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Biomedical subjects

H Kawai

Publications and source records attributed to H Kawai.

At least 127 records · Page 7Linked to original sources

Frequency and clinical characteristics of dilated cardiomyopathy caused by desmin gene mutation in a Japanese population.

AIMS: Dilated cardiomyopathy is partly caused by a mutation of some cytoskeletal or nuclear envelope proteins. It has been confirmed recently that a missense mutation of the gene encoding desmin, a cytoskeletal protein, can cause dilated cardiomyopathy. This study was aimed at elucidating the frequency and clinical characteristics of dilated cardiomyopathy caused by desmin mutation. METHODS AND RESULTS: We examined 265 Japanese patients with dilated cardiomyopathy (217 sporadic cases and 48 probands of familial dilated cardiomyopathy). The exon 8 of the desmin gene, the critical region for the pathogenesis of dilated cardiomyopathy, was analysed by polymerase chain reaction, single-strand conformation polymorphism and sequencing. The same missense mutation (Ile451Met) as reported previously was detected in three patients (1.1%). All these patients were male and sporadic, and more likely to be accompanied by characteristics such as younger age at diagnosis, lower fractional shortening and ejection fraction than each mean value of sporadic cases. The chronological changes in cardiac function were inconsistent in the three patients. CONCLUSION: The missense mutation (Ile451Met) of the desmin gene can be the genetic cause of dilated cardiomyopathy, although with very low frequency. The ages at diagnosis were younger and the cardiac function had deteriorated further than general cases of sporadic dilated cardiomyopathy.

Adult↗

Differential gene expression between chronic hepatitis B and C hepatic lesion.

BACKGROUND & AIMS: Complementary DNA (cDNA) microarray technology allows simultaneous expression analysis of hundreds to thousands of genes. We applied the cDNA microarray technique to clarify gene expression profiles in chronic viral hepatitis tissue lesions. METHODS: We made cDNA microarrays consisting of 1080 human cDNAs and analyzed gene expression using labeled cDNAs prepared from 6 normal, 12 chronic hepatitis B, and 14 chronic hepatitis C liver tissues. Relative expression ratios of individual genes were obtained by comparing hybridization of Cy5-labeled cDNAs from chronic hepatitis lesions and Cy3-labeled cDNA from normal liver tissue. RESULTS: Hierarchical clustering analysis of the gene expression profiles in 26 patients showed that the patients were clustered into 2 groups with respect to similarities in differentially expressed genes. Hepatitis B and C virus infection, but not age, sex, or histology of hepatitis, were significant factors determining clustering (P < 0.05). In hepatitis B tissue lesions, genes involved in inflammation were predominant, whereas in hepatitis C, expression of anti-inflammatory response genes was relatively dominant. CONCLUSIONS: These findings shed new light on the possible differential molecular mechanisms in the pathogenesis of hepatitis caused by hepatitis B virus and hepatitis C virus infection, from which hepatocellular carcinoma frequently develops.

Adult↗

Plasma brain natriuretic peptide as a novel therapeutic indicator in idiopathic dilated cardiomyopathy during beta-blocker therapy: a potential of hormone-guided treatment.

BACKGROUND: Plasma brain natriuretic peptide (BNP) is a sensitive and specific marker of left ventricular (LV) function. In the treatment of heart failure, especially in idiopathic dilated cardiomyopathy (IDC), beta-blocker (BB) therapy has been established as a powerful strategy. The purpose of this study was to analyze relationships between changes in BNP level and LV function during BB therapy in patients with IDC. METHODS: In 30 patients with IDC who had already received conventional therapy, measurement for plasma BNP and norepinephrine levels and echocardiographic indices were evaluated before and 2 and 6 months after carvedilol in 21 patients and at baseline and after 6 months in 9 patients who did not receive carvedilol. RESULTS: After 6 months carvedilol treatment significantly improved LV end-diastolic dimension (LVEDD) (65 +/- 8 to 61 +/- 8 mm) and LV ejection fraction (LVEF) (34% +/- 13% to 43% +/- 12%) with intergroup differences; it significantly decreased BNP (127 +/- 113 to 69 +/- 92 pg/mL) with no intergroup difference; however, it did not decrease norepinephrine. BNP correlated strongly with LVEDD, LVEF, and LV mass index in carvedilol-treated patients. The degree of change in BNP correlated with that in LVEDD or LVEF 6 months after carvedilol. All 14 patients with decreased or unchanged BNP levels showed an increase in LVEF, and 4 of 7 with a rise in BNP had decreased or unchanged LVEF. According to receiver operating characteristic analysis, the optimal BNP levels for detecting LVEF <35% before and after carvedilol were 75.5 and 69 pg/mL, respectively. CONCLUSION: Plasma BNP levels may accurately reflect alteration in LV function and structure and can be used as a therapeutic indicator for risk stratification in patients with IDC during BB therapy.

Adrenergic beta-Antagonists↗

Properties of an extracellular polysaccharide produced by a strain of enterobacter isolated from pond water.

A bacterium which was isolated from pond water and identified as Enterobacter cloacae produced a viscous extracellular polysaccharide when it was grown aerobically in a medium containing sucrose as a sole source of carbon. The maximum molecular weight of the polysaccharide was about 9.0 x 10(5). The polysaccharide was composed of fucose, galactose, glucose, and glucuronic acid in a molar ratio of 2:3:2:1, but the molecular weight and the molar ratio of the sugar component were different from those of the polysaccharide produced by the same species reported elsewhere.

Chromatography, Gas↗

Improving the freeze tolerance of bakers' yeast by loading with trehalose.

We examined the freeze tolerance of bakers' yeast loaded with exogenous trehalose. Freeze-tolerant and freeze-sensitive compressed bakers' yeast samples were soaked at several temperatures in 0.5 M and 1 M trehalose and analyzed. The intracellular trehalose contents in both types of bakers' yeast increased with increasing soaking period. The initial trehalose-accumulation rate increased with increasing exogenous trehalose concentration and soaking temperature. The maximum trehalose content was almost identical (200-250 mg/g of dry cells) irrespective of the soaking temperature and the type of bakers' yeast, but depended on the exogenous trehalose concentration. The leavening ability of both types of bakers' yeast loaded with trehalose was almost identical to that of the respective original cells, irrespective of the soaking conditions. The freeze-tolerant ratio (FTR) of both types of bakers' yeast increased with increasing intracellular trehalose content. However, FTR decreased during over-soaking after the maximum amount of trehalose had accumulated. FTR of the freeze-sensitive bakers' yeast was more efficiently improved than that of the freeze-tolerant type.

Freezing↗

[Nitric oxide spares myocardial oxygen consumption through attenuation of contractile response to beta-adrenergic stimulation in patients with idiopathic dilated cardiomyopathy].

BACKGROUND: The results of recent studies suggest that nitric oxide (NO) synthase may increase in the failing myocardium and that NO modulates the myocardial contractile response to beta-adrenergic stimulation. However, there are few data regarding the physiological role of NO in patients with heart failure. The aim of the present study was to address the role of NO in left ventricular contractile response to beta-adrenergic stimulation and corresponding oxygen expenditure in human heart failure. METHODS AND RESULTS: We studied 15 patients with heart failure due to idiopathic dilated cardiomyopathy (mean ejection fraction 0.33). We examined left ventricular contractility (Emax, the slope of end-systolic pressure-volume relation), left ventricular external work (EW), myocardial oxygen consumption (MVO2), and mechanical efficiency (measured as EW/MVO2) with the use of conductance and coronary sinus thermodilution catheters before and during dobutamine (DOB) infusion via a peripheral vein (4.8 +/- 0.3 micrograms.kg-1.min-1 i.v.). Heart rate was kept constant with atrial pacing. We carried out a similar protocol during the intracoronary infusion of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA; 200 mumol). DOB increased Emax, EW, and MVO2 (by 77 +/- 17%, 39 +/- 5%, and 21 +/- 5%, respectively), leading to an increase in mechanical efficiency (25.4 +/- 3.1% to 29.6 +/- 4.1%). L-NMMA alone did not significantly change these variables. Although the concurrent infusion of DOB with L-NMMA increased Emax, EW, and MVO2 (by 140 +/- 21%, 64 +/- 9%, and 35 +/- 5%, respectively) more than DOB alone, mechanical efficiency did not increase further (24.3 +/- 3.3% to 29.5 +/- 4.5%) because EW and MVO2 increased in parallel. CONCLUSIONS: These data suggest that in patients with idiopathic dilated cardiomyopathy, endogenous NO spares MVO2 through attenuation of left ventricular contractile response to beta-adrenergic stimulation while maintaining left ventricular energy-converting efficiency.

Cardiomyopathy, Dilated↗

Radioimmunoassay for somatostatin receptor type 2.

OBJECTIVE: To develop radioimmunoassay for somatostatin receptor type 2 (SSTR2) and search for its presence in certain rat tissues. METHODS: Anti-SSTR2 antiserum has been raised in New Zealand white rabbits immunized with a conjugate of synthetic SSTR2 with bovine serum albumin. Radioiodination of SSTR2 was performed by chloramin T method followed by purification of radioiodinated material on Sephadex G-25 column. RESULTS: The obtained antibody did not crossreact with SSTR1, SSTR3, SSTR4, SSTR5, hypothalamic hormones, pituitary hormones, neuropeptides or gut hormones. The assay was performed with a double antibody system. SSTR2 was extracted from the tissues with acid acetone. The dilution curve of acid acetone-extracts of rat hypothalamus in the radioimmunoassay system was parallel to the standard curve. The recovery of tissue SSTR2 was about 89 %, and the intra-assay and inter-assay variations were 4.9 % and 7.8 %, respectively. SSTR2 was found in the hypothalamus, cerebrum, cerebellum, pituitary, stomach and testis. CONCLUSIONS: These data suggest that this assay system is suitable for the estimation of SSTR2 in the tissues.

Acetone↗

Corticosteroid therapy in patients with IgA nephropathy and impaired renal function.

AIM: IgA nephropathy (IgAN) is a common type of primary glomerulonephritis that constitutes a major cause of end-stage renal disease. Oral and/or intravenous glucocorticoid therapy can protect against progression of IgAN in patients with preserved renal function. We evaluated steroid therapy in IgAN with established renal dysfunction. PATIENTS AND METHODS: We retrospectively analyzed the effect of methylprednisolone (MP) pulse therapy in 8 IgAN patients with serum creatinine concentrations (sCr) 2.76 +/- 1.32 mg/dl (mean +/- SD). In each patient renal function had progressively deteriorated in the 12 months preceding treatment, as indicated by negative slopes of 1/sCr plotted against time (regression coefficients). RESULTS: Regression coefficients during the 12 months following therapy improved significantly from -0.02333 +/- 0.00732 to -0.00036 +/- 0.00423 dl/mg/month, respectively. The mean difference in slope was 0.0230 +/- 0.0076 dl/mg/month (95% confidence interval, 0.0165 to 0.0295, p < 0.001). Proteinuria also significantly decreased from a mean urine protein/creatinine ratio of 2.57 +/- 1.12 before therapy to 1.12 +/- 0.84 6 months after therapy (p < 0.005). Other factors that might affect progression of renal dysfunction remained unchanged during the observation periods. CONCLUSION: Corticosteroids may attenuate progression of renal failure and delay the need for dialysis in this patient population, although a large randomized trial is necessary.

Administration, Oral↗

[Total removal of infected pacemaker lead under cardiopulmonary bypass in a case of endocarditis, bacteremia and lung abscess].

A 60-year-old man, who had undergone implantation of a transvenous pacemaker system on the left chest wall for sick sinus syndrome 19 years ago, was admitted because of endocarditis with septicemia and lung abscess 2 months after reimplantation of the generator. His blood culture revealed Staphylococcus aureus. Following debridement of the infected pacemaker pocket and antibiotics therapy, we tried to remove the pacemaker system under cardiopulmonary bypass 1 month after admission. In intraoperative inspection, the electrodes had become firmly encased with fibrous tissue within the tricuspid valve and the right ventricle. After the operation, antibiotic therapy was performed for 4 weeks. His postoperative course was uneventful. Patients with pacemaker infection should undergo aggressive total removal of the pacemaker system, particularly incase with endocarditis and bacteremia.

Bacteremia↗

[Multicystic sphenoethmoidal mucocele with intracranial extension presented with generalized convulsion: a case report].

A 53-year-old male presented with generalized convulsion. Magnetic resonance imaging and computed tomography revealed large sphenoethmoidal mucocele extending intracranially. Signal intensities between paranasal and intracranial portion of the mucocele were different. Preoperatively it was not obvious that intracranial portion of the mucocele communicated with paranasal portion of the mucocele. We approached the paranasal portion of the mucocele by transsphenoidal approach resulting in disappearance of the intracranial portion of the mucocele. Sphenoethmoidal mucocele with intracranial extension presenting with generalized convulsion was the first case in the literature. Transsphenoidal approach for sphenoethmoidal mucocele with intracranial extension is the first choice of surgical treatment, though neuroimaging shows that there is no communication between paranasal and intracranial portion of mucocele.

Brain Diseases↗

[An adult case of cerebellar mutism after removal of cerebellar hematoma].

Cerebellar mutism is a well documented complication of posterior fossa tumor surgery in children. But only one case presenting with cerebellar mutism after removal of a cerebellar hematoma in adults was reported previously. We present 64-year-old male developing cerebellar mustism after surgery for hypertensive cerebellar hemorrhage. A cerebellar hematoma was located in the right side dentate nucleus and cerebellar peduncle dominantly not extending to the cerebellar vermis. During the period of cerebellar mutism, single photon emission computed tomography revealed a decrease in the contralateral temporo-parietal cerebral blood flow. Cerebellar mutism in this case may be associated with the low blood flow in the contralateral supplementary motor cortex owing to injury to the dentate-thalamo-cortical pathway at the dentate nucleus and cerebellar peduncle. The relevant literature is reviewed.

Cerebellar Diseases↗

Diagnosis of pancreatic adenocarcinoma by detection of human telomerase reverse transcriptase messenger RNA in pancreatic juice with sample qualification.

PURPOSE: We evaluated the diagnostic efficacy of detection of human telomerase reverse transcriptase (hTERT) message, a catalytic domain of human telomerase, in endoscopic retrograde pancreatography (ERP)-derived pancreatic juice. EXPERIMENTAL DESIGN: Both hTERT and CD25 expression were detected by reverse transcription-PCR (RT-PCR) in 17 patients with pancreatic adenocarcinoma (PC), 12 patients with chronic pancreatitis (CP), and 7 patients with no ERP abnormality (N). In the same patients, beta-actin message was semiquantified by competitive RT-PCR. K-ras codon 12 mutations were concomitantly analyzed by enriched PCR-SSCP in 11 and 7 PC and CP cases, respectively. RESULTS: Expression of hTERT was detected in 88% of PC cases and 17% of CP cases but not in the normal control (N). Alterations in K-ras were detected in 73% of PC cases and 57% of CP cases, respectively. beta-Actin mRNA was expressed in >3.0 x 10(1) copies/microl in all but two PC cases in which hTERT mRNA was not detected. CD25-positive and -negative peripheral lymphocytes were isolated from a normal volunteer using a fluorescent activating cell sorter. The hTERT message was detected in CD25-positive peripheral lymphocytes and in 18, 25, and 0% of the pancreatic juice samples from PC, CP, and N cases, respectively. All CP cases expressing hTERT message were also CD25 positive. CONCLUSIONS: These results suggest that detection of hTERT mRNA in pancreatic juice is a powerful tool to discriminate PC from CP, particularly when the samples are qualified against beta-actin mRNA levels and contaminating CD25-positive lymphocytes.

Actins↗

[Pulmonary involvement, pleural effusion, and electrocardiographic abnormality in hypereosinophilic syndrome].

A 47-year-old man was admitted to our hospital with complaints of cough and shortness of breath. Chest radiography showed infiltration of the right lung and left pleural effusion, the eosinophil count increased notably in the peripheral blood, sputum, and pleural effusion. Transbronchial lung biopsy revealed the invasion of eosinophils like eosinophilic pneumonia. Heart failure easily developed in this patient after the intravenous infusion. Myocardial involvement was suspected, and hypereosinophilic syndrome was diagnosed. After prednisolone was administered, the peripheral blood eosinophil count normalized rapidly, and subsequently, the pleural effusion and infiltration shadows in the lung disappeared.

Anti-Inflammatory Agents↗

Mice expressing only monosialoganglioside GM3 exhibit lethal audiogenic seizures.

Gangliosides are a family of glycosphingolipids that contain sialic acid. Although they are abundant on neuronal cell membranes, their precise functions and importance in the central nervous system (CNS) remain largely undefined. We have disrupted the gene encoding GD3 synthase (GD3S), a sialyltransferase expressed in the CNS that is responsible for the synthesis of b-series gangliosides. GD3S-/- mice, even with an absence of b-series gangliosides, appear to undergo normal development and have a normal life span. To further restrict the expression of gangliosides, the GD3S mutant mice were crossbred with mice carrying a disrupted GalNAcT gene encoding beta1,4-N-acetylgalactosaminyltransferase. These double mutant mice expressed GM3 as their major ganglioside. In contrast to the single mutant mice, the double mutants displayed a sudden death phenotype and were extremely susceptible to induction of lethal seizures by sound stimulus. These results demonstrate unequivocally that gangliosides play an essential role in the proper functioning of the CNS.

Age Factors↗