Biomedical subjects

T Matsuzaki

Publications and source records attributed to T Matsuzaki.

At least 19 recordsLinked to original sources

PubMed2006

Genetic analysis of HLA, NA and HPA typing in type 2 diabetes and ASO.

We examined the genetic status of human leucocyte antigens (HLA), human platelet alloantigens (HPA) and neutrophil-specific antigens (NA) in patients with type 2 diabetes mellitus and diabetic arteriosclerosis obliterans (ASO). To our knowledge, the present study is the first report showing the relationship among three genetic factors in type 2 diabetes mellitus and ASO patients. HLA typing was performed by the polymerase chain reaction (PCR)-restriction fragment length polymorphism method. HPA-typing and NA-typing were by a PCR-sequence-specific primer method. The incidence of HLA-DRB1*1501 was found to be significant in type 2 diabetes and non-diabetic, particularly ASO-positive patients, compared to control subjects. There were no differences in NA1/NA2 between the control and diabetic or non-diabetic ASO groups. However, the frequency of NA2/NA2 in ASO-positive diabetes and non-diabetic ASO patients was significantly higher than controls. The a/b genotype of HPA-5a/5b was significantly lower in type 2 diabetes and non-diabetic ASO-positive patients than in controls. These findings suggest that genetic studies of HLA, NA and HPA could be useful to understand the pathogenesis of type 2 diabetes and ASO.

Adult↗

PubMed2006

Characterization of isoforms of activin receptor-interacting protein 2 that augment activin signaling.

Activin type II receptors (ActRIIs) including ActRIIA and ActRIIB are serine/threonine kinase receptors that form complexes with type I receptors to transmit intracellular signaling of activins, nodal, myostatin and a subset of bone morphogenetic proteins. ActRIIs are unique among serine/threonine kinase receptors in that they associate with proteins having PSD-95, Discs large and ZO-1 (PDZ) domains. In our previous studies, we reported specific interactions of ActRIIs with two independent PDZ proteins named activin receptor-interacting proteins 1 and 2 (ARIP1 and ARIP2). Overexpression of both ARIP1 and ARIP2 reduce activin-induced transcription. Here, we report the isolation of two isoforms of ARIP2 named ARIP2b and 2c. ARIP2, ARIP2b and ARIP2c recognize COOH-terminal residues of ActRIIA that match a PDZ-binding consensus motif. ARIP2 and its isoforms have one PDZ domain in the NH2-terminal region, and interact with ActRIIA. Although PDZ domains containing GLGF motifs of ARIP2b and 2c are identical to that of ARIP2, their COOH-terminal sequences differ from that of ARIP2. Interestingly, unlike ARIP2, overexpression of ARIP2b or 2c did not affect ActRIIA internalization. ARIP2b/2c inhibit inhibitory actions of ARIP2 on activin signaling. ARIP2 is widely distributed in mouse tissues. ARIP2b/2c is expressed in more restricted tissues such as heart, brain, kidneys and liver. Our results indicate that although both ARIP2 and ARIP2b/2c interact with activin receptors, they regulate ActRIIA function in a different manner.

Activin Receptors, Type II↗

PubMed2005

Mirthful laughter differentially affects serum pro- and anti-inflammatory cytokine levels depending on the level of disease activity in patients with rheumatoid arthritis.

OBJECTIVES: To examine the effect of mirthful laughter in rheumatoid arthritis (RA), we evaluated the levels of serum cytokines before and after patients experienced mirthful laughter. METHODS: Forty-one patients with RA and 23 healthy subjects were enrolled. They listened to 'Rakugo', a traditional Japanese comic story, to induce mirthful laughter. We measured serum IL-6, IL-1beta, TNF-alpha, IL-4 and IL-1 receptor antagonist (IL-1Ra) concentrations before and after patients listened to the story. The RA subjects were divided into two groups. One was designated the 'difficult-to-control RA' group (CRP > or =1.0 mg/dl); The other group was regarded as the 'easily controlled RA' group (CRP <1.0 mg/dl). RESULTS: The basal levels of serum IL-6 and TNF-alpha in the RA patients were significantly higher than those in the healthy group. After experiencing mirthful laughter, the levels of serum IL-6 decreased significantly in the RA group but not in the healthy subjects. Interestingly, the level of serum TNF-alpha decreased only in the easily controlled RA group. Serum IL-4 concentration in the RA group was significantly higher than that in healthy subjects before the story. After the story, the level of serum IL-4 significantly decreased in the RA group, especially in the difficult-to-control RA group. In contrast, serum IL-1Ra concentration was statistically higher in the RA group than that in healthy subjects before the story, and a further increase was observed after the story, especially in the easily controlled RA group. CONCLUSIONS: Our findings suggest that mirthful laughter affects the levels of serum pro- and anti-inflammatory cytokines differentially, depending on the RA disease activity.

Adult↗

PubMed2005

Effect of hormone replacement therapy on the production of bone-resorbing cytokines by peripheral blood cells in postmenopausal women.

We studied the effects of hormone replacement therapy (HRT) with estrogen on postmenopausal changes in the production of bone-resorbing cytokines interleukin 1 beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha). Both cytokines were measured in the supernatants of lipopolysaccharide (LPS)-stimulated whole-blood cells from 72 untreated and 44 HRT-treated women by ELISA. The levels of IL-1beta were significantly higher in women in their 40s and 50s and in postmenopausal women than in women in their teens, 20s and 30s, while the levels of TNFalpha did not show any changes related to age. Both levels in HRT-treated women were significantly lower than those in untreated women at almost every postmenopausal stage. In a prospective study, HRT induced significant declines in both levels. These results show that estrogen decreases the accelerated production of IL-1beta and reduces the production of TNFalpha in postmenopausal women at each postmenopausal stage, even in late-postmenopausal women.

Adult↗

PubMed2005

Regulatory factors on parathyroid hormone-related peptide production by primary culture of lactating rat mammary gland.

Parathyroid hormone-related protein (PTHrP) is a major cause of humoral hypercalcemia of malignancy, but has also been widely found in fetal and adult non-neoplastic tissues. Lactating mammary gland has been shown to produce large amounts of PTHrP, and high levels of PTHrP have been measured in milk. We have examined the influences of several substances on the secretion of two different forms of PTHrP by primary cultures of mammary cells isolated from lactating rats to examine the regulatory mechanisms of PTHrP production by mammary cells. Primary cultures of mammary cells seeded at a density of 10(5) cells per 35 mm culture dish were grown on collagen gels. First, after cells were left 24 hours for attachment and incubated in 2 % FCS containing medium with for 12 hours, PTHrP (1 - 87) secretions were measured in conditioned medium with hormone supplementation for 1, 24 and 48 hours. Progesterone (10(-7) - 10(-5) mol/l) significantly suppressed PTHrP (1 - 87) secretion in a dose-dependent manner (p < 0.01), while 17beta-estradiol had no influence on PTHrP (1 - 87) secretion. Prolactin, a known stimulator of PTHrP expression in vivo, had no effect in this in vitro model. Second, PTHrP (1 - 34) secretion levels from confluent lactating mammary cells for 24 hours were evaluated. The same results were obtained in the case of PTHrP (1 - 87) secretion from non-confluent cells. Furthermore, dexamethasone (10(-6) mol/l) significantly suppressed PTHrP (1 - 34) secretion (p < 0.01). These results suggest that PTHrP production from the lactating mammary gland is suppressed by progesterone as well as dexamethasone. Progesterone dramatically falls after delivery, thus possibly accelerating PTHrP production by lactating mammary glands and resulting in considerable amounts of PTHrP secreted into the milk.

Animals↗

PubMed2005

Synergistic activity of activin A and basic fibroblast growth factor on tyrosine hydroxylase expression through Smad3 and ERK1/ERK2 MAPK signaling pathways.

Activin has previously been shown to act as a nerve cell survival factor and to have neurotrophic effects on neurons. However, the role of activin in regulating neurotransmitter expression in the central nervous system and the exact mechanisms involved in this process are poorly understood. In the present study, we report that activin A and basic fibroblast growth factor (bFGF) synergistically increased the protein level of tyrosine hydroxylase (TH), and also greatly increased the TH mRNA level, in both mouse E14 striatal primary cell cultures and the hippocampal neuronal cell line HT22. Activin A and bFGF cooperatively stimulated nuclear translocation of Smad3 and specifically activated ERK1/2, but not p38 or JNK. Interestingly, a specific inhibitor for MEK, U0126, efficiently blocked the induction of TH promoter activity by activin A and bFGF, indicating that activin A collaborated with bFGF signaling to induce the TH gene through selective activation of ERK-type MAP kinase in mouse striatal and HT22 cells. These data suggest that activin A may act in concert with bFGF for the development of TH-positive neurons.

Activins↗

PubMed2005

Factors influencing neonatal therapeutic effect of anti-MRSA drugs.

OBJECTIVE: Factors influencing the neonatal therapeutic effect of anti-MRSA (methicillin-resistant Staphylococcus aureus) drugs are investigated. METHODS: This study took place over a two-year period from April 1998 to March 2000. We calculated the non-adjusted odds ratio for each influential factor to determine the therapeutic effect of anti-MRSA drugs. RESULTS: Significant factors for therapeutic effect were found to be platelet count, urea nitrogen, creatinine, and CRP, each measured before starting administration of anti-MRSA drugs; whether blood drug concentration was measured; and whether pneumonia or septicemia was present. There was a tendency where a better therapeutic effect was gained when the total protein and albumin values were high. We applied multivariate logistic regression analysis to these factors, and found the following independent significant factors: CRP (odds ratio (OR) = 1.582), albumin (OR = 3.079), Cre (OR -0.213), whether blood drug concentration was measured (OR = 3.767), and presence of pneumonia or septicemia (OR = 0.216). This result suggests that consideration should be given to these five important factors when treating MRSA patients.

Alanine Transaminase↗

PubMed2003

Discovery of temperature-dependent phenomena of muon-catalyzed fusion in solid deuterium and tritium mixtures.

A systematic experimental study on muon-catalyzed fusion was conducted using a series of solid deuterium and tritium mixtures. A variety of conditions were investigated, i.e., tritium concentrations from 20% to 70%, and temperatures from 5 to 16 K. With decreasing temperature, we observed an unexpected decrease in the muon cycling rate (lambda(c)) and an increase in the muon loss probability (W). The origins of these observed changes were interpreted by the temperature-dependence in the dt mu formation process for lambda(c) and that in the muon reactivation process after muon-to-alpha sticking for W.

Journal Article↗

PubMed2003

G-language Genome Analysis Environment: a workbench for nucleotide sequence data mining.

SUMMARY: G-language Genome Analysis Environment (G-language GAE) is an open source generic software package aimed for higher efficiency in bioinformatics analysis. G-language GAE has an interface as a set of Perl libraries for software development, and a graphical user interface for easy manipulation. Both Windows and Linux versions are available. AVAILABILITY: From http://www.g-language.org/ under GNU General Public License. CD-ROMs are distributed freely in major conferences.

Database Management Systems↗

PubMed2002

Age-specific values and cutoff levels for the diagnosis of osteoporosis in quantitative ultrasound measurements at the calcaneus with SAHARA in healthy Japanese women: Japanese population-based osteoporosis (JPOS) study.

To establish the reference values of the quantitative ultrasound (QUS) indices in healthy Japanese women and to propose a diagnostic criterion for osteoporosis by means of the QUS indices, 659 healthy women aged 20-79 years recruited from a larger cohort study (JPOS study), were examined for bone mass measurements by QUS at the calcaneus (SAHARA, Hologic Inc., USA) and by dual-energy X-ray absorptiometry at the spine, hip, and distal forearm. We presented 10-year age-specific mean values and T-scores of the QUS indices. The pattern of decrease in the T-score appeared to be linear in the QUS indices and total hip BMD but not in BMD at the spine. The T-score of the QUS of indices of the subjects in their 70s were significantly higher than that of BMD at the spine. The prevalence rates of osteoporosis in the subjects aged 50 and older diagnosed by QUS (8.7% for SOS, 10.7% for BUA) were similar to that diagnosed by total hip BMD (11.5%) and significantly lower than that by the spine BMD (36.1%) when the WHO criteria were applied. We performed receiver-operating characteristic analysis to set a cutoff level of the QUS indices for the diagnosis of osteoporosis to accurately identify the subjects diagnosed by either the spine or total hip BMD. The highest likelihood ratios for SOS and BUA were obtained at the cutoff levels of 1,517.7 m/sec (T-score: -1.58) with the sensitivity of 0.65 and the specificity of 0.65 and 59.5 dB/MHz (T-score: -1.52) with 0.66 and 0.69, respectively. The diagnostic accuracy of QUS indices for osteoporosis was not superior to that of age. However, the QUS indices showed a significant contribution to forming the diagnosis of osteoporosis independently of age and body size in multivariate diagnostic models developed by the logistic regression analysis. Therefore, the cutoff values presented in this study may be used as a tentative criterion until the cutoff levels for the QUS indices are set according to the fracture risk.

Adult↗

PubMed2002

Effects of diltiazem on in vitro cardiovascular actions of crude venom obtained from Okinawan box-jellyfish (Habu-kurage), Chiropsalmus quadrigatus.

The venom obtained from Okinawan box-jellyfish (Habu-kurage), Chiropsalmus quadrigatus, produced increases in contractions of isolated rat right atrial preparations in a concentration-dependent manner without changes in a spontaneous beating rate. These increases in contractions were significantly inhibited by diltiazem and did not show tachyphylaxis. The venom also produced increases in contractions of isolated rat aortic ring preparations (endothelium-intact) in a concentration-dependent fashion, which were reproducible with repeated application and were significantly inhibited by diltiazem or heating. These increases in vascular contractions were weakened in endothelium-denuded preparations, and almost abolished in a calcium-free medium. On the other hand, the venom at higher concentrations diminished contractions of both myocardial and vascular preparations and did not show reproducibility. These results suggest that the Habu-kurage venom is heat-labile and may increase contractions of cardiac muscle and aortic smooth muscle by increasing calcium influx into muscle cells, and that the venom at higher concentrations may produce dysfunction of muscle contractile systems due to calcium overload.

Animals↗

PubMed2002

Serum osteoprotegerin/osteoclastogenesis-inhibitory factor during pregnancy and lactation and the relationship with calcium-regulating hormones and bone turnover markers.

Pregnancy and lactation induce dynamic changes in maternal bone and calcium metabolism. A novel cytokine termed osteoprotegerin (OPG)/osteoclastogenesis-inhibitory factor (OCIF) was recently isolated; this cytokine inhibits osteoclast maturation. To define the effects of pregnancy and lactation on circulating OPG/OCIF in mothers, we studied the changes in the levels of OPG/ OCIF as well as those of calcium-regulating hormones and biochemical markers of bone turnover in the maternal circulation during pregnancy (at 8-11 weeks, at 22-30 weeks, at 35-36 weeks and immediately before delivery) and lactation (at 4 days and at 1 month postpartum). Serum intact parathyroid hormone levels did not change and were almost within the normal range in this period. In contrast, serum 1,25-dihydroxyvitamin D levels increased with gestational age and were above the normal range during pregnancy. After delivery, they fell rapidly and significantly (P<0.01) to the normal range. The levels of serum bone-specific alkaline phosphatase, one of the markers of bone formation, increased with gestational age. After delivery, these levels were further increased at 1 month postpartum. The levels at 1 month postpartum were significantly higher than those at 8-11 and 22-30 weeks of pregnancy (P<0.01 and P<0.05 respectively). The levels of serum C-terminal telopeptides of type I collagen, one of the markers of bone resorption, did not change during pregnancy. After delivery, they rapidly and significantly (P<0.01) rose at 4 days postpartum, and had then fallen by 1 month postpartum. Circulating OPG/OCIF levels gradually increased with gestational age and significantly (P<0.01) increased immediately before delivery to 1.40+/-0.53 ng/ml (means+/-S.D.) compared with those in the non-pregnant, non-lactating controls (0.58+/-0.11 ng/ml). After delivery, they fell rapidly to 0.87+/-0.27 ng/ml at 4 days postpartum and had fallen further by 1 month postpartum. These results suggest that the fall in OPG/OCIF levels may be partially connected with the marked acceleration of bone resorption after delivery.

Adult↗

PubMed2001

Genetic evidence that antibacterial activity of lysozyme is independent of its catalytic function.

A catalytically inactive mutant of hen egg white lysozyme was constructed by site-directed mutagenesis to elucidate the role of enzymatic activity on its antimicrobial activity against Gram-positive bacteria. The catalytic residue aspartic acid at position 52 of lysozyme was substituted with serine (D52S-Lz) and the mutant cDNA was inserted into a yeast expression vector, pYES-2. Western blot analysis indicated that the mutation did not affect secretion of the D52S-Lz lysozyme into the medium of the expressing Saccharomyces cerevisiae, INVSC1. In addition, circular dichroism and fluorescence spectral analysis revealed no change in the structure of D52S-Lz compared to that of wild-type (Wt-Lz) lysozyme. The mutation (D52S) abolished the catalytic activity of lysozyme. Antimicrobial tests against Staphylococcus aureus and Bacillus subtilis revealed that the catalytically inactive D52S-Lz was as bactericidal as the Wt-Lz lysozyme. Heat treatment leading to enzyme inactivation had no effect on the bactericidal activity of either wild-type or the mutant D52S-Lz lysozyme. The binding affinity of D52S-Lz to the isolated peptidoglycan of S. aureus was unaffected. Our results provide the first demonstration of direct genetic evidence that the antimicrobial activity of lysozyme is operationally independent of its muramidase activity, and strongly suggest the antimicrobial action of lysozyme is due to structural factors.

Anti-Bacterial Agents↗

PubMed2001

Follistatin-related protein (FSRP): a new member of the follistatin gene family.

The identification and characterization of follistatin related protein (FSRP) suggests that the follistatin (FS) gene family may actually contain two sub-families. The first includes FS and FSRP by virtue of their high degree of structural homology and comparable activin-binding activity, while the second sub-family contains extracellular matrix proteins that possess one or more 10-cysteine FS domains, but do not bind activin or related TGF-beta family members. Characterization of FSRP indicates that it binds activin with similar affinity and selectivity as FS, but does not bind heparin. Furthermore, although FSRP inhibits activin-mediated gene transcription in heterologous assays, FSRP is much less active than FS in the rat pituitary bioassay. When overexpressed in transgenic mice, FSRP may lead to interruption of follicular development and fertility in females but appears to have only a modest effect on males. These results suggest that FSRP is a structural, but not necessarily a functional homologue of FS.

Activins↗

PubMed2001

Intracellular and extracellular control of activin function by novel regulatory molecules.

Activin signal transduction is regulated through multiple mechanisms. We have identified novel regulatory proteins that control activin functions either intracellularly or extracellularly. As intracellular molecules, PSD-95/Dlg/ZO-1 (PDZ) proteins that specifically associate with activin type II receptors (ActRIIs) were identified. We have named the molecules as activin receptor-interacting proteins (ARIPs). ARIP1 has two WW domains and five PDZ domains, associates not only with ActRIIs but also with Smads, and controls activin functions intracellularly in neuronal cells. Another ARIP we have found has only one PDZ domain, and is likely to be involved in intracellular trafficking and sorting of activin receptor complexes in the cell. As an extracellular regulatory protein, we have identified a novel follistatin-like protein, named follistatin-related gene (FLRG). Like follistatins, FLRG binds activins and bone morphogenetic proteins (BMPs) and controls their functions extracellularly. The mode of association of follistatin and FLRG with activins and their expression patterns are different, suggesting the distinct functions of follistatin and FLRG in vivo.

Activin Receptors↗

PubMed2001

Phenotypic variation in a large Japanese family with Miyoshi myopathy with nonsense mutation in exon 19 of dysferlin gene.

Miyoshi myopathy, an autosomal recessive muscular dystrophy involving distal muscles, is caused by dysferlin mutations. We present clinical and genetic studies of two men and six women, aged 25-83 years, from a Japanese family with consanguineous marriages. Onset was between ages 17 and 59 years. Six of the patients had muscle involvement typical of Miyoshi myopathy, one initially had severe proximal muscle involvement, and one had scapuloperoneal-type muscle involvement. Three patients showed steppage gait. Genetic linkage analysis identified a maximum lod score of 3.34 (θ=0.00) at marker D2S292 in 2p13. Analysis of dysferlin revealed the mutation G2090T (Glu573Stop) in exon 19 in all affected patients. This is the largest Japanese family with Miyoshi myopathy showing intrafamilial phenotypic variation and sharing a common mutation in dysferlin.

Adult↗

PubMed2001

Bone mineral density of the spine, hip and distal forearm in representative samples of the Japanese female population: Japanese Population-Based Osteoporosis (JPOS) Study.

Low bone mineral density (BMD) is one of the most important elements for the diagnosis of osteoporosis and screening people with higher risk of fractures. To establish the criterion value of BMD for the diagnosis of osteoporosis and to estimate the prevalence rate of osteoporosis in Japanese women, we performed a Japanese population-based osteoporosis (JPOS) study. The subjects were 4550 women aged 15 through 79 years randomly selected from seven municipalities throughout Japan. The sample size was determined to ensure that the observed mean BMD would remain within 2.5% from the real value with a probability of 0.95 in each of the 5-year age groups. The study comprised bone mass measurements by dual-energy X-ray absorptiometry at the spine (L2-4), hip and distal forearm, body size measurements and detailed interviews on medical and gynecologic history. After excluding those subjects with apparent or suggested abnormalities affecting bone mass from 3985 women (87.6%) who completed the study, 3465 women remained and served as the subjects. We present 5-year age-specific mean values of BMD and cut-off values for the diagnosis of osteoporosis according to World Health Organization (WHO) and the Japanese Society of Bone and Mineral Research (JSBMR) criteria. The cut-off levels at the spine and the distal radius proposed in this study were similar to those proposed by the JSBMR but the cut-off level at the femoral neck in this study was 4.7% higher than that of the JSBMR. The prevalence rates of osteoporosis according to WHO criteria in the present subjects aged 50 through 79 years were calculated as 38.0% at the spine, 11.6% at the femoral neck and 56.8% at the distal one-third site of the radius, and those in the Japanese female population of the same age were estimated to be 35.1%, 9.4% and 51.2%, respectively. A fivefold difference was observed among the prevalence rates at different skeletal sites, which suggests that the different definitions of osteoporosis should be established for the different skeletal sites. The prevalence rate diagnosed at the femoral neck seemed to be lower in the present study than those reported for Caucasians. This might account for a lower incidence rate of hip fracture in Japanese women.

Absorptiometry, Photon↗

PubMed2001

Most apoptotic cells in mdx diaphragm muscle contain accumulated lipofuscin.

An age-related pigment, lipofuscin (LF), which accumulates in postmitotic, long-lived cells, is formed by the oxidative degradation of cellular macromolecules by oxygen-derived free radicals. In the present study we show that LF is accumulated in some myofibres, myosatellite cells and interstitial cells in the diaphragm muscles of the X chromosome-linked muscular dystrophic (mdx) mice at the age of 10 weeks when repetitive cycles of de- and regeneration of myofibres occur. In contrast, LF is virtually absent in diaphragm muscles of age-matched C57BL/10 (C57) normal control mice. Therefore, mdx muscle is more susceptible to oxidative stress than normal muscle. We hypothesise that gene-regulated cell death (apoptosis) occurs in dystrophic muscle cells that accumulate LF as a consequence of either oxidative stress or injury. We found that 74-79% of apoptotic myosatellite cells, interstitial cells and myofibres in mdx diaphragm contain accumulated or dotted LF granules, but only 12-20% of non-apoptotic cells contain LF. Apoptotic cells are very rare in the diaphragm of age-matched C57 control mice. This suggests that the regeneration of mdx diaphragm muscle initiated from myosatellite cells is impaired by their apoptosis as the result of either oxidative stress or a product of oxidative injury.

Animals↗