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Biomedical subjects

M Ikeda

Publications and source records attributed to M Ikeda.

At least 829 records · Page 46Linked to original sources

Plasma brain natriuretic peptide during ergometric exercise in hypertensive patients with left ventricular hypertrophy.

Cardiac ventricle is shown to be an important source of circulating brain natriuretic peptide (BNP) in hypertensive rats with left ventricular hypertrophy (LVH). This study examined the effect of short-term exercise with a bicycle ergometer on plasma BNP concentrations in 21 essential hypertension patients with LVH established by echocardiography. The results were compared with those from 24 age-matched hypertensives without LVH. Blood pressure, heart rate, plasma renin activity (PRA), and plasma norepinephrine level increased during exercise, but the mean increases of these parameters were not different in the two groups. Resting BNP levels were slightly but significantly higher in the LVH group than in the non-LVH group. This peptide increased during exercise in the two groups, but the exercise-induced increase (percent increase) in plasma BNP was significantly greater in the LVH group than in the non-LVH group (207% +/- 50% v 141% +/- 36%, P < .05). The exercise-induced increase in BNP was significantly correlated with the left ventricular (LV) mass index (N = 45, r = .60, P < .01). By contrast, the exercise-induced increase in BNP was not correlated with the exercise-induced increase in heart rate, systolic blood pressure, diastolic blood pressure, mean blood pressure, PRA, or noradrenaline level. These results suggest that short-term exercise induces an accelerated increase of plasma BNP in hypertensive subjects with LVH. The LV mass appeared to be related to the observed increase of plasma BNP concentration, at least in our hypertensive patients with LVH.

Adult↗

A novel benzodiazepine inverse agonist, S-8510, as a cognitive enhancer.

1. Pharmacological actions of a novel benzodiazepine receptor ligand, S-8510 (2-(3-isoxazolyl)-3,6,7,9-tetrahydroimidazo[4,5-d]pyrano+ ++[4,3-b] pyridine monophosphate monohydrate), were examined in in vitro and in vivo studies. 2. S-8510 was characterized as a partial inverse agonist with a modest GABA ratio and low efficacy. 3. S-8510 ameliorated memory impairment induced by cholinergic deficit in the water maze paradigm of Wistar rats. 4. S-8510 augmented LTP of the Schaffer collateral/commissural fiber-CA1 synapses in the hippocampal slice preparations of SD rat. 5. S-8510 increased the extracellular levels of acetylcholine and noradrenaline in the hippocampus of Wistar rat. 6. S-8510 selectively potentiated pentylenetetrazol-induced convulsion without affecting minimal electroconvulsive shock- or strychnine-induced convulsion in ddY mice. 7. S-8510 failed to induce any sign of anxiety in the Wistar rat pro-conflict test. 8. S-8510 showed antidepressant-like pharmacological actions in ddY mice. 9. These results suggest that S-8510 can be used as a therapeutic drug for senile dementia, including Alzheimer's disease with little risk for inducing anxiety or convulsion.

Animals↗

A case report of occult thyroglossal duct carcinoma.

A 50-year-old male had an occult thyroglossal duct carcinoma in the thyroglossal duct remnant attached to the upper pole of a thyroglossal duct cyst which was noticed due to extravasation of the cyst. After the patient had been struck into the thyroid cartilage with the tip of a bamboo sword while practicing Japanese fencing. The authors emphasize again that the important matter in the treatment of thyroglossal duct cysts is the removal of the whole thyroglossal duct remnant with the central portion of the hyoid bone according to Sistrunk's method in order to prevent not only recurrence of the thyroglossal duct cyst but also not to overlook any microcarcinoma.

Carcinoma↗

Insufficient calcium and iron intakes among general female population in Japan, with special reference to inter-regional differences.

Dietary intakes of calcium (Ca) and iron (Fe) were investigated in 227 women (mostly housewives) in 12 regions in Japan in 1991-1993 by the 24-hour food duplicate method. Nine regions out of 12 had been previously studied in 1977-1982. Utilizing Standard Food Composition database, mean Ca and Fe-intakes in 1991-1993 were estimated to be 602 and 10.4 mg/day, respectively; the former was barely sufficient and the latter was below sufficiency when compared with the Recommended Daily Allowance in Japan for pre-menopausal women. Ca- and Fe-intake did not increase in the 10-year period. Further analysis after classification of the women into three groups of farmers in Okinawa, farmers in Mainland Japan and urban residents showed that Ca and Fe insufficiency was most evident among Okinawa farmers. The leading Ca sources were milk, pulse, vegetables and fish-shellfish, but consumption of milk was generally low, especially among Okinawa farmers. Pulse, vegetables and fish-shellfish were 3 major Fe sources; Okinawa farmers depended more on vegetables and less on fish-shellfish.

Calcium↗

A comparison of the food composition table-based estimates of dietary element intake with the values obtained by inductively coupled plasma atomic emission spectrometry: an experience in a Japanese population.

In order to make quantitative comparison between food composition table-based estimates and instrumental measures by inductively coupled plasma atomic emission spectrometry (ICP-AES), total food duplicates were collected from 232 adult women in 10 study regions in 9 Prefectures in Japan. Daily dietary intake of 5 elements, sodium (Na), potassium (K), phosphorus (P), calcium (Ca) and iron (Fe), were estimated from the weights of food items in each duplicate by use of food composition tables. Parallel to this the intakes were measured by wet-ashing of food duplicate homogenates followed by ICP-AES analysis. Because the emission intensity of K was significantly modified by Na co-present at various concentrations, K was measured after Na concentration was reduced to the value 150 mg/L by dilution. The comparison of the two sets of the results, the estimated values and the measured values, showed that the estimated values were significantly larger than the measured values in the cases of Na, K, Ca and P (the ratio of the estimated to the measured values: 118% for Na, 115% for K, 109% for Ca; and 130% for Fe), whereas the two values essentially agreed with each other in the case of P (ratio: 93%). The differences were too large for any nutritional evaluation to be made when the method of Bland and Altman is applied. The significance of the differences in relation to nutritional evaluation of element intake is discussed.

Adult↗

Inhibition of head and neck metastatic and/or recurrent cancer by local administration of multi-cytokine inducer OK-432.

The multi-cytokine inducer OK-432 is a pulverized preparation of the low-virulence SU strain of Streptococcus pyogenes of human origin. A reduction of the tumour mass in the OK-432-injected areas was observed in 11 out of 13 patients with metastatic and/or recurrent head and neck cancer. Complete response (CR), partial response (PR) and minor response (MR) were noted in six, three and two cases respectively. OK-432 local administration therapy could create a new strategy for cancer therapy.

Adult↗

Impaired specific cellular immunity to the varicella-zoster virus in patients with herpes zoster oticus.

The possible involvement of depression on cellular immunity in reactivation of varicella-zoster virus (VZV) in herpes zoster oticus was investigated. The subjects comprised 59 cases of herpes zoster oticus, 33 cases of herpes zoster sine herpete (ZSH) with facial paralysis, and 205 cases of Bell's palsy. The transformation rate of lymphocytes to phytohaemagglutinin in herpes zoster oticus tended to be lower than that in Bell's palsy. In skin tests with purified protein derivatives of tuberculin, the positivity rate in herpes zoster oticus was significantly lower than that in Bell's palsy (p < 0.015). In skin tests using VZV antigen the positivity rate in herpes zoster oticus and ZSH were significantly lower than that of Bell's palsy (p < 0.001 and p < 0.015, respectively). Thus, it was noted that cellular immunity, especially specific cellular immunity against VZV, was significantly depressed in herpes zoster oticus and ZSH. We consider that depression of specific cellular immunity plays an important role in triggering reactivation of VZV and onset of these diseases.

Adolescent↗

Enhanced tumor delivery and antitumor activity of palmitoyl rhizoxin using stable lipid emulsions in mice.

PURPOSE: A highly lipophilic antitumor agent, 13-O-palmitoyl-rhizoxin (RS-1541), was incorporated into lipid emulsions of various sizes consisting of triglyceride ODO and surfactant HCO-60. Pharmacokinetics, toxicities, and antitumor activities were evaluated after intravenous administration to mice bearing subcutaneously inoculated M5076 sarcoma cells. METHODS: The levels of RS-1541 in the plasma and tissues including tumor, were determined by HPLC. The maximum tolerated dose (MTD) was estimated by toxic death and change in body weight. The decrease in tumor diameter was measured for antitumor activity. RESULTS: There existed large variations in pharmacokinetics of RS-1541, depending on the size of emulsion particles. Compared with a colloidal solution (reference solution), the small (110nm) and medium (230nm) size emulsions showed high concentrations of RS-1541 in the tumor, while the large emulsions (350nm-630nm) exhibited low concentrations. The MTD of RS-1541 was reduced, when incorporated in the emulsions larger than 220nm in size. At MTD, each size of emulsions (70nm-380nm) effectively retarded the tumor growth and increased survival time. The maximum effect was achieved for the 220 nm emulsions. CONCLUSIONS: When particle size is properly selected, these emulsions could be promising and effective as an injectable carrier for lipophilic antitumor agents in order to enhance the tumor delivery and efficacies while reducing toxicities.

Animals↗

Identification of putative downstream genes of Oct-3, a pluripotent cell-specific transcription factor.

BACKGROUND: Oct-3, a pluripotent cell-specific POU transcription factor, appears to be a key regulator in pluripotential early embryonic cells and germ cells. In order to study how pluripotency is maintained, it is essential to know what genes are regulated by Oct-3. RESULTS: By employing a subtraction method, we identified several pluripotent cell-specific genes. Based upon expression patterns in various cell lines lacking or possessing Oct-3 function, about half of the genes were placed downstream of Oct-3. These downstream genes included a previously-known gene (Glut-3: a gene for a glucose transporter) and novel genes (226, 383 and 880). Their expression patterns paralleled that of Oct-3: all of these genes were highly expressed in pluripotent cells such as EC/ES cells, but switched off upon differentiation. More importantly, their expression was rescued in 'revertant' cells that ectopically acquired the Oct-3 transactivating function. Furthermore, the expression profiles of Glut-3, 226 and 383 during mouse development also overlapped that of Oct-3. The Glut-3 gene possessed multiple Oct-3 binding sites in its transcriptional regulatory regions, suggesting that at least one of the downstream genes was a direct target of Oct-3. CONCLUSIONS: A large proportion of pluripotent cell-specific genes appear to be downstream targets of Oct-3.

Amino Acid Sequence↗

An endoscopic follow-up study of the development of diffuse antral vascular ectasia.

No endoscopic follow-up studies are available on the development of diffuse antral vascular ectasia (DAVE). We present here a ten-year follow-up study from discrete initial lesions to the full picture of DAVE. In a 72-year-old female patient with liver cirrhosis, the earliest findings of DAVE were several red spots, with or without a white halo, in the distal antrum. During follow-up, the spots increased in number, coalesced, and extended to the proximal antrum. Three years after the initial findings, latent hemorrhage occurred at a time when confluent lesions were formed. One year later, diffuse distribution of the antral lesions was observed, which led to the diagnosis of DAVE and developed to the full picture within three more years. Two years later, the patient presented with hematemesis, which confirmed the diagnosis of DAVE clinically. Treatment consisted of monopolar electrocoagulation, leading to a stable hemoglobin value for one year. This case study provides some substantial clues to the early detection and treatment of DAVE.

Aged↗

Effects of calcium channel blockers on steroidogenesis stimulated by ACTH and cAMP in isolated rat adrenal cells.

The effects of the calcium channel blockers verapamil, diltiazem, prenylamine and nifedipine on the ACTH- and cAMP-mediated pathway for steroidogenesis in a suspension solution of isolated rat adrenal cells were studied. Steroidogenesis stimulated by ACTH (10(-10) M) or cAMP (10(-3) M) was not inhibited by nifedipine (10(-4) M), but was strongly inhibited in a concentration-dependent manner by verapamil, diltiazem and prenylamine (10(-5) to 10(-4) M).

Adrenal Glands↗

A reproducible assay of polymerase chain reaction to detect trinucleotide repeat expansion of Huntington's disease and senile chorea.

A simple and reproducible method of polymerase chain reaction (PCR) assay was established to detect trinucleotide repeat expansion for Huntington's disease (HD) using a new DNA polymerase and buffer system. The system consists of an extremely heat stable DNA polymerase (Pfu), and a buffer supplemented with ammonium sulfate and dimethyl sulfoxide. Previous methods to amplify expanded alleles for HD have been very complex in PCR conditions, but the reproducibility was sometimes very low because of repetitive sequences around the primer sequences. With the present method, strong bands for the disease alleles were reproducibly visible in a conventional agarose gel stained with ethidium bromide without using isotopes. Three cases with sporadic HD and a case with senile chorea showed expanded alleles for HD with smaller sizes of the expansion than cases with typical HD. These results showed that the present method provides a simple and reproducible way to detect HD allele, and some cases with sporadic HD and senile chorea had expanded HD alleles.

Adult↗

Use of a food composition database to estimate daily dietary intake of nutrient or trace elements in Japan, with reference to its limitation.

Daily dietary intake of 28 trace elements (Al, As, B, Ba, Be, Bi, Cd, Co, Cr, Cu, Ga, Ge, Li, Mg, Mn, Mo, Ni, Pb, Sb, Sc, Se, Si, Sn, Sr, Ti, Tl, V and Zn) were estimated from the food intake records (collected by the 24-h total food duplicate method), taking advantage of recently published trace element composition tables for foods in Japan. Because the number of food items listed in the tables was not sufficient, the calculation was made with not all foods recorded, and the results should be taken as semi-quantitative. The estimated intake was high (i.e. > 1 mg/day as a median) for Al, Cu, Mg, Mn, Si, Sr and Zn, medium (i.e. 2-985 micrograms/day) for As, B, Ba, Be, Cr, Ge, Mo, Ni, Sb, Sc, Se, Sn and Ti, and low (i.e. < 1 microgram/day) for Cd, Co, Li, Pb and V. Comparison of the present estimates with the reported values in the literature on 15 elements showed that close agreements were observed in the cases of 10 elements (i.e. Al, B, Cr, Cu, Mg, Mn, Mo, Ni, Se and Zn) for which the present estimates are above 1 microgram/day, whereas the discrepancies were significant for four elements (i.e. Cd, Co, Pb and V) with < 1 microgram/day intake. When the expected dietary uptake was compared with that by respiration in the cases of the 16 elements for which the atmospheric concentration data in Japan are available, the uptake was exclusively attributable to the dietary route for all 16 elements with the possible exception of vanadium.

Adult↗

Intergenerational instability of the CAG repeat of the gene for Machado-Joseph disease (MJD1) is affected by the genotype of the normal chromosome: implications for the molecular mechanisms of the instability of the CAG repeat.

Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder caused by unstable expansion of a CAG repeat in the MJD1 gene at 14q32.1. To identify elements affecting the intergenerational instability of the CAG repeat, we investigated whether the CGG/GGG polymorphism at the 3' end of the CAG repeat affects intergenerational instability of the CAG repeat. The [expanded (CAG)n-CGG]/[normal (CAG)n-GGG] haplotypes were found to result in significantly greater instability of the CAG repeat compared to the [expanded (CAG)n-CGG]/[normal (CAG)n-CGG] or [expanded (CAG)nGGG]/[normal (CAG)n-GGG] haplotypes. Multiple stepwise logistic regression analysis revealed that the relative risk for a large intergenerational change in the number of CAG repeat units (< -2 or > 2) is 7.7-fold (95% CI: 2.5-23.9) higher in the case of paternal transmission than in that of maternal transmission and 7.4-fold (95% CI: 2.4-23.3) higher in the case of transmission from a parent with the [expanded (CAG)n-CGG]/[normal (CAG)n-GGG] haplotypes than in that of transmission from a parent with the [expanded (CAG)n-CGG]/[normal (CAG)n-CGG] or [expanded (CAG)n-GGG]/[normal (CAG)n-GGG] haplotypes. The combination of paternal transmission and the [expanded (CAG)n-CGG]/[normal (CAG)n-GGG] haplotypes resulted in a 75.2-fold (95% CI: 9.0-625.0) increase in the relative risk compared with that of maternal transmission and the [expanded (CAG)n-CGG]/[normal (CAG)n-CGG] or [expanded (CAG)n-GGG]/[normal (CAG)n-GGG] haplotypes. The results suggest that an inter-allelic interaction is involved in the intergenerational instability of the expanded CAG repeat.

Chromosomes, Human, Pair 14↗

Alzheimer's disease associated with mutations in presenilin 2 is rare and variably penetrant.

Missense mutations in the presenilin 2 (PS-2) gene on chromosome 1 were sought by direct nucleotide sequence analysis of the open reading frame of 60 pedigrees with familial Alzheimer's disease (FAD). In the majority of these pedigrees, PS-1 and beta-amyloid precursor protein (beta APP) gene mutations had been excluded. While no additional PS-2 pathogenic mutations were detected, four silent nucleotide substitutions and alternative splicing of nucleotides 1338-1340 (Glu325) were observed. Analysis of additional members of a pedigree known to segregate a Met239Val mutation in PS-2 revealed that the age of onset of symptoms is highly variable (range 45-88 years). This variability is not attributable to differences in ApoE genotypes. These results suggest (i) that, in contrast to mutations in PS-1, mutations in PS-2 are a relatively rare cause of FAD; (ii) that other genetic or environmental factor modify the AD phenotype associated with PS-2 mutations; and (iii) that still other FAD susceptibility genes remain to be identified.

Age of Onset↗

Blood pressure variability at annual periodic health examination for employees and cardiovascular risk factors.

The employees with hypertension at the annual periodic health examination (HE) for employees in Japan usually receive a re-examination of blood pressure (BP) on another day and are often found to be normotensive. In this study, we analyzed data from the HE at the workplace to determine whether or not such employees should receive medical care. Two groups of subjects were selected. One group (group 1) was composed of 50 subjects with normotension at the HE (controls). Another group (group 2) was composed of 33 subjects with hypertension at the annual HE but with normotension in re-examinations. Cardiovascular risk factors were significantly higher in group 2 than in group 1: mean values of the body mass index (group 1, 22 +/- 2.7 vs. group 2, 24.3 +/- 3.1 kg/m2, p < 0.01), total cholesterol (group 1, 197 +/- 36 vs. group 2, 222 +/- 42 mg/dl, p < 0.01), and low density lipoprotein (group 1, 118 +/ 32 vs. group 2, 137 +/- 38 mg/dl, p < 0.05). The proportion of the employees with high-normal BP in group 2 (42.5%) was significantly higher than that in group 1 (28.0%) (p < 0.01). These indicate that the employees with hypertension at the annual HE but with normotension in the re-examination require further medical attention and should receive medical supervision. The occupational physician should supervise these employees.

Adult↗

Adrenomedullin as a novel antiproliferative factor of vascular smooth muscle cells.

OBJECTIVE: The present study was designed to examine whether adrenomedullin affects fetal calf serum (FCS)-stimulated proliferation in cultured rat vascular smooth muscle cells (VSMCs). METHODS: Rat VSMCs were grown from explants of Sprague-Dawley rat aorta and were grown using the standard cell culture method. After incubation for 24 h with various concentrations of adrenomedullin in the presence of 5% FCS, trichloroacetic acid-insoluble tritiated thymidine was measured in a liquid scintillation counter. After incubation for 48 h, cell counts were performed. Cyclic adenosine 3',5'-monophosphate (AMP) levels were determined by radioimmunoassay. RESULTS: Rat adrenomedullin exhibited concentration-dependent inhibition of the FCS-stimulated increase in thymidine incorporation between 10(-7) and 10(-9) mol/l and of cell number at 10(-7) mol/l. However, the calcitonin generelated peptide (CGRP) receptor antagonist human CGRP(8-37) abolished these antiproliferative effects of rat adrenomedullin. Inhibition by adrenomedullin of FCS-stimulated cellular proliferation was paralleled by an increase in the cellular level of cyclic AMP. 8-Bromocyclic AMP, a cyclic AMP analogue, and forskolin, an activator of adenylate cyclase, inhibited the FCS-stimulated increase in thymidine incorporation and cell number. CONCLUSIONS: These results suggest that adrenomedullin inhibits FCS-stimulated proliferation in cultured rat VSMCs, probably through a cyclic AMP-dependent process. Taken together with the finding that adrenomedullin is synthesized in and secreted from vascular endothelial cells, adrenomedullin may play a role as an antiproliferative factor for VSMCs in a paracrine fashion.

8-Bromo Cyclic Adenosine Monophosphate↗