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Biomedical subjects

H Mikami

Publications and source records attributed to H Mikami.

At least 109 records · Page 6Linked to original sources
PubMed1994

[Effects of pravastatin administration for 12 months on serum lipid levels in aged patients with hypercholesterolemia].

To evaluate long-term efficacy of pravastatin, we administered this HMG-CoA reductase inhibitor at a mean dose of 9.9 mg/day to 208 aged patients with serum levels of total cholesterol (TC) over 220 mg/dl (mean +/- SD aged of 70 +/- 7 years; 62 males and 146 females) for 12 months. The mean serum value of TC significantly decreased from the basal level of 265 mg/dl to 216 mg/dl in the 3rd month, and this decrease was maintained throughout the observation period. Similar change was observed in the serum level of low density lipoprotein-cholesterol (LDL-C). Although the mean serum level of high density lipoprotein-cholesterol (HLC-C) in all patients did not change significantly, the HDL-C level in 34 patients with a HDL-C level below 40 mg/dl significantly increased from the 3rd month. The mean serum level of triglyceride (TG) in all patients significantly decreased from the 3rd month, and this decrease in the TG was more prominent in 101 aged patients with TG levels higher than 150 mg/dl. In 168 aged patients on 10 mg/day of pravastatin throughout the period, there were significant negative correlations between the ratio of the decrease in TC in basal serum and each of the basal serum TC levels (r = -0.345, p < 0.001) and age of the subjects (r = -0.208, p = 0.007). These results indicate that long-term administration of pravastatin is effective treatment for lipid metabolism even in aged patients.

Aged↗
PubMed1994

[Characteristics of blood pressure regulating endocrinological factors in elderly essential hypertensives].

Plasma renin activity (PRA) was lower in elderly normotensive subjects and essential hypertensives (EHT), and a significant negative correlation was found between PRA and age in both groups. In EHT, the proportion of the low renin group to total EHT increased with aging. There was a significantly positive correlation between plasma norepinephrine (PNE) and age in NT, but not in EHT. The mean value of PNE in young subjects was significantly higher in EHT than in NT, but not in the middle-aged and elderly groups, suggesting the important role of PNE in young EHT. Power spectral analysis revealed a significant reduction of both sympathetic and parasympathetic activity with aging in NT and EHT, indicating much caution may be required if sympathetic nerve activity is evaluated only by PNE levels in elderly EHT. The expanded plasma volume was another characteristic in elderly EHT, and suppressed activity of renal kallikrein-kinin, prostaglandin and dopamine may be involved with its mechanisms. Regarding insulin sensitivity in elderly EHT, it was shown that 1) the reduction of insulin sensitivity plays some role in age related acceleration of hypertension and glucose intolerance, 2) selective insulin resistance with respect to glucose metabolism already exists at lower ages in EHT, and 3) both Na retention and pressor system activation via insulin action might be a cause of blood pressure elevation in EHT.

Adult↗
PubMed1994

[The patients' right of self-decision and the discretion of physicians].

I attended the 10th liaison society of ethics committees in medical schools in Japan. Three topics on the problems of the terminal patients, Jehovah's Witness needing blood transfusion and the patients suffering from AIDS were discussed by symposists consisted of 6 physicians, 2 nurses and a jurist. I picked up key phrases from the symposists' presentations with respect to professions. The physicians used the terms of terminal care, quality of life, informed consent, etc. The nurses emphasized a labor shortage, an ideal physician, cooperation of the patient's family, etc. A jurist expressed euthanasia, death with dignity, right of living and dying, etc. The common issue relating with all terms would be "patient's right of self-decision". Physicians should recognize this right and then exercise their discretion. All patients should be regarded as social beings under the medical care, which would be realized when physicians treat diseases with the relevant patients.

Decision Making↗
PubMed1994

[Cultural background of the Japanese bioethics].

We attended the 11th Liaison Society of Ethics Committees in Medical Schools in Japan. Three symposiums were held under the themes of quality of life (QOL), stopping medical cure and the Japanese bioethics. Symposists were medical practitioners, teaching staffs in universities and a person of religion. In the first symposium, the definition of QOL, the usage of the term and the method of its evaluation were discussed. In the second symposium, an internist and a neonatologist reported several cases and stated problems and countermeasures in terminal care in cases that they could not maintain QOL. A person of religion made his opinion on the problems. In the final symposium were stated Japanese bioethics from the aspects of ethics and cultural anthropology. They emphasized differences in bioethical view between the Japanese and the Europeans and Americans, and a need to reform medical education in Japan. It is difficult to define QOL and to care patients at terminal stage, because present-day persons have various senses of value. Especially, Japanese have taken Western culture into our traditional social structures with its original style. Therefore, we have dual culture, as recognized in communication. Although it is very important to communicate sufficiently between patients and doctors, we consider that the dual communication has interrupted their mutual understandings. Incidentally, Western medicine had originally dual structure of art and technology. But we have taken only the technological aspect. That is probably the reason why human relations have been getting worse. It would be necessary for us to attend to these two dual structures in order to solve bioethical problems in Japan.

Bioethics↗
PubMed1994

Role of the renin-angiotensin system in hypertension in the elderly.

Although the activity of the renin-angiotensin system is known to decrease with age, the antihypertensive efficacy of angiotensin-converting enzyme (ACE) inhibitors has been demonstrated in the elderly. To examine the role of the renin-angiotensin system in hypertension in the elderly, we evaluated the antihypertensive response to enalapril and to TCV-116, an angiotensin II type-1 receptor antagonist, in elderly patients with essential hypertension. A single oral dose of enalapril (10 mg) increased plasma renin activity (PRA) and reduced the angiotensin II concentration, whereas a single oral dose of TCV-116 (4 mg) increased both PRA and the angiotensin II concentration. Blood pressure was significantly reduced by these drugs from 4 h after administration. Basal levels of PRA and angiotensin II declined with age. However, the changes in blood pressure produced by either TCV-116 or enalapril did not correlate with age. These results suggest that the activity of the renin-angiotensin system in plasma declines with age, and that the extrarenal renin-angiotensin system may play a role in hypertension in the elderly.

Adult↗
PubMed1994

Activated angiotensin II generation and regulation in rat mesenteric arteries following nephrectomy.

The objectives of the present study were to test the hypothesis that vascular angiotensin II (AII) generation may be negatively regulated by circulating AII in Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR), and to clarify the role of this vascular AII in the sustained hypertension seen in SHR following nephrectomy. The mesenteric arteries from kidney-intact and nephrectomised WKY and SHR were perfused, and the level of AII released into the perfusate were measured. The effects of CV-11974, a newly developed nonpeptide AII receptor antagonist, on AII release were examined to investigate the existence of a local feedback system in the blood vessels. Nephrectomy augmented vascular AII release both in WKY and SHR despite the reduction in circulating AII. CV-11974 significantly increased AII release from the mesenteric arteries of kidney-intact rats. There were no significant differences in these responses between WKY and SHR. These results suggest that WKY and SHR share a potent pathway for producing vascular AII in response to the withdrawal of circulating AII, although this pathway is not responsible for the sustained hypertension seen in SHR after nephrectomy.

Angiotensin II↗
PubMed1994

Long-term therapy with terazosin may improve glucose and lipid metabolism in hypertensives: a multicenter prospective study.

The effects of long-term monotherapy with terazosin, an alpha-1 blocker, on blood pressure, glucose tolerance, and serum lipid profiles were prospectively investigated in 53 hypertensive patients: 19 with normal glucose tolerance (NGT) and 34 with impaired glucose tolerance (IGT). The plasma glucose, serum lipids, fructosamine, and glycosylated hemoglobin A1c (HbA1c) levels were determined before and during long-term (6 months) therapy with terazosin. A 75-g oral glucose tolerance test was performed before and during long-term terazosin therapy. Significant falls in both systolic and diastolic blood pressure in both patient groups were maintained during the long-term therapy with terazosin. Neither fasting nor postglucose-load venous plasma glucose levels were altered in either group of patients, and diabetes mellitus did not develop in any patient with NGT during the study. There was no significant change in the insulinogenic index (delta IRI/delta BS at 30 minutes after glucose load) in either patient group. In patients with IGT, glucose intolerance was slightly improved with significant reductions in HbA1c and fructosamine during terazosin therapy. Serum total cholesterol (TC) and triglyceride levels were significantly decreased in patients with IGT. In addition, TC and low density lipoprotein (LDL) cholesterol were significantly decreased in patients with hypercholesterolemia (TC > 220 mg/dL). These results suggest that long-term therapy with terazosin may improve glucose and lipid metabolism in hypertensive patients and terazosin seems to be an antihypertensive agent with beneficial effects for hypertensive patients with either dyslipidemia or impaired glucose metabolism.

Adrenergic alpha-Antagonists↗
PubMed1994

[A case of examination of skeletal remains--how many bodies did they come from?].

We examined skeletal remains, with the main intention of estimating how many bodies they had come from. The samples were a skull with defect of its base, an upper jaw, two lower jaws (No. 1, No. 2) and two skeletal bodies (No. 1: with no skull, No. 2: consisting mainly of the lower extremities). In examining the mutual relationship among them, we utilized adjustability between the skull and the lower jaws at the temporomandibular joint, and between the lower jaws and the upper jaw in the biting manner of their teeth. We concluded that the most probable combination was of two bodies, i.e. [skull + lower jaw No. 1 + skeletal body No. 1] and [upper jaw + lower jaw No. 2 + skeletal body No. 2]. Beside the above presentation, we did comment on several problems in personal identification and estimation of postmortem interval.

Adult↗
PubMed1994

Association analysis of a polymorphism of the angiotensinogen gene with essential hypertension in Japanese.

An association study of the polymorphism of the angiotensinogen gene, consisting of T-->C transition at nucleotide 704 in exon 2, with essential hypertension in the Japanese population was performed by restriction fragment length polymorphism (RFLP). The allele which contained the Tth 111-I restriction site in the presence of C transition was designated 'a' and the allele that lacked restriction site was designated 'A'. The frequency of aa genotype in our normotensive group was higher than the previously reported values in Caucasians. In spite of the high frequency of the aa genotype in Japanese, the aa genotype was significantly more frequent in 108 hypertensives than in 104 normotensive subjects compared with the two other genotypes (P = 0.009). These results suggested that this molecular variant of the angiotensinogen gene may be a preserved inherited predisposition for essential hypertension in various ethnic groups, including Caucasians and Japanese.

Angiotensinogen↗
PubMed1993

Dahl's salt-resistant normotensive rat has mutations in cytochrome P450(11 beta), but the salt-sensitive hypertensive rat does not.

Molecular cloning of cytochrome P450(11 beta) cDNAs from the adrenal glands of Dahl's salt-sensitive hypertensive (DS) and salt-resistant normotensive (DR) rats was performed using a combined technique of the first strand cDNA synthesis by reverse transcriptase followed by polymerase chain reaction. The cDNA sequence of P450(11 beta)-DS was identical to that of wild type P450(11 beta). In contrast, the clone obtained from the DR rat contained six nucleotide substitutions causing five amino acid alterations (Arg-127-->Cys, Val-351-->Ala, Val-381-->Leu, Ile-384-->Leu, and Val-443-->Met). When the two cDNAs were expressed in COS-7 cells and steroid conversion rates of the transformed cells were determined, a ratio of 18-hydroxylation to 11 beta-hydroxylation of 11-deoxycorticosterone by P450(11 beta)-DS-expressed cells was 0.58, whereas that by P450(11 beta)-DR-expressed cells was 0.23. Plasma levels of 18-hydroxy-11-deoxycorticosterone and corticosterone (the 11 beta-hydroxylation product of 11-deoxycorticosterone) in DS and DR rats well reflected the steroidogenic activities of the two P450s. These results suggest that the characteristic plasma steroid level of the DR rat is caused by the mutations in P450(11 beta) gene and may act to maintain the normotensive blood pressure in this rat strain during sodium loading.

Amino Acid Sequence↗
PubMed1993

A neuropeptide Y locus on chromosome 4 cosegregates with blood pressure in the spontaneously hypertensive rat.

Recent advances in molecular biology have allowed the study of the candidate genes for essential hypertension. To identify the genes responsible for basal blood pressure in the spontaneously hypertensive rat strain, the rat model of genetic hypertension, we performed a cosegregation analysis between the genotype and blood pressure in a set of male F2 progeny obtained from SHR and Wistar-Kyoto rats, a reference normotensive strain. Our investigation revealed that a locus on the chromosome 4 cosegregates with the blood pressure in SHR, especially at neuropeptide Y locus. The degree of cosegregation with all values of blood pressure without sodium loading was moderate but consistent. We propose that neuropeptide Y locus on chromosome 4 is a new candidate for the hypertensive effect in original SHR.

Animals↗
PubMed1993

Association analysis of a polymorphism of the angiotensin converting enzyme gene with essential hypertension in the Japanese population.

An association study of the insertion/deletion (I/D) polymorphism located in intron 16 of the ACE gene with essential hypertension in the Japanese population was performed. The 287 bp I/D polymorphism was detected by polymerase chain reaction. Derived allele frequencies for insertion and deletion were not significantly different between 133 hypertensive and 104 normotensive subjects. A significant relationship between I/D polymorphism and plasma ACE activity was observed in the normotensive group, but not in hypertensives. These results suggest that I/D polymorphism of the gene is not implicated in Japanese hypertensive subjects, and that studies involving various ethnic groups are important.

Adult↗
PubMed1993

Heredity of muscle fibre composition estimated from a selection experiment in rats.

The extent to which muscle fibre composition was determined by the genes transmitted from parents was estimated by using successive selections of rats. A foundation population (G0) was established to carry out the selections; it consisted of 100 albino rats which were randomly chosen from heterogeneous stock. The heterogeneous stock was produced by random-mating of three strains, Wistar-Imamichi, Fischer 344 and Donryu. Successive selection for a high percentage of slow twitch fibres (% ST) was made from G0 to the fourth generation (G4). The mean values of % ST changed from 50.0% in G0 to 55.6% in G4. The mean value in G4 was significantly higher than that in G0. The realized heritability in G0-G4 was calculated from the regression of selection response on the cumulated selection differential. The regression coefficient was 0.17 (SEM 0.04). The realized heritability was significantly different from 0 at the 0.05 level. We concluded that in rats about 17% of the variation of muscle fibre composition was determined by the genes transmitted from parents.

Animals↗
PubMed1993

Simultaneous and separated culture of keratinocytes and fibroblasts on each side of a collagen membrane.

We have developed a new cell culture system which is of benefit for the research of dermal-epidermal interaction. In this system, normal human keratinocytes are cultured on the upper surface of a permeable collagen membrane, on the undersurface of which human fibroblasts are simultaneously and separately cultured in a lifted condition. Both the keratinocytes and fibroblasts showed good proliferation and differentiation which were revealed by phase contrast microscopy as well as light and electron microscopies. A permeability test of the collagen membrane used in the present study showed that peptides of less than 30 kDa are able to penetrate through the membrane. Using this system, we estimated the total protein content and cornified envelope formation in the keratinocytes cultured with or without fibroblasts. We found that the total protein and cornified envelope formation were significantly increased when keratinocytes were cultured together with fibroblasts. When keratinocytes were cultured with fibroblasts in the condition of air-liquid interface, synthesis of the cornified envelope was further enhanced. These results indicate that fibroblasts really effect not only the proliferation but also the differentiation of keratinocytes, and the air-liquid interface enhances their effect on differentiation. This bi-phase separated cell culture system is a useful tool for the study of keratinocyte-fibroblast interaction.

Cells, Cultured↗
PubMed1993

The role of activated vascular angiotensin II generation in vascular hypertrophy in one-kidney, one clip hypertensive rats.

OBJECTIVE: To investigate the role of vascular angiotensin II (Ang II) in the vascular thickening of one-kidney, one clip (1-K, 1C) hypertensive rats, which show normal plasma renin activity. METHODS: The type 1 Ang II receptor antagonist TCV-116 (1 mg/kg per day), the angiotensin converting enzyme (ACE) inhibitor delapril (20 mg/kg per day), hydralazine (20 mg/kg per day) or vehicle were administered to four groups of 1-K, 1C rats aged 6-10 weeks. Vehicle was also given to uninephrectomized rats. RESULTS: The aortae of 1-K, 1C rats contained significantly higher levels of Ang II than those of uninephrectomized rats and showed hypertrophy, but not hyperplasia of their medial smooth muscle cells. Hypertrophy was estimated by immunohistochemical staining of alpha-actin. Hyperplasia was estimated by DNA content and incorporation of 5-bromo-2'-deoxyuridine. The blood pressure of the 1-K, 1C rats was not affected by either TCV-116 or delapril, even at doses sufficient to induce depressor effects in spontaneously hypertensive rats. However, subdepressor doses of TCV-116 and delapril both significantly reduced the alpha-actin-stained area to 78 and 73%, respectively, of that in the 1-K, 1C rats, whereas a depressor dose of hydralazine did not affect the alpha-actin-stained area. The level of Ang II in the aorta, but not in plasma, was suppressed by delapril but not by hydralazine. CONCLUSIONS: These results suggest strongly that vascular Ang II plays a major role in the development of vascular hypertrophy, independently of plasma Ang II, bradykinin and ACE-independent pathways of Ang II generation, and in the regulation of blood pressure in this normoreninaemic hypertensive model.

Actins↗
PubMed1993

Discrepancy between renin mRNA and plasma renin level in angiotensin-converting enzyme inhibitor-treated rats.

1. To investigate the role of transcriptional and post-transcriptional factors in increasing renin synthesis secondary to angiotensin-converting enzyme (ACE) inhibitors, we studied the changes in levels of renal renin mRNA, plasma renin and other hormonal factors. 2. Spontaneously hypertensive rats were orally administered 10 mg/kg spirapril or vehicle daily for 3, 14 or 28 days. 3. Plasma renin activity in the spirapril-treated group was significantly elevated compared with that in the vehicle group at any time (P < 0.01). However, there was no significant change in plasma angiotensin II concentration between the two groups. The ratio of renal renin mRNA to beta-actin mRNA in the spirapril-treated group was higher than that in the control group (P < 0.01). 4. At 28 days, plasma renin activity in the spirapril-treated group was significantly elevated compared with that at 14 days (P < 0.05). However, there was no change in renin mRNA between 14 and 28 days after ACE inhibitor administration. 5. Plasma ACE activity in the treatment group was less than that in the control group at any time (P < 0.01). 6. Our study demonstrated a non-proportional change in plasma renin and renal renin mRNA levels. It is suggested that the main determinant of the rate of renin synthesis after administration of an ACE inhibitor may be post-transcriptional factors, and that unknown mechanisms may be involved in the increase in plasma renin level after long-term administration of ACE inhibitor in addition to the short feedback mechanism brought about by the decrease in angiotensin II.

Actins↗
PubMed1993

The angiotensin-converting enzyme inhibitor, perindopril, prevents cardiac hypertrophy in low-renin hypertensive rats.

1. To examine whether an angiotensin-converting enzyme (ACE) inhibitor prevents left ventricular (LV) hypertrophy even in low-renin hypertension, we studied the effect of the administration of perindopril on cardiac hypertrophy induced by partial renal ablation in hypertensive rats. 2. Rats that had undergone partial nephrectomy were randomly divided into four groups that received the following as drinking water: Group A, tap water; Group B, 1% sodium chloride (NaCl); Group C, NaCl + perindopril 3 mg/kg per day; and Group D, NaCl + perindopril 1 mg/kg per day. Plasma renin activity (PRA), angiotensin-II (AII) concentration and cardiac tissue AII were measured. 3. Supplementation of NaCl following nephrectomy increased the blood pressure and cardiac weight compared with rats that had undergone nephrectomy alone (P < 0.05). Treatment with perindopril (3 mg/kg per day) did not affect the blood pressure and plasma AII but inhibited the increase of cardiac weight (P < 0.05). Left ventricular AII was decreased in cases of reduced renal mass hypertension, but was not changed by treatment with perindopril. 4. These results demonstrate that perindopril may be able to prevent LV hypertrophy even in low-renin hypertension, which was not mediated by a reduction of blood pressure or suppression of the circulating and cardiac renin-angiotensin systems. Other mechanisms of ACE inhibitors may contribute to the cardioprotective effects.

Angiotensin II↗