[Artificial endocrine pancreas].
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Biomedical subjects
Publications and source records attributed to A Mimura.
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A deceased 59-year-old woman with insulin dependent diabetes mellitus complicated by chronic thyroiditis and chronic hepatitis was autopsied. She had had diabetes mellitus since she was 30 years old, and insulin therapy was started at 34 years. Laboratory findings were as follows: s-GOT 85, s-GPT 31, gamma-globulin 2.45 g/dl. Immunological tests were positive for anti-smooth muscle antibody and anti-ENA antibody with high titers of antithyroglobulin and anti-microsome antibodies. HLA analysis revealed the presence of DR-4. The thyroid biopsy specimen showed microscopic features characteristic of chronic thyroiditis at 52 years of age. She had been repeatedly admitted for the control of diabetes mellitus. She was admitted for the 9th time in June, 1987 following complaints of abdominal pain. After admission, her general condition became gradually worse, and she died of peritonitis in September, 1987. Pathological examination of the liver revealed an expansion of fibrous tissue on Glisson's capsule accompanied by lymphocytic infiltration and was diagnosed to be chronic inactive hepatitis. As for the thyroid gland, fibrous tissue replaced an extensive area of the thyroid gland, and normal thyroid tissue was not observed. Lymphocytic infiltration was less in comparison with that in the previous biopsy. As for the pancreas, atrophy of exocrine pancreatic tissue and fibrous change in interstitial tissue was observed. Lymphocytic infiltration was also seen in the interstitial exocrine tissue but not in the islet. Immunohistochemical examination of the islets using anti-insulin, glucagon and somatostatin antibodies by ABC peroxidase method showed the selective disappearance of B cells in the islets. The pathological changes in the thyroid gland, liver and pancreas suggest that autoimmune mechanism may be involved in the pathogenesis of chronic thyroiditis, chronic hepatitis and IDDM with exocrine pancreatic impairment in this case.
A growth-promoting factor for human myeloid cells was purified to apparent homogeneity from horse serum by a combination of gel filtration, blue Sepharose affinity chromatography, Mono Q anion-exchange chromatography, Mono P chromatofocusing and sodium dodecyl sulfate polyacrylamide gel electrophoresis. The growth promoter was an iron-bound, single glycopolypeptide chain with a molecular weight of 84,000, an isoelectric point of 5.4 and an amino terminal sequence of Glu-Gln-Thr-Val-Arg-Trp-Cys-Thr-Val-Ser-Asn-His-Glu-Val-Ser-Lys-. According to the results of the amino acid sequence, iron binding ability and physicochemical properties, we identified the growth-promoting factor as horse serum transferrin. It was highly active in promoting the proliferation of a human monocytic leukemia cell line, THP-1, as well as of two other human myeloid cell lines, HL-60 and K-562. It had the same activity in proliferating THP-1 cells as 5% fetal calf serum-supplemented medium. Horse serum transferrin could be substituted for human or bovine serum transferrin.
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Insulin sensitivity in terms of glucose disposal rate was determined by using the hyperinsulinemic euglycemic clamp technique in seven obese hypertensive patients and nine normotensive control subjects. The technique was used on all study subjects at baseline and on the hypertensive patients after 12 weeks of arotinolol treatment. Mean supine systolic blood pressure decreased from 155 +/- 3 mm Hg before treatment to 133 +/- 6 mm Hg after treatment (P < 0.02), and diastolic blood pressure decreased from 100 +/- 3 mm Hg before treatment to 86 +/- 3 mm Hg after treatment (P < 0.05). The mean dose of arotinolol was 10 mg/d, except for one patient who received 20 mg/d. The glucose disposal rate during the last 30 minutes of the glucose clamp procedure was not significantly affected by treatment with arotinolol. Compared with the hypertensive patients, the glucose disposal rate in the normotensive subjects was significantly increased, both before and after treatment (P < 0.01). The study results show that the obese hypertensive patients were insulin resistant and that treatment with arotinolol did not significantly affect insulin sensitivity.
Insulin sensitivity in terms of glucose disposal rate was measured by the hyperinsulinemic/euglycemic clamp technique in 10 hypertensive patients and 7 normotensive control subjects before and after 12 weeks of doxazosin therapy. Supine blood pressure fell significantly, from 150/98 mmHg before treatment to 136/90 mmHg after treatment (systolic P < 0.001/diastolic P < 0.01). The average dose of doxazosin at the end of the study was 3.3 +/- 0.4 mg/day. The glucose disposal rate during the last 30 minutes of the glucose clamp procedure was significantly increased, from 5.8 +/- 0.7 mg/kg/min before to 7.8 +/- 0.7 mg/kg/min after treatment (P < 0.02). Insulin sensitivity was 8.7 +/- 0.4 mg/kg/min in the normotensive subjects, which represented a significant difference when compared with that of the hypertensive subjects before treatment (P < 0.01). Steady-state serum insulin concentrations, as measured during the glucose clamp procedure, were 172 +/- 10.4 microU/ml before and 176 +/- 13.5 microU/ml after doxazosin treatment; these levels were significantly higher than the 137 +/- 7.0 microU/ml reading obtained in the normotensive subjects (P < 0.05). Study results show that hypertensive patients tend to be insulin resistant and that treatment with doxazosin improves insulin sensitivity.