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K Morita

Publications and source records attributed to K Morita.

At least 19 recordsLinked to original sources
PubMed2007

Microbleeds on gradient-echo T2(*)-weighted MR images from patients with multiple simultaneous intracerebral haemorrhages.

BACKGROUND: Multiple simultaneous intracerebral haemorrhages (ICH) occur rarely and the mechanism remains unknown. In this report, we compare several clinical factors of multiple haemorrhages, including microbleeds, with single intracerebral haemorrhages and discuss a potential explanation for their occurrence. METHODS: One hundred and ninety consecutive patients with intracerebral haemorrhage who were admitted within 24 hours after onset from January 2003 to November 2005 were included in the study. Several clinical factors, including the number of microbleeds on gradient-echo T2(*)-weighted magnetic resonance images, were compared between patients with single and multiple haemorrhages. FINDINGS: Computed tomography scans revealed that nine patients had multiple intracerebral haemorrhages. In all cases, five or more microbleeds were revealed on T2(*)-weighted magnetic resonance images. This was significantly higher than the number of microbleeds in patients with single intracerebral haemorrhage (p < 0.05). Systolic blood pressure on admission was > or =200 mmHg in seven of the nine patients and was higher than in patients with a single haemorrhage (p = 0.05). CONCLUSIONS: Elevated blood pressure induced by an initial haemorrhage was speculated to be the result of secondary haemorrhages in some patients with multiple microbleeds. Thus, strict blood pressure control may help to prevent the occurrence of multiple haemorrhages.

Adult↗
PubMed2006

Expression of prostate-specific antigen and androgen receptor in extramammary Paget's disease and carcinoma.

Prostate-specific antigen (PSA) is a kallikrein-like serine proteinase (human kallikrein 3) produced by epithelial cells of both benign and malignant prostate tissue. In this study, PSA expression was histologically examined in tissue specimens from 34 patients with extramammary Paget's disease (EPD; 31 cases) and extramammary Paget's carcinoma (EPC; three cases), but no associated prostate carcinoma. Tumour cells positive for PSA were found in 17 of the 34 cases. Based on this finding, we examined serum PSA level in the three EPC cases. A high level of serum PSA was observed in one case of EPC, which was correlated with disease progression. Because some reports suggest that 50-80% cases of EPD/EPC express androgen receptor (AR), we also examined expression of AR. Immunohistological staining showed correlation of PSA and AR in expression. These results suggest that PSA and the androgen signalling pathway may be involved in the pathogenesis of EPD.

Aged↗
PubMed2006

Ex vivo application of carbon monoxide in University of Wisconsin solution to prevent intestinal cold ischemia/reperfusion injury.

Carbon monoxide (CO), a byproduct of heme catalysis, was shown to have potent cytoprotective and anti-inflammatory effects. In vivo recipient CO inhalation at low concentrations prevented ischemia/reperfusion (I/R) injury associated with small intestinal transplantation (SITx). This study examined whether ex vivo delivery of CO in University of Wisconsin (UW) solution could ameliorate intestinal I/R injury. Orthotopic syngenic SITx was performed in Lewis rats after 6 h cold preservation in control UW or UW that was bubbled with CO gas (0.1-5%) (CO-UW). Recipient survival with intestinal grafts preserved in 5%, but not 0.1%, CO-UW improved to 86.7% (13/15) from 53% (9/17) with control UW. At 3 h after SITx, grafts stored in 5% CO-UW showed improved intestinal barrier function, less mucosal denudation and reduced inflammatory mediator upregulation compared to those in control UW. Preservation in CO-UW associated with reduced vascular resistance (end preservation), increased graft cyclic guanosine monophosphate levels (1 h), and improved graft blood flow (1 h). Protective effects of CO-UW were reversed by ODQ, an inhibitor of soluble guanylyl cyclase. In vitro culture experiment also showed better preservation of vascular endothelial cells with CO-UW. The study suggests that ex vivo CO delivery into UW solution would be a simple and innovative therapeutic strategy to prevent transplant-induced I/R injury.

Adenosine↗
PubMed2006

Intra-aortic stent graft in oesophageal carcinoma invading the aorta. Prophylaxis for fatal haemorrhage.

In patients with advanced oesophageal carcinoma with aortic invasion, any therapy potentially causes fatal haemorrhage. We describe here the successful application of intra-aortic stent graft to prevent haemorrhage before radical oesophagectomy for advanced oesophageal cancer. Four patients with advanced oesophageal cancer complicated by invasion of the aorta. Under general anaesthesia, aortic invasion is evaluated by an intravascular sonography. The stent graft is passed through the right femoral artery into the descending aorta. Subsequently, the stent graft is released to expand in the thoracic aorta during an artificial cardiac arrest. Aortography is performed to check for any stent migration or endoleakage. This procedure was successful in all four patients without any complications. All patients underwent radical oesophagectomy following aortic stent-grafting. One patient survived more than 2 years after stent grafting and operation. This procedure is safe and applicable for the patient with aortic invasion before radiochemotherapy or operation.

Aged↗
PubMed2006

Landiolol, an ultra-short-acting beta 1-adrenoceptor antagonist, does not alter the electroencephalographic effect of isoflurane in swine model.

BACKGROUND: beta-Adrenergic blocking agents may interact with anaesthetics, and several studies suggest that beta-blockers attenuate electroencephalographic responses during general anaesthesia. We have investigated the influence of landiolol, an ultra-short-acting beta 1-adrenoceptor antagonist, on the electroencephalographic effect of isoflurane in pigs. METHODS: Ten swine were anaesthetized through inhalation of 2% isoflurane. The inhalational concentration was then decreased to 0.5% and maintained for 25 min, before being returned to 2% and maintained for a further 25 min (control period). After control measurements, infusion of landiolol (at 0.125 mg kg(-1) min(-1) for 1 min, and then at 0.04 mg kg(-1) min(-1)) was started. After a 20 min stabilization period, the inhalational concentration was varied as in the control period (40 gamma landiolol). Finally, infusion of landiolol was increased from 0.04 to 0.2 mg kg(-1) min(-1), and after a 20 min stabilization period, the inhalational concentration was again varied as in the control period (200 gamma landiolol). End-tidal isoflurane concentrations and spectral edge frequencies were recorded throughout the study. Analysis of the pharmacodynamics was performed using a sigmoidal inhibitory maximal effect model for spectral edge frequency vs effect-site concentration. RESULTS: There were no significant differences in the effect of isoflurane among the conditions used. Landiolol did not shift the concentration-effect relationship [the effect-site concentration that produced 50% of the maximal effect was 1.35 (0.17)% under control conditions, 1.30 (0.12)% at 40 gamma landiolol, and 1.38 (0.30)% at 200 gamma landiolol]. CONCLUSION: Landiolol does not alter the electroencephalographic effect of isoflurane.

Adrenergic beta-1 Receptor Antagonists↗
PubMed2006

Optical pump-probe measurements of local nuclear spin coherence in semiconductor quantum wells.

We demonstrate local manipulation and detection of nuclear spin coherence in semiconductor quantum wells by an optical pump-probe technique combined with pulse rf NMR. The Larmor precession of photoexcited electron spins is monitored by time-resolved Kerr rotation (TRKR) as a measure of nuclear magnetic field. Under the irradiation of resonant pulsed rf magnetic fields, Rabi oscillations of nuclear spins are traced by TRKR signals. The intrinsic coherence time evaluated by a spin-echo technique reveals the dependence on the orientation of the magnetic field with respect to the crystalline axis as expected by the nearest neighbor dipole-dipole interaction.

Journal Article↗
PubMed2006

Heme arginate pretreatment attenuates pulmonary NF-kappaB and AP-1 activation induced by hemorrhagic shock via heme oxygenase-1 induction.

Hemorrhagic shock followed by resuscitation (HSR) induces oxidative stress that leads to acute lung injury. Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme catabolism, is induced by oxidative stress and is thought to play an important role in the protection from oxidative tissue injuries. We previously demonstrated that HO-1 induction by heme arginate (HA), a strong inducer of HO-1, ameliorated HSR-induced lung injury and inflammation. Cellular redox state is known to modulate the DNA biding activity of the transcription factors; nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). In the present study, we treated rats with HA (30 mg/kg of hemin) 18 h prior to HSR and examined its effect on the DNA binding activity of NF-kappaB and AP-1 at 1.5 h after HSR. HSR significantly increased the DNA binding activity of NF-kappaB as well as AP-1, while HA pretreatment markedly attenuated the activities of these transcription factors. In contrast, administration of tin mesoporphyrin, a specific competitive inhibitor of HO activity, to HA-pretreated animals abolished the suppressive effect of HA on the activities of NF-kappaB and AP-1, and increased these activities to almost the same level as those in HSR animals. Our findings indicate that HA pretreatment can significantly suppress the increased activity of NF-kappaB and AP-1 induced by HSR by virtue of its ability to induce HO-1. Our findings also suggest that HO-1 induced by HA pretreatment ameliorates HSR-induced lung injury at least in part mediated through the suppression of the activities of these transcription factors.

Animals↗
PubMed2005

Gate control of dynamic nuclear polarization in GaAs quantum wells.

Gate control of dynamic nuclear polarization under optical orientation is demonstrated in a Schottky-gated n-GaAs/AlGaAs (110) quantum well by time-resolved Kerr rotation measurements. Spin relaxation of electrons due to mechanisms other than the hyperfine interaction is effectively suppressed as the donor induced background electron density is reduced from metallic to insulating regimes. Subsequent accumulation of photoexcited electron spins dramatically enhances dynamic nuclear polarization at low magnetic field, allowing us to tune nuclear spin polarization by external gate voltages.

Journal Article↗
PubMed2005

Site- and cell-type- specific induction of intestinal inducible nitric oxide synthase in a rat model of endotoxemia.

The intestine is one of the major organs that are involved in sepsis. The inducible isoform of nitric oxide synthase (iNOS) is known to play a critical role in the pathogenesis of septic tissue injury by generating excess amount of nitric oxide (NO) in response to cytokines and endotoxin. In this study, we examined changes in gene expression of iNOS in various regions of the intestine as well as the distribution of iNOS protein in the intestinal cells in a rat model of endotoxemia produced by intraperitoneal injection of lipopolysaccharide (LPS; 10 mg/kg). While iNOS mRNA was undetectable in the intestine of untreated control animals, it underwent marked induction following LPS treatment. Induction of iNOS mRNA in the ileum was marked and biphasic, while it was also marked but monophasic in the jejunum. The induction of iNOS mRNA was maximal in the ileum. The administration of interleukin-6 (IL-6) upregulated intestinal iNOS gene expression specifically in the ileum. Consistent with enhanced iNOS gene expression, iNOS protein was markedly expressed in the ileum after LPS treatment, exclusively in the mucosal epithelium both at crypt and villus cells, although more prominently in the former. These findings suggested that intestinal iNOS expression was upregulated both at transcriptional and protein levels not only in a site-specific, but also in a cell type-specific manner in a rat model of endotoxemia, possibly through increasing serum IL-6 levels. Differential regulation of iNOS expression along the longitudinal and crypt-villus axes of the gut might be a determinant of the pattern of sepsis-induced intestinal damage.

Animals↗
PubMed2005

SPET in cardiology. Diagnosis, prognosis, and management of patients with coronary artery disease.

Stress myocardial perfusion imaging has been considered as a most valuable means for diagnosis and treatment strategy in patients with suspected and known coronary artery disease. (99m)Tc perfusion imaging agents provide excellent myocardial perfusion images. In addition, greater photon flux from the tracer permits simultaneous assessment of regional perfusion and function with use ECG-gated acquisition. Gated SPET imaging technique has a potential for higher diagnostic accuracy for diagnosis of coronary artery disease and assessment of the disease severity. In addition, radionuclide imaging plays an important role to differentiate reversible ischemic myocardium which may improve LV function after revascularization from irreversible scar in patients with history of myocardial infarction. While FDG-PET is considered as a most reliable means for myocardial assessment, SPET imaging has been widely used for the viability assessment, with gaining higher accuracy for predicting reversible ischemia. Recently a variety of new radiopharmaceutical agents have been introduced to probe myocardial function in vivo. [(123)I]BMIPP, a branched fatty acid analog, has been used for metabolic imaging using SPET. Less uptake of BMIPP than perfusion is often observed in the ischemic myocardium. Such a perfusion metabolic mismatch which seems to be similarly observed in FDG-PET is identified in the stunned or hibernating myocardium with regional dysfunction. Severe ischemia is identified as reduced BMIPP uptake at rest, suggesting its role as an ischemic memory imaging. These new techniques will provide insights into new pathological states in the ischemic heart disease and enable to select optimal treatment of these patients.

Cardiology↗
PubMed2004

Transport of dopamine and levodopa and their interaction in COS-7 cells heterologously expressing monoamine neurotransmitter transporters and in monoaminergic cell lines PC12 and SK-N-SH.

The present study investigated the effects of levodopa, a precursor of dopamine (DA) therapeutically used for the treatment of Parkinson's disease, on DA transport in the two different systems, COS-7 cells heterologously expressing rat monoamine transporter cDNA and in monoaminergic cell lines PC12 and SK-N-SH. Levodopa enhanced uptake of [3H]DA and [3H]norepinephrine (NE) but not [3H]serotonin in the transfected COS-7 cells in a concentration-dependent manner. On the other hand, in PC12 and SK-N-SH cells where NET is functionally expressed, levodopa enhanced [3H]DA and [3H]NE uptake at low concentrations and inhibited the uptake at higher concentrations. The effects of levodopa on catecholamine transporters in the opposite direction suggest a different mechanism at the intra- and extracellular sites in a levodopa transport-dependent and independent manner.

Animals↗
PubMed2004

Effect of tacrolimus and cyclosporine on renal microcirculation and nitric oxide production.

OBJECTIVES: Cyclosporine (CSA) and tacrolimus (TAC) frequently induce nephrotoxicity and similar pathologic changes. Acute CSA-induced nephrotoxicity has been reported to be mediated by activation of vasoconstrictors such as endothelin. The purpose of the present study was to investigate the acute effects of TAC and CSA on the renal microcirculation and upon a vasodilator such as nitric oxide (NO) production. METHODS: Renal blood flow (RBF) in the microcirculation was measured by a Laser Doppler flow meter in uninephrectomised rats. RBF, mean arterial pressure (MAP), and renal vascular resistance (RVR) were measured in the following groups: (a) TAC (0.1 to 2.0 mg/kg/h, n = 3 approximately 6); CSA (20 and 50 mg/kg/h, n = 5); (b) L-NAME (10 mg/kg), an NO synthase inhibitor, 8 minutes prior to TAC (0.5 and 1.5 mg/kg/h, n = 5), or CSA (20 and 50 mg/kg/h, n = 5). Stable NO end-products, serum NO(2) and NO(3), were measured by the Griess method (n = 5). RESULTS: None of the parameters were changed by TAC alone, whereas TAC with L-NAME significantly reduced RBF (-28 +/- 7%) and increased RVR (46 +/- 17%) in a dose-dependent manner. CSA alone significantly reduced RBF (-37 +/- 6%) and increased RVR (69 +/- 22%) without any changes in MAP. The effects of CSA were enhanced by L-NAME. Serum concentration of NO(2) + NO(3) was significantly reduced by both L-NAME alone and CSA (50 mg/kg) (P < .05), while there were no changes with TAC (1.5 mg/kg). CONCLUSIONS: Blockade of NO production enhance the vasoconstrictive effect of CSA, and unmasked such an effect of TAC. These results suggest that the nephrotoxicity of CSA and TAC may involve the NO system.

Animals↗
PubMed2004

Therapeutic efficacy of targeting chemotherapy using local hyperthermia and thermosensitive liposome: evaluation of drug distribution in a rat glioma model.

A method was developed of targeting chemotherapy using thermosensitive liposomes to treat malignant gliomas. Using the brain heating system, when the tumour core is heated to >43 degrees C, the tumour infiltrating zone is exposed to mild hyperthermia (40-43 degrees C). Thermosensitive liposomes were designed to release their contents at 40 degrees C to target both the tumour core and tumour infiltrating zone. The present study investigated the anti-tumour effect on rat glioma models in tumour drug uptake and tumour growth delay studies. Elevated accumulation of ADR in the rat C6 glioma after treatment was obtained in the area heated to >40 degrees C. However, there was no significant difference between the areas heated to 40-42 degrees C and >43 degrees C. Furthermore, it was found that ADR concentrations in the mildly hyperthermic areas were significantly higher following treatment with liposomal ADR than with free ADR. The animals treated with the new combination therapy had significantly longer overall survival time in comparison to those receiving other treatments. Thus, thermosensitive liposomes release their contents in response to mild hyperthermia and this combination therapy has a greater therapeutic efficacy for malignant brain tumours. This method is a promising approach for the treatment of malignant glioma patients.

Animals↗
PubMed2004

Preparation and pharmaceutical evaluation for clinical application of high specific activity S-(-)[11C]CGP-12177, a radioligand for beta-adrenoreceptors.

BACKGROUND: Although S-(-)[C]CGP-12177 is a useful positron emission tomography (PET) ligand for beta-adrenoreceptors, the difficulty in radiolabelling the compound has prevented its extensive clinical application. Recently, we have developed a simple synthesis method for S-(-)[C]CGP-12177. In the present study, we attempted to prepare S-(-)[C]CGP-12177 with a high specific activity for intravenous injection which is feasible for the clinical evaluation of beta-adrenoreceptors. METHODS: The [C]methane produced during irradiation of a N2--H2 (95/5) mixture with an 18 MeV proton beam (20 microA, 30 min) was chlorinated using Cl2 to yield [C]carbon tetrachloride. S-(-)[C]CGP-12177 was synthesized by reacting the diamino precursor with [C]phosgene produced by oxidizing [C]carbon tetrachloride on a Fe--Fe2O3 column. The product was purified by using reversed phase, high-performance liquid chromatography (RP-HPLC) and the radioactive fraction containing S-(-)[C]CGP-12177 was collected and evaporated to dryness. S-(-)[C]CGP-12177 dissolved in physiological saline was sterilized through a 0.22 microm membrane filter. The radiochemical purity and the mass of the compound were determined with RP-HPLC. The residual organic solvents were determined with GC. Tests for sterility and the presence of bacterial endotoxins were also performed. RESULTS: S-(-)[C]CGP-12177 for intravenous injection was prepared in 25 min after the end of bombardment with a yield of 1.5+/-0.2 GBq. Specific activity was found to be 385.4+/-133.0 GBq/ micromol at the end of synthesis (EOS) (n=3). Radiochemical purity was found to be more than 99%. Toluene was not detected in the solution. The ethanol concentration was determined to be 60.3+/-52.5 ppm. Tests for sterility and bacterial endotoxins showed negative results. CONCLUSION: We successfully prepared S-(-)[C]CGP-12177 formulated for intravenous injection with high purity and high specific activity, which is feasible for the clinical evaluation of beta-adrenoreceptors.

Drug Evaluation, Preclinical↗
PubMed2004

Tight junction-associated proteins (occludin, ZO-1, claudin-1, claudin-4) in squamous cell carcinoma and Bowen's disease.

BACKGROUND: The epidermis, which is a typical stratified epithelium, has tight junctions (TJs) in the granular layer, as do simple epithelia. So far, abnormalities of TJs and involvement of claudin-1 have been reported in tumours of simple epithelia. OBJECTIVES: To examine the expression of TJ-associated proteins (occludin, ZO-1, claudin-1 and claudin-4) in normal human epidermis and in malignant disorders of keratinization. METHODS: Expression of the proteins in normal human epidermis, five cases of squamous cell carcinoma (SCC) of the skin and five cases of Bowen's disease (BD) was examined by immunofluorescence staining. RESULTS: In normal human epidermis, occludin, ZO-1 and claudin-4 were expressed at the cell-cell borders in the granular layer specifically or dominantly, whereas claudin-1 was expressed in the whole epithelium. In SCC, occludin, ZO-1, claudin-1 and claudin-4 were strongly expressed in tumour cells with keratinization such as cancer pearls. Claudin-1 was heterogeneously expressed in unkeratinized tumour cells, whereas expression of occludin, ZO-1 and claudin-4 was decreased or absent. In BD, aberrant expression of occludin, ZO-1, claudin-1 and claudin-4 was observed at the cell-cell borders in addition to their expression patterns observed in normal epidermis. CONCLUSIONS: Expression of occludin, ZO-1 and claudin-4 is associated with keratinization in SCC and BD. However, the heterogeneous expression of claudin-1 in SCC is not determined only by keratinization.

Aged↗
PubMed2004

Association of increased platelet-associated immunoglobulins with thrombocytopenia and the severity of disease in secondary dengue virus infections.

Severe thrombocytopenia and increased vascular permeability are two major characteristics of dengue haemorrhagic fever (DHF). To develop a better understanding of the roles of platelet-associated IgG (PAIgG) and IgM (PAIgM) in inducing thrombocytopenia and its severity of disease in patients with secondary dengue virus infection, the relationship between the PAIgG or PAIgM levels and disease severity as well as thrombocytopenia was examined in 78 patients with acute phase secondary infection in a prospective hospital-based study. The decrease in platelet count during the acute phase recovered significantly during the convalescent phase. In contrast, the increased levels of PAIgG or PAIgM that occurred during the acute phase of these patients decreased significantly during the convalescent phase. An inverse correlation between platelet count and PAIgG or PAIgM levels was found in these patients. Anti-dengue virus IgG and IgM activity was found in platelet eluates from 10 patients in an acute phase of secondary infection. Increased levels of PAIgG or PAIgM were significantly higher in DHF than those in dengue fever (DF). An increased level of PAIgM was associated independently with the development of DHF, representing a possible predictor of DHF with a high specificity. Our present data suggest that platelet-associated immunoglobulins involving antidengue virus activity play a pivotal role in the induction of thrombocytopenia and the severity of the disease in secondary dengue virus infections.

Adolescent↗
PubMed2004

Heme oxygenase-1: a novel therapeutic target in oxidative tissue injuries.

Oxidative stresses such as oxidant stimuli, inflammation, exposure to xenobiotics, or ionizing irradiation provoke cellular protective responses, principally involving transcriptional activation of genes encoding proteins which participate in the defense against oxidative tissue injuries. Excess of free heme, which is released from hemeproteins under such conditions, may constitute a major threat because it can catalyze the formation of reactive oxygen species (ROS). Exposure of mammalian cells to oxidative stimuli induces heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme degradation, as well as a 33-kDa heat shock protein. In various model systems, HO-1 induction confers protection on tissues from further injuries, while the abrogation of its induction accelerates cellular injuries. In this article, we review recent advances in the regulatory mechanism of ho-1 gene expression and the role of HO-1 in various models of experimental oxidative tissue injuries, and its potential therapeutic implications.

Acute Kidney Injury↗