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Biomedical subjects

Y Doi

Publications and source records attributed to Y Doi.

At least 109 records · Page 6Linked to original sources

2,3-Butanedione monoxime suppresses primarily total calcium handling in canine heart.

Whether 2,3-butanedione monoxime (BDM, < or = 5mmol/l) suppresses primarily crossbridge cycling or total Ca(2+) handling in the blood-perfused whole heart remains controversial. Although BDM seems to suppress primarily total Ca(2+) handling in canine hearts, more evidence is lacking. We therefore analyzed the cardiac mechanoenergetics, namely, E(max) (contractility), PVA (total mechanical energy), and O(2) consumption of canine BDM-treated hearts by our recently developed integrative method to assess myocardial total Ca(2+) handling. This method additionally required the internal Ca(2+) recirculation fraction. We obtained this from the beat constant of the exponential decay component of the postextrasystolic potentiation. Our analysis indicated significant decreases in both internal Ca(2+) recirculation fraction and total Ca(2+) handling in the BDM-treated heart, but virtually no change in the reactivity of E(max) to total Ca(2+) handling. This result corroborates the view that BDM suppresses primarily total Ca(2+) handling rather than crossbridge cycling in the canine blood-perfused heart.

Animals↗

Prevalence of sleep disturbance and hypnotic medication use in relation to sociodemographic factors in the general Japanese adult population.

This study was the first nationwide population-based study to estimate the prevalence rates of sleep disturbance and hypnotic medication use in the general Japanese adult population. In 1997, 2,800 Japanese adults aged 20 years and over were randomly selected from the 1995 Census and 1,871 were examined using the Pittsburgh Sleep Quality Index. The respective estimated overall prevalences of insomnia (INS), difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS), poor perceived quality of sleep (PQS) and hypnotic medication use (HMU) were 17.3%, 8.6%, 12.9%, 17.8%, and 3.5% in males and 21.5%, 12.6%, 16.2%, 20.2% and 5.4% in females. Among males, DIS (OR = 2.76) and PQS (OR = 2.12) were associated with never having married. DMS was associated with being 60 years and older (OR = 2.68) or divorced/separated (OR = 3.74). Among females, DMS was associated with being widowed (OR = 1.65), unemployed (OR = 1.60), 40 to 59 years old (OR = 0.57) or never having married (OR = 0.39). DIS was associated with being widowed (OR = 1.67) or unemployed (OR = 1.58). HMU was associated with advancing age (OR = 8.26-10.7), being widowed (OR = 2.12) or never having married (OR = 2.84). PQS was associated with advancing age (OR = 0.63-0.50). Our study showed sleep disturbance and hypnotic medication use were prevalent among Japanese adults and some sociodemographic factors contributed to them.

Adult↗

[Early management of acute myocardial infarction in the elderly].

UNLABELLED: The efficacy of reperfusion treatment has been established in patients with acute myocardial infarction (AMI), however, its role is still controversial in the elderly patients. Data from Kochi Acute Myocardial Infarction Registry, consisting of 1,248 cases, showed that, compared to younger patients, elderly patients had greater ratio of women, painless infarction, delayed presentation, worse Killip classes, lower reperfusion procedure and higher mortality. To clarify the early management of AMI in the elderly, we analyzed the clinical data of 1,160 cases, according to age subgroup (317 advanced elderly, aged 75-84; 438 elderly, aged 65-74; 405 middle-aged, aged 45-64) and according to the period (term I, 1990-92; term II, 1993-95; term III, 1996-98). RESULTS: 1) The advanced elderly received less reperfusion treatment (37% vs. 65%) and showed higher mortality (21% vs. 8%), compared to middle-aged patients. 2) In advanced elderly patients, mortality was reduced (term I, 27%; term II, 20%; term III, 19%), according to increasing application of reperfusion treatment (term I, 22%; term II, 45%; term III, 40%). 3) Inoadvanced elderly patients with reperfusion treatment, thrombolysis resulted in a higher mortality (17% vs. 7%) compared to direct angioplasty, probably due to increased incidence of cardiac rupture and pump failure in this age group. CONCLUSIONS: Reperfusion treatment improves mortality of AMI even in elderly patients. To minimize complications, direct angioplasty may be better for elderly patients.

Age Factors↗

[The comparison of blood pressure of community-dwelling elderly subjects in Okinawa and Shikoku].

In Japan hypertension is frequent, but the prevalence of hypertension in Okinawa has been known to be lower than in other areas in Japan. Now it has been almost 30 years since Okinawa reverted to Japan. So we investigated to know whether the prevalence of hypertension was still lower today or not. We compared the differences of prevalence of hypertension and blood pressure (BP) levels between the two community-dwelling elderly subjects aged 75 years or more: 305 in Ie in Okinawa (M:F = 107:198, mean age: 81 years old), and 99 in Omogo in Ehime, Shikoku (M:F = 45:54, mean age: 81 years old). We visited the homes of the elderly and measured their BP twice in a sitting position and asked them whether they were taking medicine for hypertension or not. According to the 1999 revised guidelines on the treatment of hypertension in the elderly by the Japanese Society of Geriatrics, we defined hypertension as systolic BP (SBP) > or = 160 mmHg or diastolic BP (DBP) > or = 90 mmHg or taking medicine for hypertension, and normotension as SBP < 160 mmHg and DBP < 90 mmHg and not taking medicine for hypertension. Hypertension rates were 52% in Ie, and 59% in Omogo, indicating no significant difference. However, in Ie only 54% of the elderly with hypertension were taking medicine for hypertension, as opposed to 74% in Omogo. These results suggest the possibility that in Okinawa hypertension is thought to be less important than in other districts in Japan.

Aged↗

[Psychiatric distress and related risk factors of family caregivers who care for the demented elderly at home].

The objectives of our study were to assess psychiatric distress of caregivers who had been caring for the demented elderly at home and to examine the association of caregivers' psychiatric distress with putative risk factors. Subjects were 294 caregivers living in Amakusa, Kumamoto Prefecture of Japan, whose spouses, parents or other family members were registered at Amakusa Public Health Center as demented elderly. In 1998, Survey on Caregivers' Mental Health was conducted using the General Health Questionnaire (GHQ12) as a measurement for general psychiatric state of caregivers. Two hundred and eighty-two caregivers responded to interviews with complaints of the following psychological symptoms: feelings of unhappiness (55.7%), of stress (41.8%), insomnia (29.4%) and depressed mood (29.1%). Seventy-six caregivers (27.2%) were identified as being above the cut-off point 4 for psychiatric distress caseness. Multivariate logistic regression analysis indicated caregivers' psychiatric distress was statistically associated with caregivers' age, the caregivers' perception of the severity of dementia, the number of years devoted to caregiving at home and perceived financial state. Being 50 to 69 years (OR = 0.37, 95% CI: 0.17-0.81) and being 70 years or older (OR = 0.35, 95% CI: 0.14-0.83) were negatively associated with caseness as compared to being 20 to 49 years. Caseness was positively related to the severity of the elderly's demented state (OR = 6.93, 95% CI: 1.99-24.19), 1 year to 2 years devoted to caregiving at home (OR = 3.26, 95% CI: 1.02-10.38), no family or social support (OR = 2.99, 95% CI: 1.12-7.96) and lower perceived financial state (always OR = 6.99, 95% CI: 2.77-17.64, sometimes OR = 2.41, 95% CI: 1.19-4.85). Reduction of caregivers' psychiatric distress is important for not merely the enhancement of quality of care for demented elders and caregivers' life but for the prevention of elder abuse or neglect. Our study suggests that a comprehensive assessment and intervention program is needed for the demented elderly and their caregivers, in order for caregivers to be able to adapt well to the challenges of caregiving and find personal meaning through caregiving.

Aged↗

Efficacy of cholesterol-lowering treatment in Japanese elderly patients with coronary artery disease and normal cholesterol level using 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor.

The clinical benefit of cholesterol-lowering treatment is unknown in the Japanese elderly in whom the prevalence of morbidity and mortality related to coronary artery disease are known to be low. To evaluate the efficacy of cholesterol-lowering treatment with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor in Japanese elderly patients with documented coronary artery disease, 121 patients with serum cholesterol > or = 150 mg/dl prospectively received HMG-CoA reductase inhibitor, and 271 patients undergoing cholesterol-lowering treatment based on dietary therapy alone served as historical controls. The 143 elderly patients age > or = 65 years in the 2 groups had similar baseline serum total cholesterol level (201 +/- 30 vs 202 +/- 31 mg/dl), age (71 +/- 4 vs 70 +/- 4 years), proportion of men (37/53 vs 64/90), number of diseased vessels (1.7 +/- 0.9 vs 1.5 +/- 1.0), and incidences of other classical coronary risk factors, including hypertension, diabetes mellitus, smoking, obesity and family history of coronary artery disease. In all 392 patients, similar trends were observed, including serum total cholesterol level (208 +/- 33 vs 201 +/- 34 mg/dl). With HMG-CoA reductase inhibitors, serum total cholesterol level was reduced by 14% in the elderly subjects and by 13% in all patients. During the follow-up of approximately 3 years, cardiac events occurred in 5 patients (one elderly) in the treatment group and 38 patients (12 elderly) in the control group. Kaplan-Meier survival estimates revealed a higher event-free survival rate with HMG-CoA reductase inhibitors in the elderly subjects (98% vs 85%, p < 0.05) and in all patients (94% vs 86%, p < 0.05). Cox proportional hazard modeling also demonstrated a significant reduction in risk for cardiac events with drug therapy (relative risk 0.32, p < 0.05), in addition to the number of diseased vessels (relative risk 1.8, p < 0.01). In contrast, no additional risk was observed with advancing age. Cholesterol-lowering treatment with HMG-CoA reductase inhibitors is effective to improve the prognosis of Japanese elderly patients, including those with normal serum cholesterol level.

Anticholesteremic Agents↗

Factors affecting the freeze-fracture morphology of in vivo polyhydroxyalkanoate granules.

Interesting morphologies were observed when Comamonas acidovorans containing polyhydroxyalkanoates (PHA) of various compositions was freeze-fractured at temperatures far below the glass transition temperatures of PHA. In vivo granules of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) comparatively showed the most ductility, and could be stretched extensively. Contrary to the uniform needle-type deformation shown by the poly(3-hydroxybutyrate) homopolymer when fractured at -110 degrees C, copolymers containing 3-hydroxyvalerate units showed various deformation structures. Similar observations were made when in vivo granules of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) were freeze-fractured, although the ductility of the latter was much reduced. In addition, it was found that fracturing at -160 degrees C resulted in decreased ductility of the PHA granules with the concomitant increase in the number of mushroom-type deformation structures. Our results suggest that PHA granules with higher resistance to freeze-fracture deformation show less ductility, and therefore produce the mushroom-type morphology. This is the first report on the freeze-fracture morphology of PHA copolymers containing short-chain-length monomers.

Cupriavidus necator↗

[Clinical evaluation of cardiac valve surgery combined with coronary artery bypass grafting].

Between 1991 and 1999, 23 cases underwent cardiac valve surgery concomitant with myocardial revascularization at our institution. Twelve cases (group I) had a primary valvular disease combined with coronary atherosclerosis, and other 11 cases (group II) were due to ischemic mitral insufficiency. There were 2 hospital deaths in group I (17%) and 4 in group II (36%). Three deaths in group II underwent left ventricular volume reduction surgery. On the basis of this observation, we concluded severe mitral regurgitation with ischemic cardiomyopathy was a particularly difficult management problem with disappointing clinical results. On the other hands, we considered concomitant revascularization should be done in the case of primary valvular disease when angiographically significant coronary artery stenosis was present.

Aged↗

Ketoacidosis accompanied by epileptic seizures in a patient with diabetes mellitus and mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS).

We herein report a rare case of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) and diabetes mellitus with ketoacidosis. An 18-year-old female patient was diagnosed to have diabetes mellitus and insulin therapy was thereafter initiated. At 26 years of age, she was hospitalized for diabetic ketoacidosis, soon followed by a loss of consciousness, left-sided dysmetria, and ataxic speech. MELAS was diagnosed because of the presence of ragged red fibers in a muscle biopsy. At 33 years of age, she was admitted to our hospital because of ketoacidosis and partial status epilepticus. A blood gas examination revealed as follows; arterial pH, 6.88; bicarbonate, 2.1 mmol/l; base excess - 29.8 mmol/l. The serum level of glucose had also increased to 30 mmol/l. The serum levels of lactate and B-hydroxybutyrate were elevated to 11.4 mmol/l and 1,990 micromol/l, respectively. Ketoacidosis improved by fluid replacement and continuous intravenous insulin infusion. A brain MRI demonstrated hyperintensity areas on FLAIR images in the bilateral temporal lobes and the cerebellum. A proton MRS demonstrated the abnormal lactate accumulation in the bilateral temporal and occipital lobes. Since epileptic seizures are rare in patients with diabetic ketoacidosis, such seizures may indicate the existence of MELAS syndrome.

Adult↗

Osteoclastic responses to various calcium phosphates in cell cultures.

Disks made of hydroxyapatite, beta-tricalcium phosphate, carbonate apatite, tetracalcium phosphate, alpha-tricalcium phosphate, dicalcium phosphate dihydrate, and octacalcium phosphate were incubated in osteoclastic cell cultures for 2 days. The first five salts were sintered and the last two were compressed before incubation. Osteoclasts resorbed only the sintered carbonate apatite disks. However, osteoclasts were able to resorb octacalcium phosphate disks that were preincubated for 1 day in medium without cells, indicating that surface conditioning was important for osteoclastic resorption of this calcium phosphate. Although resorption did not occur, medium calcium and phosphorus changed to an appreciable extent after a 2-day incubation of beta-tricalcium phosphate, tetracalcium phosphate, alpha-tricalcium phosphate, and dicalcium phosphate dihydrate. These changes in the medium calcium and phosphate concentrations could explain why osteoclasts appeared to have lost their activity on these calcium phosphate disks and were not capable of resorbing them. With hydroxyapatite disks no changes were observed in the medium calcium and phosphorus before and after incubation. Moreover, the osteoclasts appeared to be essentially the same as with the sintered carbonate apatite disks and with bone slices used as a control. Nevertheless, no pits or lacunae were observed on the hydroxyapatite disks, indicating that sintered carbonate apatite should be superior to sintered hydroxyapatite as a bioresorbable bone substitute.

Animals↗

Co-expression of 3-ketoacyl-ACP reductase and polyhydroxyalkanoate synthase genes induces PHA production in Escherichia coli HB101 strain.

The Escherichia coli 3-ketoacyl-ACP reductase gene (fabGEc) was cloned using a PCR technique to investigate the metabolic link between fatty acid metabolism and polyhydroxyalkanoate (PHA) production. Three plasmids respectively harboring fabGEc and the poly-3-hydroxyalkanoate synthesis genes phaCAc and phaC1Ps from Aeromonas caviae and Pseudomonas sp. 61-3 respectively were constructed and introduced into E. coli HB101 strain. On a two-stage cultivation using dodecanoate as the sole carbon source, recombinant E. coli HB101 strains harboring fabGEc and phaC genes accumulated PHA copolymers (about 8 wt% of dry cell weight) consisting of several (R)-3-hydroxyalkanoate units of C4, C6, C8, and C10. It has been suggested that overexpression of the fabGEc gene leads to the supply of (R)-3-hydroxyacyl-CoA for PHA synthesis via fatty acid degradation.

3-Oxoacyl-(Acyl-Carrier-Protein) Reductase↗

Injection of antisense oligos to nNOS into nucleus tractus solitarii increases blood pressure.

We investigated the cardiovascular effects of bilateral microinjection of antisense oligodeoxynucleotides (oligos) into the nucleus tractus solitarii (NTS) to neuronal nitric oxide synthase (nNOS) to suppress the expression of nNOS molecular biologically. In urethane-anesthetized, paralyzed Wistar-Kyoto rats, bilateral microinjection of nNOS antisense oligos (20 pmol in a 50nl volume) into the NTS produced a significant increase in mean arterial blood pressure at 30-60min after injection, compared with rats injected with nNOS sense or scrambled oligos. Immunohistochemical study demonstrated that nNOS immunoreactivity in the rat NTS was suppressed by nNOS antisense oligos. These results indicate that suppression of the nNOS gene using antisense in the NTS increases blood pressure.

Animals↗

Polymorphism of the D12S391 microsatellite in a Japanese population sample.

Using the polymerase chain reaction (PCR), we studied the short tandem repeat (STR) polymorphism observed at the D12S391 locus. In 350 Japanese examined, 14 different alleles ranging from 209 bp to 261 bp were detected. Allele 18 (221 bp) showed the highest frequency at 0.30. Observed and expected values of respective genotypes satisfied the Hardy-Weinberg equilibrium (chi 2 = 24.08, P = 0.24, df = 20). In addition, 18 additional sequence structures (suballeles), were detected in this study. Within the suballeles, sequence variants, in which the initial repeat of (AGAT) was replaced with (AGGT), was found in five samples. It was found that the analysis of single-strand conformation polymorphism (SSCP) before sequence analysis was useful for distinguishing these suballeles.

Alleles↗

Normal development of mice and unimpaired cell adhesion/cell motility/actin-based cytoskeleton without compensatory up-regulation of ezrin or radixin in moesin gene knockout.

Ezrin/radixin/moesin (ERM) proteins are general cross-linkers between the plasma membrane and actin filaments. Because their expression is regulated in a tissue-specific manner, each ERM protein has been proposed to have unique functions. On the other hand, experiments at the cellular level and in vitro have suggested their functional redundancy. To assess the possible unique functions of ERM proteins in vivo, the moesin gene located on the X chromosome was disrupted by gene targeting in embryonic stem cells. Male mice hemizygous for the mutation as well as homozygous females were completely devoid of moesin but developed normally and were fertile, with no obvious histological abnormalities in any of the tissues examined. In the tissues of the mutant mice, moesin completely disappeared without affecting the expression levels or subcellular distribution of ezrin and radixin. Also, in platelets, fibroblasts, and mast cells isolated from moesin-deficient mice, targeted disruption of the moesin gene did not affect their ERM-dependent functions, i.e. platelet aggregation, stress fiber/focal contact formation of fibroblasts, and microvillar formation of mast cells, without compensatory up-regulation of ezrin or radixin. These findings favor the notion that ERM proteins are functionally redundant at the cellular as well as the whole body level.

Actins↗

Co-expression of polyhydroxyalkanoate synthase and (R)-enoyl-CoA hydratase genes of Aeromonas caviae establishes copolyester biosynthesis pathway in Escherichia coli.

Polyhydroxyalkanoate biosynthesis genes of Aeromonas caviae were expressed in Escherichia coli LS5218 (fadR atoC(Con)), and the polyhydroxyalkanoate-producing ability of the recombinants was investigated. A LS5218 strain harboring only phaCAc (polyhydroxyalkanoate synthase gene) did not accumulate any polyhydroxyalkanoate from dodecanoate in spite of the existence of translated polyhydroxyalkanoate synthase protein, whereas co-expression phaCAc and phaJAc ((R)-specific enoyl-CoA hydratase gene) resulted in the accumulation of P(3-hydroxybutyrate-co-3-hydroxyhexanoate) copolymer up to 7-11 wt% of dry cell weight from octanoate and dodecanoate. These results indicated that both phaCAc and phaJAc are essential for E. coli LS5218 to establish the polyhydroxyalkanoate biosynthesis pathway from alkanoic acids. The copolyester content in the strain expressing both the genes under the lac promoter control reached to 38 wt% from dodecanoate. Enzyme assays suggest that efficient monomer formation via beta-oxidation by a high level expression of phaJAc was important to achieve a high polyhydroxyalkanoate content in the recombinant E. coli.

Acyltransferases↗