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Biomedical subjects

Y Matsukawa

Publications and source records attributed to Y Matsukawa.

At least 19 recordsLinked to original sources

Prevalence of Helicobacter pylori in NSAID users with gastric ulcer.

OBJECTIVE: Regarding the interaction of Helicobacter pylori and non-steroidal anti-inflammatory drugs (NSAIDs), we cannot accept unanimous conclusions in inducing gastric ulcer. We therefore evaluated the role of Helicobacter pylori and NSAIDs in inducing gastric ulcer. METHODS: Dyspeptic patients receiving NSAIDs underwent endoscopic examination. Gastric ulcer formation and H. pylori status were investigated. Biopsy specimens from the antrum and lower body of the stomach were prepared for the rapid urease test and pathological evaluation. Anti-H. pylori antibody was measured by enzyme-linked immunosorbent assay. RESULTS: Two hundred and twenty-six patients receiving NSAIDs (220 chronic and six on-demand users) underwent gastrofibrescopic examination. There were 110 patients with gastric ulcer and 111 non-ulcer patients with gastritis. The remaining five patients had neither. NSAID users with gastric ulcer showed a low prevalence of H. pylori compared with those without them [55/110 (50.0%) vs 79/111 (71.2%), P < 0.01]. The same tendency was seen when patients receiving low-dose aspirin and those with rheumatoid arthritis were analysed separately [13/29 (44.8%) vs 50/62 (80.6%), P < 0.01, and 11/33 (33.3%) vs 16/26 (61.5%), P < 0.06 with Yates' correction, respectively]. CONCLUSION: Helicobacter pylori infection appeared to be a risk factor for developing gastritis, but we found no evidence that it increases gastric ulcer formation in NSAID users with dyspepsia.

Aged↗

Long-term administration of beraprost, an oral prostacyclin analogue, improves pulmonary diffusion capacity in patients with systemic sclerosis.

The objective of this study was to assess the effect of beraprost sodium, an oral prostacyclin analogue, on pulmonary function in patients with systemic sclerosis. Seventeen patients, with systemic sclerosis and predicted percent values of carbon monoxide diffusion capacity (%DLCO) of less than 95, received beraprost sodium for at least 12 months. Conventional testing for pulmonary function was performed at 12-month intervals and changes were evaluated with special reference to DLCO. Twelve patients completed the treatment. Nine patients showed improvement in DLCO (12.1 +/- 2.3 to 15.5 +/- 4.4 ml/min/mmHg, P < 0.006) and 10 patients showed an increase in %DLCO (66.6 +/- 11.9 to 87.7 +/- 23.2%, P < 0.004). Total lung capacity, vital capacity and forced expiratory volume remained unchanged. This study showed that DLCO levels in patients with systemic sclerosis improved after the administration of beraprost sodium, probably due to the decrease in pulmonary vascular resistance accompanied by increased cardiac output.

Administration, Oral↗

Patients with systemic lupus erythematosus show a normal responsive search score in exploratory eye movement analysis: comparison with schizophrenia.

OBJECTIVE: To assess whether a difference in psychiatric vulnerability exists between patients with systemic lupus erythematosus (SLE) and those with schizophrenia. METHODS: Twenty women with SLE underwent exploratory eye movement analysis, and a responsive search score (RSS) was obtained, two months after the onset of the disease. Fifteen women with schizophrenia in remission also underwent this analysis. Exploratory eye movement was recorded by an eye mark recorder, which detects corneal reflection of infrared light. The number of eye fixations (instance of more than 0.2 seconds of eye fixation time) was recorded, and the RSS was calculated from eye fixation analysis. RESULTS: Mean (SD) RSS differed significantly between patients with SLE and those with schizophrenia (9.85 (1.87) v 7.27 (1.58) points, respectively, p<0.0001), whereas no difference in mean RSS was found between patients with SLE and 19 normal women. No difference in mean RSS was found between patients with active SLE and those with inactive SLE (9.51 (1.87) v 10.0 (1.77) points). CONCLUSION: The psychiatric vulnerability in patients with SLE, measured by the RSS, differs from that in patients with schizophrenia.

Adult↗

Alterations of quantitative EEG and mini-mental state examination in interferon-alpha-treated hepatitis C.

We have recently observed a diffuse slowing of brain waves using serial quantitative electroencephalographic (qEEG) examinations in interferon (IFN)-alpha-treated chronic hepatitis C patients. However, it remains unclear how this alteration could be assessed. We evaluated the correlation between the qEEG changes and three tests of mental status, including the Mini-Mental State Examination (MMSE), in such patients. This is the first study to undertake a clinical evaluation of the adverse effects on brain function due to IFN. We undertook blind, prospective and serial qEEG examinations on 56 chronic hepatitis C patients at three independent hospitals. IFN-alpha was administered intramuscularly at a dose of 9 x 10(6) IU daily for the first 4 weeks and then 3 times/week for the next 20 weeks. Serial EEGs were obtained before, at 2 and 4 weeks of treatment, and after the IFN-alpha treatment. The absolute power values of each frequency band in each patient at different stages of treatment were recorded by qEEG. Each patient was assessed by the MMSE, Hamilton Rating Scale for Depression (HSD), and Hamilton Rating Scale for Anxiety (HSA). We statistically evaluated the correlations between the changes in power values and alterations of scores on the mental status tests during IFN-alpha treatment. The decreased scores observed on the MMSE ranged from 2 to 5 points at both 2 and 4 weeks of IFN-alpha treatment. There were no significant differences in age distribution for each decreased score on the MMSE. As the alteration in MMSE score during IFN treatment increased, the alteration in absolute power values for the slow waves during IFN treatment increased significantly, while that for the alpha 2 and fast waves during treatment decreased significantly. However, the changes in the HDS and HSA revealed no significant correlations. The alteration of the qEEG was reversible after the treatment. MMSE scores represent one screening method for the clinical assessment of IFN-alpha-induced alterations of brain function.

Adult↗

Fatal cases of gabexate mesilate-induced anaphylaxis.

Gabexate mesilate, ethyl-4-(6-guanidinohexanoyloxy) benzoate monomethanesulfonate (C16H23N3 O4CH4O3S: M.W. 417.48), is a synthetic protease inhibitor and was introduced for clinical use in 1978. It rarely induces anaphylaxis, and patients with gabexate mesilate-induced shock had been reported to survive with appropriate treatments including respiratory support. However, there were increasing reports on fatal cases in recent years: 6 cases have been reported to develop fatal anaphylaxis following dripping infusions of gabexate mesilate. All the fatal cases rapidly developed anaphylaxis (within 5 minutes), whereas 7 out of 11 in recovered cases developed it 5 or more minutes after the injection. Venous access should be kept for at least 30 minutes to prepare for and to treat this fatal reaction in patients receiving gabexate mesilate repeatedly.

Anaphylaxis↗

Galectin-12, an Adipose-expressed Galectin-like Molecule Possessing Apoptosis-inducing Activity.

Galectins constitute a family of proteins that bind to beta-galactoside residues and have diverse physiological functions. Here we report on the identification of a galectin-like molecule, galectin-12, in a human adipose tissue cDNA library. The protein contained two potential carbohydrate-recognition domains with the second carbohydrate-recognition domain being less conserved compared with other galectins. In vitro translated galectin-12 bound to a lactosyl-agarose column far less efficiently than galectin-8. Galectin-12 mRNA was predominantly expressed in adipose tissue of human and mouse and in differentiated 3T3-L1 adipocytes. Caloric restriction and treatment of obese animals with troglitazone increased galectin-12 mRNA levels and decreased the average size of the cells in adipose tissue. The induction of galectin-12 expression by the thiazolidinedione, troglitazone, was paralleled by an increase in the number of apoptotic cells in adipose tissue. Immunocytochemical analysis revealed that galectin-12 was localized in the nucleus of adipocytes, and transfection with galectin-12 cDNA induced apoptosis of COS-1 cells. These results suggest that galectin-12, an adipose-expressed galectin-like molecule, may participate in the apoptosis of adipocytes.

3T3 Cells↗

Pharmacokinetic behaviour of cisplatin in peritoneal fluid after intraperitoneal administration of cisplatin-loaded microspheres.

The objective of this study was to establish a pharmacokinetic model for the estimation of unchanged cis-dichlorodiammine-platinum (II) (CDDP) concentration in peritoneal fluid after intraperitoneal administration of cisplatin-loaded microspheres (CDDP-MS) and to elucidate the accuracy of this model by comparisons between actual and simulated values after intraperitoneal administration of CDDP-MS. We developed a method enabling the precise and quick assessment of the drug concentration in the peritoneal cavity. The pharmacokinetic parameters obtained after intravenous bolus injection at a dose of 2 mg kg(-1) were total body clearance (1026 mL h(-1) kg(-1)), elimination rate constant (3.24 h(-1)) and distribution volume of systemic circulation (316.7 mL kg(-1)). After an intraperitoneal bolus injection at a dose of 5 mg kg(-1), the absorption rate constant from the peritoneal cavity (3.64 h(-1)) and the distribution volume of the peritoneal cavity (13.5 mL kg(-1)) were determined. The protein-binding rate constant in ascites was 0.58 h(-1). Using these pharmacokinetic parameters, we established a pharmacokinetic model consisting of two compartments. Administration of CDDP-MS at a dose of 10 mg kg(-1), which released CDDP over 7 days in-vitro, yielded sustained concentrations of unchanged CDDP (1-2 mg mL(-1)) in the peritoneal cavity that persisted for 7 days, and that were predictable by applying the in-vitro dissolution profile to the pharmacokinetic model. The findings obtained from this study are useful for understanding the basic pharmacokinetic characteristics of unchanged CDDP in the peritoneal cavity and may also be important in the development of optimized CDDP-MS formulations.

Algorithms↗

Genomic structure and mutations in adipose-specific gene, adiponectin.

BACKGROUND: Adiponectin is a collagen-like plasma protein specifically synthesized in adipose tissue. Plasma adiponectin concentrations are decreased in obesity whereas it is adipose-specific. OBJECTIVE: To clarify the significance of the genetic variations in adiponectin gene on its plasma concentrations and obesity. SUBJECTS: Two hundred and nineteen unrelated adult Japanese subjects (123 men and 96 women, age: 20-83 y, BMI: 16-43 kg/m2) including 77 obese subjects (BMI>26.4 kg/m2). MEASUREMENT: Human adiponectin gene was isolated from PAC DNA pools. Mutations in the adiponectin gene were screened by direct sequencing or restriction-fragment polymorphism. The levels of plasma adiponectin were determined by the enzyme-linked immunosorbent assay (ELISA). RESULTS: Adiponectin gene spanned 17 kb on chromosome 3q27, consisting of three exons and two introns. Within 2.1 kb of the 5'-flanking region, there were two octamer elements present in the promoter of adipsin. Two nucleotide changes were identified. One was a polymorphism (G/T) occurring in exon 2, and the other was a missense mutation (R112C) in exon 3. The mean plasma adiponectin levels of the subjects carrying G allele were low (G/G: 4.5 microg/ml; G/T: 5.9 microg/ml; and T/T: 6.3 microg/ml), but were not statistically significant. The allelic frequency between the obese and the non-obese showed no significant difference. The subject carrying R112C mutation showed markedly low concentration of plasma adiponectin. CONCLUSION: Two nucleotide changes have been identified in the adiponectin gene. G/T polymorphism in exon 2 was associated with neither plasma adiponectin concentrations nor the presence of obesity. A subject carrying missense mutation (R112C) showed markedly low plasma adiponectin concentration.

Adipocytes↗

Mutation in bombesin receptor subtype-3 gene is not a major cause of obesity in the Japanese.

Bombesin receptor subtype-3 (BRS-3) is one of the candidate genes of obesity. The mice lacking BRS-3 have been shown to develop mild obesity. These mice also showed hypertension and impaired glucose metabolism, supporting these mice as a good model for human obesity. We screened 104 Japanese obese men (BMI > 26.4, 26.5-44.1) to investigate whether there is any genetic defect in BRS-3 gene. The DNA fragments containing each exon of BRS-3 gene were amplified by polymerase chain reaction (PCR) and were directly sequenced. No mutation, nor polymorphism was found in the coding region of BRS-3, suggesting that mutation of this gene is not a major cause of obesity in humans.

DNA Primers↗

Rates of protein transport across rat alveolar epithelial cell monolayers.

The transport of model proteins, ranging from 12,300 to 150,000 Da, across tight rat alveolar epithelial cell monolayers (> 2000omegacm2) grown on polycarbonate filters, was studied. Model proteins were 14C-cytochrome c, 14C-ovalbumin, granulocyte-colony stimulating factor (G-CSF), 14C-bovine serum albumin (BSA), 125I-transferrin, and 14C-immunoglobulin G. Cytochrome c was extensively metabolized, as indicated by < 10% of the dose being translocated in intact form. This contrasts with 20-80% for the other model proteins studied. The flux of cytochrome c and G-CSF was symmetric in the apical-to-basolateral (ab) and basolateral-to-apical (ba) directions. By contrast, the flux of intact ovalbumin, BSA, transferrin and immunoglobulin G showed asymmetry, with the ab flux being higher by 2-5 times. There was no relationship between ab or ba fluxes and the molecular weights of these four model proteins. Since some of the proteins were translocated at much greater rates than are consistent with restricted diffusion or pinocytosis, receptor-mediated or adsorptive transcytosis may be involved.

Animals↗

Serum concentration of interferon-alpha: a comparison between once-a-day and twice-a-day administration.

The aim of this study was to determine the possible mechanism of the antiviral activity of twice daily administration of interferon (IFN)-alpha for active hepatitis C and to evaluate serum concentrations of IFN-alpha with enzyme-linked immunosorbent assay (ELISA). Forty-seven patients with active hepatitis C received IFN-alpha intramuscularly for 24 weeks. They were divided into once-a-day and twice-a-day groups. Changes in serum IFN-alpha levels were assessed during the treatment period. Compared with twice-a-day treatment, the once-a-day group showed no increase in serum IFN-alpha at the end of daily treatment (p < 0.03). In contrast, one-third of the twice-a-day group showed increased IFN-alpha at the end of daily treatment (p < 0.02). In conclusion, measured with ELISA, twice-daily administration of IFN-alpha manifested prolonged elevation in serum levels when compared with once daily administration.

Adult↗

[The frequency of Streptococcus pneumoniae strains and sensitivity surveillance for several antibiotics in Gifu Prefecture].

The frequency and the antibacterial sensitivity of Streptococcus pneumoniae strains isolated from 6 key hospitals (in 5 areas) and 1 otorhinolaryngology clinic in Gifu Prefecture from February to March, 1999, were investigated with several antibiotics. A total of 128 strains of Streptococcus pneumoniae were isolated throughout the study: 47 strains (36.7%) of penicillin-susceptible S. pneumoniae (PSSP), 51 strains (39.8%) of penicillin-intermediate S. pneumoniae (PISP), and 30 strains (23.4%) of penicillin-resistant S. pneumoniae (PRSP); the resistant bacteria being relatively prominent. In these hospitals, PSSP was isolated by 38.8% in all the key hospitals and by 30% in the otolaryngology clinic with almost no discernible difference. PISP was isolated by 63.3%, higher in the otolaryngology clinic and PRSP by 28.6%, higher in the key hospitals conversely. The MIC90s in PISP and PRSP were determined with the antibiotics. In result, only cefditoren (CDTR) showed favorable antibacterial activities with the MIC90 of 0.78 microgram/ml among penicillins or oral cephems. The MIC90s of carbapenems such as imipenem (IPM), meropenem (MEPM), and panipenem (PAPM) were less than 0.39 microgram/ml; particularly, PAPM showed the highest antibacterial activities. Among new quinolones such as tosufloxacin (TFLX), levofloxacin (LVFX), sparfloxacin (SPFX), and ciprofloxacin (CPFX), TFLX showed the highest antibacterial activities with the MIC90 of 0.39 microgram/ml. Other agents showed very low antibacterial activities as the MIC90s were 25 micrograms/ml in minocycline (MINO) and more than 100 micrograms/ml in clarithromycin (CAM) and clindamycin (CLDM).

Amoxicillin↗

Growth inhibition of A549 human lung adenocarcinoma cells by L-canavanine is associated with p21/WAF1 induction.

L-Canavanine (CAV) is a higher plant nonprotein amino acid and a potent L-arginine antimetabolite. CAV can inhibit the proliferation of tumor cells in vitro and in vivo, but little is known regarding the molecular mechanisms mediating these effects. We demonstrated that the treatment of human lung adenocarcinoma A549 cells with CAV caused growth inhibition; G1 phase arrest is accompanied by accumulation of an incompletely phosphorylated form of the retinoblastoma protein, whose phosphorylation is necessary for cell cycle progression from G1 to S phase. In addition, CAV induces the expression of p53 and subsequent expression of a cyclin-dependent kinase inhibitor, p21/WAF1. The p53-dependent induction of p21/WAF1 and the following dephosphorylation of the retinoblastoma protein by CAV could account for the observed CAV-mediated G1 phase arrest.

Adenocarcinoma↗