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Biomedical subjects

S Morimoto

Publications and source records attributed to S Morimoto.

At least 19 recordsLinked to original sources
PubMed2006

Decreased CD161+CD8+ T cells in the peripheral blood of patients suffering from rheumatic diseases.

OBJECTIVES: Although it has been reported that the numbers of both CD4(-)CD8(-) and CD4(+) natural killer T (NKT) cells are selectively decreased in the peripheral blood of patients with rheumatic diseases, there have been no reports concerning a novel subpopulation of CD8(+) NKT cells. To examine whether CD161(+)CD8(+) T cells, which are closely related to CD8(+) NKT cells, are also decreased in patients with rheumatic diseases, we have investigated the expression of CD161, together with that of CD28, CD25 and CD62L, on T cells in the peripheral blood of these patients. METHODS: The rheumatic diseases evaluated in this study were systemic lupus erythematosus (SLE) (n= 54), mixed connective-tissue disease (MCTD) (n= 15), systemic sclerosis (SSc) (n= 14), polymyositis/dermatomyositis (PM/DM) (n= 13) and rheumatoid arthritis (RA) (n= 24). Healthy donors were examined as controls (n= 18). The expression of CD161, CD28, CD25 and CD62L on T cells was analysed by flow cytometry. RESULTS: Both the frequency of CD161 expression on CD8(+) cells and the absolute number of CD161(+)CD8(+) cells were significantly decreased in patients with SLE, MCTD, SSc and PM/DM. Only the absolute number of CD161(+)CD8(+) T cells was significantly decreased in RA. CD161 expression on CD28(-)CD8(+) T cells was significantly decreased in SLE, MCTD and SSc. The absolute number of CD161(+)CD8(+)CD62L(-) T cells was significantly decreased in SLE, MCTD and SSc. CONCLUSIONS: Both the frequency and the absolute number of CD161(+)CD8(+) T cells were decreased in the peripheral blood of patients suffering from SLE, MCTD, SSc and PM/DM. This result suggests that there is also an abnormality of NKT cells in the CD8(+) population.

Adult↗
PubMed2005

Facilitated nitration and oxidation of LDL in cigarette smokers.

BACKGROUND: Cigarette smoking increases the risk of developing atherosclerosis and ischaemic heart disease. Smoking-induced oxidative stress is considered to favour oxidation of low-density lipoprotein (LDL) and subsequently promotes the atherogenic process. We investigated whether peroxynitrite, a reaction product of cigarette smoke, is involved in facilitated oxidation of LDL in smokers. MATERIALS AND METHODS: Plasma LDL was obtained from 10 healthy asymptomatic cigarette smokers and 10 healthy nonsmokers. The state of enhanced oxidative stress in the plasma was assessed by LDL subfraction assay using anion-exchange high-performance liquid chromatography (AE-HPLC) and measurements of thiobarbituric acid-reactive substances (TBARS), 8-hydroxydeoxyguanosine (8-OHdG), vitamin E, 3-nitrotyrosine and 3-chlorotyrosine. RESULTS: Smokers showed a significantly higher level of TBARS and 8-OHdG as well as a significantly lower level of vitamin E than nonsmokers, even after stopping smoking for 10 h or more. The LDL subfraction assay demonstrated an increase in oxidatively modified LDL, as expressed by lower levels of LDL1 and higher levels of LDL2. The 3-nitrotyrosine levels in apolipoprotein B in LDL were significantly higher in smokers than nonsmokers, while the 3-chlorotyrosine levels remained unchanged. In addition, these changes observed in the smokers were further accelerated within 30 min after resumption of cigarette smoking when compared with the levels before smoking resumption. CONCLUSION: The present study suggests that peroxynitrite plays a significant role in oxidative modification of plasma LDL induced by cigarette smoking.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2005

Osteoclast-like cells express receptor activity modifying protein 2: application of laser capture microdissection.

Receptor activity modifying proteins (RAMPs) act as receptor modulators that determine the ligand specificity of receptors for the calcitonin (CT) family. The purpose of this study was to analyze the expression of RAMPs in osteoclast-like cells using the laser capture microdissection (LCM) technique. Mouse bone marrow and spleen cells were co-cultured on a film designed for LCM. After 10 days, 250 osteoclast-like cells were captured using the LCM system. Total RNA from these cells was used to synthesize cDNA and RT-PCR analysis was performed. Osteoclast-like cells expressed CT receptor (CTR), CT receptor-like receptor (CRLR) and RAMP2, but did not express RAMP1 or RAMP3. These results indicated (1) that a pure population of osteoclast-like cells can be prepared by LCM and gene expression of this population can be analyzed by RT-PCR and (2) that RT-PCR shows that osteoclast-like cells express RAMP2, CTR and CRLR, suggesting the potential for adrenomedullin binding to osteoclast-like cells. This is the first report that osteoclast-like cells express RAMP2.

Animals↗
PubMed2005

Protective effect of testosterone on early apoptotic damage induced by streptozotocin in rat pancreas.

Beta-cell apoptosis is responsible for the development of insulin-dependent diabetes mellitus in the streptozotocin (STZ) rat model. It has been demonstrated that steroid hormones possess antioxidant and protective antiapoptotic effects in many tissues. The aim of the present study was to investigate the early apoptotic damage induced by STZ in rat pancreas, and the effect of testosterone in preventing apoptosis of pancreatic beta cells. Intact and castrated adult male Wistar rats were subjected to a unique injection of STZ 60 mg/kg (body weight) in citrate buffer, and the kinetics of apoptosis in beta cells was assessed. Insulin and glucose were measured by RIA and a glucometer respectively, and in pancreatic tissue by immunohistochemistry. At 6 h after STZ injection, a marked increase in apoptotic beta cells was detected; however, glucose and insulin serum levels were not significantly different from the controls. The castrated animals presented higher percentages of apoptotic beta cells (65.75 +/- 5.42%) than intact males (20.6 +/- 4.38%) and castrated, testosterone-substituted males (30.66 +/- 1.38%). The decrease in apoptotic beta cells induced by testosterone was reversed by the antiandrogen flutamide (67.69 +/- 3.45%). The overall results indicate that early apoptotic damage produced by STZ in castrated animals was reversed by testosterone, suggesting that this hormone exerts a natural protective effect in rat pancreas. This effect could help to explain some sexual differences in diabetes mellitus incidence in man, reinforcing the idea that new approaches in steroid hormone therapies should be considered for treatment of this disease.

Alkylating Agents↗
PubMed2004

Inherited cardiomyopathies as a troponin disease.

Troponin, one of the sarcomeric proteins, plays a central role in the Ca(2+) regulation of contraction in vertebrate skeletal and cardiac muscles. It consists of three subunits with distinct structure and function, troponin T, troponin I, and troponin C, and their accurate and complex intermolecular interaction in response to the rapid rise and fall of Ca(2+) in cardiomyocytes plays a key role in maintaining the normal cardiac pump function. More than 200 mutations in the cardiac sarcomeric proteins, including myosin heavy and light chains, actin, troponin, tropomyosin, myosin-binding protein-C, and titin/connectin, have been found to cause various types of cardiomyopathy in human since 1990, and more than 60 mutations in human cardiac troponin subunits have been identified in dilated, hypertrophic, and restrictive forms of cardiomyopathy. In this review, we have focused on the mutations in the genes for human cardiac troponin subunits and discussed their functional consequences that might be involved in the primary mechanisms for the pathogenesis of these different types of cardiomyopathy.

Cardiomyopathy, Dilated↗
PubMed2003

Expression of NKB1 on peripheral T cells in patients with rheumatoid arthritis.

NKB1 inhibits cytoxic activity of T lymphocytes mediated by superantigens, which is one of the contributing factors in the pathogenesis of rheumatoid arthritis (RA). In this study, we determined the expression of NKB1 on peripheral blood T cells in patients with RA. Our findings revealed that among patients with RA, NKB1(+) CD8(+ )T cells decreased significantly in comparison to controls (ratio: P < 0.05; absolute number: P < 0.005), and this decrease was not related to or influenced by HLA-Bw4 as a ligand of NKB1. This result may suggest that decreased expression of NKB1(+) CD8(+ )T cells contributes to the pathogenesis of RA mediated by the activation of CD8(+) T cells.

Adult↗
PubMed2002

The role of the hypothalamic nitric oxide in the pressor responses elicited by acute environmental stress in awake rats.

We quantitatively investigated the change in nitric oxide (NO) in the hypothalamic paraventricular nucleus (PVN) and its effect on cardiovascular regulation during shaker stress (SS) using brain microdialysis in awake rats. Male Wistar rats were fed either N(G)-nitro-L-arginine methyl ester (L-NAME, 0.7 g/L) or tap water for 2 weeks. Two days after implantation of an arterial catheter and guide shaft, a microdialysis probe was placed to perfuse the PVN with degassed Ringer solution at 2 microl/min in awake normotensive Wistar (CONTROL) and chronic L-NAME-treated hypertensive rats. After the rat was placed in a plastic cage set on a shaker, the blood pressure and heart rate was monitored and 10-min SS was loaded at a frequency of 200 cycles/min. Dialysate samples were analyzed by NO analyzer (based on the Griess reaction) every 10 min, and NOx (NO(2)(-) + NO(3)(-)) was measured. Plasma NOx was also measured before and after SS. Pressor responses elicited by SS were significantly greater in L-NAME-treated rats than in the CONTROL. Although NOx in the PVN dialysate were increased by SS in the CONTROL, these responses were attenuated in chronic L-NAME-treated rats. Resting plasma NOx were higher in the CONTROL than in L-NAME-treated rats. SS elicited no difference between two groups in plasma NOx. These results indicated that NO within the PVN, but not in systemic circulation, may play a role on the attenuation of the pressor responses elicited by SS. The dysfunction of NO release within the PVN may, in part, play a role in the exaggerated pressor responses in acute environmental stress.

Acute Disease↗
PubMed2002

Pressure-induced transition from a charge-disproportionated antiferromagnetic state to a charge-uniform ferromagnetic state in Sr(2/3)La(1/3)FeO3.

The perovskite oxide Sr(2/3)La(1/3)FeO3 has been found to switch its electronic ground state drastically at 23 GPa through measurements of 57Fe Mössbauer spectroscopy and powder x-ray diffraction up to 56 GPa. In the low-pressure region a first-order transition from a charge-uniform paramagnetic metallic phase to a charge-disproportionated (3Fe(11/3+)-->2Fe(3+)+Fe5+) antiferromagnetic insulating phase occurs at 207 K at 0.1 MPa and 165 K at 21 GPa, typically. Above 25 GPa, however, a charge-uniform ferromagnetic (and most probably metallic) phase persists below 300 K. This switching occurs at a lattice volume of V(23 GPa)/V(0)(0.1 MPa) = 0.89.

Journal Article↗
PubMed2002

Ca(2+)-desensitizing effect of a deletion mutation Delta K210 in cardiac troponin T that causes familial dilated cardiomyopathy.

A deletion mutation Delta K210 in cardiac troponin T (cTnT) was recently found to cause familial dilated cardiomyopathy (DCM). To explore the effect of this mutation on cardiac muscle contraction under physiological conditions, we determined the Ca(2+)-activated force generation in permeabilized rabbit cardiac muscle fibers into which the mutant and wild-type cTnTs were incorporated by using our TnT exchange technique. The free Ca(2+) concentrations required for the force generation were higher in the mutant cTnT-exchanged fibers than in the wild-type cTnT-exchanged ones, with no statistically significant differences in maximal force-generating capability and cooperativity. Exchanging the mutant cTnT into isolated cardiac myofibrils also increased the free Ca(2+) concentrations required for the activation of ATPase. In contrast, a deletion mutation Delta E160 in cTnT that causes familial hypertrophic cardiomyopathy (HCM) decreased the free Ca(2+) concentrations required for force generation, just as in the case of the other HCM-causing mutations in cTnT. The results indicate that cTnT mutations found in the two distinct forms of cardiomyopathy (i.e., HCM and DCM) change the Ca(2+) sensitivity of cardiac muscle contraction in opposite directions. The present study strongly suggests that Ca(2+) desensitization of force generation in sarcomere is a primary mechanism for the pathogenesis of DCM associated with the deletion mutation Delta K210 in cTnT.

Adenosine Triphosphatases↗
PubMed2002

Evidence that steroid 5alpha-reductase isozyme genes are differentially methylated in human lymphocytes.

The synthesis of dihydrotestosterone (DHT) is catalyzed by steroid 5alpha-reductase isozymes 1 and 2, and this function determines the development of the male phenotype during embriogenesis and the growth of androgen sensitive tissues during puberty. The aim of this study was to determine the cytosine methylation status of 5alpha-reductase isozymes types 1 and 2 genes in normal and in 5alpha-reductase deficient men. Genomic DNA was obtained from lymphocytes of both normal subjects and patients with primary 5alpha-reductase deficiency due to point mutations in 5alpha-reductase 2 gene. Southern blot analysis of 5alpha-reductase types 1 and 2 genes from DNA samples digested with HpaII presented a different cytosine methylation pattern compared to that observed with its isoschizomer MspI, indicating that both genes are methylated in CCGG sequences. The analysis of 5alpha-reductase 1 gene from DNA samples digested with Sau3AI and its isoschizomer MboI which recognize methylation in GATC sequences showed an identical methylation pattern. In contrast, 5alpha-reductase 2 gene digested with Sau3AI presented a different methylation pattern to that of the samples digested with MboI, indicating that steroid 5alpha-reductase 2 gene possess methylated cytosines in GATC sequences. Analysis of exon 4 of 5alpha-reductase 2 gene after metabisulfite PCR showed that normal and deficient subjects present a different methylation pattern, being more methylated in patients with 5alpha-reductase 2 mutated gene. The overall results suggest that 5alpha-reductase genes 1 and 2 are differentially methylated in lymphocytes from normal and 5alpha-reductase deficient patients. Moreover, the extensive cytosine methylation pattern observed in exon 4 of 5alpha-reductase 2 gene in deficient patients, points out to an increased rate of mutations in this gene.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2002

Mutation induction in human cells after low dose X ray exposure.

Mutations induced after low dose ionising radiation exposure have been intensively analysed not only for radiation risk estimation but also for basic understanding of cellular responses. Human lymphoblastoid TK6-20C cells were irradiated with 100 mGy of X rays and mutation at the heterozygous thymidine kinase (TK) locus was selected by trifluorothymidine (TFT) resistance. Although the mutation frequency at the TK locus increased from 5.6 x 10(-6) to 7.4 x 10(-6), this increase was not statistically significant. However, molecular analysis of TK mutants exhibiting loss of heterozygocity (LOH) demonstrated a clear effect of such low dose IR exposure. Exposure to 100 mGy X ray increased the fraction of hemizygous-LOH from 10% to 42%. In previous experiments, a similar tendency in the increase of hemizygous-LOH was also observed in TK6 cells after exposure to a 2 Gy dose of X rays. This type of LOH can be considered as a result of end-joining repair of DNA double strand breaks.

Cell Line↗
PubMed2002

Cellular responses to low dose heavy-ion exposure in human cells.

The human lymphoblastoid cell line TK6 was used to study the cellular responses after low-dose (100, 200, 500 mGy) or high-dose (3 Gy) of X rays, C (22 keV.micron-1) and Fe (1000 keV.micron-1) ion exposures. p53 protein induction in individual cells was determined by indirect immunofluorescence staining. Cell-cycle progression after heavy-ion exposure was determined by using a laser scanning cytometer. A characteristic pattern of cell-cycle progression was observed with 3 Gy exposure of Fe ions but not with 100 mGy. Similarly such a pattern with 100 mGy C ion exposure did not match that with 3 Gy. The proportion of p53-induced cells is proportional to the probability of cell being hit by a primary heavy ion. The observed low-dose effect can be reflected in the probability of a hit, although detailed nature about their energy deposition must be considered for more precise estimation of such an effect. New detection methodology must be developed for identification of heavy-ion specific cellular responses.

Cell Cycle↗
PubMed2002

Clinical characteristics of non-immune-mediated, idiopathic type 1 (type 1B) diabetes mellitus in Japanese children and adolescents.

To clarify the characteristics of idiopathic type 1 (type 1B) diabetes mellitus (DM), we compared the clinical features of immune-mediated type 1 (type 1A) DM and type 1B DM in 85 Japanese children and adolescents with DM. The prevalence of type 1B DM was 16.5%. The patients with type 1B DM were significantly younger at diagnosis and had a higher frequency of preceding viral infection before onset, compared to those with type 1A DM. They displayed more severe metabolic decompensation with a higher frequency of ketoacidosis at diagnosis than patients with type 1A DM. They had strong, HLA-defined genetic susceptibility, similar to that in type 1A DM. Some patients with type 1B DM exhibited a remarkably abrupt onset and rapid loss of beta-cell capacity. From these findings, it is considered that type 1B DM differs from type 1A DM with respect to age at onset and the trigger event, such as viral infection, leading to rapid destruction of beta-cells without autoimmunity in the etiology of the disease.

Adolescent↗
PubMed2001

Synthesis and antibacterial activity of acylides (3-O-acyl-erythromycin derivatives): a novel class of macrolide antibiotics.

Introduction of an acyl group to the 3-O-position of erythromycin A derivatives instead of L-cladinose led to a novel class of macrolide antibiotics that we named "acylides". The 3-O-nitrophenylacetyl derivative TEA0777 showed significantly potent activity against not only erythromycin-susceptible Gram-positive pathogens but also inducibly macrolides-lincosamides-streptogramin B (MLS(B))-resistant Staphylococcus aureus and efflux-resistant Streptococcus pneumoniae. These results indicated that acylides have potential as next-generation macrolide antibiotics.

Animals↗
PubMed2001

Prognostic determinants of long-term survival in Japanese patients with cardiac sarcoidosis treated with prednisone.

Cardiac involvement is an important prognostic factor in sarcoidosis, but reliable indicators of mortality risk in cardiac sarcoidosis are unstudied in a large number of patients. To determine the significant predictors of mortality and to assess the efficacy of corticosteroids, we analyzed clinical findings, treatment, and prognosis in 95 Japanese patients with cardiac sarcoidosis. Twenty of these 95 patients had cardiac sarcoidosis proven by autopsy; none of these patients had received corticosteroids. We assessed 12 clinical variables as possible predictors of mortality by Cox proportional hazards model in 75 steroid-treated patients. During the mean follow-up of 68 months, 29 patients (73%) died of congestive heart failure and 11 (27%) experienced sudden death. Kaplan-Meier survival curves showed 5-year survival rates of 75% in the steroid-treated patients and of 89% in patients with a left ventricular ejection fraction > or = 50%, whereas there was only 10% 5-year survival rate in autopsy subjects. There was no significant difference in survival curves of patients treated with a high initial dose (> 30 mg) and a low initial dose (> or = 30 mg) of prednisone. Multivariate analysis identified New York Heart Association functional class (hazard ratio 7.72 per class I increase, p = 0.0008), left ventricular end-diastolic diameter (hazard ratio 2.60/10 mm increase, p = 0.02), and sustained ventricular tachycardia (hazard ratio 7.20, p = 0.03) as independent predictors of mortality. In conclusion, the severity of heart failure was one of the most significant independent predictors of mortality for cardiac sarcoidosis. Starting corticosteroids before the occurrence of systolic dysfunction resulted in an excellent clinical outcome. A high initial dose of prednisone may not be essential for treatment of cardiac sarcoidosis.

Aged↗
PubMed2001

Elevated blood pressure in transgenic mice with brain-specific expression of human angiotensinogen driven by the glial fibrillary acidic protein promoter.

In addition to the circulatory renin (REN)-angiotensin system (RAS), a tissue RAS having an important role in cardiovascular function also exists in the central nervous system. In the brain, angiotensinogen (AGT) is expressed in astrocytes and in some neurons important to cardiovascular control, but its functional role remains undefined. We generated a transgenic mouse encoding the human AGT (hAGT) gene under the control of the human glial fibrillary acidic protein (GFAP) promoter to experimentally dissect the role of brain versus systemically derived AGT. This promoter targets expression of transgene products to astrocytes, the most abundant cell type expressing AGT in brain. All transgenic lines exhibited hAGT mRNA expression in brain, with variable expression in other tissues. In one line examined in detail, transgene expression was high in brain and low in tissues outside the central nervous system, and the level of plasma hAGT was not elevated over baseline. In the brain, hAGT protein was mainly localized in astrocytes, but was present in neurons in the subfornical organ. Intracerebroventricular (ICV) injection of human REN (hREN) in conscious unrestrained mice elicited a pressor response, which was abolished by ICV preinjection of losartan. Double-transgenic mice expressing the hREN gene and the GFAP-hAGT transgene exhibited a 15-mm Hg increase in blood pressure and an increased preference for salt. Blood pressure in the hREN/GFAP-hAGT mice was lowered after ICV, but not intravenous losartan. These studies suggest that AGT synthesis in the brain has an important role in the regulation of blood pressure and electrolyte balance.

Angiotensinogen↗
PubMed2001

Morphine metabolism in the opium poppy and its possible physiological function. Biochemical characterization of the morphine metabolite, bismorphine.

We identified a novel metabolic system of morphine in the opium poppy (Papaver somniferum L.). In response to stress, morphine is quickly metabolized to bismorphine consisting of two morphine units, followed by accumulation in the cell wall. This bismorphine binds predominantly to pectins, which possess high galacturonic acid residue contents, through ionical bonds. Our newly developed method using artificial polysaccharides demonstrated that bismorphine bridges are formed between the two amino groups of bismorphine and the carboxyl groups of galacturonic acid residues, resulting in cross-linking of galacturonic acid-containing polysaccharides to each other. The ability of bismorphine to cross-link pectins is much higher than that of Ca2+, which also acts as a cross-linker of these polysaccharides. Furthermore, we confirmed that cross-linking of pectins through bismorphine bridges leads to resistance against hydrolysis by pectinases. These results indicated that production of bismorphine is a defense response of the opium poppy. Bismorphine formation is catalyzed by anionic peroxidase that pre-exists in the capsules and leaves of opium poppies. The constitutive presence of morphine, together with bismorphine-forming peroxidase, enables the opium poppy to rapidly induce the defense system.

Carbohydrate Sequence↗