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Biomedical subjects

Masahiko Kato

Publications and source records attributed to Masahiko Kato.

At least 19 recordsLinked to original sources
PubMed2006

A longitudinal study on the nutritional state of elderly women at a nursing home in Japan.

OBJECTIVE: Elderly people at nursing homes often suffer from malnutrition, which is characterized by a loss of muscle mass and hypoalbuminemia. This malnourished state is closely associated with an impaired activity of daily living (ADL). We analyzed the nutritional state of such elderly individuals longitudinally over 3 years by anthropometry, serum albumin, and muscle and fat volume as estimated by MRI. PATIENTS AND METHODS: The subjects consisted of 16 elderly women aged 83 +/- 7 (mean +/- SD) years who resided at a nursing home in an urban area of central Japan. We determined their ADL levels using the Barthel Index (BI) at entry. Seven women belonged to group A (BI; 65-100), thus implying either a mild or no decline in ADL, while the other 9 were in group B (BI; 0-60) and they demonstrated a severe decline in ADL. We measured the following parameters every year from 2000 to 2003; anthropometry including height, body weight, arm circumference (AC), and arm muscle circumference (AMC), thigh muscle and fat volume as estimated by MRI [thigh muscle volume (TMV) and thigh fat volume (TFV)], serum albumin, and plasma amino acid levels by blood biochemistry. The anthropometric values were converted into percentages of the age- and sex-matched reference values for Japanese. RESULTS: In all subjects, the TMV, %AMC, and serum albumin level decreased significantly during the three-year period (p<0.05, respectively). The change in TMV correlated significantly with those in the %AC and %AMC (p<0.05, respectively). Group B showed significantly larger decreases in the %AMC and serum albumin level than group A. CONCLUSION: Both the muscular and visceral protein levels were found to decrease with aging in the subjects at the nursing home. This decrease depends partly on the ADL level of each subject.

Activities of Daily Living↗
PubMed2006

A sensitive and reliable quantification method for mouse interleukin-12 p70 based on fluorometric sandwich ELISA (FS-ELISA).

Interleukin-12 (IL-12) p70 is an important cytokine secreted by antigen-presenting cells in response to antigenic stimulation; it is a heterodimer of p35 and p40 subunits. Here, we report a new, highly sensitive, and reliable method that employs fluorometric sandwich ELISA for quantification of the mouse IL-12 (moIL-12) p70 protein. Our method could quantify moIL-12 p70 in the range of approximately 0.5 to 500 pg/ml. In the assay, no signals were produced by the moIL-12 p40 monomer, homodimer [(p40)2], or mouse IL-23 even up to a concentration of 500 pg/ml; this ensures that our assay has a high specificity for moIL-12 p70. To demonstrate that our method can determine natural moIL-12 in real physiological/pathological samples, we monitored the moIL-12 p70 secretion from peritoneal exudative cells after lipopolysaccharide (LPS) stimulation. IL-12 p70 secretion as early as 3h after LPS stimulation was reliably detected due to the high sensitivity of the method.

Animals↗
PubMed2006

Overweight and obesity increase the risk for liver cancer in patients with liver cirrhosis and long-term oral supplementation with branched-chain amino acid granules inhibits liver carcinogenesis in heavier patients with liver cirrhosis.

We conducted a multicenter, randomized, controlled trial to investigate the effect of long-term oral supplementation with branched-chain amino acids (BCAA) on the event-free survival in 622 patients with decompensated cirrhosis. In the present study, the development of liver cancer was analyzed as an endpoint in particular. Subjects received either treatment with BCAA at 12g/day or dietary therapy containing the matched daily energy and protein intake. A Cox regression analysis was carried out to estimate the hazard ratios for different background factors stratified by treatment group. Liver cancer was noted in 89 patients. The risk for liver cancer was significantly higher for males, patients with concurrent diabetes mellitus, patients with an alpha-fetoprotein (AFP) level of 20ng/mL or higher, patients with higher body mass index (BMI), and patients with lower serum albumin levels. When the BCAA group and the diet group were compared for factors that interacted with the treatment arms, the risk for liver cancer was significantly reduced in the BCAA group with a BMI of 25 or higher and with an AFP level of 20ng/mL or higher. Oral supplemental treatment with BCAA may reduce the risk of liver cancer in cirrhotic patients with these specific factors.

Journal Article↗
PubMed2006

Catabolism of adenine nucleotides favors adenosine production following exercise in patients with chronic heart failure.

BACKGROUND: Adenosine 5'-triphosphate is catabolized to adenosine 5'-monophosphate (AMP), which is further degraded by 2 pathways: deamination to inosine 5'-monophosphate and ammonia by AMP deaminase, or dephosphorylation to adenosine and inorganic phosphate by 5'-nucleotidase. Because adenosine is believed to be cardioprotective and we have reported that ammonia production decreased after exercise in patients with chronic heart failure (CHF), we determined if plasma adenosine levels after exercise increases in patients with CHF. METHODS AND RESULTS: Maximal ergometer exercise tests with expired gas analysis were performed in 51 patients with CHF (age = 61 +/- 2 years, New York Heart Association [NYHA] class I/II/III = 19/18/14) and 20 age-matched normal controls. Serial changes in both plasma ammonia and adenosine levels were determined. The ratio for delta ammonia to peak work rate became smaller (control, NYHA I/II/III: 0.59 +/- 0.13/0.41 +/- 0.06/0.37 +/- 0.10/0.22 +/- 0.11 microg/dL x watts, respectively) and the ratio for delta adenosine to peak work rate was significantly higher in class III CHF (control, NYHA I/II/III: 0.93 +/- 0.21/0.86 +/- 0.14/1.11 +/- 0.27/2.92 +/- 0.67 nmol/L x watts, respectively). CONCLUSION: In patients with CHF after exercise, the plasma levels of adenosine increased along with the decrease in the plasma levels of ammonia. Considering the physiologic cardioprotective actions of adenosine, the enhanced adenosine production after exercise may be an important adaptive response in patients with CHF.

Adenine Nucleotides↗
PubMed2006

Phylogenetic analysis of envelope glycoprotein (E1) gene of rubella viruses prevalent in Japan in 2004.

We performed a molecular epidemiological study on the envelope glycoprotein gene (E1 gene) obtained by PCR amplification from specimens of 17 rubella patients in certain areas (Gunma, Saitama, and Kagoshima prefectures, and Tokyo metropolitan area) in Japan in 2004. In these sequences of partially amplified DNAs (283 bases) within the E1 gene, no nucleotide substitution was observed. They were classified into genotype 1D of clade 1 in the constructed phylogenetic tree. One amino acid substitution was found between the amino acid sequence predicted from these DNAs and those of Japanese strains [To-336 vaccine strain (To-336 vac) and its wild progenitor (To-336 wt)]. The results suggest that the rubella viruses (RV) prevalent in certain areas of Japan in 2004 were highly homologous and were closely related with Japanese vaccine strain.

Adolescent↗
PubMed2006

Usefulness of rapid low-dose/high-dose 1-day 99mTc-sestamibi ECG-gated myocardial perfusion single-photon emission computed tomography.

BACKGROUND: The clinical usefulness of a rapid rest low-dose/stress high-dose (dose ratio =1:5) (99m)Tc-sestamibi myocardial perfusion single-photon emission computed tomography (SPECT) protocol for the detection of coronary artery disease was evaluated. METHODS AND RESULTS: In 89 patients, rest images were obtained immediately after the injection of (99m)Tc-sestamibi (256.1+/-28.4 MBq) followed by drinking water (400 ml). Exercise or vasodilator stress test was performed immediately after the completion of rest imaging with the injection of (99m)Tc-sestamibi (1312.3 +/-167.6 MBq). Prior to the post-stress imaging, patients were asked again to drink water (400 ml) in order to eliminate subdiaphragmatic tracer activity. The myocardial count ratio (stress/rest) of (99m)Tc-sestamibi was calculated. Image quality was scored using a 4-point scale system (4= excellent, 3= good, 2= poor, 1= unacceptable). Coronary angiography was performed in 56 patients within 1 month of the SPECT scan. All patients successfully performed the protocol and total examination time was 108+/-7 min. The myocardial count ratio of (99m)Tc-sestamibi was always greater than 6. The image quality was satisfactory both at rest (3.4+/-0.9) and after stress (3.9+/-0.2). The sensitivity and specificity to detect coronary artery stenosis >50% was 84% and 97%, respectively. CONCLUSIONS: This rapid one-day (99m)Tc-sestamibi protocol provides adequate image quality and diagnostic accuracy for detecting coronary artery disease.

Adult↗
PubMed2006

Omenn syndrome--review of several phenotypes of Omenn syndrome and RAG1/RAG2 mutations in Japan.

Omenn syndrome (OS) is a form of severe combined immunodeficiency (SCID) characterized by erythrodermia, hepatosplenomegaly, lymphadenopathy, and alopecia. In patients with OS, B cells are mostly absent, T-cell counts are normal to elevated, and T cells are frequently activated and express a restricted T-cell receptor (TCR) repertoire. Thus far, inherited hypomorphic mutations of the recombination activating genes either 1 or 2 (RAG1/2) have been detected in most OS patients. We have recently experienced a rare case of OS showing the revertant mosaicism due to multiple second-site mutations leading to typical OS clinical features with RAG1-deficient SCID. In this review, we will focus on the variation of several phenotypes of OS.

DNA-Binding Proteins↗
PubMed2006

Role of protein kinase C in eosinophil function.

Protein kinase C (PKC) isoforms are being elucidated as an increasingly diverse family of enzymes involved in the downstream signal transduction and cell function in various types of cells. To date, 11 PKC isoforms have been identified; they are grouped according to their molecular structure and mode of activation: conventional PKCs (alpha, beta I, beta II, and gamma), novel PKCs (delta, epsilon, mu, theta, and eta), and atypical PKCs (zeta, and iota/lambda). Eosinophils are involved in the pathogenesis of allergic diseases such as bronchial asthma, pollinosis, and atopic dermatitis as well as in the inflammatory response to parasitic infections. Recent studies using selective activators and inhibitors of individual PKC isoforms have revealed that this enzyme is involved in eosinophil dynamics such as cell motility and other functions. However, the role of PKCs in eosinophil functions has been not wholly understood. In this review, we have focused upon and summarized the current knowledge regarding the role of PKC isoforms in eosinophil functions.

Animals↗
PubMed2005

Elevation of cytokine concentrations in asphyxiated neonates.

BACKGROUND: Various cytokines are reportedly associated with many neonatal diseases. Asphyxia is considered to result in ischemia-reperfusion injuries and induces abnormal inflammatory responses involving excessive cytokine production. OBJECTIVES: To evaluate alteration in sera levels of various cytokines/chemokines in case of perinatal asphyxia at birth. METHODS: In order to determine the concentrations of various cytokines/chemokines in sera, we used a highly sensitive fluorescence microsphere method. We measured the concentration of 8 types of cytokines/chemokines in sera obtained from 17 cases of asphyxia, 10 normal neonates, and 6 healthy adults. RESULTS: The concentrations of IL-6, IL-8, and IL-10 in the sera of asphyxiated neonates were higher than those in the normal neonates. Irrespective of the presence or absence of asphyxia, sera concentrations of IL-2, IL-4, IFN-gamma, and TNF-alpha were higher in the neonates than those in the adults. The concentration of IFN-gamma in the asphyxiated neonates was lower than that in the normal neonates. Sera levels of IL-10 were higher in the asphyxiated cases than those in the normal neonates. The sera levels of IL-6, IL-8, and IL-10 in asphyxiated neonates with either a poor outcome or death were higher than those without poor outcomes. CONCLUSIONS: The concentrations of various types of cytokines/chemokines were different in neonatal sera and some of them increased drastically during asphyxia. The concentration of an anti-inflammatory cytokine IL-10 was elevated in asphyxiated neonates immediately after birth, thereby suggesting that IL-10 might be associated with neuroprotective functions.

Asphyxia Neonatorum↗
PubMed2005

Status of endothelial dependent vasodilation in patients with hyperuricemia.

Hyperuricemia has been associated with an increased risk for cardiovascular disease and increased mortality. However, the biologic mechanisms that link elevated serum uric acid to cardiovascular disease are uncertain. This study tested the hypothesis that elevated serum uric acid is associated with impaired endothelial function in hyperuricemic patients without any overt cardiovascular disease. Seventeen male patients with hyperuricemia (mean age 42+/-4 years) and 9 control subjects (mean age 45+/-5 years) were studied. All subjects were nonsmokers. All patients had never been treated for hyperuricemia, were on no medications, and were free of any other known diseases. Endothelial function was evaluated by flow-mediated dilation measured by ultrasound. Flow-mediated dilation was significantly impaired in patients with hyperuricemia (4.0+/-0.7%) compared with control subjects (6.4+/-0.8%) (p=0.044). Flow-mediated dilation correlated inversely with uric acid levels (r=-0.4, p=0.05). Nitrate-induced dilation was 12.3+/-1.0% in patients with hyperuricemia and 11.8+/-2.3% in control subjects (p=0.82). Impaired endothelial-dependent vasodilation is present in hyperuricemic patients even in the absence of any overt cardiovascular disease. The elevated serum uric acid, per se, may constitute a novel risk factor for endothelial dysfunction.

Adult↗
PubMed2005

Detection and sequence analysis of DNA polymerase and major envelope protein genes in koi herpesviruses derived from Cyprinus carpio in Gunma prefecture, Japan.

Koi herpesvirus (KHV), which is believed to be an emerging virus, causes fatal diseases in carps. Since the 1990s, the presence of KHV has been confirmed in several countries. In Japan, from 2003 to 2004, large outbreaks of KHV infection in farmed carps resulted in the death of numerous fishes. From April to May 2004, we collected 43 dead or dying carps exhibiting typical symptoms of KHV infection in Gunma prefecture. To conduct a molecular epidemiologic study of KHV in our prefecture, we amplified DNA polymerase and the major envelope protein genes of KHV derived from carp gills using newly designed primers. We also performed sequence analysis of both genes of KHV. Sensitivity of our PCR method for amplification of DNA polymerase and the major envelope protein genes of KHV was 3 x 10(2) (100 fg) and 3 x 10(3) (1000 fg) copies of KHV genome, respectively. We detected both DNA polymerase and major envelope protein genes in 37 of 43 carps (86%). No mutation was found in both the genes sequenced from 11 strains, which included two foreign strains and one domestic strain. The results suggested that KHV strains derived from carps in our prefecture were closely related genetically to the other KHV strains.

Animals↗
PubMed2005

Differential role of an atypical protein kinase C, PKC zeta, in regulation of human eosinophil and neutrophil functions.

BACKGROUND: Protein kinase C (PKC) comprises a family of isoenzymes playing a key role in downstream signaling and cell functions. PKCs are grouped according to molecular structure and mode of activation: 'conventional' PKCs (alpha, betaI, betaII, gamma), 'novel' PKCs (delta, epsilon, mu, theta, eta), and 'atypical' PKCs (zeta, tau/lambda). Here we compared the influence of PKC zeta on the function of human eosinophils and neutrophils. METHODS: After pretreating the cells with a myristoylated specific PKC zeta inhibitor, a myristoylated PKC eta inhibitor, or bisindolylmaleimide I (Bis I; an inhibitor of conventional and novel PKCs), we examined N-formyl-methionyl-leucyl-phenylalanine (FMLP)- or 4-phorbol 12-myristate 13-acetate (PMA)-evoked superoxide anion (O(2)(-)) generation. Induced PKC translocation was characterized using confocal laser scanning microscopy. RESULTS: The PKC zeta inhibitor significantly blocked FMLP- or PMA-induced O(2)(-) generation by eosinophils. However, this inhibitor attenuated PMA- but not FMLP-induced O(2)(-) generation by neutrophils. In contrast, Bis I inhibited FMLP-induced O(2)(-) generation by eosinophils and neutrophils in a similar manner. The PKC eta inhibitor had no significant effect, since both cell types lack PKC eta; this confirmed specificity of PKC zeta inhibitor effects. Finally, the translocation of PKC zeta to the plasma membrane induced by FMLP in both eosinophils and neutrophils was started at 1 min while the translocation was maintained for 15 min in eosinophils but not in neutrophils. CONCLUSION: An atypical PKC, PKC zeta, regulates human eosinophil and neutrophil functions in a differential manner.

Cell Movement↗
PubMed2005

Oligoclonal expansion of T lymphocytes with multiple second-site mutations leads to Omenn syndrome in a patient with RAG1-deficient severe combined immunodeficiency.

Omenn syndrome (OS) is a rare primary immunodeficiency characterized by the presence of activated/oligoclonal T cells, eosinophilia, and the absence of circulating B cells. OS patients carry leaky mutations of recombination activating genes (RAG1 or RAG2) resulting in partial V(D)J recombination activity, whereas null mutations cause severe combined immunodeficiency with absence of mature T and B cells (T-B- SCID). Here we describe somatic mosaicism due to multiple second-site mutations in a patient with RAG1 deficiency. We found that he is homozygous for a single base deletion in the RAG1 gene, which results in frameshift and likely abrogates the protein function. However, the patient showed typical OS features. Molecular analysis revealed that several second-site mutations, all of which restored the RAG1 reading frame and resulted in missense mutations, were demonstrated in his T cells. These findings suggest that his revertant T-cell mosaicism is responsible for OS phenotype switched from T-B- SCID.

Cell Proliferation↗
PubMed2005

Clinical comparison of branched-chain amino acid (l-Leucine, l-Isoleucine, l-Valine) granules and oral nutrition for hepatic insufficiency in patients with decompensated liver cirrhosis (LIV-EN study).

This multicenter study compared the effects of branched-chain amino acid granules (Livact((R)) Granules, LIV) and an enteral nutrient for chronic hepatic failure (Aminoleban((R)) EN, EN) on serum albumin in patients with decompensated liver cirrhosis. This study enrolled "patients with decompensated liver cirrhosis associated with hepatic encephalopathy who were suffering from hypoalbuminemia in spite of adequate food intake," a condition for which both drugs are indicated. Enrolled patients were randomized to the two groups according to the central registration method. This study continued for 24 weeks. Selected foods were supplied to each patient in principle so that caloric and protein intakes were standardized between the two groups. A total of 281 patients were enrolled. LIV was not inferior to EN concerning the primary efficacy endpoint changes in serum albumin.

Journal Article↗
PubMed2005

Gender-selective interaction between aging, blood pressure, and sympathetic nerve activity.

The mechanisms mediating the more striking age related increase in cardiovascular disease in women than in men are poorly understood. We tested the hypothesis that aging has a greater impact on sympathetic traffic in women than in men. Muscle sympathetic nerve activity (MSNA), blood pressure, and heart rate were measured in 120 healthy males and 96 healthy females aged 20 to 72 years. MSNA increased with age in both sexes, but age explained 53% of MSNA variance in female subjects and only 8% of MSNA variance in male subjects. Both the slope and intercept of the regression lines were significantly different between male and female groups (P<0.01 and P<0.001, respectively). For each decade of life, women showed an increase of 6.5 bursts/min in comparison to an increase of 2.6 bursts/min in males. Menopause did not explain the age-related increase in sympathetic traffic. For every 10-burst/min increment in MSNA in subjects older than 40, mean blood pressure increased by 2.7 mm Hg in men and by 6.1 mm Hg in women. Aging is accompanied by a greater increase in sympathetic traffic in women than in men, independent of menopausal status. Sympathetic neural mechanisms may contribute importantly to the more marked influence of age on blood pressure and cardiovascular disease in women.

Adult↗
PubMed2005

Effects of oral branched-chain amino acid granules on event-free survival in patients with liver cirrhosis.

BACKGROUND & AIMS: Nutritional intervention with branched-chain amino acid (BCAA) is reported to increase serum albumin concentration in patients with decompensated cirrhosis. However, a definite conclusion on whether it can improve patients' survival has not yet been reached. The present study aimed to test possibilities of improving survival of patients with decompensated cirrhosis by using a BCAA preparation that is suitable for long-term oral administration. METHODS: A multicenter, randomized, and nutrient intake-controlled trial on the comparative effects of BCAA orally administered at 12 g/day for 2 years versus diet therapy with defined daily food intake (1.0-1.4 g protein kg(-1) day(-1) including BCAA preparation and 25-35 kcal kg(-1) day(-1)) was conducted in 646 patients with decompensated cirrhosis. The primary end point was a composite of death by any cause, development of liver cancer, rupture of esophageal varices, or progress of hepatic failure (event-free survival). The secondary end points were serum albumin concentration and health-related quality of life (QOL) measured by Short Form-36 questionnaire. RESULTS: The incidence of events comprising the primary end point significantly decreased in the BCAA group as compared with the diet group (hazard ratio, 0.67; 95% confidence interval, 0.49-0.93; P = .015; median observation period, 445 days). Serum albumin concentration increased significantly in the BCAA group as compared with the diet group (P = .018). The "general health perception" domain in Short Form-36 measures was also improved (P = .003). Patients' adherence to the prescription was favorable. CONCLUSIONS: Oral supplementation with a BCAA preparation that can be administered for a long period improves event-free survival, serum albumin concentration, and QOL in patients with decompensated cirrhosis with an adequate daily food intake.

Administration, Oral↗
PubMed2005

Cleavage of nonmuscle myosin heavy chain-A during apoptosis in human Jurkat T cells.

We have previously reported that calpastatin, an endogenous inhibitory protein of calpain, is cleaved by a caspase-3-like protease during apoptosis in human Jurkat T cells [Kato, M. et al. (2000) J. Biochem. 127, 297-305]. In this study, we found that nonmuscle myosin heavy chain-A (NMHC-A) is cleaved during apoptosis in Jurkat cells by using a cleavage-site-directed antibody for calpastatin. The cleavage-site-directed antibody was raised against the amino-terminal fragment of calpastatin, and this antibody detected the in vitro cleaved calpastatin fragment. Although cleaved calpastatin was not detected, a 95-kDa polypeptide (p95) was detected in apoptotic cells by this antibody. This p95 was identified as the carboxyl-terminal fragment of NMHC-A based on the results of peptide mass spectrometry fingerprinting and amino-terminal sequencing. Furthermore, two cleavage sites on NMHC-A, Asp-1153 and Asp-1948, were determined, and three cleaved fragments of NMHC-A, one cleaved at Asp-1153 and the other two cleaved at Asp-1948, were detected by cleavage-site-directed antibodies against each cleavage site. The results of confocal immunofluorescence microscopic analysis show that the cleavage at Asp-1948 occurs faster than that at Asp-1153 during apoptosis. In addition, the Asp-1153 cleaved fragment was distributed diffusely in the cytoplasm of apoptotic cells, whereas the Asp-1948 cleaved fragments were detected as condensed dots. In conclusion, our findings can be summarized as follows: (i) NMHC-A is cleaved at two sites during apoptosis, (ii) the timing of cleavage is different between these two cleavage sites, and (iii) the distribution of cleaved fragments is different in apoptotic cells.

Amino Acid Sequence↗