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Biomedical subjects

M Murakami

Publications and source records attributed to M Murakami.

At least 37 records · Page 2Linked to original sources

Conjugated estrogen plus medroxyprogesterone does not impair blood rheological properties in hypertensive postmenopausal women.

OBJECTIVES: Hypertension and estrogens are both prothrombotic. We used the microchannel method to investigate whether hormone replacement therapy (HRT) with conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA) affects blood flow through the microchannels in hypertensive postmenopausal women being treated with antihypertensive drugs and in normotensive postmenopausal women. METHODS: Sixty-two consecutive postmenopausal women were randomly assigned to a hypertensive HRT group (n=16), hypertensive control group (n=15), normotensive HRT group (n=16) and normotensive control group (n=15). Each HRT group received CEE 0.625 mg plus MPA 2.5 mg daily orally for 12 months. Both hypertensive groups were being treated with antihypertensive drugs before the study. Microvascular blood flow was assessed on the basis of blood passage time, the time required for 100 microl of whole blood to pass through a cylinder, was determined before and 12 months after the start of HRT by the microchannel method (micro channel array flow analyzer). RESULTS: CEE plus MPA therapy did not change blood passage time in any of the groups. Microscopic observation showed that the whole blood passed smoothly through the microchannels in every group. CONCLUSIONS: CEE plus MPA therapy may not impair blood flow through the microchannels in hypertensive postmenopausal women receiving antihypertensive drugs or in normotensive postmenopausal women. However, administration of CEE plus MPA to postmenopausal women with hypertension warrants caution against the occurrence of thromboembolic events.

Aged↗

Aberrant promoter methylation in human DAB2 interactive protein (hDAB2IP) gene in gastrointestinal tumour.

The human DOC-2/DAB2 interactive protein (hDAB2IP) gene is a novel member of the Ras GTPase-activating family and has been demonstrated to be a tumour-suppressor gene inactivated by methylation in several cancers. In this study, we analysed the methylation and expression status of hDAB2IP in gastrointestinal tumours. The promoter region of hDAB2IP was divided into two regions (m2a and m2b) based on our previous report, and the methylation status was determined by bisulphite DNA sequencing in gastric cancer cell lines. The gene expression was semiquantified by real-time RT-PCR, and the results indicated that the m2b promoter region might be an authentic methylation-mediated key regulator of the gene expression. Based on the sequence data, we developed a methylation-specific PCR (MSP) for the m2a and m2b regions and applied it to the samples. Methylation-specific PCR revealed aberrant methylation in the m2a region in eight of 12 gastric cancer cell lines (67%), 16 of 35 gastric cancer tissues (46%) and 29 of 60 colorectal cancer tissues (48%), and in the m2b region in eight of 12 cell lines (67%), 15 of 35 gastric cancer tissues (43%) and 28 of 60 colorectal cancer tissues (47%). On the other hand, seven (12%) and 11 (19%) of 59 gastrointestinal nonmalignant mucosal specimens showed methylation in the m2a and m2b regions, respectively, suggesting that hDAB2IP methylation might play a causative role in carcinogenesis. The 5-aza-2'-deoxycytidine treatment restored the gene expression in the m2b-methylated cell lines, confirming that the methylation caused gene downregulation. We also examined the relationship between hDAB2IP methylation and the clinicopathological features in patients with primary tumours, and determined that methylation in the m2b region was associated with location of the tumour in the stomach. In summary, our results demonstrated that hDAB2IP methylation is frequently present in gastrointestinal tumours and that the resulting gene silencing plays an important role in gastrointestinal carcinogenesis.

Azacitidine↗

Surgical treatment for bilateral carotid arterial stenosis.

Carotid endarterectomy (CEA) is a beneficial procedure for patients with high-grade carotid stenosis. However, patients with bilateral carotid stenosis have a higher surgical risk during CEA. Since the introduction of carotid stenting (CAS) may decrease some of the surgical complications of CEA, a combined treatment using CEA and CAS may be favorable for patients with bilateral carotid stenosis. We analyzed the safety and efficacy of this treatment strategy. Eighteen patients with bilateral carotid stenosis were treated from January 2000. Bilateral CEA was performed on the first two patients, CAS then CEA of contra-lateral symptomatic side in 13 patients, and bilateral CAS in three patients. There were no perioperative neurological complications or strokes during the follow-up period (mean 17 months). The combined treatment of CAS and CEA was a safe and effective strategy for bilateral carotid stenosis.

Aged↗

Stenting for vertebrobasilar artery stenosis.

We report our experience with stenting for symptomatic vertebrobasilar artery stenosis. One hundred and sixteen patients with vertebrobasilar artery stenosis (101 vertebral ostial stenosis, 15 intracranial vertebrobasilar artery stenosis) were treated with stenting. Indication criteria of treatment were 1) symptomatic lesion, 2) angiographical stenosis more than 60%. Under local anesthesia, pre-dilatation was first performed, then stents were placed to the lesion. Successful dilatation was obtained in 115 cases. The stenosis rate reduced to 2% post-stenting in ostial lesions and 16% in intracranial lesions. Transient neurological complications developed in 2 patients. Follow-up angiographies more than 6 months after stenting were performed in 94 patients with ostial lesions and all patients with intracranial lesions. Of these, 8 patients (9.5%) with ostial lesions and 4 patients (27%) with intracranial lesions developed restenosis. All patients with restenosis were treated successfully with PTA (percutaneous transluminal angioplasty). During the follow-up period, 3 patients developed recurrence of VBI (vertebro-basilar insufficiency) symptoms due to restenosis. One patient developed brain stem infarction due to in-stent occlusion 8 months after stenting. Conclusion. Stenting for vertebrobasilar artery stenoses is feasible and safe. Prevention of restenosis, especially in intracranial arteries, is the next problem to be solved.

Aged↗

Involvement of aquaporin-5 water channel in osmoregulation in parotid secretory granules.

Aquaporins (AQPs) are a family of channel proteins that allow water or very small solutes to pass, functioning in tissues where the rapid and regulated transport of fluid is necessary, such as the kidney, lung, and salivary glands. Aquaporin-5 (AQP5) has been demonstrated to localize on the luminal surface of the acinar cells of the salivary glands. In this paper, we investigated the expression and function of AQP5 in the secretory granules of the rat parotid gland. AQP5 was detected in the secretory granule membranes by immunoblot analysis. The immunoelectron microscopy experiments confirmed that AQP5 was to be found in the secretory granule membrane. Anti-AQP5 antibody evoked lysis of the secretory granules but anti-aquaporin-1 antibody did not and AQP1 was not detected in the secretory granule membranes by immunoblot analysis. When chloride ions were removed from the solution prepared for suspending secretory granules, the granule lysis induced by anti-AQP5 antibody was inhibited. Furthermore, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, an anion channel blocker, blocked the anti-AQP5 antibody-induced secretory granule lysis. These results suggest that AQP5 is, expressed in the parotid gland secretory granule membrane and is involved in osmoregulation in the secretory granules.

Animals↗

The influence of mycophenolate mofetil versus azathioprine and mycophenolic acid pharmacokinetics on the incidence of acute rejection and infectious complications after renal transplantation.

PURPOSE: The present retrospective study investigated the influence of mycophenolate mofetil (MMF) instead of azathioprine (AZA) as part of tacrolimus-based immunosuppression. Mycophenolic acid (MPA) pharmacokinetic (PK) parameters were used for associations with the incidence of acute rejection (AR) episodes and infectious complications after renal transplantation. METHODS: The 66 consecutive renal transplant recipients reported herein excluded ABO-incompatible transplants or cytomegalovirus (CMV)-seronegative recipients. The immunosuppressive regimen consisted of tacrolimus, steroids, and AZA 1-2 mg/kg/d in 22 patients (between February 1998 and December 2000) or MMF 2 g/d in 44 patients (since January 2001). CMV infection was defined as positive CMV-antigenemia. MPA PK was studied on day 28 after transplantation in 21 recipients. RESULTS: AR occurred in 13.6% of patients in the MMF group compared with 18.2% in the AZA group. The viral infection (CMV, varicella zoster virus, adenovirus hemorrhagic cystitis, and malignancy related to Epstein-Barr [EB] virus) rate was 22.7% in the MMF group and 0% in the AZA group (P = .015). There were no bacterial or fungal infections observed in the 2 groups. MMF dose per body weight was significantly lower among patients with AR than those without AR (25.1 vs 35.6 mg/kg; P = .026). There were no differences in MPA PK parameters between patients with and without viral infections. CONCLUSIONS: Patients treated with MMF required less treatment for AR, however, there were no significant differences. MMF dose per body weight may play an important role in the occurrence of AR. Although virus infections occurred in recipients treated with MMF, MPA PK did not influence the infectious complications after renal transplantation.

Adult↗

Th1-biased humoral immune responses against Wilms tumor gene WT1 product in the patients with hematopoietic malignancies.

The Wilms' tumor gene WT1 is highly expressed in leukemias and myelodysplastic syndrome (MDS), and WT1 expression levels increase along with the disease progression in chronic myeloid leukemia and MDS. We previously reported that IgM and IgG WT1 antibodies were detected with significantly higher detection rate and antibody titers in leukemias and MDS compared to those in healthy volunteers. In this study, whether IgG humoral immune responses against WT1 protein were Th1- or Th2-type were determined by measurement of four subclasses of IgG WT1 antibody, IgG1, IgG2, IgG3, and IgG4. In leukemias and MDS, Th1-type WT1 antibodies such as IgG1, IgG2, and IgG3 were significantly increased in both detection rate and antibody titers compared to those in healthy volunteers, whereas Th2-type WT1 antibody such as IgG4 did not increase. These results showed that Th1-biased humoral immune responses against WT1 protein were generated in leukemias and MDS. These results should allow us to consider that Th1-biased cellular immune responses against WT1 protein, which was essentially needed for cancer immunotherapy targeting WT1, should be elicited in patients with hematopoietic malignancies.

Antibody Formation↗

Role of the phosphoinositide 3-kinase pathway in mouse embryonic stem (ES) cells.

Mouse ES (embryonic stem) cells maintain pluripotency with robust proliferation in vitro. ES cells share some similarities with cancer cells, such as anchorage-independent growth, loss of contact inhibition and tumour formation. After differentiation, ES cells lose pluripotency and tumorigenicity. Recent studies showed that the PI3K (phosphoinositide 3-kinase) pathway is important for proliferation, survival and maintenance of pluripotency in ES cells. The PI3K pathway is activated by growth factors and cytokines including insulin and leukaemia inhibitory factor. In addition to these exogenous factors, the PI3K pathway is endogenously activated by the constitutively active Ras family protein ERas (ES cell-expressed Ras). The PI3K pathway utilizes multiple downstream effectors including mTOR (mammalian target of rapamycin), which we have shown to be essential for proliferation in mouse ES cells and early embryos.

Animals↗

Helium gas pneumoperitoneum can improve the recovery of gastrointestinal motility after a laparoscopic operation.

The use of laparoscopic surgery contributes to faster recovery of postoperative gastrointestinal motility. Several authors have demonstrated the benefits of laparoscopic surgery using carbon dioxide (CO2) pneumoperitoneum. However, there have been few investigations of the effects of other insufflation gases on gastrointestinal motility. The aim of this study was to investigate the effect of CO2 and helium pneumoperitoneum on the recovery of postoperative gastrointestinal motility. For this study, male Sprague-Dawley rats were divided into four groups: control, CO2 insufflation (10 mmHg), helium insufflation (10 mmHg) and open laparotomy for one hour. Arterial pH values and PaCO2 were measured after surgery. Gastrointestinal motility was evaluated by quantifying the distribution of markers placed into the stomach at the end of procedures until 24 hours after surgery. In the CO2 insufflation group, the arterial pH value was significantly lower than that of the helium insufflation group, and significant hypercapnia persisted until six hours after surgery. The gastric emptying and transit time was significantly prolonged in the CO2 group compared with the helium insufflation group. This study demonstrates that helium pneumoperitoneum can improve the recovery of postoperative gastrointestinal motility because of the reduction of hypercapnia and a tendency to suffer acidosis compared with CO2 pneumoperitoneum.

Journal Article↗

Expression of type V secretory phospholipase A in myocardial remodelling after infarction.

AIMS: Secretory phospholipase A2 is associated with ischaemic injury in the human heart, but the distribution of type V secretory phospholipase A2 (sPLA2-V) remains unknown. The significance of sPLA2-V in myocardial infarction was investigated histopathologically. METHODS: Sequential changes in the localization of sPLA2-V and its mRNA in myocardial tissues obtained from 30 autopsied hearts were examined by immunohistochemistry and in situ hybridization and compared with those of fibronectin, vascular endothelial growth factor (VEGF), interleukin (IL)-1beta, tumour necrosis factor (TNF)-alpha, and cyclooxygenase-2 (COX-2). RESULTS: No expression of sPLA2-V was observed in normal heart, but it was promptly expressed in wavy myofibres positive for fibronectin just after the onset of infarction. sPLA2-V was subsequently expressed in ischaemic cardiomyocytes around the lesion. The expression decreased at the granulation tissue and disappeared at the chronic stage with scar formation. The distribution of the signal for sPLA2-V mRNA paralleled that of the protein. Ischaemic myocytes around the lesion expressed VEGF, IL-1beta, TNF-alpha and COX-2 at all stages. CONCLUSIONS: sPLA2-V production in myocardium is limited to the acute phase of infarction. sPLA2-V may play a dual role, acting both to remove degraded cell-membrane through cooperative activity with COX-2 in necrotic areas and to attack ischaemic myocytes around the lesion via degradation of membrane phospholipids.

Adult↗

Relationship between oxygen consumption and sex of bovine in vitro fertilized embryos.

The present study was conducted to examine the relationship between the oxygen consumption rate and sex ratio of bovine in vitro fertilized embryos on each day of blastocyst formation. The quality of blastocysts collected on day 7, 8, and 9 after in vitro fertilization (IVF) were categorized as ranks A and B (excellent and good, respectively) based on microscopic observation of the morphology. The oxygen consumption rate and sex of individual blastocysts were evaluated using two novel techniques: scanning electrochemical microscopy (SECM) and loop-mediated isothermal amplification (LAMP), respectively. The oxygen consumption rates of embryos of rank A were significantly higher (p < 0.05) than those of rank B, irrespective of the day of blastocyst appearance after IVF. Neither did the proportion of male embryos of ranks A and B differ significantly from each other at any of the days examined, nor from the average proportion (53%). The oxygen consumption rate of embryos of rank B collected on day 8 was significantly higher (p < 0.05) in female embryos than in male embryos collected on the same day. However, there were no apparent differences of oxygen consumption rates at each day of blastocyst appearance between male and female embryos of rank A. These results indicate that the oxygen consumption rate of individual embryos reflects their quality but does not correlate with the sex ratio of embryos of excellent quality.

Animals↗

Analysis of DNA fragmentation of porcine embryos exposed to cryoprotectants.

The chemical toxicity of cryoprotectants to porcine embryos was examined by the evaluation of survival and DNA damage after exposure to cryoprotectants. Porcine blastocysts were exposed to 10% of ethylene glycol (EG), 1,2-propanediol (PD) or glycerol (GLY) for 1 h at room temperature (23-25 degrees C) and then cultured in vitro for 24 h. The survival rates of blastocysts exposed to PD and GLY were significantly lower than those of control blastocysts in which the embryos were exposed to carrier solution without cryoprotectants. Significantly more DNA-fragmented nuclei occurred in the cryoprotectant-exposed blastocysts, compared with the control blastocysts. Moreover, the indices of DNA-fragmented nuclei in the blastocysts without blastocoele re-formation after culture were significantly higher than those with blastocoele re-formation, irrespective of the exposure treatment. These results indicate that the exposure of porcine blastocysts to cryoprotectant decreases the survival rates and increases the DNA-fragmented nuclei in embryos.

Animals↗

Development of cat embryos produced by intracytoplasmic injection of spermatozoa stored in alcohol.

This study was conducted to examine whether cat spermatozoa stored in ethanol for 1 month was capable of developing into pronuclei and of supporting normal embryonic development. In vitro matured oocytes were injected with frozen-thawed spermatozoa and ethanol-stored spermatozoa. The status of oocytes and sperm nuclei was examined at 4 and 18 h after injection of spermatozoa, and the presumptive zygotes were cultured for 7 days to assess the development of oocytes injected with each storage sperm. The percentage of enlarged sperm head at 4 h after injection was higher in ethanol-stored spermatozoa than in frozen-thawed spermatozoa, but there was no significant difference in the development of oocytes and sperm nuclei at 18 h after injection between the two groups. The development of oocytes to the blastocyst stage after injection of spermatozoa was observed only in oocytes with frozen-thawed spermatozoa. Of oocytes injected with ethanol-stored spermatozoa, two (2.8%) oocytes developed to the 16-cell stage. These results indicate that cat spermatozoa stored in ethanol can decondense and form male pronuclei after intracytoplasmic injection. However, the oocytes injected with ethanol-stored spermatozoa did not have the ability to develop to the blastocyst stage.

Animals↗

Structured assessment of current mental state in clinical practice: an international study of the reliability and validity of the Current Psychiatric State interview, CPS-50.

OBJECTIVE: To develop a reliable standardized assessment of psychiatric symptoms for use in clinical practice. METHOD: A 50-item interview, the Current Psychiatric State 50 (CPS-50), was used to assess 237 patients with a range of psychiatric diagnoses. Ratings were made by interviewers after a 2-day training. Comparisons of inter-rater reliability on each item and on eight clinical subscales were made across four international centres and between psychiatrists and non-psychiatrists. A principal components analysis was used to validate these clinical scales. RESULTS: Acceptable inter-rater reliability (intra-class coefficient > 0.80) was found for 46 of the 50 items, and for all eight subscales. There was no difference between centres or between psychiatrists and non-psychiatrists. The principal components analysis factors were similar to the clinical scales. CONCLUSION: The CPS-50 is a reliable standardized assessment of current mental status that can be used in clinical practice by all mental health professionals after brief training.

Cross-Cultural Comparison↗

Model description of storage and infiltration functions of infiltration facilities for urban runoff analysis by a distributed model.

Although there have been simulation researches focusing on reduction of stormwater peak flow by introduced infiltration facilities, model simulation of dynamic runoff behavior is still limited for frequently occurring rainfall events with weak intensity. Therefore, dynamic simulation was carried out in two urban drainages with infiltration facilities incorporated with a distributed model using two methods for describing functions of infiltration facilities. A method adjusting effective rainfall model gave poor simulation of runoff behavior in light rainfalls. Another method considering dynamic change of storage capacity as well as infiltration rate gave satisfactory estimation of the runoff in both drainages. In addition, assumption of facility clogging improved the agreement between measured and simulated hydrographs in small and medium-sized rainfall. Therefore, the proposed method might be useful for quantifying the secondary effects of the infiltration facilities on groundwater recharge and urban non-point pollutant trapping as well as runoff reduction.

Models, Theoretical↗

Serial changes in the regional cerebral blood flow of patients with hypertensive intracerebral hemorrhage -- long-term follow-up SPECT study.

We analyzed serial changes in the regional cerebral blood flow (rCBF) of 13 patients with intracerebral hemorrhage by single photon emission computed tomography (SPECT) during the acute- to chronic stage (2 hr to 55 weeks). The (99m)Tc-ethyl cysteinate dimmer ((99m)Tc-ECD) was used as the nuclear mediator. The SPECT timing within 48 hours after the onset was considered to be acute stage, from 48 hours to 4 weeks to be subacute stage, and after 4 weeks to be chronic stage. The region of interest was each hemisphere in the whole brain without ventricles at the thalamic level. For semi-quantitative analysis of rCBF, we used the Brain Uptake Ratio method. Of the 13 patients (mean age 65.5 years), 3 had thalamic-, 4 putaminal-, 5 subcortical-, and one a cerebellar hemorrhage; the hematoma volume varied from 4-50 ml (<20 ml, n=9; 20-30 ml, n=1; >30 ml, n=3; mean 17 ml). The rCBF changes during the long-term follow-up were classified as increase-, decrease-, and unchanged type. Of 5 patients with increased rCBF, 4 made a good recovery and one was severely disabled; of 5 patients with decreased rCBF, 1 made a good recovery, 3 were moderately-, and one was severely disabled. All 3 patients with unchanged rCBF were moderately disabled. Our findings suggest that among patients with hypertensive intracerebral hemorrhage, those with increased rCBF over time may have a favorable outcome. We further need more cases with intracerebral hemorrhage to clarify this trend.

Aged↗

The elasticity of the MgSiO3 post-perovskite phase in the Earth's lowermost mantle.

MgSiO3 perovskite has been assumed to be the dominant component of the Earth's lower mantle, although this phase alone cannot explain the discontinuity in seismic velocities observed 200-300 km above the core-mantle boundary (the D" discontinuity) or the polarization anisotropy observed in the lowermost mantle. Experimental and theoretical studies that have attempted to attribute these phenomena to a phase transition in the perovskite phase have tended to simply confirm the stability of the perovskite phase. However, recent in situ X-ray diffraction measurements have revealed a transition to a 'post-perovskite' phase above 125 GPa and 2,500 K--conditions close to those at the D" discontinuity. Here we show the results of first-principles calculations of the structure, stability and elasticity of both phases at zero temperature. We find that the post-perovskite phase becomes the stable phase above 98 GPa, and may be responsible for the observed seismic discontinuity and anisotropy in the lowermost mantle. Although our ground-state calculations of the unit cell do not include the effects of temperature and minor elements, they do provide a consistent explanation for a number of properties of the D" layer.

Journal Article↗