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Biomedical subjects

T Ogihara

Publications and source records attributed to T Ogihara.

At least 487 records · Page 27Linked to original sources

Carrier detection of Werner's syndrome using a microsatellite that exhibits linkage disequilibrium with the Werner's syndrome locus.

Werner's syndrome (WS) is a rare autosomal recessive disorder, one of the progeroid syndromes, characterized by features of premature aging. The genetic defect in WS is unknown but recently the genetic linkage of WS to several markers on the short arm of chromosome 8 has been reported. Genetic analysis of 25 families with WS demonstrated that D8S339 was the closest marker linked to the gene locus for Werner's syndrome (WRN), with a peak lod score of 18.29 at recombination frequency 0.001, and showed a linkage disequilibrium with the WRN locus. We studied two unrelated families with WS using ANK1, D8S339, and D8S360. The mutative haplotype identified through the generations in pedigrees provides a means of carrier detection and presymptomatic diagnosis.

Female↗

Absence of association of TAP and LMP genes with type 1 (insulin-dependent) diabetes mellitus.

Although one of the major genes which cause type 1 (insulin-dependent) diabetes mellitus is located in the class II HLA region in humans, its precise location is still unknown. In order to investigate whether TAP (Transporter associated with Antigen Processing) and LMP (Low Molecular Weight Polypeptide) genes, which are located in the class II HLA region, are HLA-linked diabetogenic genes, the association of TAP1, TAP2 and LMP2 genes with type 1 diabetes was analyzed in the Japanese population. No difference in allele frequencies of these genes was detected between diabetic patients and control subjects. On the other hand, DQA1 and DQB1 genes showed significant association with type 1 diabetes. These data suggest that the diabetogenic gene in the class II HLA region may be located near the DQA1 and DQB1 loci, rather than the TAP and LMP loci.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Early-onset type 2 (non-insulin-dependent) diabetes mellitus is associated with glucokinase locus, but not with adenosine deaminase locus, in the Japanese population.

To investigate the possible contribution of glucokinase (GCK) and adenosine deaminase (ADA) loci to the genetic susceptibility to type 2 (non-insulin-dependent) diabetes mellitus, we studied the association of these loci with type 2 diabetes in the Japanese population. Fifty patients with type 2 diabetes and 50 control subjects were analyzed for microsatellite polymorphism 3' to the GCK gene and PstI polymorphism in the ADA gene by polymerase chain reaction. The frequency of the most common GCK allele (Z) was significantly lower in type 2 diabetic patients than that in control subjects and a longer Z + 2 allele was more common in type 2 diabetic patients (26% vs. 15%, P = 0.053), particularly in those with younger age of onset (33% vs. 15%, younger onset type 2 diabetes vs. control, P = 0.014). The frequency of genotypes containing at least one Z + 2 allele was significantly more common in type 2 diabetic patients (46% vs. 28%, P < 0.05), particularly in those with younger age of onset (61% vs. 28%, relative risk 4.00, P < 0.01). In contrast, there was no difference in allelic or genotypic frequencies of PstI polymorphism in the ADA gene between the two groups. Despite the association between the GCK locus and type 2 diabetes, none of the patients had known mutations (Glu265-->AM265, Glu279-->AM279, Gly299-->Arg299, Glu300-->Gln300, Leu309-->Pro309). These results suggest that the GCK locus, but not the ADA locus, contributes to the genetic susceptibility to type 2 diabetes in Japanese.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Deaminase↗

Comparative effects of monatepil, a novel calcium antagonist with alpha 1-adrenergic-blocking activity, and nitrendipine on lipoprotein and carbohydrate metabolism in patients with hypertension.

The effects of monatepil, a new calcium antagonist with alpha 1-blocking activity, and nitrendipine on lipoprotein and carbohydrate metabolism in 86 patients with mild-to-moderate hypertension were examined in a randomized, open-label, multicenter (32 hospitals) study. Thirty-nine patients treated with monatepil and 33 patients treated with nitrendipine completed the 12-week study. Monatepil and nitrendipine each significantly decreased both systolic and diastolic blood pressure. Changes in heart rate were not seen in either group. Monatepil administration significantly decreased total cholesterol, low density lipoprotein (LDL) cholesterol, the LDL cholesterol to high density lipoprotein (HDL) cholesterol ratio, apolipoprotein (Apo) B levels, and HbA1c levels, whereas no changes in these measurements were observed in nitrendipine-treated patients. Monatepil also significantly decreased lipoprotein(a) levels, but there were no significant changes in HDL cholesterol, Apo-AI, or Apo-E levels. After nitrendipine treatment, the C peptide concentration decreased significantly, although no significant changes were observed in fasting blood glucose or immunoreactive insulin levels. On the basis of these results, it can be concluded that monatepil belongs to a new class of antihypertensive calcium antagonist with favorable carbohydrate metabolism and lipid-lowering activity, although the clinical importance of these findings has not been established.

Adrenergic alpha-Antagonists↗

Antihypertensive effects of the neutral endopeptidase inhibitor SCH 42495 in essential hypertension.

The antihypertensive effects and safety of a novel neutral endopeptidase inhibitor, SCH 42495, were investigated in hypertensive patients. A multicenter, open clinical trial was conducted in 27 patients with essential hypertension, WHO Stage I or II. Mean age was 64 +/- 1 years. After 2 to 4 weeks of a placebo run-in, 50 mg twice daily, was started, with the dose increased to 100 mg twice daily, and 200 mg twice daily, every 2 weeks, if necessary, to achieve a predetermined response. Blood pressure and pulse rate were monitored every 2 weeks. Blood chemistry, plasma atrial natriuretic peptide (ANP), and plasma cGMP levels were determined before and after the 8-week treatment period. Blood pressure was significantly reduced, from 171 +/- 1/100 +/- 1 mm Hg to 146 +/- 3/84 +/- 2 mmHg (P < .001) at the end of the 8-week treatment period. No change in pulse rate was noted. Efficacy rate was evaluated in 25 patients treated for 4 weeks or more. Efficacy rate was 44% with 50 mg twice daily, 60% with 100 mg twice daily, and 80% with 200 mg twice daily. Adverse reactions such as headaches and palpitation were observed in six patients (22.2%), with treatment discontinued in five. Significant correlation was observed between increment in plasma ANP levels and blood pressure reductions (r = -0.53, P < .05). Increase in plasma cGMP was positively correlated with increments in plasma hANP (r = 0.80, P < .001). SCH 42495 has potent antihypertensive effect associated with an enhancement of endogenous hANP and may be clinically useful as a new class of antihypertensive drug.

Aged↗

Bone mineral density of the lumbar spine in psoriatic patients with long term etretinate therapy.

Etretinate has been known to produce a variety of skeletal manifestations when administered for prolonged periods. To study whether osteoporotic changes occurred during the treatment bone mineral density (BMD) was measured by dual energy X-ray absorptiometry in 13 psoriatic patients who received long term etretinate therapy (average 3.7 yrs). The values of BMD of the lumbar spine in these patients were decreased from those of age-matched controls (92.3 +/- 9.7%), p < 0.01), while those in psoriatic patients who received topical corticosteroid applications alone showed no significant decrease. Our findings suggest that long term etretinate intake induces an increased risk of osteoporotic changes.

Absorptiometry, Photon↗

Augmentation of angiotensin II release from isolated mesenteric arteries of Wistar-Kyoto and spontaneously hypertensive rats following nephrectomy.

1. We previously reported that angiotensin II release from the mesenteric arteries of Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) increased in a time-dependent manner as a result of the isolation of the arteries and perfusion. This phenomenon appeared to be due to the withdrawal of circulating angiotensin II (AII). 2. The purpose of the present study was to test the hypothesis that vascular AII generation may be negatively regulated by circulating AII in WKY and SHR, and to clarify the role of this vascular angiotensin II in the sustained hypertension of SHR following nephrectomy. 3. The mesenteric arteries from kidney-intact and nephrectomized WKY and SHR were perfused and the amount of AII released into the perfusate was measured. The effects of the angiotensin converting enzyme inhibitor, captopril, and the effects of supplementation of renal renin and circulating angiotensins to nephrectomized rats, by blood exchange between kidney-intact and nephrectomized rats, on AII release were examined to clarify the pathway of vascular AII generation after nephrectomy. 4. Nephrectomy caused augmentation of vascular AII release both in WKY and SHR in spite of the abolishment of circulating renin. Captopril reduced this enhanced release of AII, but blood exchange did not affect it. There was no significant difference in these responses between WKY and SHR. 5. These results suggest that WKY and SHR have in common a potent pathway for production of vascular AII in response to the withdrawal of circulating AII, although this pathway is not responsible for the sustained hypertension of SHR after nephrectomy. The precise pathophysiological role of this pathway remains to be elucidated.

Angiotensin II↗

The effects of central administration of angiotensin II type-1 receptor antagonist, CV-11974, in nephrectomized spontaneously hypertensive rats.

1. The role of the brain renin-angiotensin system in the pathogenesis of genetic hypertension was evaluated using a specific non-peptide angiotensin II type-1 receptor antagonist, TCV-116. 2. CV-11974 (active metabolite of TCV-116) was acutely injected either intravenously (i.v.) or intracerebroventricularly (i.c.v) in male spontaneously hypertensive rats (SHR; 12 week old). In separate groups of nephrectomized and sham-operated SHR, graded doses of CV-11974 were administered either i.v. or i.c.v. for 2 days using an osmotic minipump. In another group, the effects of nephrectomy on the depressor effect of chronic treatment with CV-11974 were investigated. Haemodynamics at three points: before infusion, before nephrectomy and 48 h after nephrectomy, were monitored. 3. Acute i.c.v. injection of CV-11974 decreased blood pressure in the presence of the kidney. Prolonged i.c.v. administration of the drug for 2 days decreased blood pressure even at the lowest dosage, which had no hypotensive effects when given i.v. The hypotensive effect of centrally administered CV-11974 was noted even 48 h after bilateral nephrectomy. 4. These results suggest that the brain renin-angiotensin system has a primary role in the maintenance of hypertension after eliminating the circulating renin-angiotensin system in SHR.

Angiotensin Receptor Antagonists↗

Differential control of vascular tone and heart rate by different amino acid neurotransmitters in the rostral ventrolateral medulla of the rat.

1. To test the hypothesis that a central mechanism may play a role in the minimal reflex tachycardia noted in response to peripheral converting enzyme inhibition, we compared the effects of intravenous (i.v.) ceronapril (CER) with nitroglycerin (NTG) on neurotransmitter release in the rostral ventrolateral medulla (RVLM), using an in vivo microdialysis method in pentobarbital anaesthetized rats. 2. CER (0.1 mg/kg, i.v.) caused a progressive decrease in glutamate (GLU) release (CER 65 +/- 7% vs NTG 83 +/- 3% of each baseline at 140 min, P < 0.05) and attenuated the increase in glycine (GLY) release (CER 100 +/- 8% vs NTG 122 +/- 9%, P < 0.05). 3. Prevention of blood pressure reduction due to i.v. CER by concomitant infusion of a subpressor dose of angiotensin II (AII) attenuated the progressive reduction of GLU release (87 +/- 4%, P < 0.05 compared with NTG group), whereas GLY release was not affected (106 +/- 5%, NS compared with NTG group). 4. Perfusion of GLU into this area at approximately physiological concentrations resulted in a sustained tachycardia with an attenuation of the depressor effect of i.v. CER and perfusion of GLY solely lowered blood pressure. 5. These results demonstrate that i.v. converting enzyme inhibitor reduces the release of GLU in the RVLM, which was specifically caused by reducing circulating AII, without any effect on GLY release, thus resulting in the reduction of blood pressure with minimal effect on the heart rate.

Anesthesia↗

Effect of nicotine in migration and proliferation of rabbit gastric mucosal cells in a culture cell model.

The aim of this study was to assess the effects of nicotine on the gastric epithelial restoration using primary cultured rabbit gastric mucosal cell model. Confluent monolayer mucosal cell sheets consisting of mainly mucous cells were wounded using a rotating silicon tip. The process of restoration was monitored, and the size of wound was measured and analysed quantitatively. Artificial wounds recovered in 36 h in controls. The nicotine treatment (10(-5), 10(-4) and 10(-3) mol/L) did not cause any effects on the process of wound repair. Bromodeoxyuridine (BrdU) positive cells appeared around the wound 24-36 h after injury and then disappeared after the complete repair in controls and also in nicotine-treated groups. However, in the morphological observation, numerous vacuoles were detected in parietal cells of nicotine-treated groups. This effect of nicotine was reversible by removing nicotine from the medium. Present data suggest that nicotine has no direct effects on the mucosal restoration but might have an effect on the structure and function of parietal cells.

Animals↗

Myxoid leiomyoma of the vulva mimicking aggressive angiomyxoma.

A case of vulvar leiomyoma with extensive myxoid change in a 40 year old female is described. The tumor had a unique connection with a non-degenerative leiomyoma that compressed the rectum and the bladder. Scattered smooth muscle cells in a loose myxoid stroma were immunoreactive for desmin. Fibroblast-like spindle cells were immunoreactive for vimentin but not for desmin. The initial, although incorrect, pathological diagnosis of the tumor was aggressive angiomyxoma based on the similarity in both clinical and pathological aspects with this more invasive tumor. Myxoid vulvar leiomyoma should also be differentiated from angiomyofibroblastoma. The key to the differential diagnosis is the presence of interlacing smooth muscle cells and an awareness of tendency toward myxoid change in vulvar leiomyomas.

Adult↗

A case of tetrasomy 9p.

A case of mosaic 9p tetrasomy (46,XX/47,XX, + dic[9] [q21]) is reported. Clinical manifestations of the patient were generalized hypotonia, severe mental retardation and characteristic dysmorphic features of 9p tetrasomy. A brief review of the literature is also included.

Chromosome Aberrations↗