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Biomedical subjects

J G Knight

Publications and source records attributed to J G Knight.

24 records · Page 2Linked to original sources
PubMed1977

The genetic contribution of the NZB mouse to the renal disease of the NZB x NZW hybrid.

The occurrence of lupus nephritis in (NZB x NZW)F1 mice appears to depend on the action of at least two dominant or co-dominant genes (at least one gene from each parent) as neither of the inbred parental strains shows the disorder. Identifying affected animals by antemortem determinations of renal function, using improved methods of measuring proteinuria and renal clearance, we have studied the incidence of the renal disease in 230 (NZB x NZW)F1 x NZW backcross mice. The incidence was 49-6% which indicates that NZB strain contributes only one gene, or cluster of closely linked genes, to the renal disorder of the F1 hybrid. The gene(s) must be dominant or co-dominant, as it expresses its effect in the heterozygous state. Study of the H-2 status of the backcross mice showed a loose linkage of the NZB renal disease gene(s) to the D end of the H-2 complex, the crossover frequency being 32-6+/-3-1%.

Aging↗
PubMed1976

Histocompatibility antigens in Graves' disease.

Histocompatibility antigen typing was undertaken in 100 Caucasian patients with Graves' disease (autoimmune thyrotoxicosis) and in 100 healthy Caucasian blood donors. Standard lymphocyte microcytotoxicity methods were used to tests for the presence of 22 HL-A antigens in all subjects. There was a significant difference between the groups in respect of the HL-A 8 antigen which was present in 40 patients and in 25 controls (P less than 0-0023). There was no significant difference between the patients and controls with respect to the frequency of occurrence of any of the other HL-A antigens tested.

Adult↗
PubMedDate not supplied

On the nature of the genes influencing the prevalence of Graves' disease.

Burnet's theory that Graves' and other autoimmune diseases are caused by forbidden clones of immunocytes, reactive against host antigens and emerging in post-natal life due to somatic events (somatic mutations of V genes and inter-clonal deletions), remains the most comprehensive and likely concept of the pathogenesis. The MHC antigens, B8 and D/DR3, have a predisposing influence of X 2.5 and X 3.7 respectively, whilst male sex has a protective influence, divided by 6. Family studies testing for associated inheritance of Graves' disease and immunoglobulin allotypes (Gm and Km), by observation of the segregation of known heterozygous allotypes and also by Penrose's sibling pair method, have failed to show involvement of immunoglobulin genes. The H gene theory, prompted by studies on the inheritance of autoimmune diseases in the New Zealand mice, postulates that germline genes influencing the prevalence of Graves' and other autoimmune diseases code for major and minor histocompatibility or other alloantigens. By deleting complementary clones, alloantigens alter the immune response repertoire of each individual and this could alter the chance of emergence of a forbidden clone by the somatic mutations and the inter-clonal deletions envisaged by Burnet and Jerne. The H gene theory is superior to the linkage disequilibrium theory in that it accounts for all the known genetic features of Graves' disease, including the female sex preponderance, which is ascribed to the effect of clonal deletions imposed by the H-Y antigen.

Animals↗
PubMedDate not supplied

Estimating compliance with diuretic therapy: urinary hydrochlorothiazide-creatinine ratios in normal subjects.

We gave 21 healthy young men 100 mg of hydrochlorothiazide daily to determine whether or not urinary detection of the drug was feasible as a measure of compliance on a standard antihypertensive regimen. All subjects took the drug daily for 6 days, after which they were divided into four groups with differing patterns of medication administration. Urine hydrochlorothiazide and creatinine measurements were obtained to validate the urinary hydrochlorothiazide-creatinine ratio (UHCR) as an accurate quantitative index of compliance. The subjects achieved a constant level of UHCR of 13 +/- 3.0 within 48 hours of hydrochlorothiazide administration. The UHCR levels decreased to 5.0 +/- 0.8 48 hours after discontinuation of the drug (p less than 0.001). UHCR values in the range of 13 +/- 6 indicate that the subject has ingested hydrochlorothiazide 24 hours previously. The UHCR is a potentially useful means of assessing compliance in hypertensive patients taking hydrochlorothiazide.

Adult↗
PubMedDate not supplied

An informative case of Graves' disease with implications for schizophrenia.

The aetiology of schizophrenia and the other psychoses is not yet established. The Knight model, based on genetic and other evidence, proposes that schizophrenia is an autoimmune disease, caused by the development of forbidden clones of B lymphocytes that secrete autoantibodies that accidentally stimulate cell surface receptors on certain neurons, affecting the limbic system of the brain. An unusual defect in a Maori man with Graves' disease rendered him unresponsive to the usually effective antithyroid drugs, prompting his being treated with prednisone, a non-specific immunosuppressant agent. This was highly successful, reducing the blood level of the causative thyroid-stimulating autoantibodies with reduction of thyroid hormone levels and thyroid gland size. Unfortunately, high dosage prednisone can be used for only a month, because of steroid toxicity. A research pathway to effective therapy of receptor-mediated autoimmune diseases, which probably include the psychoses, is now apparent. It involves finding the autoantibodies, then cloning of their antigenic targets, as has been done for Graves' disease. This will provide knowledge of the peptide sequences necessary for constructing therapeutic agents for selectively destroying the pathogenic forbidden clones. Meanwhile, usage of short-term therapy with prednisone could be helpful in the management of schizophrenia and should be explored.

Antithyroid Agents↗