic families.

Cholesterol

Immunoglobulin subclass-specific immunodeficiency in mice with an X-linked B-lymphocyte defect.

CBA/N mice express an X-linked deficiency in their antibody response to many bacterial carbohydrates; we have shown recently that these antigens normally elicit antibody responses predominantly of the IgM and IgG3 isotypes. Here we demonstrate that mice, with the CBA/N phenotype have perferential deficiencies of IgM and IgG3 immunoglobulin expression, both when measured in serum and in cells secreting these isotypes, and that this deficiency is only partially corrected by polyclonal activation of B cells. This suggests that CBA/N mice may lack a subpopulation of B cells that contain most of the IgG3 precursors.

Animals

Is hyperviscosity a treatable component of diabetic microcirculatory disease?

Blood viscosity at low shear-rates was significantly higher in sixty-four patients with longstanding diabetes than in sixty-one matched non-diabetic controls. This increase was most striking in patients with either proliferative retinopathy or nephropathy, although it was present to a lesser extent in diabetic patients with evidence of myocardial or peripheral ischaemia. Erythrocyte deformability was lower in the fourteen diabetic patients with the most extensive microangiopathy than in twenty-two diabetics with slight or no complications or in controls. Hyperviscosity and reduced erythrocyte deformability may well be important and potentially treatable factors in the aetiology or progression of microcirculatory disease is diabetes.

Adult

Family similarities in the age at coronary death in familial hypercholesterolaemia.

In a combined Norwegian and British study of the age at death from coronary heart disease of heterozygotes for familial hypercholesterolaemia (FH) the correlation coefficients within families for 43 sib pairs was 0-70 and for 14 first cousin pairs 0-61. There was no significant correlation between the age at death and serum cholesterol concentration in either series. The intrafamilial correlations suggest that information about the age at death from coronary heart disease in heterozygotes within families may have some prognostic value and may also be interpreted as evidence for genetic heterogeneity in FH.

Adult

Lipid and lipoprotein concentrations in 1604 men and women in working populations in north-west London.

Serum lipid and lipoprotein concentrations in men and women vary with age, and so-called "normal" limits should take account of this. Serum cholesterol, triglyceride, and phospholipid concentrations were measured in 1027 men and 577 women in five working populations in north-west London, and lipoprotein electrophoresis and quantitative analyses of lipoprotein concentrations were also performed. In men the best fit between serum cholesterol, triglycerides, and phospholipids, on the one hand, and age, on the other, was given by a curvilinear relationship expressed as a quadratic regression. In women the best fit was given by a linear regression. White men had higher serum cholesterol and triglyceride concentrations than Black men, and these differences were reflected in the distributions of the lipoproteins. There were no differences between values in White and Black women. Young women on oral contraceptives had lipid concentrations similar to those of older women not on these preparations. These data suggest that the adoption of concentrations of serum cholesterol (275-300 mg/100 ml (7-1-7-8 mmol/l) and triglycerides (175-200 mg/100 ml (2-0--2-3 mmol/l) recommended by a recent report on the prevention of coronary disease as limits above which special attention should be given to the management of hyperlipidaemia could result in as few as 2% of younger men or as many as 31% of older men being selected for treatment.

Adolescent

Diagnosing familial hypercholesterolaemia in childhood by measuring serum cholesterol.

The serum cholesterol concentrations of 134 children aged 1-16 years who had at least one first-degree relative with presumed familial hypercholesterolaemia showed a bimodal distribution, and, using the maximum likelihood technique, two overlapping curves could be fitted. The mean value of the affected children (heterozygotes) was 8-9 mmol/l and that of the unaffected 4-9 mmol/l. The two curves intersected at 6-77 mmol/l, and at this point 5% of the unaffected children had values over 6-77 mmol/l and 3-5% of the heterozygotes had values under 6-77 mmol/l. If this cholesterol concentration is used as a cut-off point 4-25% of cases would be misdiagnosed.

Adolescent

Restriction in the immune response to flagellar proteins in inbred mice.

Anti-idiotypic sera prepared in both AL/N mice and rabbits identify specificities common to the IgA MOPC 467 myeloma protein and day-7 affinity-absorbed antibodies to Salmonella milwaukee polymerized flagellin (S. mil-POL) raised in BALB/c and C57BL/Ka mice. Isoelectric focusing (IEF) of reduced and alkylated BALB/c anti-S. mil-POL gave a banding pattern of L and H-chains identical to MOPC 467. C57BL/Ka anti-S. mil-POL had a similar L-chain pattern but a different H-chain pattern. Both BALB/c and C57BL/Ka contain predominantly IgA. The IEF patterns in the two strains are consistent with a monoclonal response at day 7.

Animals

Influence of heredity and environment in determination of skinfold thickness in children.

Triceps and subscapular skinfold thicknesses were measured in 222 pairs of like-sex twins (78 monozygotic and 144 dizygotic) aged 3-15 years. Log transformations of the measurements were standardized for age and sex and the results used to estimate heritability--that is, the proportion of total variation determined by genetic factors. The overall contribution of non-genetic familial effects was small. There were appreciable differences in heritability between limb and trunk fat and between the sexes and at different ages. Over the age of 10 heritability was high for both sites in boys and girls. In younger children environmental factors contributed more to the variation.

Adolescent

The genetic contribution to coronary heart disease through lipoprotein concentrations.

Many factors both genetic and environmental contribute to the liability to coronary heart disease and one of the genetically determined risk factors is the concentration of lipoproteins in the blood. The evidence so far is that serum cholesterol level is polygenically determined, but that in a minority of the population it is determined by a single mutant gene of large effect. There is evidence that the risk of coronary death for affected individuals is very high and that the condition warrants a maximum effort at identification and treatment. For the remainder of the population whose hyperlipidaemia is polygenically determined, the liability to coronary heart disease might be substantially reduced by simple and appropriate environmental measures aimed at reducing the total liability. The measures if correctly applied should effectively improve the population risks of early coronary death.

Cholesterol