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Biomedical subjects

D Doniach

Publications and source records attributed to D Doniach.

At least 55 records · Page 3Linked to original sources
PubMed1980

Complement-fixing islet-cell antibodies in type-I diabetes: possible monitors of active beta-cell damage.

Evidence is presented for the existence of a separate species of islet-cell antibodies which fix complement. Investigations in type I diabetics, non-diabetic polyendocrine patients, and unaffected first-degree relatives of type I diabetic probands show that the complement-fixing islet-cell antibodies are more closely related to the onset of clinical disease than the conventional islet-cell antibody, and they tend to disappear more rapidly. The complement-fixing antibodies may reflect damage of pancreatic beta cells more selectively and may be preferable to the conventional antibody as a serological marker for studying the natural history of type I diabetes.

Adolescent↗
PubMed1980

Mitochondrial antibodies in chronic liver diseases and connective tissue disorders: further characterization of the autoantigens.

The heterogeneity of mitochrondrial autoantibodies in a variety of diseases states has been critically re-examined by a combination of immunofluorescence staining (IFL) and complement fixation tests (CFT). The different mitochondrial IFL patterns described by other workers were confirmed and extra criteria using new substrates are presented for their differential recognition. Biochemically defined mitochondrial subfractions were used in the CFT to confirm and extend the IFL classifications. The 'M1' cardiolipin antibodies of syphilis did not react with the ATPase fraction but the antigen was present in all membrane preparations and found to be chemically resistant. The major antibody specificity of the 'M3' pattern associated with drug-induced pseudolupus syndrome is a firmly bound, outer membrane component; and a second, minor reactivity is apparently to a mercurial-insensitive antigen present in the chloroform-released ATPase preparation. The 'M5' antibody pattern correlates with a digitonin-sensitive outer membrane component. Although it was not possible to differentiate within the group of liver diseases between the 'M2' antibodies of primary biliary cirrhosis and the previously described 'M4' antibodies of other chronic liver diseases, several antibody specificities were demonstrated. All sera from liver disease patients contain the antibody directed against a mercurial-sensitive protein found in the chloroform-released ATPase preparation, and, in addition, varying titres of antibodies against two or more mercurial-resistant membrane components, of which at least one is on the inner membrane and one on the outer membrane.

Adenosine Triphosphatases↗
PubMed1980

Primary biliary cirrhosis: the prevalence of hypothyroidism and its relationship to thyroid autoantibodies and sicca syndrome.

A survey of thyroid function in 95 patients with primary biliary cirrhosis revealed the presence of thyroid antibodies in 24 females and 1 male. Thirteen (52%) of this thyroid antibody positive group (all female) had biochemical evidence of thyroid disease: 8 (32%) were hypothyroid (7 of whom showed signs of myxedema), 2 had elevated thyroid stimulating hormone (TSH) levels, and 3 had abnormal responses to stimulation with thyrotropin releasing hormone (TRH). In contrast, only 3 (4%) of the thyroid antibody negative patients had reduced serum thyroxine (T4) levels and none were clinically hypothyroid. Evidence of an increase in thyroid hormone binding, as reported by other workers, was not found, and both the resin uptake of radioactive triiodothyronine and the free thyroxine indices were normal in both groups. The presence of thyroid antibodies showed a highly significant association with lacrimal gland dysfunction but not with liver histologic staging or liver function tests.

Adult↗
PubMed1980

Inhibition of parietal cell function by human gammaglobulin containing gastric parietal cell antibodies.

Parietal cell antibodies (PCA) are found in up to 90% of sera from pernicious anaemia patients but it is often stated that they could represent an epiphenomenon without being directly responsible for the achlorhydria. In the present studies a direct effect of these antibodies on the secretory function of gastric acid-secreting cells has been demonstrated in two different experimental systems. In one set of experiments IgGs containing PCA activity were shown to inhibit acid secretion specifically in the living gastric mucosa of the bull frog suspended as a diaphragm between two chambers. The other system demonstrated their inhibition of carbonic anhydrase activity in a cytochemical bioassay for human G17-gastrin, suggesting a blocking effect on the gastrin receptors in the canalicular microvilli or the cell membrane. These experiments suggest a direct pathogenic role for PCA in autoimmune fundal gastritis and in pernicious anaemia.

Anemia, Pernicious↗
PubMed1980

Azathioprine in primary biliary cirrhosis: a preliminary report of an international trial.

The effects of azathioprine on the course of primary biliary cirrhosis were studied prospectively in a multinational, double-blind randomized clinical trial involving 236 patients, of which 124 received azathioprine and 112 placebo. No significant effects were seen on survival, clinical course, hepatic histologic features, hepatic tests, or immunologic abnormalities after a median follow-up period of 18 mo, but most of the trends observed were in favor of azathioprine. The results obtained so far indicate that the effect of azathioprine as a single treatment is limited and probably of little clinical importance, but more years of follow-up will be needed to provide a definite conclusion.

Actuarial Analysis↗
PubMed1980

Autoantibodies to duodenal gastric-inhibitory-peptide (GIP) cells and to secretin (S) cells in patients with coeliac disease, tropical sprue and maturity-onset diabetes.

The presence of autoantibodies detected by immunofluorescence to single endocrine cells, of human duodenum is described in three groups of patients and two control groups. Of 173 coeliac cases, four had GIP cell antibodies, one had secretin cell antibodies and twenty-one reacted with both cell types. Of twelve tropical sprue sera, four reacted with the same two cells. Among fifty elderly diabetics treated with hypoglycaemic drugs, seven sera gave a positive cytoplasmic IFL on duodenal substrate. Four were identified as GIP cells by use of the appropriate hormone antiserum and three reactions were against cells distinct from those stained by anti-GIP, -secretin, -somatostatin, -glucagon and -gastrin. Additional gut hormone antisera will have to be tested to identify these APUD cells. Thirty blood donors and seventy-three sera from autoimmune endocrine patients gave entirely negative results on unfixed cryostat sections of duodenal mucosa. Although impaired GIP and secretin responses have been reported in coeliac disease, and abnormal GIP values were found in Type II diabetes, there is as yet no data to correlate these metabolic dificiencies with the presence of endocrine cell antibodies in the serum. These studies are in progress.

Adult↗
PubMed1980

Prevalence of autoimmune diseases and autoantibodies in Ethiopia.

Analysis of 7,966 hospital admissions and other available data suggest that disease associated with autoimmunity are rare in Ethiopia. Sera from 107 patients with dyspepsia and 80 healthy Ethiopians were studied for autoantibodies. Using the immunofluorescence technique and anti-Fab-FITC conjugate, a search for organ-specific autoantibodies against thyroid (microsomal and thyroglobulin) cells as well as for non-organ-specific autoantibodies against nuclear material, smooth muscle, mitochondria, cardiolipin, glomerular basement membrane and connective tissue (reticulin antibodies) revealed that they were uncommon. Thus, both clinical and serological studies confirm that previously held views concerning the rarity of autoimmune diseases in many parts of Africa are also true in Ethiopia. It is suggested that the few Ethiopians who develop autoimmune diseases may have an overwhelming hereditary predisposition which is unable to overcome inhibitory factors in the environment.

Adult↗
PubMed1980

Clinical pattern and course of disease in primary biliary cirrhosis based on an analysis of 236 patients.

A prospective study of the clinical pattern and course of primary biliary cirrhosis based on the data of 236 patients (211 females, 25 males) in an international randomized trial has been performed mainly using life-table technique. The median follow-up period has been 18 mo. After the entry into the study, at which time the median duration of symptoms was 2.1 yr, the estimated 5-yr increase in the cumulative percentage of patients was for pruritus from 75% to 95%, jaundice 59% to 82%, hepatomegaly 54% to 86%, pigmentation 54% to 85%, xanthomas 27% to 50%, GI bleeding 17% to 46%, ascites 7% to 49%, and vertebral collapse 3% to 20%. The frequency of cirrhosis increased from 30% to 82% in 4 yr. The mitochondrial antibody titer showed a high rate of progression with time. In analysis of subgroups, age, histologic stage, and particularly the serum bilirubin level were important prognostic factors. Sex, duration of symptoms, and character of first symptom or sign had no independent prognostic influence. The most important indication of seriously progressive course was rapid development of severe cholestasis independent of the histologic stage.

Adult↗
PubMed1979

Autoantibodies to gastrin-producing cells in antral (type B) chronic gastritis.

Autoantibodies that react exclusively with the gastrin-secreting cell of human antrum have been detected by immunofluorescence in eight of 106 patients with histologic evidence of chronic atrophic gastritis, Type B, involving mainly the antrum. These antibodies were of the IgG class and of low titer. However, follow-up studies one to two years later showed persistently positive reactions, despite symptomatic treatment. These data support the concept of an autoimmune variant of chronic "antral" gastritis, Type B.

Adult↗
PubMed1979

Islet cell antibodies and diabetes mellitus in Pima Indians.

Pancreatic islet cell antibodies and 12 other autoantibodies were measured at the time of diabetes diagnosis in 46 Pima Indians, aged 17--47 years, and in 46 age-sex matched non-diabetic controls. Islet cell antibodies were found in only two diabetics, aged 20 and 25, compared with none of 46 controls. Neither of the subjects with islet cell antibodies had other autoantibodies. At least one type of autoantibody was found in 14 (30%) of the diabetics and in 14 controls, but none was significantly associated with diabetes. This study indicates that diabetes in the Pima Indians, even those with an onset below 25 years of age, is almost entirely of type II, in that the disease is not associated with islet cell antibodies, ketoacidosis, or insulin dependence.

Adolescent↗
PubMed1978

Evidence for a primary autoimmune type of diabetes mellitus.

Sixty-eight patients with longstanding diabetes and persistent islet-cell antibody and 35 with coexistent diabetes and Graves's disease or primary myxoedema were studied with particular reference to the HLA system and autoantibody patterns. A higher incidence of HLA-B8 than normal was observed in the two groups. An additive relative risk exists when type I diabetes and autoimmune thyroid disease coexist, indicating that different HLA-linked genes may confer susceptibility to the pancreatic and thyroid disorders. Other characteristics, including female predominance, a later onset of diabetes, and a strong family history of autoimmune endocrinopathy, provide further evidence that this form of diabetes is aetiologically distinct from that generally seen in children. These results support the hypothesis of a primary autoimmune type of diabetes mellitus.

Adolescent↗
PubMed1978

Autoimmunity in juvenile diabetics and their families.

Pancreatic islet cell, thyroid, and gastric antibodies were studied in 116 young insulin-dependent diabetics and 257 relatives. Seventy-four per cent of the diabetics studied within three months of diagnosis had islet-cell antibodies but only 20% of those studied three years or more after diagnosis. Persistence of these antibodies was associated with a high prevalence of thyrogastric autoimmunity, which suggests that some cases have an aetiology similar to that of "polyendocrine" autoimmune disease. Retinopathy or nephropathy, or both, was present in 10 diabetics, who were all members of "autoimmune" families, in which one or more members had organ-specific antibodies. Nine of the 10 healthy relatives with islet-cell antibodies and all families with more than one diabetic were also in this autoimmune group. These data suggest that an autoimmune factor may contribute to juvenile diabetes and that such autoimmune diabetes has a tendency to run in families and may be more likely to cause complications.

Adolescent↗
PubMed1978

Impairment of lachrymal and salivary secretion and cellular immune responses to salivary antigens in rheumatoid arthritis.

During a systematic investigation of 100 unselected outpatients with rheumatoid arthritis, 58 were found to have reduced lachrymal or salivary secretion. No correlation could be detected between the presence or absence of secretory abnormalities and the age or sex of the patient, the presence of nodules or salivary duct antibody, or the occurrence of vasculitis. However, there was a significant correlation between diminished salivary of lachrymal flow and the occurrence of cellular immune responses to a protein fraction of normal human saliva, sensitisation being found in 94% of those with impairment of salivary and lachrymal secretion as compared with 33% of those without.

Aged↗