[The pathogenesis of NIDDM: genetic defects and environmental factors].
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DNA, Mitochondrial↗
Biomedical subjects
C Nakagawa
Publications and source records attributed to C Nakagawa.
A new variant case of muscle phosphofructokinase deficiency, coexisting with gastric ulcer, gouty arthritis, and increased hemolysis.
Muscle phosphofructokinase (PFK) deficiency includes both clinically and genetically heterogeneous conditions. A 22-year-old man with muscle PFK deficiency due to previously unrecognized mutation was admitted because of gastric ulcer. He had noticed mild fatigability on vigorous exercise, but had never experienced painful cramps and myoglobinuria. His history included five time relapses of gastric ulcer and gouty arthritis at ages 19 and 21 years. His laboratory data showing impaired muscle glycolysis, increased hemolysis, and myogenic hyperuricemia had aspects in common with those reported for the classic form of this disease, except that lactate concentrations in his blood increased considerably after exercise. The mutant PFK enzyme of this patient, who was demonstrated to have a missense mutation, could exert some catalytic activity that permitted glycolytic flux in vivo, thus leading to the absence of typical myopathic symptoms. The association of relapsing gastric ulcer with muscle PFK deficiency was detected for the first time. There is a possibility that oxygen radical-induced tissue damage resulting from increased hypoxanthine on exertion plays a role in the pathogenesis of ulceration, since the patient is more tolerant to exercise than reported cases with the classic form of muscle PFK deficiency.
Adult↗
Effect of doxorubicin on postrest contraction in isolated rat hearts.
Clinical use of doxorubicin is limited by its cardiotoxicity. In doxorubicin-induced cardiomyopathy, vacuolization of the sarcoplasmic reticulum (SR) has been reported. We investigated whether doxorubicin had a direct action on the sarcoplasmic reticulum (SR) in isolated perfused rat hearts. The left and right atria were trimmed to maintain heart rate (HR) <200 beats/min. Postrest contractions, which are believed to be due primarily to Ca2+ release from the SR, were evoked with a programmable stimulator after variable rest intervals. The amplitude of the postrest contractions increased markedly as the rest interval increased. Doxorubicin (0.1 mM) significantly suppressed this potentiation of the postrest contractions. Furthermore, doxorubicin slowly induced aftercontractions and an increase in left ventricular diastolic pressure (LVDP), phenomena that are usually associated with ouabain intoxication. We conclude that doxorubicin-induced cardiomyopathy may be due to SR dysfunction, leading to intracellular Ca2+ overload.
Animals↗
Glucose infusion paradoxically accelerates degradation of adenine nucleotide in working muscle of patients with glycogen storage disease type VII.
We investigated the effect of glucose infusion on adenosine triphosphate degradation in skeletal muscle of patients with glycogen storage disease type VII. Three patients and six healthy subjects exercised on a bicycle ergometer twice, once with 20% glucose infusion and once with saline infusion. The glucose infusion increased plasma glucose levels to 170 to 182 mg/dl and serum insulin levels to 30 to 50 microU/ml, while it markedly decreased plasma free fatty acid levels. The exercise-induced increases in plasma ammonia, inosine, and hypoxanthine were much larger with glucose than with saline infusion in the patients. Urinary excretion of inosine and hypoxanthine with glucose infusion was twice as high as that with saline infusion. No such differences were present between glucose and saline infusion in the healthy subjects. Glucose infusion therefore accelerates the energy crisis in working muscle of patients with glycogen storage disease type VII, probably due to a decrease in fatty acid utilization.
Adenine Nucleotides↗
Effect of nicorandil on cardiac dysfunction during reperfusion in normotensive and spontaneously hypertensive rats.
The cardioprotective effect of nicorandil, an opener of ATP-sensitive potassium channels, was studied in the isolated perfused hearts of the spontaneously hypertensive rat (SHR) and normotensive Wistar-Kyoto (WKY) rat. The hearts were subjected to 30 min of global ischemia followed by 30 min of reperfusion. Controls received no drug. In the nicorandil group, the hearts were treated with 0.03 to 0.3 mmol/L nicorandil for 15 min before ischemia. Left ventricular developed pressure (LVDP) and end diastolic pressure (LVEDP) at 30 min of reperfusion were significantly lower and larger, respectively, in SHR than in WKY rats. Nicorandil improved LVDP and decreased LVEDP at 30 min of reperfusion in both SHR and WKY rats dose-dependently. The hypertensive heart in the early stage is already susceptible to reperfusion-cardiac dysfunction. Nicorandil has a beneficial effect on the post-ischemic dysfunction in both SHR and WKY rats.
Animals↗
[A study of ceftriaxone concentration in serum and tissue of patients with chronic sinusitis].
After an intravenous drip infusion of 1 g or 2 g of ceftriaxone (CTRX), its concentrations in serum and tissue were determined using the bioassay for 18 surgical patients with chronic paranasal sinusitis. 1. The serum levels observed at 75-105, 135-165, 195-225 minutes after an intravenous drip infusion of 1 g, averaged 98 +/- 38, 92 +/- 13 and 73 +/- 13 micrograms/ml, respectively. 2. The tissue levels at 75-105, 135-165, 195-225 minutes after an intravenous drip infusion of 1 g, averaged 27 +/- 13, 27 +/- 7 and 25 +/- 9 micrograms/g. 3. CTRX appears to be a useful drug for the treatment of chronic paranasal sinusitis.
Adult↗
Characterization of the adrenoceptor antagonistic and antihypertensive activity of oral amosulalol, a combined alpha- and beta-adrenoceptor antagonist, in hypertensive rats.
The adrenoceptor antagonistic and antihypertensive effects of amosulalol, 5-[1-hydroxy-2-[[2-(o- methoxy)ethyl]-2-ethylbenzenesulfonamide HCl, a combined alpha- and beta-adrenoceptor antagonist, were examined in hypertensive rats. Oral administration of amosulalol (1-30 mg/kg) produced a dose-dependent antihypertensive effect without reflex tachycardia in conscious spontaneously hypertensive rats (SHR) with a duration > 10 h after the higher doses (10 and 30 mg/kg). Amosulalol was approximately threefold more potent than labetalol and arotinolol in decreasing blood pressure (BP) in conscious SHR. Oral (p.o.) administration of amosulalol 10 mg/kg produced equally potent reductions in mean arterial BP (MBP) without reflex tachycardia in deoxycorticosterone acetate-salt rats (DHR) and renal hypertensive rats (RHR) as it did in SHR. Repeated oral administration (1, 4, 8, or 12 weeks) of amosulalol 10 mg/kg elicited an antihypertensive effect without evidence of tolerance in conscious SHR and produced a rightward shift in phenylephrine (PE)-induced vasopressor and isoproterenol (ISO)-induced positive chronotropic responses with dose ratios of 3.3-12.5 and 3.7-6.4, respectively, in pithed SHR. In addition, single p.o. administration of amosulalol 10 mg/kg produced a rightward shift in these responses with dose ratios of 12.1 and 3.5, respectively, in pithed SHR. Amosulalol exerted antihypertensive activity without tachycardia through blockade of vascular alpha- and cardiac beta-adrenoceptors, and its activities were constant even after repeated p.o. administration.
Administration, Oral↗
Retrovirus gag protein p30 in the islets of non-obese diabetic mice: relevance for pathogenesis of diabetes mellitus.
We investigated the presence of retroviral protein in the pancreatic islets of non-obese diabetic mice to prove that the virus-like particle observed specifically in the pancreatic Beta cell of these mice was retrovirus. Western blot analysis probed with anti-retrovirus antibody demonstrated the existence of retroviral gag (group specific antigen) protein p30 in the islets of female non-obese diabetic mice. Islets of non-obese diabetic mice which were treated with cyclophosphamide, known to accelerate the development of insulitis and diabetes mellitus, have shown both a significantly increased number of retrovirus-like particles (type C) and enhanced expression of gag protein p30, compared to those of mice not treated with cyclophosphamide. These results confirmed the presence of type C retrovirus in non-obese diabetic mouse Beta cells and suggest a role for retrovirus in the development of insulitis and diabetes in these mice.
Animals↗
New monoclonal antibodies for the detection of immediate early antigens of cytomegalovirus.
Two new monoclonal antibodies, CIE-1 and CIE-2, were developed for the rapid detection of human cytomegalovirus (HCMV) infection. They were found to be reactive with immediate early protein of HCMV in the nuclei of infected fibroblasts, as early as 3 hours post-infection. By radioimmunoprecipitation, CIE-1 was found to react with a protein with an apparent molecular weight of 70,000, whereas CIE-2 precipitated 2 proteins of 70,000 and 72,000 daltons, respectively. Both monoclonal antibodies recognized three prototype strains of HCMV: AD-169, Towne, and Davis, and did not cross-react with other human herpesviruses. CIE-1 and CIE-2 were compared with four commercial anti-HCMV monoclonal antibodies (Clonab, Dupont, Sera-Lab and Syva) by testing 88 clinical isolates. Culture confirmation tests and shell vial assays showed that CIE-1 and CIE-2 were more sensitive than several of these reagents and equally sensitive to the Dupont reagent. Moreover, CIE-1 and CIE-2 produced a bright, sharp staining of the nuclei of infected cells. These monoclonal antibodies should thus be valuable in rapid diagnosis of HCMV.
Animals↗
Interferon-gamma inhibits thyroid-stimulating hormone-induced morphological changes and induces the expression of major histocompatibility complex class II antigen in thyroid follicles in suspension culture.
The effects of interferon-gamma (IFN gamma) on the morphology of thyroid follicles and the expression of major histocompatibility complex (MHC) class II antigens were examined. The thyroid follicles were suspended in RPMI-1640 containing 10% fetal calf serum with or without IFN gamma (200 U/ml). After culture for 5 days, follicles were incubated in the presence of TSH (10 mU/ml) for 1 h and fixed for electron microscopic and immunohistochemical examination. Regardless of the presence of IFN gamma, suspended follicles became inverted within 5 days. However, MHC class II antigens were expressed only in inverted follicles cultured with IFN gamma. In inverted follicles cultured without IFN gamma, TSH stimulation induced remarkable morphological changes, such as elongation of microvilli and an appearance of pseudopods. On the other hand, the follicles cultured with IFN gamma showed poor response to TSH. Thus, IFN gamma induced the expression of MHC class II antigens of cultured thyroid follicles and inhibited TSH-induced morphological changes in the cells.
Animals↗
[Viral infection and diabetes mellitus].
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Animals↗
Preventive effect of a new immunosuppressant FK-506 on insulitis and diabetes in non-obese diabetic mice.
We investigated the effect of an immunosuppressant FK-506 on histological change of islets, the onset of diabetes, and the change of spleen cell subsets in female non-obese diabetic mice. Mice administered intraperitoneally with FK-506 from 5 to 20 weeks of age showed marked suppression of mononuclear cell infiltration (insulitis) at 10 weeks of age. Among the subsets of the spleen cells, a significant decrease in the population of Thyl.2-positive T cells (pan-T), L3T4-positive T cells (mainly helper/inducer), and Lyt2-positive T cells (mainly suppressor/cytotoxic) was observed in FK-506-treated mice. Furthermore, glucose tolerance of the mice at 15 weeks of age was clearly improved. Cumulative incidence observed up to 40 weeks of age was 86% in control mice and 23% in FK-506-treated mice (p less than 0.01). These data indicate that FK-506 has a preventive effect on insulitis and diabetes by the suppression of cell-mediated autoimmunity in non-obese diabetic mice.
Animals↗
Interferon-gamma reduces actin filaments and inhibits thyroid-stimulating hormone-induced formation of microvilli and pseudopods in mouse monolayer thyrocytes.
To study the role of interferon-gamma (IFN gamma), which is released from activated lymphocytes in the development of lymphocytic thyroiditis, we investigated the effects of IFN gamma on the morphology of mouse thyrocytes, using scanning electron microscopy. Thyrocytes were cultured in monolayers for 5-7 days and incubated with TSH (10 mU/ml) for 1 h before fixation. IFN gamma (200 U/ml) was added to the culture medium for 1 h to 5 days before TSH stimulation. Coculture of thyrocytes with IFN gamma for more than 24 h inhibited TSH-induced morphological changes in the thyrocytes; IFN gamma inhibited the increase in the number of and elongation of microvilli and the appearance of pseudopods. IFN gamma also reduced the number of actin filaments in thyrocytes, as confirmed by immunofluorescence photometry. These results suggest that IFN gamma inhibits the morphological response of thyrocytes to TSH stimulation by the reduction of actin filaments.
Actins↗
[Clinical significance of anti human N-myc protein antibody assay as a tumor marker].
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Antibodies↗
The N-myc gene product in primary retinoblastomas.
The N-myc gene product in retinoblastomas was examined using the antisera against the N-myc gene product, which was produced as a fusion protein by Escherichia coli. The N-myc gene product was detected not only in the retinoblastoma cell line Y79 but also in primary retinoblastomas as a pair of bands of approximately 62 kilodaltons (KD) by immunoblotting. Immunohistochemical analysis showed positively stained cells with the antibody against the N-myc gene product in a few rosettes or fleuretts containing area of the tumor. The nuclei of the cells were positively stained. The N-myc gene product was not detected in the normal part of the retina or in other parts of the eye. The results suggested that the level of the N-myc gene product may be inversely correlated with the differentiation of retinoblastoma cells and that the detection of the N-myc gene product may be useful in the diagnosis of retinoblastoma. Because the undifferentiated form of retinoblastoma carries a worse prognosis than the differentiated forms, the level of the N-myc gene product may be related to the aggressiveness of the tumor cells. It remains to be seen whether metastatic retinoblastoma has a higher concentration of the N-myc gene product.
Cell Line↗
[Physiological changes in white blood cell count in peripheral blood of radiation workers].
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Adult↗
[Immunohistochemistry of the human fetal mesonephros with anti-human N-myc protein antibody].
Expression of a N-myc gene has been found in Wilms' tumor. N-myc protein, which is a N-myc gene product, can be detected using an anti-N-myc antibody. Paraffin sections of the fetal tissues at the seventh week of gestation were prepared for immunohistochemistry, stained by PAP method. The N-myc gene product was observed in the cells consisting of the mesonephric ductular wall. This result may suggest that Wilms' tumor is originated from the mesonephric tissue.
Amino Acid Sequence↗