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Biomedical subjects

K Arakawa

Publications and source records attributed to K Arakawa.

At least 19 recordsLinked to original sources
PubMed2001

A novel autosomal dominant spinocerebellar ataxia (SCA16) linked to chromosome 8q22.1-24.1.

OBJECTIVE: To characterize a distinct form of autosomal dominant cerebellar ataxia (ADCA) clinically and genetically. BACKGROUND: ADCAs are a clinically, pathologically, and genetically heterogeneous group of neurodegenerative disorders. Nine responsible genes have been identified for SCA-1, -2, -3, -6, -7, -8, -10, and -12 and dentatorubral-pallidoluysian atrophy (DRPLA). Loci for SCA-4, -5, -11, -13, and -14 have been mapped. METHODS: The authors studied a four-generation Japanese family with ADCA. The 19 members were enrolled in this study. The authors performed the mutation analysis by PCR and a genome-wide linkage analysis. RESULTS: Nine members (five men and four women) were affected. The ages at onset ranged from 20 to 66 years. All affected members showed pure cerebellar ataxia, and three patients also had head tremor. Head MRI demonstrated cerebellar atrophy without brain stem involvement. The mutation analysis by PCR excluded diagnoses of SCA-1, -2, -3, -6, -7, -8, and -12 and DRPLA. The linkage analysis suggested linkage to a locus on chromosome 8q22.1-24.1, with the highest two-point lod score at D8S1804 (Z = 3.06 at theta = 0.0). The flanking markers D8S270 and D8S1720 defined a candidate region of an approximately 37.6-cM interval. This candidate region was different from the loci for SCA-4, -5, -10, -11, -13, and -14. CONCLUSION: The family studied had a genetically novel type of SCA (SCA-16).

Adult↗
PubMed2001

Effect of coronary risk factors on arterial compensatory enlargement in japanese middle-aged patients with de novo single-vessel disease--an intravascular ultrasound study.

BACKGROUND: Compensatory enlargement (CE) of atherosclerotic human arteries has been reported; however, the pattern of arterial remodeling in response to plaque formation is not unique. HYPOTHESIS: The study was undertaken to determine the extent of coronary artery compensatory enlargement at stenotic lesions and to correlate the arterial compensatory enlargement with risk factors. METHODS: We studied 62 patients with stable angina and de novo single-vessel disease using intravascular ultrasound and obtained good images in 42 patients (68%). The vessel cross-sectional area (VA), lumen cross-sectional area (LA), and plaque cross-sectional area (PA) were measured at the lesion site and at proximal and distal reference sites. Positive CE was defined as increase in VA of lesion site > 10% compared with that of proximal reference site (CE group, n = 15); shrinkage was defined as reduction in VA of lesion site > 10% compared with that of proximal reference site (S group, n = 14); inadequate CE was defined as intermediate between CE and S (IE group, n = 13). All subjects had coronary risk factors measured before this study. RESULTS: There was no difference in VA, LA, or PA among the three groups at the proximal and distal reference sites, nor in LA at the lesion site; however, VA and PA were significantly smaller in the S group than in the other groups (p < 0.01). Of coronary risk factors, increased systolic blood pressure (SBP), increased diastolic blood pressure (DBP), and decreased high-density lipoprotein cholesterol (HDL-c) levels had the strongest association with shrinkage (p < 0.05). CONCLUSION: Hypertension and decreased HDL level may contribute to the shrinkage response in middle-aged patients with stable angina.

Aged↗
PubMed2001

MR imaging of primary malignant lymphoma in the larynx.

We present MR findings in a patient with primary laryngeal lymphoma. The MR images showed a homogeneous mass in the right supraglottic larynx extending to the true vocal cord through the paraglottic space, of which signal intensity was intermediate both on T1- and T2-weighted images. The tumor was moderately enhanced and preserved mucosal layers were demonstrated as hyperintense bands on gadolinium-enhanced fat-suppressed T1-weighted images. Primary laryngeal lymphoma should be included in the differential diagnosis for a homogeneous solid mass in the supraglottic submucosal area.

Aged↗
PubMed2001

Alcohol consumption and severity of angiographically determined coronary artery disease in Japanese men and women.

The relation of alcohol consumption to the severity of coronary atherosclerosis was examined among 323 men and 220 women who underwent coronary arteriography. Severity of coronary atherosclerosis was assessed by the number of vessels obstructed > or =75% in diameter and Gensini's severity score. Alcohol consumption was divided into 5 categories in men (never, past, 1-24, 25-49, and > or =50 ml per day) and 3 categories in women (never, past, and current). Among men, odds ratios of severe stenosis (multiple-vessel disease or Gensini's score >15) decreased substantially and significantly in all current drinking categories but without dose-response effect. There was a weak, inverse association of current alcohol consumption with one-vessel disease, but not with moderate stenosis in terms of Gensini's score (< or =15). Past drinkers showed a fairly large, but statistically nonsignificant, decrease in the odds ratios of not only severe stenosis but also of moderate stenosis. Among women, current drinkers showed a small, statistically nonsignificant decrease in the risk of severe stenosis in terms of Gensini's score. These associations with alcohol use did not change after adjustment for known coronary risk factors. The present findings add to evidence that alcohol drinking confers protection against coronary atherosclerosis.

Adult↗
PubMed2001

Effect of AVT antisense oligodeoxynucleotides on AVT release induced by hypertonic stimulation in chicks.

In birds, arginine vasotocin (AVT) and mesotocin (MT) are the neurohypophyseal hormones. AVT is known to be an avian antidiuretic hormone and is released from the neurohypophysis by dehydration or hyperosmotic stimulation. The purpose of this study was to determine whether the mechanism of AVT synthesis is related to the mechanism of hormone release from the neurohypophysis. Four-day-old chicks received an AVT antisense oligodeoxynucleotide (ODN) injection into the cerebral ventricle (icv). Following antisense administration, the chicks received hypertonic saline stimulation. Plasma levels of AVT and MT were measured by radioimmunoassays. In control birds, a hypertonic saline injection resulted in the increase of plasma AVT level. The administration of a high dose (50 microg) of antisense ODN inhibited the increase of plasma AVT level induced by the hypertonic saline stimulation. Plasma levels of MT did not change with the administration of hypertonic saline or antisense ODN. These results suggest that the mechanisms that regulate the secretion of AVT from the neurohypophysis may be coupled to the mechanisms that regulate the synthesis of AVT.

Animals↗
PubMed2001

Adult-onset hereditary sensory and autonomic neuropathy accompanied by anosmia but without skin ulceration.

We report a novel type of hereditary sensory and autonomic neuropathy (HSAN) with adult onset in a Japanese family. One male and 2 females of 6 siblings were affected. They developed anosmia initially at the ages of 20-50 years, followed by anhidrosis and sensory loss. Skin ulceration was absent. Both superficial and deep sensation were impaired in the most distal parts of all 4 limbs. Orthostatic hypotension was present in all patients. This is a unique subtype of HSAN distinct from the HSAN I-V described by Dyck.

Adult↗
PubMed2001

Improved diabetic syndrome in C57BL/KsJ-db/db mice by oral administration of the Na(+)-glucose cotransporter inhibitor T-1095.

1. The therapeutic effects of an orally active inhibitor of Na(+)-glucose cotransporter (SGLT), T-1095 (a derivative of phlorizin; 3-(benzo[b]furan-5-yl)-2',6'-dihydroxy-4'-methylpropiophenone 2'-O-(6-O-methoxycarbonyl-beta-D-glycopyranoside)) were examined in C57BL/KsJ-db/db (db/db) mice, a genetic animal model of obese type 2 diabetes. 2. The higher renal SGLT activity in db/db mice than normoglycaemic C57BL/KsJ-db/+m (db/+m) mice may support the rationale for using an SGLT inhibitor in the treatment regimen for type 2 diabetes. Both T-1095 and its metabolite, T-1095A, which had approximately 10 times more potency, effectively inhibited renal SGLT activity of these mice in vitro. 3. Single oral administration of T-1095 (10, 30, 100 mg kg(-1), p.o.) to db/db mice caused a dose-dependent reduction in blood glucose levels and a concomitant increase in glucose excretion into urine. In contrast, T-1095 only slightly affected blood glucose levels in db/+m mice. 4. Chronic administration of T-1095 (0.1% w w(-1) pellet chow, for 12 weeks) decreased blood glucose and haemoglobin A(1C) levels, and improved glucose intolerance in db/db mice. The age-related decrease in plasma insulin levels was markedly inhibited and there was a 2.5 fold increase of insulin content in the pancreas of T-1095-treated db/db mice. Food consumption was not changed, while impaired body weight gain was ameliorated by T-1095 treatment. 5. Both the development of albuminuria and the expansion of glomerular mesangial area in db/db mice were significantly suppressed by chronic T-1095 treatment, indicating the prevention of the progression of diabetic nephropathy. 6. These results demonstrate that the SGLT inhibitor T-1095 is able to improve the metabolic abnormalities and inhibit the development of diabetic complications in db/db mice. Thus, T-1095 can be used for therapy of type 2 diabetic patients.

Animals↗
PubMed2001

Obesity, body fat distribution and coronary atherosclerosis among Japanese men and women.

OBJECTIVE: To investigate the relation of the obesity and body-fat distribution with angiographically defined coronary atherosclerosis. DESIGN: Cross-sectional study in a clinical setting. SUBJECTS: Three hundred and twenty men (median age, 59 y) and 212 women (median age, 67 y) who underwent coronary angiography for suspected or known coronary heart disease at 5 cardiology departments between September 1996 and August 1997. Patients with disease duration >1 y were excluded. MEASUREMENTS: The body mass index (BMI) and the waist to hip circumference ratio (WHR) were used as main exposure variables, and either the presence of significant coronary stenosis or the Gensini's score (> or =10 vs<10) as an outcome variable, in a sex-specific multiple logistic regression analysis controlling for age, hospital, and other coronary risk factors. RESULTS: Among male patients, BMI was progressively higher with an increasing number of vessels involved (P trend=0.05); the adjusted odds ratios for the presence of significant stenosis across quartiles of BMI were 1.0 (reference), 1.1, 1.9 and 2.5 (P trend=0.02), and the positive association was more pronounced for younger patients. Among females, however, such associations were not evident. Employing the Gensini's score as an outcome gave similar results. WHR was not significantly associated with either outcome regardless of sex. CONCLUSION: These results suggested that BMI was predictive of coronary stenosis among male patients, but not among female patients. Unlike most previous studies, this study failed to detect a positive association with WHR.

Adipose Tissue↗
PubMed2001

Thyroid gland tumour, pemphigus foliaceus and myasthenia gravis in the daughter of a woman with myasthenia gravis.

We describe a rare case of pemphigus foliaceus associated with familial myasthenia gravis (MG). A 35-year-old woman developed MG during oral corticosteroid treatment for pemphigus foliaceus. She had been operated on for a thyroid gland tumour that was confirmed histopathologically to be papillary carcinoma without metastasis. At the time of treatment, her mother had had MG for 30 years and undergone thymectomy 22 years ago. A specific ELISA technique showed that antidesmoglein 1 antibody was present in the daughter. There are many reports of multiple diseases such as pemphigus, thymoma, malignancy, and other autoimmune diseases associated with MG. However, familial MG following pemphigus foliaceus has not been reported previously.

Adult↗
PubMed2001

ATP analogue binding to the A subunit induces conformational changes in the E subunit that involves a disulfide bond formation in plant V-ATPase.

Vacuolar H+-ATPase (V-ATPase) consists of a catalytic head, a stalk part and a membrane domain. We indirectly investigated the interaction between the A subunit (catalytic head) and the E subunit (stalk part) using an ATP analogue, adenosine 5'-[beta,gamma-imino]triphosphate (AMP-PNP), which holds the enzyme in the substrate-binding state. AMP-PNP treatment caused a mobility shift of the E subunit with a faster migration in SDS/polyacrylamide gel electrophoresis without a reductant, while ATP treatment did not. A mobility shift of the E subunit has been detected in several plants. As polypeptides with intramolecular disulfide bonds migrate faster than those without disulfide bonds, the mobility shift may be due to the formation of an intramolecular disulfide bond by two cysteine residues conserved among several plant species. The mobility shift may be involved in the binding of AMP-PNP to the ATP-binding site, which exists in the A and B subunits, as it was inhibited by the addition of ATP. Pretreatment with 2'-3'-O-(4-benzoylbenzoyl)-ATP (Bz-ATP), which modifies the ATP-binding site of the B subunit under UV illumination, did not inhibit the mobility shift of the E subunit caused by AMP-PNP treatment. The response of V-ATPase following the AMP-PNP binding may cause a conformational change in the E subunit into a form that is susceptible to oxidation of cysteine residues. This is the first demonstration of interaction between the A and E subunits in the substrate-binding state of a plant V-ATPase.

Adenosine Triphosphate↗
PubMed2001

Genetic, dietary, and other lifestyle determinants of plasma homocysteine concentrations in middle-aged and older Chinese men and women in Singapore.

BACKGROUND: Epidemiologic studies have identified the plasma homocysteine concentration as a risk factor for atherothrombotic vascular disease. There is little information on the distributions and determinants of homocysteine concentrations in Asian populations. OBJECTIVE: The present study was designed to examine the relations between genetic and lifestyle factors and plasma homocysteine concentrations among Chinese in Singapore. DESIGN: Plasma total homocysteine, folate, vitamin B-12, and vitamin B-6 concentrations and genetic variation at the methylenetetrahydrofolate reductase (MTHFR) locus were measured in 486 Chinese men and women aged 45-74 y in Singapore. Data on dietary and other lifestyle factors were collected in face-to-face interviews. RESULTS: Men had higher plasma concentrations of total homocysteine than women (P = 0.0001). Age was positively associated with plasma homocysteine in both sexes (P for trend = 0.0001). Plasma concentrations of folate, vitamin B-12, and vitamin B-6 were inversely associated with homocysteine concentrations. Among individuals with low plasma folate, those possessing 2 copies of MTHFR mutant alleles had significantly higher homocysteine concentrations than did those with > or = 1 copy of the wild-type allele. Cigarette smoking, daily coffee consumption, and physical inactivity were positively related to plasma homocysteine concentrations in both sexes (P < 0.05). However, these associations disappeared after adjustment for plasma folate concentrations. CONCLUSIONS: Age, sex, plasma folate, vitamin B-12 and B-6 concentrations, and MTHFR genotype are independent determinants of plasma homocysteine in middle-aged and older Chinese in Singapore. These factors combined could account for up to 40% of the total variation in homocysteine concentrations in this Asian population.

Aged↗
PubMed2001

The effects of lidocaine on superoxide production and p47 Phox translocation in opsonized zymosan-activated neutrophils.

UNLABELLED: Superoxide is generated by reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase that exists in the cell membrane of neutrophils and contains p47 phox in the enzyme complex. Superoxide is closely related to various diseases, including infection, myocardial infarction, and aspiration pneumonia. Therefore we performed this study to establish how lidocaine acts on NADPH oxidase. We examined the effects of lidocaine on superoxide production in neutrophils using the method of 2-methyl-6-phenyl-3,7-dihydro [1,2-a] pyrazin-3-one (CLA phenyl)-dependent chemiluminescence activated by opsonized zymosan (OZ). Treatment with lidocaine 15 microM suppressed OZ-activated CLA phenyl-dependent chemiluminescence by approximately 40% compared with that of OZ only-activated neutrophils. It was further demonstrated that the suppressive effect of lidocaine on superoxide production was dependent on the concentration of lidocaine. Translocation of p47 phox from the cytosol to the cell membrane was studied using immunoblot analysis with a polyclonal anti-p47 phox antibody. Lidocaine suppressed OZ-induced p47 phox translocation in a dose-dependent manner. Our results suggest that suppression of superoxide production by a therapeutic dose of lidocaine correlates strongly with suppression of p47 phox translocation. IMPLICATIONS: We report on the effects of lidocaine on superoxide production in opsonized zymosan-activated neutrophils. Lidocaine suppresses superoxide production in a dose-dependent manner. This suppression correlates strongly with the suppression of translocation of p47 phox, a new subunit of NADPH-oxidase.

Adult↗
PubMed2001

Cold acclimation-induced WAP27 localized in endoplasmic reticulum in cortical parenchyma cells of mulberry tree was homologous to group 3 late-embryogenesis abundant proteins.

We have shown that two 27-kD proteins, designated as WAP27A and WAP27B, were abundantly accumulated in endoplasmic reticulum-enriched fractions isolated from cortical parenchyma cells of mulberry tree (Morus bombycis Koidz.) during winter (N. Ukaji, C. Kuwabara, D. Takezawa, K. Arakawa, S. Yoshida, S. Fujikawa [1999] Plant Physiol 120: 480--489). In the present study, cDNA clones encoding WAP27A and WAP27B were isolated and characterized. The deduced amino acid sequences of WAP27A and WAP27B cDNAs had 12 repeats of an 11-mer amino acid motif that was the common feature of group 3 late-embryogenesis-abundant proteins. Under field conditions, transcripts of WAP27 genes were initially detected in mid-October, reached maximum level from mid-November to mid-December, and then gradually decreased. The transcript levels of WAP27 genes in cortical parenchyma cells harvested in October was drastically induced by cold treatment within a few days, whereas those in cortical parenchyma cells harvested in August were low even by cold treatment for 3 weeks. Immunocytochemical analysis by electron microscopy confirmed that WAP27 was localized specifically in vesicular-form ER and also localized in dehydration-induced multiplex lamellae-form ER. The role of WAP27 in the ER is discussed in relation to acquisition of freezing tolerance of cortical parenchyma cells in mulberry tree during winter.

Acclimatization↗
PubMed2001

Inhibitory effect of hyperglycemia on insulin-induced Akt/protein kinase B activation in skeletal muscle.

To determine the molecular mechanism underlying hyperglycemia-induced insulin resistance in skeletal muscles, postreceptor insulin-signaling events were assessed in skeletal muscles of neonatally streptozotocin-treated diabetic rats. In isolated soleus muscle of the diabetic rats, insulin-stimulated 2-deoxyglucose uptake, glucose oxidation, and lactate release were all significantly decreased compared with normal rats. Similarly, insulin-induced phosphorylation and activation of Akt/protein kinase B (PKB) and GLUT-4 translocation were severely impaired. However, the upstream signal, including phosphorylation of the insulin receptor (IR) and insulin receptor substrate (IRS)-1 and -2 and activity of phosphatidylinositol (PI) 3-kinase associated with IRS-1/2, was enhanced. The amelioration of hyperglycemia by T-1095, a Na(+)-glucose transporter inhibitor, normalized the reduced insulin sensitivity in the soleus muscle and the impaired insulin-stimulated Akt/PKB phosphorylation and activity. In addition, the enhanced PI 3-kinase activation and phosphorylation of IR and IRS-1 and -2 were reduced to normal levels. These results suggest that sustained hyperglycemia impairs the insulin-signaling steps between PI 3-kinase and Akt/PKB, and that impaired Akt/PKB activity underlies hyperglycemia-induced insulin resistance in skeletal muscle.

Animals↗
PubMed2001

Singapore Chinese Health Study: development, validation, and calibration of the quantitative food frequency questionnaire.

This report describes the development and validation/calibration of a structured food frequency questionnaire for use in a large-scale cohort study of diet and health in Chinese men and women aged 45-74 years in Singapore, the development of a food composition database for analysis of the dietary data, and the results of the dietary validation/calibration study. The present calibration study comparing estimated intakes from 24-hour recalls with those from the food frequency questionnaires revealed correlations of 0.24-0.79 for energy and nutrients among the Singapore Chinese, which are comparable to the correlation coefficients reported in calibration studies of other populations. We also report on the nutritional profiles of Singapore Chinese on the basis of results of 1,880 24-hour dietary recalls conducted on 1,022 (425 men and 597 women) cohort subjects. Comparisons with age-adjusted corresponding values for US whites and blacks show distinct differences in dietary intakes between the Singapore and US populations. The Singapore cohort will be followed prospectively to identify dietary associations with cancer risk and other health outcomes.

Aged↗
PubMed2001

Mechanism of the cardioprotective effect of inhibition of the renin-angiotensin system on ischemia/reperfusion-induced myocardial injury.

Inhibition of the renin-angiotensin system (RAS) has been shown to be beneficial in providing cardioprotective effects in humans, but the mechanism of these effects is not well understood. In this study, we examined the effects and mechanism of RAS inhibitors on ischemia/reperfusion (IR)-induced myocardial injury in rats. Rats were randomly divided into five groups and treated with vehicle (C), angiotensin converting enzyme inhibitor (ACE-I), angiotensin II type 1 receptor antagonist (AT1-A), angiotensin II type 2 receptor antagonist (AT2-A) or ACE-I plus bradykinin B2 antagonist. Ten minutes after administration, the left main coronary artery was ligated for 45 min, and then reperfused for 120 min. IR-induced cardiomyocyte apoptosis was assessed by terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay and confirmed by typical DNA laddering. Mitogen-activated protein kinase, extracellular signal-regulated protein kinase (ERK) and c-Jun NH2-terminal protein kinase (JNK) activity in the ischemic zone were measured by an in vitro kinase assay. The duration of ventricular tachycardia (VT) during ischemia was reduced by AT2-A and ACE-I, and increased by AT1-A and ACE-I+icatibant. ACE-I and AT2-A reduced apoptosis (by 54% and 53%) and infarct size (by 42% and 41%), while AT1-A increased apoptosis (by 86%) and infarct size (by 45%). These changes were negatively correlated with the change in ERK activity. The effects of ACE-I on apoptosis and infarct size were abolished by the coadministration of icatibant. Apoptosis was correlated with the occurrence of VT (r=0.837, p<0.001). These results suggest that both the accumulation of bradykinin and inhibition of AT2 receptor are cardioprotective against IR injury through the activation of ERK, but not JNK.

Angiotensin Receptor Antagonists↗