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Biomedical subjects

M Nagano

Publications and source records attributed to M Nagano.

At least 19 recordsLinked to original sources

Absence of a putative ATP/GTP binding site in the rat prolactin receptor.

Two types of the long form of the rat prolactin receptor have been identified by two independent groups. One type of receptor has a consensus sequence for a putative ATP/GTP binding site in the cytoplasmic domain, while the other does not. Since this site would confer kinase activity to the prolactin receptor and represent an important element in the process of signal transduction, we wanted to clarify this discrepancy. To that end, three procedures capable of detecting a point mutation were performed: Southern analysis of reverse transcribed polymerase chain reaction (PCR) products, allele-specific PCR, and S1 nuclease analysis. All results clearly indicated that the sequence for the putative ATP/GTP binding site does not exist in the prolactin receptor.

Adenosine Triphosphate

Genetic analysis of dilated cardiomyopathy--HLA and immunoglobulin genes may confer susceptibility.

To identify genetic factors in the immune system which control the susceptibility to dilated cardiomyopathy (DCM), HLA class II DNA typing was performed in 61 Japanese patients, using PCR/SSO probe analyses. The frequencies of HLA-DQB1*0503 (15% vs 5%; RR = 3.06, chi 2 = 7.19) and DQB1*0604 (21% vs 10%; RR = 2.41, chi 2 = 6.20) were significantly increased and that of HLA-DQB1*0502 (RR = 1.74) was slightly increased in the DCM patients. The frequency of DQB1*0303 (16% vs 31%; RR = 0.44, chi 2 = 5.16) was significantly decreased in the patients. The increased HLA-DQB1 alleles have a histidine residue in common at the 30th codon for the HLA-DQ beta chain. Among the genetic markers studied by Southern blot analyses, IGLV (immunoglobulin lambda light chain, pV3.3) showed a strong association with DCM, i.e. A2/A2 genotype was found in 37.7% of patients whereas it was observed in only 18.9% of the control subjects (RR = 2.6, chi 2 = 7.77). The frequency of this genotype was higher in patients under age 45 years at the time of diagnosis (45.5%, RR = 3.6, chi 2 = 10.02). These results suggest that HLA and immunoglobulin genes are closely linked to susceptibility to DCM.

Adolescent

[Work history, health conditions and hearing loss of Ishigaki fishermen].

Based on our previous health survey among Ishigaki fishermen in 1979, this study aimed at clarifying the relations of their work histories to physical characteristics, physiological functions, blood conditions and hearing levels. Medical examination was conducted in 1987 on 118 fishermen inclusive of 33 followed-up fishermen, and in 1989 noise-level and noise-induced temporary threshold shift of hearing was measured for different fishing methods. The results were as follows; 1) Fishing history was not specifically associated with any physical characteristics. 2) High HDL cholesterol, which was observed among divers using diving apparatus, was considered to be a survival effect for divers, since HDL cholesterol is amplified by intensive muscle work. 3) Abnormalities of ECG except for a high R wave were notably observed among the divers, who once changed from unassisted diving to diving with apparatus and then to fishing lines. The main reason for switching jobs was claimed to be caisson disease, and it was suggested that diving with apparatus was related to a high risk of health hazards in the central nervous system and/or respiro-circulatory system. 4) Acoustic acuity greatly declined with aging, and which was commonly observed in groups with different work histories. By way of explanation, exposure to ship engine sounds during daily travelling was the most likely cause. It was also revealed that several hours' exposure to the engine sounds was needed to detect a temporary threshold shift of hearing before and after work.

Cardiovascular Diseases

Effect of manidipine, a novel calcium channel blocker, on quality of life in hypertensive patients.

A multicenter open study was performed to evaluate manidipine monotherapy for 6 months on quality of life in hypertensive patients. One hundred and sixty-six patients with essential hypertension were enrolled. Of these, 2 were excluded because of violation of entry criteria, 4 withdrew from treatment because of side effects, and 12 for personal reasons. Manidipine treatment observed at a daily dose of 10 to 20 mg produced effective reduction in blood pressure during the course of the study. Adverse reactions such as palpitation or headache were experienced by 5 of 166 (3%) patients. Quality of life (QOL), assessed grossly by attending physicians, was rated as improved in 62% and unchanged in 36% of patients. Significant improvements in mean QOL scores were noted in general symptoms, physical symptoms and general well-being, work performance and satisfaction, sleep scale, emotional state, cognitive function, sexual function, and self-control. Elderly patients, age 60 years and older, achieved significant improvement in the same QOL items as in all cases; there was no difference between younger and older age groups. In conclusion, manidipine monotherapy is useful for treating patients, including the elderly, with essential hypertension, and this therapy improves their quality of life.

Adult

Regression of hypertension-induced vascular hypertrophy by an ACE inhibitor and calcium antagonist in the spontaneously hypertensive rat.

This study was designed to investigate the effects of antihypertensive drugs on vascular hypertrophy and vascular angiotensin II in vivo in spontaneously hypertensive rats (SHR). Hydralazine (10 mg/kg/day), delapril (angiotensin converting enzyme inhibitor; 20 mg/kg/day), manidipine (calcium channel blocker; 10 mg/kg/day), and vehicle were given by gavage to four groups of SHR between 4 and 5 months of age. The aortic angiotensin II level was measured by highly sensitive radioimmunoassay coupled with high pressure liquid chromatography; aortic morphologic studies were performed. Each drug treatment effectively lowered blood pressure to the same level. However, the aortic wall thickness, medial-intimal areas, and wall to lumen ratio of abdominal aorta decreased significantly (p < 0.05, p < 0.01, p < 0.01, respectively) with delapril and manidipine but not hydralazine. Delapril significantly decreased aortic angiotensin II levels (p < 0.05), whereas manidipine treatment significantly increased them (p < 0.05). The aortic angiotensin II level was not changed by hydralazine. These results show that delapril and manidipine caused regression of hypertension-induced vascular hypertrophy in SHR. The probable mechanism of regression of aortic hypertrophy by delapril was inhibition of vascular angiotensin II formation, but the mechanism for manidipine was unclear.

Angiotensin II

Intracellular pH and plateau duration of internally perfused squid giant axons.

The effects of changing the intracellular pH on the action potential duration and other electrophysiological properties were studied in squid giant axons perfused intracellularly with TEA(tetraethylammonium)-containing solutions and under Ca-Na bi-ionic conditions. The duration of the action potential plateau, produced by TEA, was markedly decreased with acidic intracellular solutions and increased with alkaline intracellular solutions. The normalized duration, d, was calculated by dividing the plateau duration by that of the standard intracellular pH of 7.3, and plotted against the intracellular pH. The curve could be expressed by the formula log [d/(D-d)] = n(pH-pK') where D is the saturated value of d, n a constant and pK' the value of pH at which d becomes D/2. The values selected for D and n were 2.6 and 1.4, respectively. The pK' was found to be 7.5. Lowering of the extracellular pH to 6.2 only slightly changed the plateau duration. Voltage clamp analysis revealed that acidic intracellular solutions decreased the size of the inward current and the slope conductance which were measured at the late period of the depolarizing clamping pulse. Alkaline intracellular solutions increased the size of the inward current and the slope conductance measured at this late period. Intracellular perfusion with a low pH solution also shortened the duration of the Ca-Na bi-ionic action potential. It is argued that the remarkable generality of the pH effect on the plateau duration implies the existence of a common mechanism of formation of the plateau under widely differing experimental conditions.

Action Potentials

Alteration of sialoglycoprotein in the glomerular basement membrane of diabetic glomerulosclerosis.

The alteration of glycoprotein in the glomerular basement membrane in diabetic glomerulosclerosis was studied with preparative polyacrylamide gel electrophoresis by Uniphor column. Normal glomerular basement membrane was fractionated into 32 glycoprotein fractions. Decrease in sialic acid residue of sialoprotein was the characteristic finding observed in diabetic glomerulosclerosis. A hypothesis which explains the alteration of sialoglycoprotein is proposed.

Basement Membrane