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Biomedical subjects

M Arai

Publications and source records attributed to M Arai.

At least 127 records · Page 7Linked to original sources

Cardiac ankyrin repeat protein is a novel marker of cardiac hypertrophy: role of M-CAT element within the promoter.

CARP, a cardiac doxorubicin (adriamycin)-responsive protein, has been identified as a nuclear protein whose expression is downregulated in response to doxorubicin. In the present study, we tested the hypothesis that CARP serves as a reliable genetic marker of cardiac hypertrophy in vivo and in vitro. CARP expression was markedly increased in 3 distinct models of cardiac hypertrophy in rats: constriction of abdominal aorta, spontaneously hypertensive rats, and Dahl salt-sensitive rats. In addition, we found that CARP mRNA levels correlate very strongly with the brain natriuretic peptide mRNA levels in Dahl rats. Transient transfection assays into primary cultures of neonatal rat cardiac myocytes indicate that transcription from the CARP and brain natriuretic peptide promoters is stimulated by overexpression of p38 and Rac1, components of the stress-activated mitogen-activated protein kinase pathways. Mutation analysis and electrophoretic mobility shift assays indicated that the M-CAT element can serve as a binding site for nuclear factors, and this element is important for the induction of CARP promoter activity by p38 and Rac1. Thus, our data suggest that M-CAT element is responsible for the regulation of the CARP gene in response to the activation of stress-responsive mitogen-activated protein kinase pathways. Moreover, given that activation of these pathways is associated with cardiac hypertrophy, we propose that CARP represents a novel genetic marker of cardiac hypertrophy.

Animals↗

Unclassified connective tissue disease presenting as cardiac tamponade: a case report.

This report describes a case of cardiac tamponade as the initial manifestation of unclassified connective tissue disease (UCTD). A 68-year-old Japanese woman was admitted to hospital because of dyspnea and edema. She had undergone a radical left mastectomy for the treatment of breast cancer 18 years before. On admission, bilateral leg edema, hepatomegaly, and a paradoxical pulse were noted on physical examination. The erythrocyte sedimentation rate was elevated and the C-reactive protein was 2.8 mg/dl. Antinuclear antibodies and anti-SS-A/Ro antibodies were present. The scl-70 and anticentromere antibodies were elevated. Chest radiography showed cardiomegaly. Echocardiography revealed a large pericardial effusion, but the pericardial fluid did not contain malignant cells or bacteria. She did not meet the diagnostic criteria for any known connective tissue diseases, so was diagnosed with cardiac tamponade due to UCTD. Prednisolone (30 mg/day) was administered, which resulted in a gradual resolution of the pericardial effusion. Although connective tissue diseases are known to cause pericardial effusion, cardiac tamponade as the initial manifestation of the disease in the absence of other symptoms is quite rare.

Aged↗

Cloning and sequencing of an endoglucanase gene from Scopulariopsis brevicaulis TOF-1212, and its expression in Saccharomyces cerevisiae.

The egI gene, encoding a major endoglucanase (EGI) of Scopulariopsis brevicaulis TOF-1212, was cloned and sequenced. The eglgene consisted of 868 bp with one intron and encoded a protein of 229 amino acids with a calculated molecular mass of 22,392 daltons. The EGI was assigned to a family 45 of glycosyl hydrolases and showed high similarity with other fungal endoglucanases, especially with those of Humicola grisea and Fusarium oxysporum, on the basis of hydrophobic cluster analysis. The egI gene was expressed under the promoter of the phosphoglycerate kinase gene (PGK) in Saccharomyces cerevisiae. The transformed cells were able to secrete the enzyme efficiently in an active form.

Amino Acid Sequence↗

Function and regulation of sarcoplasmic reticulum Ca2+-ATPase: advances during the past decade and prospects for the coming decade.

In cardiac muscle, the contraction-relaxation cycle is tightly controlled by the regulated release and uptake of intracellular Ca2+ between sarcoplasmic reticulum and cytoplasm. A major protein controlling Ca2+ cycling is Ca2+-ATPase (SERCA2a) located in the sarcoplasmic reticulum membrane. The function of SERCA2a protein is regulated by the phosphorylatable protein, phospholamban. Phosphorylation of phospholamban releases its inhibitory effect on SERCA2a through direct molecular interaction. Recently, mice whose SERCA2a function is increased (overexpression of the gene) or lost (knock out) were developed. These mice demonstrated that SERCA2a pump levels are a major determinant of cardiac muscle contractility and relaxation. These studies open the prospect that the overexpression of SERCA2a can correct cardiac dysfunction seen in heart failure. Advances in knowledge concerning the function and gene regulation of SERCA2a are discussed in this review.

Animals↗

Therapy with the nonpeptide endothelin receptor antagonist 97-139 in a murine model of congestive heart failure: reduction of cardiac mass and myofiber hypertrophy.

Endothelin-1 (ET-1) is a potent vasoconstrictor. This peptide exerts numerous effects on the heart, including regulation of cardiomyocyte growth during hypertrophy. The effects of the structurally novel, nonpeptide, ET-1-selective, competitive antagonist (ETA) 97-139 were investigated in mice with congestive heart failure (CHF) and myocardial hypertrophy. Morphological and microscopical analyses were conducted on day 56 after viral inoculation following 28 day treatment with 99-139. Eight week-old DBA2 mice were intraperitoneally inoculated with encephalomyocarditis virus at a dose of 500 pfu/mouse. The 30 mice were divided into two groups--an ETA treated group and an untreated group. Heart weight (HW) in the infected group was significantly (p < 0.05) increased compared to that in the uninfected group. HW and the HW/body weight (BW) ratio were significantly (p < 0.05) reduced in the ETA treated group compared with the untreated group (HW; 127.7 +/- 6.2 mg vs 144.3 +/- 4.2 mg, HW/BW; 4.9 +/- 0.9 x 10(-3) vs 5.4 +/- 0.5 x 10(-3)). Myofiber diameter in the ETA treated group was significantly reduced compared with the untreated group (12.1 +/- 1.5 microm vs 14.3 +/- 1.9 microm). These results suggest the ET-1 receptor antagonist 97-139 has an effect on the reduction of cardiac mass and myofiber hypertrophy, and that 97-139 may be a useful agent for CHF due to viral myocarditis.

Animals↗

Alternate numbness in the upper extremities as the initial symptom of basilar migraine: an electrophysiological evaluation using EEG power topography.

A case of basilar migraine (BM) with alternate numbness as the initial symptom is described. The patient's chief complaint was alternate numbness in the right and left upper extremities. After angiography the patient fell into a drowsy state, followed by excitation, and finally confusion. The EEG power topography showed slow alpha, theta and delta power in the right occipital area, and alternatively in the right and left parietal area. These findings suggest that the cause of BM is not only based on a vasoconstriction mechanism, but also cortical spreading depression. BM should be suspected as a cause of sensory symptoms.

Adolescent↗

Arborcandins A, B, C, D, E and F, novel 1,3-beta-glucan synthase inhibitors: production and biological activity.

Arborcandins A, B, C, D, E and F, which possess potent 1,3-beta-glucan synthase inhibitory activity, were isolated from the culture broth of a filamentous fungus, strain SANK 17397. Arborcandins are novel cyclic peptides, that are structurally different from known glucan synthase inhibitors such as echinocandins. The 1,3-beta-glucan synthases of Candida albicans and Aspergillus fumigatus were inhibited by arborcandins with IC50 ranging from 0.012 to 3 microg/ml. The apparent Ki value of arborcandin C for C. albicans and A. fumigatus were 0.12 microM and 0.016 microM, respectively. The inhibition against these two 1,3-beta-glucan synthases by arborcandin C was noncompetitive. These compounds exhibited potent fungicidal activity against Candida spp. with MIC ranging from 0.25 to 8 microg/ml. The growth of A. fumigatus was suppressed by arborcandins with concentrations ranging from 0.063 to 4 microg/ml.

Anti-Bacterial Agents↗

Effect of fungal metabolites cytochalasans on lipid droplet formation in mouse macrophages.

Effects of seven cytochalasans including cytochalasins B, D and E and novel phenochalasins A and B were tested on cytosolic lipid droplet formation and neutral lipid synthesis in mouse peritoneal macrophages. Phenochalasin A inhibited lipid droplet formation in a dose-dependent manner at least up to 20 microM without any morphological changes in macrophages. Cytochalasins D and E also inhibited lipid droplet formation only in a narrow range of concentrations, around 1 and 0.1 microM, respectively. At higher concentrations they gave morphological changes in macrophages. The other four cytochalasans only showed severe morphological changes in macrophages. Phenochalasin A and cytochalasins D and E inhibited cholesteryl ester (CE) synthesis specifically with IC50 values of 0.61, 2.4 and 0.20 microM, respectively, while the other cytochalasans inhibited both CE and triacylglycerol syntheses. Thus, among the cytochalasans tested, phenochalasin A showed very specific inhibition of CE synthesis and gave the lowest morphological changes in macrophages, resulting in the best inhibitor of lipid droplet formation in macrophages.

Animals↗

[Quantitation of human immunodeficiency virus type 1 RNA by ultrasensitive method in the analysis of samples with low viral load].

With the introduction of combination therapy to the patients with Human Immunodeficiency Virus Type 1(HIV-1) infection, HIV-1 RNA levels in plasma have been reduced, frequently to less than limit of quantitation(400 copies/ml). To achieve enhanced sensitivity, a modified specimen preparation procedure that allows the quantitation of plasma HIV-1 RNA levels as low as 50 copies/ml was developed. Of 67 samples with less than 400 copies/ml of HIV-1 RNA by standard method, 39(58.2%) were not detected by the "ultrasensitive" method. Among 5 samples obtained from patients who were treated with 2 nucleoside reverse transcriptase inhibitors, 4 samples still had detectable copies of HIV-1 RNA. Those suggest that the ultrasensitive assay for HIV-1 RNA has advantage for clinical practice.

HIV Infections↗

Intracranial aneurysms and autosomal dominant polycystic kidney disease: followup study by magnetic resonance angiography.

PURPOSE: Intracranial aneurysms are known to complicate autosomal dominant polycystic kidney disease. We assess the value of magnetic resonance angiography to detect intracranial aneurysms early in patients with autosomal dominant polycystic kidney disease. MATERIALS AND METHODS: We evaluated 15 patients with asymptomatic autosomal dominant polycystic kidney disease treated at our hospital between 1992 and 1998. Magnetic resonance angiography was performed at presentation and was repeated 18 to 72 months after treatment. RESULTS: On the initial magnetic resonance angiogram 3 intracranial aneurysms were detected in 3 patients. The intracranial aneurysms ranged from 4 to 8 mm. in diameter, and were in the anterior communicating artery in 1, in the vertebral artery in 1, and at the bifurcation of the internal carotid artery and ophthalmic artery in 1 case. Repeat magnetic resonance angiography 18 to 72 months after treatment revealed new intracranial aneurysms in 2 patients. In 1 case the lesion was 7 mm. in diameter, in the internal carotid artery and posterior communicating artery, and detected 69 months after the initial angiogram. In the other patient the lesion was 4 mm. in diameter, in the anterior communicating artery and detected 71 months after treatment. CONCLUSIONS: Since new intracranial aneurysms were demonstrated in patients followed for a long time periodic repeat magnetic resonance angiography is important.

Adult↗

[Evaluation of the diagnostic reagents which detect rotavirus and adenovirus with the immunochromatographical method].

Dipstick 'Eiken' Rota and Dipstick 'Eiken' Adeno were the reagents used for the diagnosis of viral acute gastroenteritis using the immunochromatographical method. Dipstick 'Eiken' Rota and Dipstick 'Eiken' Adeno were evaluated for their sensitivity and specificity. Dipstick 'Eiken' Rota had a capacity to detect a purified rotavirus antigen in a concentration of 50 ng/ml. The sensitivity of Dipstick 'Eiken' Rota was 10 times higher than the sensitivity of the latex agglutination tests (Serodirect 'Eiken' Rota and ROTALEX DRY) and was almost the same as the immunochromatography test (Immu- noCard ST ROTAVIRUS) and the simplified EIA (TESTPACK ROTAVIRUS). With a concentration of 25 ng/ml, Dipstick 'Eiken' Adeno detected a purified adenovirus antigen. Dipstick 'Eiken' Adeno also detected adenovirus antigen in 64 higher dilutions than the latex agglutination test (ADENOLEX DRY). When Dipstick 'Eiken' Rota was compared with Serodirect 'Eiken' Rota among 100 fecal specimens of healthy children and children with viral acute gastroenteritis, the sensitivity was 100.0%, the specificity was 98.0%, and the agreement was 97.0%. When Dipstick 'Eiken' Adeno was compared with ADENOLEX DRY among 55 fecal specimens of healthy children and children with viral acute gastroenteritis, the sensitivity was 100.0 , the specificity was 93.8%, and the agreement was 96.4%. Dipstick 'Eiken' Rota and Dipstick 'Eiken' Adeno are found to be useful diagnostic assays for viral acute gastroenteritis in the clinical laboratories.

Adenoviridae↗

[Sudden bilateral hearing loss with vertigo due to vertebral artery occlusion].

We report a case of sudden bilateral hearing loss associated with an occlusion of the right vertebral artery. A 66-year-old man was admitted to hospital suffering from sudden onset vertigo, deafness, and vomiting. He could not walk due to truncal ataxia. There was positional nystagmus to the right; spontaneous and gaze-evoked nystagmus were absent. He had no facial nerve palsy, dysarthria, pyramidal tract signs, limb ataxia, and sensory impairment. Pure tone audiometry demonstrated a profound sensorineural deafness of both ears. A tentative diagnosis of sudden deafness was made. He was treated with intravenous infusion of corticosteroid; hearing loss of the left ear slightly improved. Cranial MR imaging demonstrated fresh small infarcts in the right cerebellar tonsil, the left cerebellar medulla, and the left middle cerebellar peduncle. MR angiography demonstrated an occlusion of the right vertebral artery. It is possible that reduced perfusion of the anterior inferior cerebellar arteries and internal auditory arteries on both sides resulted in multiple "border zone" infarcts and damage to the inner ear. Clinicians should be aware of the possibility of vertebrobasilar occlusive disease in case of sudden bilateral hearing impairment, even when brainstem or cerebellar signs are absent.

Aged↗

The conserved tryptophan-arginine-tyrosine motif of a proteinaceous alpha-amylase inhibitor T-76 from Streptomyces nitrosporeus is important for inhibition of animal alpha-amylases but not for an alpha-amylase from Bacillus sp. no. 195.

Site-directed mutagenesis of Trp-16, Arg-17, and Tyr-18, which were thought to form a putative active site in proteinaceous alpha-amylase inhibitor T-76 from Streptomyces nitrosporeus for inhibition, was performed. The mutation at the site (W16A, R17A, and Y18A) resulted in a marked decrease in inhibitory activity against all animal alpha-amylases tested. Only the alpha-amylase from Bacillus sp. no. 195 (BAA) remained sensitive to all the constructed mutant inhibitors. A competition between T-76 mutants and the wild-type for porcine pancreatic alpha-amylase (PPA) suggest that the loss of inhibitory activity against PPA in mutant inhibitors was due to the decrease in their binding ability for PPA. T-76 formed a complex with BAA as well as PPA at the stoichiometric ratio of 1:1. A competition between BAA and the PPA/T-76 complex suggests that PPA and BAA might bind to the same region or regions close to each other on the T-76 molecule. These results indicate that the conserved Trp-Arg-Tyr motif of T-76 is involved in the interaction between T-76 and PPA while other amino acid residues seem to be important for the T-76/BAA interaction. Since the BAA-type alpha-amylase is the actual target of the inhibitors from microbes in comparison with animal alpha-amylases, BAA might be a better material than PPA to elucidate the "true" function of proteinaceous alpha-amylase inhibitors.

Journal Article↗