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Biomedical subjects

D D Adams

Publications and source records attributed to D D Adams.

At least 37 records · Page 2Linked to original sources
PubMed1984

Immunoglobulin heavy chain haplotypes in caucasian New Zealanders.

In the course of studies on the genetic basis of autoimmune disease, immunoglobulin allotypes were measured in New Zealand people of caucasian origin. We report the observed frequencies of the various allotypes of the gamma heavy chains, together with the frequencies of the combinations observed to occur in individuals (phenotypes) and the nature and frequency of the combinations on individual chromosomes (haplotypes), as calculated by application of Kurczynski and Steinberg's computer programme MAXIM.

Female↗
PubMed1984

A solution to the genetic and environmental puzzles of insulin-dependent diabetes mellitus.

Studies of the segregation of heterozygous immunoglobulin allotypes in families with several cases of insulin-dependent diabetes mellitus (IDDM) show that germline heavy-chain V (variable region) genes are not major genetic determinants for IDDM, but data for IDDM and Graves' disease together suggest involvement of kappa light-chain V genes. Absence of IDDM at birth, the semi-random age of onset, and the 50% discordance of identical twins suggest that somatic mutation of germline V genes is involved in the development of the pathogenetic anti-beta-cell clones. The effect of histocompatibility and other alloantigens on the prevalence of IDDM is readily accounted for by the effect of the "holes" they induce, by natural tolerance, in the immune response repertoire; these alterations apparently affect the chance of emergence of anti-beta-cell clones by the somatic mutations and network of interclonal deletions that constantly change the fringes of the repertoire. Histocompatibility antigens can also influence repertoire development by changing the specificity of conjoint presentation of foreign antigens by macrophages. Antigenic stimulation by particular environmental microorganisms is probably essential to the repertoire development necessary for the occurrence of IDDM. Additionally, beta-cell damage by local infection may play a part by facilitating autoantigen presentation to the immune system.

Antigens, Viral↗
PubMed1984

Effects of an anabolic steroid on acute uremia in the dog.

Four groups of dogs made acutely uremic were treated with placebo, 0.5 mg/kg, 1.0 mg/kg, and 1.5 mg/kg of an anabolic steroid (3-oxo-delta 1,4 androstadiene-17 beta-ol-undecylenate). Pretreatment and posttreatment measurements of food intake, body weight, PCV, serum creatinine concentration, plasma albumin concentration, nitrogen balance, lean body mass, and limb circumference did not indicate any beneficial effect of this drug in this model of acute uremia.

Animals↗
PubMed1983

Soluble HLA antigens not detected in human immunoglobulin preparations.

Immunoglobulin concentrates prepared from subjects of known HLA specificity were assayed for the presence of soluble HLA antigens by the inhibition of cytotoxic HLA alloantisera using a microabsorption procedure. The immunoglobulin preparations inhibited alloantisera of all specificities tested, regardless of the HLA type of the immunoglobulin donor, indicating that the observed inhibition was non-specific. Addition of extra complement reduced the inhibitory effects of the immunoglobulin concentrates. It is concluded that the inhibition of HLA alloantisera demonstrated by this technique is due to the anticomplementary activity of the immunoglobulin preparations, rather than their content of specific soluble HLA antigens.

Complement System Proteins↗
PubMed1983

Absence of allotypic variation in the autoantigen for thyroid stimulating autoantibodies.

The question of whether autoimmune reactions result from abnormality of the autoantigen or of the autoantibody is fundamental. When reaction of the thyroid stimulating autoantibodies (TSaab) of Graves' disease with their autoantigen is measured in the mouse bioassay which has a very sensitive dose-response curve this provides a favourable system for detecting any influence of allotypic variation in the autoantigen on the affinity of the corresponding autoantibodies. Seven high potency long acting thyroid stimulator (LATS) sera were tested for degree of neutralization by soluble extracts from nine thyroids, using the mouse bioassay to measure changes in LATS activity. The thyroid extracts differed in neutralizing potency and the LATS sera differed in susceptibility to neutralization, but these variations were consistent enough to enable ranking and there were no significant exceptions from especially strong or weak reactions between any individual thyroid extract and any individual LATS serum. Even autologous reactants had no greater or lesser affinity than homologous ones. Five LATS protector (LATSP) sera, tested against six thyroid extracts, including their own, again showed no evidence of allotypic variation in the autoantigen, nor did 55 LATSP sera tested with one of four thyroid extracts. Altogether we have looked at over 200 individual reactions between soluble thyroid antigen and thyroid stimulating autoantibody (LATS and LATSP). We have not found a single significant instance of any exceptionally strong or weak affinities, even with autologous antigen. The findings are in accord with Burnet's theory that autoimmune reactions are due to the emergence of forbidden clones of lymphocytes, reactive with normal self antigens.

Animals↗
PubMed1982

The genetic basis of autoimmune disease.

The genetic predisposition to autoimmune disease in man is largely specific for each disease, indicating that these diseases are based not on a generalized breakdown of a tolerance mechanism, but on highly specific abnormalities of immune responsiveness which are subject to genetic transmission. In the presence of particular antigens encoded in the major histocompatibility complex (MHC) the relative risk of certain autoimmune diseases is increased, or in some cases decreased, and the increased risk has been widely attributed to linkage disequilibrium with unidentified disease-causing genes. Our studies on the inheritance of spontaneous autoimmune diseases in New Zealand mice have revealed that small numbers of dominant genes, some associated with the MHC but the remainder elsewhere in the genome, determine susceptibility to these diseases. That MHC-linked genes are not of paramount importance casts doubt on the linkage disequilibrium hypothesis. An alternative possibility is that major and minor histocompatibility antigens themselves predispose to the development of autoimmune diseases by altering the immune response repertoire through the effect of their clonal deletions on the network of paratope-idiotope clonal interactions. Such alterations could influence the chances of emergence, by somatic mutation, of pathogenic forbidden clones.

Anemia, Hemolytic↗
PubMed1982

Development of Sarcocystis suicanis Erber, 1977 in the pig.

Twenty-eight weanling pigs inoculated with sporocysts from an isolate of Sarcocystis suicanis from Georgia were examined at intervals ranging from 2 to 90 days postinoculation (DPI). Merogony was first observed histologically within the heart muscle 12 DPI and within 23 of 35 tissues examined 13 DPI. Most infected cells were "floating" in extravascular spaces and were near intact endothelial cells. In some cases, the infected cell clearly was an endothelial cell comprising a portion of the capillary wall. Immature sarcocysts containing metrocytes were observed in striated muscle 27 DPI, and bradyzoites were detected by digestion techniques 52 DPI. Sarcocysts matured between 27 and 80 DPI, after which thickness of the cyst wall and morphology of bradyzoites changed little. Dissolution of sarcocysts was detected as early as 38 DPI and was accompanied by ingress of plasma cells, lymphocytes, and occasionally, eosinophils. Based on information presented herein, feeder pigs reared on pasture may become infected, and infections mature well within the 100-day period usually considered necessary for production of marketable swine.

Animals↗
PubMed1981

Genes determining autoimmune disease in New Zealand mice.

The genetic basis of autoimmune haemolytic anaemia in NZB mice has been investigated using crosses and backcrosses with the NZC strain. These mating combinations reveal two dominant or co-dominant genes governing occurrence of the disorder. One of these, Aia-2, is common to both the NZB and the NZC strains. The other gene, Aia-1, is peculiar to the NZB strain and is linked to the b (black/brown) coat colour locus on chromosome 4. The cross-over value of 37+/-4% places this gene in the neighbourhood of the minor histocompatibility locus H-18, provided it is on the same side of the b locus. Previously, we have obtained evidence that the lupus nephritis of the (NZB X NZW)F(1) mice is determined by three dominant or co-dominant genes, Lpn-1, Lpn-2 and Lpn-3. Lpn-2 appears to be tightly linked to the H-2 complex, Lpn-1 has a cross-over frequency of 33+/-3% with H-2 placing it in the neighbourhood of a hybrid histocompatibility (Hh) locus on chromosome 17, and Lpn-3 is on a separate, unknown chromosome. In this paper we present data from an out-cross study between (NZW X NZC)F(1) and NZB mice, which indicate that Lpn-3 is not linked to Igh-C and is therefore not an immunoglobulin heavy chain V gene. Whilst it remains possible that Lpn-3 is a kappa or lambda light chain V gene and that Aia-2 is a V gene, Lpn-1 and Aia-1 are clearly not H or kappa V genes, nor are they in the major histocompatibility gene complex. Their apparent association with the Hh and H-18 loci suggests that they may be genes coding for minor histocompatibility loci. Such genes could influence immune response repertoire, and hence genetic predisposition to autoimmune disease, through the clonal deletion and paratope-idiotope network reactions which we have postulated to be the mechanisms mediating the effect of the major histocompatibility antigen genes.

Anemia, Hemolytic↗
PubMed1980

H gene theory of inherited autoimmune disease.

Autoimmune disease in inbred mice is probably determined by co-dominant genes associated with both the major and minor histocompatibility loci. It is postulated that the genes involved are histocompatibility-antigen (H) genes themselves, which delete complementary clones in fetal life, in accord with Burnet's theory of clonal selection. Such deletions cause perturbations in the paratope-idiotope network reactions envisaged by Jerne. As well as having negative effects on immune-response capacity, the perturbations have positive effects, because the deletion of clones with specificity for the idiotopes of other clones permists immune responses which would otherwise be absent. Such perturbations can influence the chance of emergence of a forbidden clone by somatic mutations occurring in the V genes of dividing immunocytes and so can provide a genetic predisposition to autoimmune disease.

Animals↗
PubMed1980

Autoantibodies with intrinsic biological activity.

Thyroid-stimulating autoantibodies (TSaab) react with the thyrotrophin receptor of the thyroid cells to cause the hyperthyroidism of Graves' disease. Studies using thyroid receptors from various animal species have demonstrated the existence of a fine variation in the specificity of TSaab from various patients. Such variation provides an explanation for the clinical variety seen in some autoimmune diseases and also for the occurrence of inconstant complications such as exophthalmos, chorea, diabetic retinopathy and diabetic nephropathy, which may be based on cross-tissue reactivity.

Animals↗
PubMed1978

Three genes for lupus nephritis in NZB x NZW mice.

The occurrence of early severe lupus nephritis in (NZB x NZW)F1 mice must depend on the action of at least two dominant or codominant 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, we have studied the incidence of the renal disease in 230 (NZB x NZW) x NZW backcross mice (an earlier study) and, in this study, in 150 (NZB x NZW) x NZB backcross mice. The data indicate that the NZB strain contributes only one gene and the NZW strain contributes two genes, or clusters of closely linked genes, to the renal disorder of the F1 hybrid. One of the NZW genes was found to be linked to the H-2 complex. All three genes must be dominant or codominant, as their effect is expressed in the heterozygous state.

Animals↗
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

Evidence that mouse thyroid stimulator does not stimulate the human thyroid gland.

Thyroid 131I uptake and human thyroid stimulator (HTS) level were measured in 20 untreated thyrotoxic patients who also showed mouse thyroid stimulator (MTS) ACtivity. The correlation between thyroid uptake and HTS level was highly significant (P less than 0-005), the coefficient, r, being 0-66, comparable with the value 0-68 obtained in a previous study of patients not showing MTS. Thus, the presence of widely varying amounts of MTS does not impair the close correlation existing between HTS level and thyroid 131I uptake in thyrotoxic people. There was no correlation between MTS level and thyroid 131I uptake (r = 0-11, n.s.). It is concluded that MTS, a potent stimulator of the thyroid glands of mice, guinea pigs and monkeys, does not stimulate the human thyroid gland.

Animals↗