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Biomedical subjects

K Matsui

Publications and source records attributed to K Matsui.

At least 163 records · Page 9Linked to original sources
PubMed1999

Estimation of in vivo bone mineral density (BMD) and shape characterization for diagnosing osteoporosis by ultrasonic inspection.

A new method for estimating in vivo bone mineral density (BMD) and characterizing the shape of cancellous bone has been proposed using the results of ultrasonic inspection for the diagnosis of osteoporosis. The method is based on two-dimensional bone area fraction S (percent bone area between bone and bone marrow) calculated from the difference in the speed of ultrasonic wave propagation through cancellous bone. It was shown that the two-dimensional area fraction of a heel bone gives a good relationship to the BMD by DXA (dual energy x-ray absorptiometry) testing of human heel bone (calcaneus) and spine (vertebrae lumbar), as expressed by the relation, BMD (g/cm2) = 0.0167S for heel bone (r = 0.83), and BMD (g/cm2) = 0.0254S + 0.123 for the spine (r = 0.77). Shape characterization is based on the image simulation procedure employing eight random variables from a computer and the statistical results of fractal analysis for numerous cancellous bone patterns. We also demonstrate the validity of the shape characterization using autopsy specimens as a diagnostic tool for osteoporosis.

Absorptiometry, Photon↗
PubMed1999

High IL-18 (interferon-gamma inducing factor) concentration in a purine nucleoside phosphorylase deficient patient.

The plasma concentration of IL-18 (interferon-gamma inducing factor) was severely increased in a 3 year old boy with purine nucleoside phosphorylase (PNP) deficiency. The presence and activity of IL-18 were confirmed by immunoblotting and bioassay, respectively. These results suggest that IL-18 may be abundantly produced and secreted into plasma by PNP deficient macrophages in PNP deficiency.

Biomarkers↗
PubMed1999

Inflammatory pseudotumor of the urinary bladder and sigmoid colon.

We report an unusual case of an inflammatory pseudotumor of the bladder. A biopsy specimen prior to surgical treatment suggested leiomyosarcoma, and computerized tomography and magnetic resonance imaging strongly suggested bladder tumor with sigmoid colon invasion. Accordingly, radical surgical treatment consisting of total cystectomy, anterior resection of the sigmoid colon, and ileal conduit was performed. After operation, however, histological examination revealed an inflammatory pseudotumor of bladder and sigmoid colon. These findings were confirmed by immunohistochemical staining for smooth muscle specific actin, desmin, S-100, and vimentin. Histological examination revealed a diverticulum of the sigmoid colon in the middle of the pseudotumor, and this diverticulum may have ruptured to cause the inflammatory pseudotumor of bladder and sigmoid colon.

Biopsy, Needle↗
PubMed1999

SV40LT highly mutates and immortalizes two fibroblast strains from patients with Wilms' tumor.

In order to analyze in detail the process of immortalization of human cells, SV40LT was introduced into two chromosome 11p- fibroblast strains from Wilms' tumor patients. Both fibroblasts, hereafter referred to as CM1 and CM2, displayed the mutant phenotype in the crisis stage of cellular aging. In comparison to a control fibroblast, the density of the CM1 strain was abnormally high while the crisis period of the CM2 strain was abnormally long. The CM1 immortalization was 7 times greater than the control and the CM2 strain had the highest frequency of immortalization, 7 times greater than the CM1. These findings indicate that genes associated with chromosome 11p- may be involved in the immortalization of human cells. During their abnormal crisis periods, the cells derived from the patients with Wilms' tumor showed an extremely high frequency of chromosomal aberrations and mutations (6TGs --> 6TGr). These results indicate that when the growth-arrested cells from Wilms' patients are induced to grow with the introduction of SV40LT at the crisis stage they are highly mutable, resulting in their immortalization in vitro.

Antigens, Viral, Tumor↗
PubMed1999

[Successful treatment for disseminated intra-vascular coagulation due to sepsis and brain abscess with low molecular weight heparin in a patient with antiphospholipid syndrome].

The management of disseminated intravascular coagulation (DIC) in a 22-year-old female patient with antiphospholipid syndrome is reported. Gabexate mesilate was given by continuous drip infusion at 1.5 g/day. No effect was seen, therefore Dalteparin sodium (DS) was administered by continuous drip infusion at 70 U/kg/day. The DIC score improved gradually during the first 4 days to normalization by 10 days. However, convulsive seizure was developed. Computed tomographic scan of brain demonstrated brain abscess at lt-basal ganglia. Continuous drainage was performed while administered continuous drip infusion of DS. Follow-up CT after operation showed reduction of low density area which means brain abscess. Finding in this case suggest that DS may play a role in the management of DIC accompanying intracranial infection.

Adult↗
PubMed1999

Molecular and cellular mechanisms regulating T and B cell apoptosis through Fas/FasL interaction.

Fas (CD95) and Fas ligand (FasL) are a receptor/ligand pair critically involved in lymphocyte homeostasis and peripheral tolerance such that genetic defect in either Fas or FasL results in an autoimmune lymphoproliferative syndrome. Fas is a type I transmembrane protein and a member of the tumor necrosis factor receptor (TNFR) family whereas FasL is a type II transmembrane protein and a member of TNF family. Binding of Fas by FasL induces apoptosis of the Fas-expressing cells. In the past few years, Fas/FasL interaction has been connected to a series of important phenomena previously viewed as independent immune processes. The activation-induced T cell death (AICD) and the FasL-mediated cytotoxicity by activated T cells are two critical mechanisms that can account for most of these phenomena. It is in the context of the two mechanisms that we discuss in this review the molecular and cellular events that occur during T/T and T/B interactions that account for the down-regulation of the immune response. We have also discussed recent advances in the areas of FasL gene regulation, lymphokine regulation of AICD, and regulation of B cell susceptibility to FasL. Investigation in these areas should help elucidate the role of Fas/FasL in the complex network of regulatory mechanisms that control immune response and autoimmunity.

Animals↗
PubMed1999

Erythrocyte P1 group antigen expression in VTEC-associated hemolytic uremic syndrome.

BACKGROUND: The P1 blood group antigen has been postulated as a protective host factor against the development of the verotoxin-associated with hemolytic uremic syndrome (HUS). PATIENTS AND METHODS: In this study the P1 blood group antigen in 59 Japanese children with a past history of hemorrhagic colitis (HC) was scored with a direct agglutination method using a commercial anti P1 antibody. RESULTS: The P1 antigen was positive in 4 (21.1%) of 19 patients with a history of postdiarrheal HUS and in 11 (28.0%) of 40 patients with no history. There were no significant differences in the frequency of the P1 phenotype between the 2 groups (p = 0.629). CONCLUSION: We concluded that the P1 blood group antigen is not a protective factor against the development of HUS from verotoxin-producing Escherichia coli(VTEC)-infected hemorrhagic colitis in Japanese individuals.

Bacterial Toxins↗
PubMed1999

Management of patients with acute myocardial infarction at five academic medical centers: clinical characteristics, resource utilization, and outcome.

BACKGROUND: Although variability in management of cardiovascular syndromes has been demonstrated among regions, the extent to which variability exists among academic medical centers in different countries in uncertain. METHODS: This retrospective cohort study includes data on consecutive patients (n = 694) with acute myocardial infarction who were admitted to five teaching hospitals from different countries (84, Brigham and Women's Hospital, USA; 97, Iizuka Hospital, Japan; 64, Hospital de Clinicas de Porto Alegre, Brazil; 62, Universitätsklinikum Charité, Germany; and 387, Hôpital Cantonal Universitaire de Genève, Switzerland) during a one-year period. Data were collected via chart review on clinical characteristics, rates of diagnostic and therapeutic interventions, complications and mortality, length of stay, and one-year follow-up outcomes. RESULTS: Patients' clinical characteristics varied among these institutions, with the lowest prevalence of antero-septal myocardial infarction at the US hospital. The US hospital had the lowest rate of use of thrombolytic therapy and did not have the highest rate for any invasive procedure. Average length of stay ranged from 7.7 +/- 4.3 days in the US hospital to 47.2 +/- 27.9 days in the Japanese hospital. There were no differences in one-year mortality among the four institutions (4% to 8%, P = 0.881) for which data were available. CONCLUSIONS: In this nonrandom sample of academic medical centers, the use of aggressive therapies for acute myocardial infarction was at least as common at non-US as US hospitals. Length of stay was much shorter at the US hospital. Despite these variations in management, evidence for differences in outcomes at one year were not detected.

Academic Medical Centers↗
PubMed1999

Ischemic heart attacks following cessation of aspirin before coronary artery bypass surgery: A report of two cases.

We present herein two patients who suffered life-threatening ischemic heart attacks following the preoperative discontinuation of aspirin. Since their cardiac conditions were stable in the long-term while under medication, the cessation of aspirin was highly suspected to have caused or at least to have contributed to their ischemic events. We thus discuss the appropriate timing for discontinuation of aspirin before surgery in patients with ischemic heart disease.

Aged↗
PubMed1999

[Phase I study of gemcitabine hydrochloride (LY 188011) combination therapy with cisplatin in the patients with non-small cell lung cancer].

The combination Phase I study of gemcitabine hydrochloride with cisplatin was conducted in the patients with non-small cell lung cancer (NSCLC) at 5 investigation sites. Gemcitabine was administrated on day 1, 8 and 15 and cisplatin on day 1 of each 28-day cycle. The dosage of cisplatin was fixed to 80 mg/m2 and the dosage of Gemcitabine was gradually escalated in 3 dosing level from 600, 800 to 1,000 mg/m2. The maximum tolerated dose (MTD) and the recommended dose was determined with Continual Reassessment Method. For each dose level, 6 cases, 3 cases and 6 cases were registered respectively and all 15 cases were evaluable. In the dose level 3 with 1,000 mg/m2 of gemcitabine and 80 mg/m2 of cisplatin, grade 4 neutropenia was observed as DLT in 3 out of 6 cases, thus dose level 3 was considered as MTD and the recommended dose. Major adverse events were leukopenia, neutropenia, nausea/vomiting and anorexia. The incidence of such adverse events seemed to be dose-dependent and especially the grade of neutropenia seemed to be more serious as the dose increased. Also, the grade of liver function tests abnormal seemed to be more serious as the dose increased but the incidence as well as the grade did not have tendency of dose-dependent in another events including renal function tests abnormal. On the other hand, as to the efficacy PR was observed in 4 out of 15 cases. Based upon the results, it is necessary to discuss further the efficacy in the recommended dose in the combination therapy of gemcitabine and cisplatin.

Adenocarcinoma↗
PubMed1999

Absorption, distribution, metabolism, and excretion of donepezil (Aricept) after a single oral administration to Rat.

Donepezil hydrochloride (Aricept) is a drug for the treatment of Alzheimer's disease. The absorption, distribution, metabolism, and excretion of donepezil were investigated in male Sprague-Dawley rats after a single oral administration. Orally administered (14)C-labeled donepezil was absorbed rapidly. The plasma level of unchanged donepezil declined more rapidly than that of radioactivity, and the brain level of radioactivity declined almost in parallel with the plasma level of unchanged donepezil. The ratio of donepezil to total radioactivity in brain was 86.9 to 93.0%, indicating low permeability of the metabolites through the blood-brain barrier. No heterogeneous localization of radioactivity was recognized in the brain and the concentration in each part of the brain was 1.74 to 2.24 times the plasma concentration. Cumulative biliary, urinary, and fecal excretion of radioactivity in bile duct-cannulated rats was 72.9, 24.4, and 8.84%, respectively, of the administered radioactivity at 48 h after administration. These results indicate that the absorption of donepezil is almost complete, and that its metabolites are mainly excreted into feces through the bile and some of them are subject to enterohepatic circulation. The metabolism of donepezil was extensive in rats and involved O-demethylation, aromatic hydroxylation, N-dealkylation, N-oxidation, and glucuronide conjugation of O-demethylate. The structures of the metabolites were determined by mass spectrometry and (1)H-NMR analysis. In plasma, urine, and bile, O-glucuronides accounted for the majority of the radioactivity, and in brain, unchanged donepezil was mostly detected. No metabolites were found in brain. There was no notable accumulation of radioactivity in whole blood and tissues.

Administration, Oral↗
PubMed1999

Sodium/hydrogen ion exchange inhibitor ameliorates ischaemia-reperfusion injuries in the rat hind limb.

PURPOSE: This study was designed to investigate the effect of a newly synthesised sodium/hydrogen ion exchange inhibitor, SM-20550, on ischaemia-reperfusion induced injury in a rat hind limb model. METHODS: In order to induce ischaemia of the hind limbs, the abdominal aorta just distal to the renal arteries and the bilateral femoral arteries were clamped. Nineteen rats were divided into three groups. In the sham group (n=5), the vessels were only dissected and a vehicle solution was administered. In the control group (n=7), the vessels were clamped for five hours, and a vehicle solution was administered 10 minutes prior to clamping and continued for five hours after reperfusion. In the SM group (n=7), clamping was maintained for five hours with a bolus injection of SM-20550 and continuous infusion of the solution for five hours after reperfusion. Water content of the left gastrocnemius muscle was calculated. The right gastrocnemius was fixed in 10% formalin. A transverse thin section was stained with antimyoglobin antibody. Stained cells of the right gastrocnemius were counted and the myoglobin staining index was calculated. RESULTS: Water content was significantly (p<0.002) lower in the SM group than in the control group. The myoglobin staining index was significantly (p<0.01) higher in the SM group than in the control group. There was no significant difference between the control and the SM groups in creatinine phosphokinase (CPK) and lactate dehydrogenase (LDH). CONCLUSIONS: Our results indicate that the sodium/hydrogen ion exchange inhibitor, SM-20550, ameliorates oedema formation and ischaemia-reperfusion induced injury of the skeletal muscle.

Amidines↗
PubMed1998

The stereo-specific effect of D-serine ethylester and the D-cycloserine in ataxic mutant mice.

Spinocerebellar ataxia is one of the most common neurological disorders. However, few therapeutics are effective for the treatment of this disorder. In the present study, we investigated the efficacy of d-serine ethylester and a related substance, d-cycloserine, as therapeutic agents for ataxia in a murine model. Both compounds are known to stereospecific modulate N-methyl-d-aspartate type glutamate receptors, and impaired glutamate-mediated signaling has been implicated in spinocerebellar ataxia. Using a microdialysis method, we found that intraperitoneal administration of d-serine ethylester increases the extracellular content of endogenous d-serine in the mouse cerebellum for at least 3 h. Maximum elevation of the extracellular d-serine was observed at 40 min after injection. An open-field study was used to assay the effect of the d-serine derivatives on movement and ataxia. In mice exhibiting cytosine arabinoside-induced ataxia, d-serine ethylester reduced the falling index in a dose-dependent manner. The effect of d-serine ethylester was stereo-specific in that l-serine ethylester had no effect on the falling index at the maximum doses tested, and was partially inhibited by 5,7-dichlorokynurenate, an antagonist that binds to the glycine-binding site. Locomotor activity was not changed by the d-serine ethylester treatment. d-cycloserine also significantly reduced the falling index of the mice. Both d-serine ethylester and d-cycloserine had longer lasting effects than other potential therapeutic reagents for ataxia. Growing evidence suggests the essential involvement of endogenous d-serine in mammalian brain function, and our results suggest that d-serine derivatives may represent an effective new therapeutic for the treatment of spinocerebellar ataxia.

Animals↗
PubMed1998

Identification of two NF-kappa B sites in mouse CD95 ligand (Fas ligand) promoter: functional analysis in T cell hybridoma.

Fas ligand (FasL) gene expression is critically involved in peripheral T cell tolerance and lymphocyte homeostasis. Previous studies have suggested that nuclear translocation of NF-kappaB during T cell activation is a critical event for FasL gene activation. In the present study we have identified two NF-kappaB sites (designated FasL-kappaB1 and FasL-kappaB2) on the promoter (approximately 700 bp) of FasL. The NF-kappaB sites were identified by electrophoretic mobility shift assay. Transient transfection reporter analyses showed that the FasL promoter activity was comparable between a construct that contains both sites and a shorter construct (433 bp) that contains only the FasL-kappaB1 site. Furthermore, elimination of FasL-kappaB1 by site-directed mutagenesis significantly inhibited FasL promoter activity. These observations provide strong evidence that NF-kappaB directly binds to the FasL-kappaB1 site and up-regulates FasL gene expression.

Animals↗
PubMed1998

Homonojirimycin isomers and N-alkylated homonojirimycins: structural and conformational basis of inhibition of glycosidases.

A series of natural epimers of alpha-homonojirimycin and its N-alkylated derivatives have been prepared to investigate the contribution of the different chiral centers and conformation of the specificity and potency of inhibition of glycosidases. These epimers and N-alkylated derivatives are alpha-homonojirimycin (1), beta-homonojirimycin (2), alpha-homomannojirimycin (3), beta-homomannojirimycin (4), alpha-3,4-di-epi-homonojirimycin (5), beta-4,5-di-epi-homonojirimycin (6), N-methyl-alpha-homonojirimycin (7), and N-butyl-alpha-homonojirimycin (8). Compound 1 was a potent inhibitor of a range of alpha-glucosidases with IC50 values of 1 to 0.01 microM. Compounds 2, 3, and 4 were surprisingly inactive as inhibitors of beta-glucosidase and alpha- and beta-mannosidases but were moderately good as inhibitors of rice and some mammalian alpha-glucosidases. Compound 4 was active in the micromolar range toward all alpha-glucosidases tested. Furthermore, compound 4, which superimposes well on beta-l-fucose, was a 10-fold more effective inhibitor of alpha-l-fucosidase than 1-deoxymannojirimycin (12) and 3, with a Ki value of 0.45 microM. Only compounds 5 and 6 showed inhibitory activity toward alpha- and beta-galactosidases (6with an IC50 value of 6.4 microM against alpha-galactosidase). The high-resolution structure of 1 has been determined by X-ray diffraction and showed a chair conformation with the C1 OH (corresponding to the C6 OH in 1-deoxynojirimycin) predominantly equatorial to the piperidine ring in the crystal structure. This preferred (C1 OH equatorial) conformation was also corroborated by 1H NMR coupling constants. The coupling constants for 7 suggest the axial orientation of the C1 OH, while in 8 the C1 OH axial conformation was not observed. The C1 OH axial conformation appears to be responsible for more potent inhibition toward processing alpha-glucosidase I than alpha-glucosidase II. It has been assumed that the anti-HIV activity of alkaloidal glycosidase inhibitors results from the inhibition of processing alpha-glucosidase I, but 1, 7, and 8 were inactive against HIV-1 replication at 500 microg/mL as measured by inhibition of virus-induced cytopathogenicity in MT-4 cells. In contrast, the EC50 value for N-butyl-1-deoxynojirimycin (11), which also inhibits processing alpha-glucosidase I, was 37 microg/mL. Compound 7 has been shown to be a better inhibitor of alpha-glucosidase I than 1 and 8 both in vitro and in the cell culture system. These data imply that inhibition of HIV by glycosidase inhibitors can be due to factors other than simply inhibition of processing alpha-glucosidase I.

1-Deoxynojirimycin↗
PubMed1998

Excitatory synaptic transmission in the inner retina: paired recordings of bipolar cells and neurons of the ganglion cell layer.

Properties of glutamatergic synaptic transmission were investigated by simultaneously voltage-clamping a pair of connected bipolar cells and cells in the ganglion cell layer (GLCs) in the newt retinal slice preparation. Activation of the Ca2+ current in a single bipolar cell was essential for evoking the glutamatergic postsynaptic current in the GLC. Depolarization for as short as 15 msec activated both NMDA and non-NMDA receptors. On the other hand, analysis of the spontaneous glutamatergic synaptic currents of GLCs revealed that these currents consisted of mainly non-NMDA receptor activation with little contribution from NMDA receptors. This suggests that non-NMDA receptors of GLCs are clustered in postsynaptic membrane regions immediately beneath the release sites of bipolar cells and that NMDA receptors have lower accessibility to the released transmitter than non-NMDA receptors. Glutamate that is spilled over from the release sites may activate the NMDA receptors. When a prolonged depolarizing pulse was applied to a bipolar cell, the response induced by non-NMDA receptors was limited greatly by their fast desensitization, whereas NMDA receptors were able to produce a maintained response. The relationship between the pulse duration applied to the bipolar cell and the integrated charge of the response evoked in the GLC was almost linear. Therefore, we propose that both non-NMDA and NMDA receptors cooperate to transfer the graded photoresponses of bipolar cells proportionally to GLCs.

Animals↗