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A L Notkins

Publications and source records attributed to A L Notkins.

At least 181 records · Page 10Linked to original sources
PubMed1983

Virus-induced diabetes in mice.

Encephalomyocarditis (EMC) virus infects and destroys pancreatic beta cells when inoculated into mice. This results in hypoinsulinemia and hyperglycemia. The development of virus-induced diabetes is dependent on the genetic background of the host and the genetic makeup of the virus. In addition to the acute metabolic changes, animals with diabetes for six months show some long-term complications, including reduced life span, glomerulosclerosis, and ocular changes. The development of virus-induced diabetes in mice can be prevented by a live attenuated vaccine.

Animals↗
PubMed1983

Cell-bound and circulating IgE antibody to herpes simplex virus.

Mice immunized with ultraviolet-inactivated herpes simplex virus (HSV) or injected with infectious virus developed IgE-specific antibody to HSV. Cell-bound IgE was detected by measuring the release of histamine from peritoneal mast cells challenged in vitro with virus antigens. Circulating IgE antibody was detected by sensitizing rat basophilic leukaemia (RBL-2H3) cells with sera from HSV-immunized mice and then challenging these cells with virus or control antigens to release histamine. IgE antibody may contribute to the pathogenesis of virus infections.

Animals↗
PubMed1982

Multiple interferons in the circulation of patients with systemic lupus erythematosus and vasculitis.

Recently, we found interferon in the sera of patients with systemic lupus erythematosus, rheumatoid arthritis, scleroderma, and Sjögren's syndrome. In this study, we surveyed a variety of other immunologically mediated diseases. We did not find interferon in the sera of patients with Wegener's granulomatosis, sarcoidosis, infectious mononucleosis, minimal change nephritis, kidney transplants, myasthenia gravis, or uveitis, but we did find this protein in the sera of patients with active systemic and cutaneous vasculitis. Attempts to characterize the interferon in the sera of patients with systemic lupus erythematosus and vasculitis revealed that antibody to alpha (leukocyte) interferon, but not to beta (fibroblast) interferon, partially or completely neutralized the antiviral activity. The failure of antibody to alpha interferon to completely neutralize the antiviral activity in certain specimens and the lability of the antiviral activity in some specimens to pH 2.0 treatment both suggest that more than one type of interferon was present.

Humans↗
PubMed1982

Homology between murine and human cellular DNA sequences and the terminal repetition of the S component of herpes simplex virus type 1 DNA.

DNA from trigeminal ganglia of mice latently infected with herpes simplex virus type 1 was cloned in bacteriophage lambda Charon 27. Three recombinant clones that cross-hybridize to each other and hybridize to the S-segment terminal repeat region of the herpesvirus genome were obtained. The region of homology maps within a 1.1 kb Sma l fragment approximately 400 bp from the S-segment terminal repeat terminus, outside the domain of the a sequences. The insert DNAs in these clones, as well as the Sma l fragment of viral DNA that contains the region of homology, hybridize to uninfected mouse brain DNA with a pattern indicative of the presence of repeated sequences, and also hybridize to discrete Eco Rl fragments of human DNA. These recombinant clones contain intermediate repetitive mouse genomic DNA sequences related to a small region of the viral S-segment terminal repeat, and those sequences are evolutionarily conserved in mammalian DNA.

Animals↗
PubMed1982

HLA antigens, cytoplasmic islet cell antibodies, and carbohydrate tolerance in families of children with insulin-dependent diabetes mellitus.

Cytoplasmic pancreatic islet cell antibodies were found in 21% of 244 unaffected first degree relatives of type I diabetic patients. Twenty-five percent of HLA-identical, 35% of HLA-haploidentical, 16% of HLA-nonidentical siblings, and 14% of parents were ICA-positive. In the HLA-identical sibs, irrespective of ICA, and in the 18 ICA-positive parents but not the other groups, increased plasma glucose levels were observed after the administration of glucose. In most children, these were associated with reduced insulin levels, while in the adults elevated insulin responses were noted. In 48% of the ICA-positive children and 84% of the ICA-positive parents, other evidence of "autoimmunity" was obtained either by history or by testing for specific autoantibodies. Two of the originally unaffected HLA-identical and ICA-positive siblings developed diabetes during the course of the study. These findings, plus previously reported data in families with two diabetic sibs demonstrating that the empiric risk for developing IDDM is of the order of 30% for HLA-identical sibs but less than 5% for those that are HLA-haploidentical, suggest that HLA-identity may be a useful predictor of potential type I diabetes. The presence of ICA may, at times, portend the need for future antidiabetic therapy but prospective studies must be continued to fully elucidate this relationship.

Adolescent↗
PubMed1982

Virus-induced diabetes mellitus. Glucose abnormalities produced in mice by the six members of the Coxsackie B virus group.

The capacity of Coxsackie B viruses (CBVs) to produce diabetes in mice was studied before and after passage in various cell types. CBVs that had been passaged in monkey kidney cells or in mouse embryo fibroblasts failed to produce abnormal glucose tolerance tests, whereas virus passaged five or more times in the pancreata of mice or in beta-cell cultures produced transient abnormal glucose tolerance tests. Immunofluorescence and histologic studies revealed that passage of CBVs in cultured beta-cells changed the tropism of these viruses from the acinar pancreas to the islets of Langerhans. Although all six CBV serotypes that had been passaged in beta-cell cultures behaved very similarly, substantial variation was observed with the different virus passages and in some experiments, beta-cell damage and the glucose abnormalities were minimal. From these and other experiments, we conclude that the six members of the CBV group have the potential for infecting and damaging pancreatic beta-cells in mice.

Animals↗
PubMed1982

Abnormalities of immunoregulatory T cell subsets in patients with insulin-dependent diabetes mellitus.

Patients with insulin-dependent diabetes mellitus (IDDM) have autoantibodies that react with cells in the islets of Langerhans. To determine whether these patients suffer from a more generalized immunoregulatory disorder, the ratio of phenotypic helper to suppressor cells was evaluated by specific monoclonal antibodies. Our experiments showed that the helper/suppressor cell ratio was significantly increased in patients with IDDM of less of 2 mo duration and then gradually returned to normal. Despite the alteration in the helper/suppressor cell ratio, there was no evidence for polyclonal activation as measured by the number of immunoglobulin-secreting plaque-forming cells in the peripheral blood. There was, however, a significant increase in the number of spontaneous plaque-forming cells in patients suffering from both IDDM and Hashimoto's thyroiditis (HT). Nonetheless, immunoglobulin production after stimulation with pokeweed mitogen was not different in diabetics with or without HT when compared to normal controls. These findings suggest that subtle changes in the immunoregulatory system occur during the early stages of IDDM.

Adolescent↗
PubMed1981

Role of mucosal injury in initiating recurrent aphthous stomatitis.

The buccal mucosa of 30 patients with recurrent aphthous stomatitis and 15 healthy controls was injured by suture and penetration with a tenaculum and a hypodermic needle and each of the six puncture wounds produced monitored for up to seven days for the development of ulcers. Altogether 26 lesions were induced in 13 patients, whereas none occurred in the controls (p less than 0.001). Sutures caused most of the lesions (15), and those so induced had a mean maximum diameter of 2.3 mm and lasted for an average of four days. Ulcers induced mechanically were clinically indistinguishable from those usually seen in the patients, except that they were generally smaller and healed more quickly. These findings confirm that mechanically induced injury of the oral mucosa may cause ulceration in people susceptible to aphthous stomatitis. Such a procedure may therefore be helpful in identifying subsets of patients.

Adult↗
PubMed1981

Virus-induced diabetes mellitus. XX. Polyendocrinopathy and autoimmunity.

Mice infected with reovirus type 1 developed transient diabetes and a runting syndrome. The diabetes was characterized by hyperglycemia, abnormal glucose tolerance tests, and hypoinsulinemia. Inflammatory cells and viral antigens were found in the islets of Langerhans, and virus particles were seen in alpha, beta, and delta cells. The runting syndrome consisted of retarded growth, oily hair, alopecia, and steatorrhea. Inflammatory cells and viral antigens were found in the anterior, but not posterior pituitary. Electron microscopy revealed virus particles in growth hormone (GH)-producing cells and radioimmunoassay showed that the concentration of GH in the blood was decreased. Examination of sera from infected mice revealed autoantibodies that, by immunofluorescence, reacted with cytoplasmic antigens in the islets of Langerhans, anterior pituitary, and gastric mucosa of uninfected mice. Absorption studies and enzyme-linked immunosorbent assays designed to identify the reactive antigens showed that some of the autoantibodies were directed against insulin and others against GH. Reovirus type 3, in contrast to reovirus type 1, did not induce autoantibodies to GH. By use of recombinant viruses, the segment of the reovirus genome responsible for the induction of autoantibodies to GH was identified. Virus containing the S1 gene segment from reovirus type 1, which codes for the sigma 1 polypeptide (i.e., hemagglutinin), infected cells in the anterior pituitary and induced autoantibodies to GH, whereas virus containing the S1 gene segment from reovirus type 3 failed to infect cells in the anterior pituitary and did not induce autoantibodies to GH. We conclude that reovirus type 1 infection can lead to polyendocrinopathy and autoimmunity and that the S1 gene segment is required for the induction of autoantibodies to GH.

Animals↗
PubMed1981

HLA antigens and islet cell antibodies in gestational diabetes.

The HLA antigens of 136 patients with gestational diabetes are compared with control populations. No significant variations are observed in their frequencies, particularly for those antigens associated with Type 1 diabetes mellitus. Islet cell antibodies have also been studied in the serum of 52 of these patients and 20 of them were positive, whereas only one of 37 pregnant nondiabetic women had such antibodies (chi 2 = 15.2). A very high association between ICA and DR3 and DR4 was encountered (chi 2 = 17, with two df); half of the patients positive for either one of these antigens were ICA positive. These results indicate that ICA associates equally with DR3 and DR4, against the hypothesis that this expression of autoimmunity is more a characteristic of DR3- than of DR4-associated genetic susceptibility. These patients will be followed to determine if the ICA+ individuals are at increased risk for the development of insulin-dependent diabetes.

Adult↗