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Biomedical subjects

D Stenger

Publications and source records attributed to D Stenger.

13 recordsLinked to original sources
PubMed1998

Combined use of autoantibodies (IA-2 autoantibody, GAD autoantibody, insulin autoantibody, cytoplasmic islet cell antibodies) in type 1 diabetes: Combinatorial Islet Autoantibody Workshop.

The aim of this workshop was to assess the ability of individual autoantibody (ab) assays and their use in combination to discriminate between type 1 diabetic and control sera. Coded aliquots of sera were measured in a total of 119 assays by 49 participating laboratories in 17 countries. The sera were from 51 patients with new onset type 1 diabetes and 101 healthy control subjects with no family history of diabetes. In the final analysis, data on diabetic sera were restricted to 43 subjects younger than age 30 years. The laboratories were asked to report results for these sera using their currently available anti-islet autoantibody assays. In addition, they were asked to combine information from their assays to classify sera as having high, moderate, or low probability of originating from a patient with type 1 diabetes. Actual strategies for combining assays were determined by each laboratory. There were no significant differences in sensitivity among 19 radioimmunoassays (RIAs) for IA-2 autoantibodies (cytoplasmic islet cell antibody [ICA] 512) using different constructs that included the intracellular portion of the molecule (mean sensitivity 73%). However, an enzyme-linked immunosorbent assay (ELISA) using the extracellular portion of the IA-2 molecule did not discriminate between diabetic and control sera. Among GAD autoantibody assays that achieved sensitivity >70%, 26 were RIAs and one was an ELISA. When the sera were ranked according to their autoantibody levels, the concordance for insulin autoantibodies (IAAs) in different laboratories was markedly less than for IA-2ab and GADab. Using a combination of autoantibody assays, several laboratories achieved excellent discrimination between diabetic and control sera (sensitivity up to 80% with false-positive rate of 0%). A variety of strategies for combining information from different assays were successful (e.g., those including and excluding ICA), and no one strategy emerged as clearly superior. In conclusion, IA-2/ICA512 autoantibodies are a marker of type 1 diabetes and can be measured consistently by most assays. Several different strategies for combining assays achieved high sensitivity with a low false-positive rate.

Adolescent↗
PubMed1996

The diabetic BB rat. Neither Th1 nor Th2?

A long term objective of our work has been to identify and characterize the T cells responsible for causing autoimmune type I diabetes in the spontaneously diabetic BB rat. Based on the Th1/Th2 paradigm encompassing "regulated" and "regulatory" T cells, our analyses show that there are very few "regulatory" peripheral Th2 cells. The "regulated" T cells that remain express an unusual, immature phenotype that is neither Th1 nor Th2. Our data also indicate that transcript expression for p56lck, an enzyme required for T cell development, is abnormal in BB peripheral T cells. We discuss the role abnormal transcript expression of p56lck might play in retarding the development of mature regulatory Th2 cells while simultaneously influencing the escape of autoreactive T cells from the thymus.

Animals↗
PubMed1995

Heterogeneity of islet pathology in two infants with recent onset diabetes mellitus.

The mechanisms by which the beta cells of pancreatic islets are destroyed in insulin-dependent diabetes mellitus (IDDM) are poorly understood. In this report the pancreatic histo- and immunopathology of two children, both HLA-DR 3/4, DQ 2/8 positive and who both died from cerebral oedema within a day of clinical diagnosis of IDDM, were investigated. Patient 1, a 14-month-old girl, had a 4-week history of polydipsia and polyuria. Patient 2, a 3-year-old boy, had 2 days of illness. Both patients had a similarly severe loss of insulin cells but differed markedly as to the extent of lymphocytic islet infiltration (insulitis). Apart from insulitis, marked islet macrophage infiltration was demonstrated in both patients with the HAM-56 monoclonal antibody. Neither patient showed aberrant expression of HLA class II antigens on insulin-immunoreactive cells, but allele-specific HLA-DQ8 expression was evident on endothelial cells. Glutamic acid decarboxylase immunoreactivity was detected in both insulin- and glucagon-immunoreactive cells. It is concluded that the heterogeneity of islet pathology, especially insulitis, may reflect different dynamics and extent rather than different pathomechanisms of immune destruction of islets in IDDM.

Child, Preschool↗
PubMed1995

Polymorphic amino acid variations in HLA-DQ are associated with systematic physical property changes and occurrence of IDDM. Members of the Swedish Childhood Diabetes Study.

The association between human leukocyte antigen (HLA) and insulin-dependent diabetes was studied in a large population-based investigation using genotyping of 425 new-onset patients, 0-14 years of age, and 367 matched control subjects. As many as 97% of patients compared with 75% of control subjects were positive for one or several of DQA1*0301, DQA1*0501, DQB1*0302, or DQB1*0201. Asp-57 DQB was present among 28% of patients, indicating that this residue alone does not confer protection. Combining Asp-57 DQB1 with either Arg-52 DQA1 or Leu-69 DQA1 did not explain susceptibility or protection either. DQA1*0301-DQB1*0302 (DQ8) and DQA1*0301-DQB1*0301 (DQ7) are identical except for four amino acid substitutions in the beta-chain, but DQ8 was positively (odds ratio 8.07; P < 0.001) and DQ7 negatively (odds ratio 0.38; P < 0.001) associated with the disease. Molecular modeling was used to determine whether physiochemical properties such as steric factors and surface electrostatic potentials also differ in a systematic way for various DQ molecules. Amino acids were substituted systematically at the four polymorphic sites, and the solvent-accessible surfaces and electrostatic potentials were computed for each molecule. Dramatic alterations in electrostatic potential were seen for double substitutions at position 45 (G45E) and 57 (A57D) of DQB1. The variation of physicochemical properties due to polymorphic substitutions may be significant to the mechanism of HLA-DQ association with insulin-dependent diabetes, via the effect these property variations have on peptide antigen binding selectivity and subsequent interactions with specific T-cell receptors.

Adolescent↗
PubMed1988

[Etiology and therapy of peritonitis in childhood].

The causes of peritonitis in childhood, particularly in infancy, were found to differ substantially from those in adult age. An overall account is given in this paper of general and differential diagnosis of extra-abdominal diseases which may be potentially mistaken for peritonitis. Clinical diagnosis is of crucial importance in childhood. Perforated appendicitis was the absolutely major cause of peritonitis in 119 children who received surgical treatment in the course of 18 years. An initial antibiotic combination of gentamicin with ampicillin, and metronidazole together with immune treatment have proved to be an effective therapeutic approach to this form of peritonitis.

Appendicitis↗
PubMed1987

Effect of IgG subclasses on in vivo bioavailability and metabolic fate of immune-complexed insulin in Lewis rats.

The bioavailability, distribution, and metabolic fate of 125I-labeled insulin complexed to antibodies in guinea pig antiserum, purified guinea pig IgG1, IgG2, a mixture of IgG1 and IgG2, and homologous Lou/m rat antiserum were studied in inbred Lewis rats. 125I-insulin complexed to purified guinea pig IgG2 antibodies was rapidly cleared from the blood and sequestered in increasing amounts with time in the liver. Large amounts of the 125I-insulin complexed to guinea pig IgG1 antibodies remained in the blood for at least 30 min. The bioavailability of 125I-insulin bound to IgG1 and IgG2 antibodies was inhibited for at least 30 min because significantly less was available for rapid binding to insulin receptors on hepatocytes and renal tubular cells and its subsequent rapid degradation. The bioavailability of 125I-insulin was further decreased when bound to antibodies in native guinea pig antiserum or a mixture of IgG1 and IgG2 antibodies compared with the 125I-insulin complexed to either purified IgG1 or IgG2 antibodies alone. The 125I-insulin bound to antibodies in native guinea pig antiserum or a mixture of IgG1 and IgG2 antibodies was distributed in vivo in a manner reflecting the relative concentrations of the IgG1 and IgG2 antibodies present. The bioavailability, distribution, and metabolic fate of 125I-insulin in immune complexes prepared with homologous Lou/m rat insulin antiserum was qualitatively similar to that observed with immune complexes prepared with guinea pig insulin antiserum. It appears that the Lewis rat can be used as an in vivo model to study the bioavailability,distribution,and metabolic fate of insulin bound to xenogenic or homologous insulin antibodies.

Animals↗
PubMed1987

[Brachyonychia of different types in a mother and daughter].

Different types of brachyonychia were observed in a mother and her daughter. The mother presented a unilateral racket thumb-nail (localized brachyonychia "en raquette" of Basset). In the case of the daughter the thumbs and three middle fingers of both hands were involved, the nails of the little fingers being normal (generalized brachyonychia "en raquette" of Basset). Also, the daughter's toe-nails were short and wide. There was a family history of short nails "on all fingers" occurring in the two sisters of the mother's father. We believe that localized and generalized types of racket nails are variants of the same inherited anomaly. As far as we know, this is the first report of brachyonychia of the toe-nails.

Adolescent↗
PubMed1986

[Superficial cutaneous lipomatous nevus (Hoffmann-Zurhelle)].

Nevus lipomatosus of Hoffmann-Zurhelle is a rare condition characterized by ectopic accumulation of adipose tissue which is located almost always on the lower trunk. We present a typical case and give a detailed survey on the pertinent literature.

Adipose Tissue↗
PubMed1985

Penicillamine-induced pemphigus foliaceus-like dermatosis. A case with unusual features, successfully treated by plasmapheresis.

A case of a severe, widespread bullous dermatosis clinically resembling pemphigus foliaceus occurred during treatment with penicillamine hydrochloride in a patient with rheumatoid arthritis. Histologically, the disease showed changes compatible with pemphigus vulgaris as well as with a bullous drug eruption. Treatment by plasmapheresis proved to be effective in controlling the disease.

Dermatitis, Exfoliative↗
PubMed1984

[The long-eyelash syndrome (trichomegaly syndrome, Oliver-McFarlane)].

Two children with abnormally long eyelashes and bushy brows ("trichomegaly") present at birth and associated with pigmentary degeneration of the retina and general growth retardation are described. This combination of findings has been observed previously in three cases. Mental retardation, sparse scalp hair, endocrinologic deficiencies and (in one of our cases) koilonychia may be found in addition, but not necessarily.

Abnormalities, Multiple↗
PubMed1983

[Standardized recall antigen testing in patients with malignant melanoma, endogenous eczema patients and healthy humans].

By means of a new test kit (Multitest), intracutaneous tests have been performed on several groups of patients in order to evaluate the degree of cellular immunity. This test system affords the simultaneous application of seven quantitatively and qualitatively standardized antigens. In comparison to healthy people, patients suffering from malignant melanoma showed a slightly higher immunity reaction whereas patients with atopic dermatitis revealed a significantly lesser degree of reactivity to the recall-antigens. Chemotherapy with Dacarbazine did not change the amount of reactivity to the Multitest. This paper discusses the advantages of the new test kit as well as the difficulties of recall-antigen testing with regard to the evaluation of cellular immunity.

Antigens↗
PubMed1982

Effects of cyproterone acetate and oestradiol benzoate on the rat testis. Morphometric study after treatment over 35 days.

The testes of juvenile and adult rats were subjected to a histomorphometric and ultramorphometric examination after a 5-week cyproterone acetate and oestradiol benzoate treatment respectively. In the cyproterone acetate animals only minor changes of spermatogenesis are found in contrast to the oestradiol benzoate ones. The juvenile rats were not differing from those in the control group. In the older rats a reduction of the spermatocytes area portion in the basal zone of seminiferous epithelium can be proven. Oestradiol benzoate leads to an arrest of spermatogenesis at the stage of spermatocytes or the early spermatids respectively. At the same time the median diameter of seminiferous tubulus and the total area of seminiferous epithelium has considerably decreased in comparison to the treatment with anti-androgen. By the applied method an influence of the two substances on the spermatogonia was not recognizable.

Age Factors↗