Biomedical subjects

S Ogawa

Publications and source records attributed to S Ogawa.

At least 73 records · Page 4Linked to original sources

PubMed2004

Predictors for severe cardiac complications after hematopoietic stem cell transplantation.

The value of pre-transplant factors for predicting the development of cardiac complications after transplantation has been inconsistent among studies. We analyzed the impact of pre-transplant factors on the incidence of severe cardiac complications in 164 hematopoietic stem cell transplant recipients. We identified eight patients (4.8%) who experienced grade III or IV cardiac complications according to the Bearman criteria. Seven died of cardiac causes a median of 3 days after the onset of cardiac complications. On univariate analysis, both the cumulative dose of anthracyclines and the use of anthracyclines within 60 days before transplantation affected the incidence of severe cardiac complications (P=0.0091 and 0.011). The dissociation of heart rate and body temperature, which reflects "relative tachycardia", was also associated with a higher incidence of cardiac complications (P=0.024). None of the variables obtained by electrocardiography or echocardiography were useful for predicting cardiac complications after transplantation, although the statistical power might not be sufficient to detect the usefulness of ejection fraction. On a multivariate analysis, the cumulative dose of anthracyclines was the only independent significant risk factor for severe cardiac complications. We conclude that the cumulative dose of anthracyclines is the most potent predictor of cardiac complications and the administration of anthracyclines should be avoided within two months before transplantation.

Adult↗

PubMed2004

Recovery of Valpha24+ NKT cells after hematopoietic stem cell transplantation.

Human Valpha24+ natural killer T (NKT) cells have an invariant T-cell receptor-alpha chain and are activated in a CD1d-restricted manner. Valpha24+ NKT cells are thought to regulate immune responses and to play important roles in the induction of allograft tolerance. In this report, we analyzed the recovery of Valpha24+ NKT cells after hematopoietic stem cell transplantation and its correlation with graft-versus-host disease (GVHD). Patients who received a dose-reduced conditioning regimen, antithymocyte globulin- or CAMPATH-1H-containing conditioning regimen were excluded. NKT cells were reconstituted within 1 month after transplantation in peripheral blood stem cell transplantation recipients, while their numbers remained low for more than 1 year in bone marrow transplantation (BMT) recipients. The number of Valpha24+ NKT cells in BMT recipients with acute GVHD was lower than that in patients without acute GVHD, and both the CD4+ and CD4- Valpha24+ NKT subsets were significantly reduced. With regard to chronic GVHD, BMT recipients with extensive GVHD had significantly fewer Valpha24+ NKT cells than other patients. Furthermore, the number of CD4+ Valpha24+ NKT cells was also significantly reduced in patients with chronic extensive GVHD. Our results raise the possibility that the number of Valpha24+ NKT cells could be related to the development of GVHD.

Adolescent↗

PubMed2004

Expression of the arginine vasopressin gene in response to salt loading in oxytocin gene knockout mice.

Accumulating evidence suggests that both oxytocin and arginine vasopressin (AVP) are vital components in the regulation of body fluid balance. However, the physiological role of oxytocin and possible cooperative interactions between oxytocin and AVP in sodium balance remain obscure, even though recent studies using oxytocin knockout (OTKO) mice suggested that oxytocin may contribute to the regulation of salt appetite. In the present study, we examined the effects of salt loading (drinking 2% NaCl for 5 days) on the expression of the AVP gene in the paraventricular (PVN) and supraoptic nuclei (SON) of wild-type, OTKO and heterozygous littermates using in situ hybridization histochemistry. In addition, the effects of salt loading on the expression of the oxytocin gene were also examined in wild-type and heterozygous mice. Under the non salt-loaded condition, the levels of AVP mRNA in the PVN and SON of OTKO mice were significantly decreased compared to those in wild-type mice. Nevertheless, the up-regulation of the expression of the AVP gene in response to salt loading was preserved in OTKO mice. The degree of the up-regulation in OTKO mice tended to be greater compared to those in wild-type mice, suggesting compensatory up-regulation of the expression of the AVP gene in OTKO mice after salt loading. The basal levels of oxytocin mRNA in the PVN and SON of heterozygous mice were significantly lower than those in wild-type mice. Salt loading caused an increase of oxytocin mRNA levels in the PVN and SON of both wild-type and heterozygous mice. The ratios of increase of oxytocin mRNA levels were very similar between wild-type and heterozygous mice, suggesting that the single remaining oxytocin gene in heterozygous mice responds normally to an osmotic cue. Finally, salt loading tended to increase the serum concentration of sodium regardless of genotype, and there were no genotype differences in both the control and salt-loaded groups. These results suggest ways in which oxytocin may play a cooperative role together with AVP in the regulation of sodium balance.

Animals↗

PubMed2004

Acarbose lowers serum triglyceride and postprandial chylomicron levels in type 2 diabetes.

AIM: This study was designed to examine the therapeutic effect of acarbose on serum triglyceride (TG), free fatty acid (FFA), very low-density lipoprotein (VLDL) and chylomicron (CM) in the meal tolerance test (MTT) before and after acarbose treatment in type 2 diabetes mellitus (DM2). METHODS: Effects of acarbose on postprandial lipid metabolism were examined in DM2 patients. The subjects with normotriglyceridaemia (TG > or = 1.7 mmol/l, n = 60) were divided to three groups (A, B and C), and DM2 patients with hypertriglyceridaemia (TG > 1.7 mmol/l, n = 20) were designated group D. Group A was a control, and group B was designed to examine the one-dose effect of acarbose (100 mg) on lipid levels in MTT using the balanced food of 400 kcal. In groups C and D, acarbose 300 mg/day was administered for 8 weeks, and MTT with the one-dose acarbose administration was performed. We determined the levels of fasting and postprandial levels of glucose, insulin, FFA and TG-rich lipoproteins such as CM and VLDL. RESULTS: Acarbose treatment lowered plasma glucose levels and insulin secretion. In comparison among study groups A, B and C, acarbose significantly lowered serum TG levels in postprandial state. In group D, after the 8-week acarbose administration, fasting or postprandial FFA, TG and VLDL levels were also lowered. Interestingly, postprandial increase in CM was suppressed by acarbose administration in group B, C or D. CONCLUSIONS: Acarbose lowers postprandial TG and CM levels in DM2 with either normotriglyceridaemia or hypertriglyceridaemia. Improvement of insulin resistance with acarbose may also reduce fasting TG levels in DM2 with hypertriglyceridaemia. Acarbose is a beneficial therapeutic agent to reduce TG levels in DM2 patients, thereby leading to suppression of cardiovascular events.

Acarbose↗

PubMed2004

Oxytocin and estrogen receptor alpha and beta knockout mice provide discriminably different odor cues in behavioral assays.

Social behavior involves both the recognition and pro-duction of social cues. Mice with selective deletion(knockout) of either the gene for oxytocin (OT) or genes for the estrogen receptor (ER) -c or -B display impaired social recognition. In this study we demonstrate that these gene knockout mice also provide discriminably different social stimuli in behavioral assays. In an odor choice test, which is a measure of social interest and discrimination, outbred female Swiss-Webster mice discriminated the urine odors of male knock-outs IKO: OTKO, alphaERKO, betaERKO) from the odors of their wildtype littermates (WT: OTWT, alphaERWT, betaERWT). Females showed marked initial choices of the urine odors of OTWT and betaERWT males over those of OTKOand PERKO males, and alphaERKO males over alphaERWT males. The odors of OTKO and betaERKO males also induced aversive, analgesic responses, with the odors of WTs having no significant effects. Odors of both the alphaERWT andalphaERKO males induced aversive, analgesic responses,with the odors of the WT inducing significantly greater analgesia. The odors of restraint stressed WT and KO males also elicited analgesia with, again, females dis-playing significantly greater responses to the odors of stressed OTKO and betaERKO males than their WTs, and significantly lower analgesia to the odors of stressedalphaERKO than alphaERWT males. These findings show that the KO mice are discriminated from their WTs on the basis of odor and that the various KOs differ in the relative attractiveness/aversiveness of their odors. Therefore, in behavioral assays one causal route by which gene inactivation alters the social behavior of knockout mice may be mediated through the partners'modified responses to their odors.

Animals↗

PubMed2003

Genetic contributions to generalized arousal of brain and behavior.

We have identified a generalized arousal component in the behavior of mice. Analyzed by mathematical/statistical approaches across experiments, investigators, and mouse populations, it accounts for about 1/3 of the variance in arousal-related measures. Knockout of the gene coding for the classical estrogen receptor (ER-alpha), a ligand-activated transcription factor, greatly reduced arousal responses. In contrast, disrupting the gene for a likely gene duplication product, ER-beta, did not have these effects. A combination of mathematical and genetic approaches to arousal in an experimentally tractable mammal opens up analysis of a CNS function of considerable theoretical and practical significance.

Animals↗

PubMed2003

Serial diffusion-weighted imaging in a patient with MELAS and presumed cytotoxic oedema.

A patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) was studied with serial diffusion-weighted MRI (DWI) after stroke-like episodes and the apparent diffusion coefficient (ADC) was measured in an infarct-like lesion. In the acute and subacute stages, the affected area gave high signal on DWI and its ADC was much lower than that in a normal control region. In the chronic stage, the ADC became higher than that in normal brain. We therefore suggest that the stroke-like episodes did not cause vasogenic oedema but were related to energy failure and cytotoxic oedema.

Brain Edema↗

PubMed2003

Observation of B0-->pLambda(pi)(-).

We report the first observation of the charmless hyperonic B decay, B0-->pLambda(pi)(-), using a 78 fb(-1) data sample recorded on the Upsilon(4S) resonance with the Belle detector at KEKB. The measured branching fraction is B(B0-->pLambda(pi)(-))=(3.97(+1.00)(-0.80)+/-0.56)x10(-6). Searches for B0-->pLambda(K)- and pSigma(0)pi(-) yield no significant signals and we set 90% confidence-level upper limits of B(B0-->pLambda(K)-)<8.2x10(-7) and B(B0-->pSigma(0)pi(-))<3.8x10(-6).

Journal Article↗

PubMed2003

Observation of B0 -->D0K0 and B0 -->D0K*0 decays.

We report on a search for B(0)-->D(*0)K(*0) decays based on 85 x 10(6) BB events collected with the Belle detector at KEKB. The B(0)-->D0K(0) and B(0)-->D0K(*0) decays have been observed for the first time with the branching fractions B(B(0)-->D0K(0))=(5.0(+1.3)(-1.2)+/-0.6)x10(-5) and B(B(0)-->D0K(*0))=(4.8(+1.1)(-1.0)+/-0.5)x10(-5). No significant signal has been found for the B(0)-->D(*0)K*0) and B(0)-->D(*0)K(*0) decay modes, and upper limits at 90% C.L. are presented.

Journal Article↗

PubMed2003

Relation of coffee, green tea, and caffeine intake to gallstone disease in middle-aged Japanese men.

A possible protective effect of coffee or caffeine intake in the formation of gallstones has been suggested in some epidemiological studies. We examined the relation of coffee, green tea, and caffeine intake to gallstone disease in middle-aged Japanese men, distinguishing known gallstones from unknown diagnosed gallstones. Study subjects were 174 cases of gallstones as determined by ultrasonography, 104 cases of postcholecystectomy, and 6889 controls of normal gallbladder in the total of 7637 men who received a health examination at four hospitals of the Self-Defense Forces (SDF). Of the 174 cases of prevalent gallstones, 50 had been aware of having gallstones. Previously diagnosed gallstones and postcholecystectomy were combined as known gallstone disease. The consumption of coffee and green tea was ascertained by a self-administered questionnaire, and caffeine intake was estimated. Statistical adjustment was done for body mass index, smoking, alcohol use, rank in the SDF, and hospital. Coffee and caffeine intake were associated each with a statistically significant increase in the prevalence odds of known gallstone disease, but unrelated to newly diagnosed gallstones. Adjusted odds ratios of known gallstone disease were 1.7 (95% confidence interval [CI] 1.1-2.8) for coffee consumption of five cups or more per day vs. no consumption and 2.2 (95% CI: 1.3-3.7) for caffeine intake of 300 mg/day or more vs. less than 100 mg/day. The consumption of green-tea showed no material association with either unknown gallstones or known gallstone disease. The findings do not support a hypothesis that coffee drinking may be protective against gallstone formation.

Caffeine↗

PubMed2003

Impaired discrimination of and aversion to parasitized male odors by female oxytocin knockout mice.

A major cost of social behavior is the increased risk of exposure to parasites, with animals utilizing social information to recognize and avoid infected conspecifics. In mice, females can discriminate between infected and uninfected males on the basis of social cues, displaying aversive responses to the odors of infected males. In the present study, using female mice whose gene for oxytocin (OT) has been selectively deleted (OT knockout mice (OTKO)), we show that at least one normal allele for OT is required for the mediation of the recognition and avoidance of parasitized males. Female wild type (OTWT) and heterozygous (OTHZ) mice distinguished between the odors of individual males infected with the louse, Polyplax serrata, and uninfected males while the KO mice did not. Exposure to the odors of infected males induced analgesia in OTWT and OTHZ females, with OTKO females displaying attenuated analgesia. OTWT and OTHZ females, but not the OTKO females, also distinguished between the odors of novel and familiar infected males and modulated their analgesic responses on the basis of prior familiarity. In an odor choice test, OTWT and OTHZ females displayed a marked initial choice for the odors of uninfected males, whereas the OTKO females showed no consistent choice. This impairment was specific to the odors of infected males. OTKO females displayed normal analgesic responses to another aversive social odor, that of a stressed male, and an aversive non-social odor, that of a cat. The OTKOs had normal non-social olfactory memory, but were impaired in their social odor memory. These findings indicate that a normal OT gene comprises an essential part of the central recognition mechanism whereby females can both reduce the transmission of parasites to themselves and select for parasite-free males.

Animals↗

PubMed2003

Male predominance among Japanese adult patients with late-onset hemorrhagic cystitis after hematopoietic stem cell transplantation.

Late-onset hemorrhagic cystitis (LHC) after hematopoietic stem cell transplantation (HSCT) is mainly caused by viral infections. We retrospectively analyzed the records of 141 Japanese adult patients who underwent a first allogeneic HSCT from 1995 to 2002. In all, 19 patients developed LHC a median of 51 days after HSCT. Adenovirus (AdV) was detected in the urine of 10 LHC patients, of whom eight had AdV type 11. Five of the six available serum samples from these patients were also positive for AdV type 11, but the detection of AdV in serum was not associated with a worse outcome. Male sex and the development of grade II-IV acute graft-versus-host disease were identified as independent significant risk factors for LHC. Male predominance was detected in LHC after HSCT, as has been previously shown in children with AdV-induced acute HC. The detection of AdV DNA in serum did not predict a poor outcome.

Adenoviridae Infections↗

PubMed2003

Identification of a novel fusion gene, TTL, fused to ETV6 in acute lymphoblastic leukemia with t(12;13)(p13;q14), and its implication in leukemogenesis.

ETS variant gene 6 (ETV6)/translocation, ETS, leukemia (TEL)-involving chromosomal translocations are frequently observed in various hematologic neoplasms. We describe here a novel ETV6-involving translocation, t(12;13)(p13;q14), found in the case of acute lymphoblastic leukemia, in which ETV6 fused with a previously unknown gene, named Twelve-thirteen Translocation Leukemia gene (TTL), at 13q14. TTL was weakly but ubiquitously expressed in normal human tissues as detected by reverse transcribed-PCR. Three TTL splicing forms were identified, TTL-T from a human testis cDNA library, with an open-reading frame of 402 bp encoding 133 amino acids (aa), and TTL-B1 and -B2 from a human brain cDNA library. These proteins have no homology to known proteins. In leukemic cells from the patient, both reciprocal fusion transcripts, ETV6/TTL and TTL/ETV6, were expressed. The predominant fusion transcript, TTL/ETV6-1, encodes a predicted 530 aa fusion protein containing 89 aa of the N-terminal TTL fusing to the helix-loop-helix domain and ETS-binding domain of ETV6. Although the function of TTL is yet to be elucidated, our findings will provide another insight into the molecular pathogenesis of leukemia having ETV6-involving translocations.

Alternative Splicing↗

PubMed2003

Enhanced up-regulation of corticotropin-releasing hormone gene expression in response to restraint stress in the hypothalamic paraventricular nucleus of oxytocin gene-deficient male mice.

The neuropeptide oxytocin is released not only into the blood, but also within the brain in response to various stressors. Accumulating evidence suggests that central oxytocin may play a major role in the regulation of neuroendocrine responses to stress. In the present study, using the oxytocin knockout mouse model, we tested whether oxytocin might act to attenuate stress-induced up-regulation of corticotropin-releasing hormone (CRH) mRNA expression in the brain. The expression of CRH mRNA in the paraventricular nucleus (PVN) after 4 h of restraint stress was examined in oxytocin gene-deficient (OTKO), wild-type and heterozygous male mice using in situ hybridization histochemistry. We found that basal levels of CRH mRNA were not different among the three genotypes. Although restraint stress resulted in a significant increase of CRH mRNA expression in the PVN regardless of genotype, the degree of stress induced-up-regulation was significantly higher in OTKO mice than in wild-type mice. The effects of restraint stress on the expression of the arginine vasopressin (AVP) and the oxytocin genes were also examined. Unlike CRH mRNA, basal expression (in nonstressed control groups) of AVP mRNA in OTKO mice, as well as oxytocin mRNA in heterozygous mice, was significantly lower in the PVN and the supraoptic nucleus than in wild-type mice. After restraint stress, the expression of AVP mRNA was significantly increased in the PVN of OTKO mice compared to the nonstressed control group, whereas the expression of both AVP and oxytocin mRNA were unchanged in the PVN and the supraoptic nucleus of wild-type and heterozygous mice. Finally, in a separate set of mice, restraint stress-induced Fos expression was also examined in several brain regions involved in stress response, including the lateral septum, the bed nucleus of the stria terminalis (BNST), the medial preoptic area, the PVN, the medial and central amygdala using immunohistochemistry. After 90 min of restraint stress, the number of Fos-expressing cells significantly increased in all brain regions examined regardless of genotype. However, the number of stress-induced Fos-expressing cells in the BNST and the medial amygdala of OTKO mice was significantly lower than in wild-type mice. Collectively, the findings in the present study suggest that oxytocin may regulate stress-induced CRH gene expression in the PVN. Furthermore, neuronal activity in the BNST and the medial amygdala may be involved in this neuroendocrine regulatory system.

Animals↗

PubMed2003

Treatment for ovarian hyperstimulation syndrome using an oral dopamine prodrug, docarpamine.

Dopamine treatment constitutes a major advance towards the management of severe ovarian hyperstimulation syndrome (OHSS) by causing renal and mesenteric vasodilatation as well as diuretic and positive inotropic actions. Docarpamine, an oral dopamine prodrug, is converted into dopamine after enteral administration, and the generated dopamine causes renal vasodilatation and diuresis. The purpose of this study was to assess whether docarpamine had beneficial effects in patients with OHSS. Twenty-seven patients, hospitalized because of OHSS and refractory to the initial therapy with intravenous albumin, were treated by docarpamine, after informed consent had been obtained. A 750-mg tablet of docarpamine was taken every 8 h. In some cases, the plasma levels of free dopamine were measured. The daily urinary outputs before and 1, 2, 3 and 4 days after the docarpamine treatment were 839 +/- 424 ml, 1121 +/- 608 ml, 1168 +/- 504 ml, 1325 +/- 815 ml and 1133 +/- 509 ml, respectively. There were significant differences between the first and each of the others (p < 0.05). In 19 (86.4%) of 22 patients treated, clinical symptoms associated with ascites were gradually improved after administrating docarpamine. The plasma free dopamine concentration rose to as high as 55.9 +/- 33.2 mg/ml during the first hour, which corresponded to the usual intravenous drip infusion treatment with dopamine. Moreover, there were no major adverse effects of docarpamine in this study. This was the first demonstration of docarpamine treatment in patients with intravenous albumin-resistant OHSS. Although no effect was seen in pregnant women, diuresis was increased in some women, and ascites decreased. These findings indicate that oral docarpamine administration could be one of the options in the management of patients with OHSS using dopamine therapy.

Adult↗

PubMed2002

Potentiation of the excitatory action of NMDA in ventrolateral periaqueductal gray by the mu-opioid receptor agonist, DAMGO.

Several lines of evidence have suggested that mu-opioids, generally regarded as inhibitory, also have effects that stimulate neural activity. To look for possible excitatory opioid action in the rat periaqueductal gray (PAG), we first re-examined data from a previous study and found that met-enkephalin could evoke a delayed, sluggish excitation, suggestive of modulation by the opioid on the action of certain excitants. This observation, coupled with other studies that show mu-opioids can modulate NMDA receptor activation, prompted us to perform extracellular recording of the responses of single ventrolateral PAG (vlPAG) neurons in brain slices to DAMGO, a mu-opioid, and to NMDA. When applied alone, DAMGO at nM concentrations, like met-enkephalin, often evoked the delayed excitation and occasionally an inhibition. When applied after a brief exposure to NMDA, DAMGO at doses as low as 0.1 nM potentiated the excitation produced by a subsequent pulse of NMDA. This occurred, depending on cell type, in 23-100% of vlPAG neurons. The potentiating action of DAMGO was blocked by naloxone, suggesting it was mediated by mu-opioid receptors. Characterization of these mu-opioid actions revealed that the potentiation and the delayed excitation, unlike the inhibition, was not blocked by another opioid antagonist, nalmefene, nor by an inhibitor of the G protein of the G(i) class, N-ethylmaleimide. Moreover, the potentiating action was distinct from the inhibition in that it was: (a) enhanced by repeated opioid applications, (b) exhibited low effective doses, (c) had a long time course (minutes to develop and last tens of minutes) and (d) was present in distinct though overlapping cell populations. These data reveal an unconventional action of opioids in PAG neurons, that is, a potentiation of excitation produced by NMDA. This effect appeared mechanistically distinct from opioid inhibition or disinhibition and may be related to established examples of direct opioid excitation. These observations may help understanding behaviorally important mechanisms linked to acute and chronic opioid functions in the vlPAG.

Action Potentials↗

PubMed2002

Optical intersubband transitions and femtosecond dynamics in Ag/Fe(100) quantum wells.

The optical intersubband transitions and femtosecond dynamics of electrons in quantum well states in Ag/Fe(100) are investigated by interferometric time-resolved two-photon photoemission. The quantum well wave functions and transition probabilities are evaluated from the two-photon photoemission resonance energies and intensities using an extended phase accumulation model. Direct femtosecond pump-probe correlation measurements elucidate the importance of interfaces in confined structures.

Journal Article↗

PubMed2002

Evaluation of oestrogen receptor beta wild-type and variant protein expression, and relationship with clinicopathological factors in breast cancers.

We addressed the clinicopathological significance of the oestrogen receptor (ER) beta protein, including an ERbeta variant, ERbetacx, in normal human breast and breast cancer. The reverse transcriptase-polymerase chain reaction (RT-PCR) showed that wild-type ERbeta (ERbetaw) mRNA expression was higher in normal than cancer tissues, and that ERbetacx mRNA was higher in cancer than in normal tissues. Immunohistochemistry of 22 normal breast tissues and 57 breast cancers was performed with three different ERbeta antibodies and one ERbetacx antibody. All normal breast samples showed staining with the three ERbeta antibodies, suggesting that ERbetaw might have a physiological role in oestrogen signalling in the normal breast. In breast cancer, expression of the ERbetaw protein correlated well with the expression of the ERalpha and progesterone receptor (PgR), as well as histological grade (HG), and tended to indicate a better prognosis than when ERbetaw was absent. Thirty-one (54%) breast cancer samples contained ERbetacx, whereas the corresponding tissue for normal breast samples stained positive in only two (9%).

Adult↗