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Biomedical subjects

K Misawa

Publications and source records attributed to K Misawa.

At least 37 records · Page 2Linked to original sources
PubMed1999

Spontaneous regression of hepatocellular carcinoma.

A 62-year-old Japanese man with hepatitis B virus-related liver cirrhosis revealed alpha-fetoprotein (AFP) elevation. Dynamic computed tomography, taken at this time, showed a liver tumor in the anterior segment. As the patient refused any further medical treatment, he was observed in an outpatient clinic. The size of the tumor reduced and the serum level of AFP decreased gradually without any treatment. Twelve months after the initial diagnosis, the tumor could not be detected by computed tomography (CT) scan, and the level of AFP had declined to the normal range. Blood supply is essential for tumor growth and an arterioportal shunt near the tumor may change the dynamics of blood flow to the tumor. The shunt found in this patient was thought to be one of the causative factors leading to regression, but it could not be denied that immunological mechanisms may have played an important role in the spontaneous regression of hepatocellular carcinoma.

Biomarkers, Tumor↗
PubMed1999

[Treatment of cancer ascites by combined intraperitoneal administration of low-dose CDDP and reinfusion of ultra-filtrated and concentrated ascitic fluid in patients].

Ascites due to carcinomatous dissemination is a severe problem for end-stage cancer patients. We attempted treating patients on an outpatient basis with the administration of low-dose CDDP-i.p. and reinfusion of ultrafiltrated and concentrated ascites. From 1995, we performed this therapy on 16 patients with concentrated ascites 6-8 fold and reinfusion, combined with low-dose CDDP-i.p. and drip infusion of 5-FU intravenously. The ascitic fluid was significantly decreased after treatment in 8 patients, and 2 patients had lasting low concentrations of CA 125. CA 125 decreased in 83.3% of patients, who tended to have extended survival times after remarkable ascites pooling and treatment with low-dose CDDP-i.p. and reinfusion therapy. This treatment is a useful cant method for decreasing ascites and improving QOL.

Adult↗
PubMed1998

Induction of synaptosomal-associated protein-23 kD (SNAP-23) by various cytokines.

Cytokines manifest their function through regulation of gene expression. We searched for immediate-early cytokine responsive genes by the mRNA differential display technique using interleukin-3 (IL-3)-dependent OTT-1 cells, and have isolated a novel cDNA which encodes 210 amino acids and shows 87% amino acid identity to human SNAP-23 (synaptosomal-associated protein of 23 kD). The message for this protein (mouse SNAP-23) was induced in OTT-1 cells by IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-5. The experiment using C-terminal deletion mutants of the common beta subunit (betac) of IL-3/GM-CSF/IL-5 receptors showed that expression of SNAP-23 was associated with the Ras-Raf-MAPK pathway, but not with the JAK-STAT pathway. Moreover, SNAP-23 was induced in response to a wide variety of cytokines, including IL-2, IL-3, IL-5, IL-10, stem cell factor, G-CSF, GM-CSF, leukemia inhibitory factor, and erythropoietin. Constitutive expression of SNAP-23 was seen in various tissues, including heart, lung, kidney, liver, spleen, and small intestine. Possible involvement of SNAP-23 in cytokine signal transduction is discussed.

Amino Acid Sequence↗
PubMed1998

A new histological procedure for re-evaluation of the serological test for Helicobacter pylori.

To re-evaluate the accuracy of the serological test for Helicobacter pylori, fixation of biopsy specimens with Carnoy's solution (preserving the mucous layer in tissue preparations) followed by immunohistochemical staining (a new histological procedure) was used as the reference histological method instead of 10% formalin fixation followed by hematoxylin-eosin staining (the conventional histological procedure). Biopsy specimens (antrum and body) from 114 patients with gastritis (including non-ulcer dyspepsia) or gastric and/or duodenal ulcers were obtained by endoscopy and used for both bacteriological culture and histological examination. Serum samples were taken from all patients at the time of endoscopy. The serum levels of specific IgG and IgA antibodies for Helicobacter pylori were measured by commercial enzyme immunoassay kits. The reliability of the IgG and IgA measurements was evaluated by analyzing receiver operating characteristic curves obtained using the two histological procedures. With the conventional histological procedure as the reference, the sensitivity and specificity levels of the serological test were 87.2% and 82.1%, respectively. With the new histological procedure as reference, sensitivity and specificity were 94% and 96.7%, respectively. The insufficient accuracy reported for the serological test could be due to false-positive or false-negative results obtained when the conventional histological procedure is used as the reference. The new histological procedure used here revealed that the serological test for Helicobacter pylori is more reliable than previously thought.

Antibodies, Bacterial↗
PubMed1998

Mesh plug repair for a small incisional hernia in a cirrhotic patient with ascites: report of a case.

We report herein the case of a patient with severe liver ascites due to cirrhosis in whom a small incisional hernia on a midline incision was successfully treated by a mesh plug repair, a method most commonly employed for groin hernia repair. The hernia sac was dissected and inverted into the abdominal cavity by the mesh plug under epidural anesthesia. The patient's recovery was quick and relatively painless, and there has been no recurrence after 1 year of followup. This case report demonstrates that the method of mesh plug repair may be appropriate for small incisional hernias as well as groin hernias, performed under epidural anesthesia.

Ascites↗
PubMed1998

Acquisition versus loss of Helicobacter pylori infection in Japan: results from an 8-year birth cohort study.

Studies of the pattern of change in the epidemiology of Helicobacter pylori infection are scarce. A longitudinal cohort study consisted of 644 children and adults, and two independent cross-sectional surveys were conducted in rural Japan between 1986 and 1994. The anti-H. pylori IgG seroconversion rates were 1.1% and 1% per year for children and adults, respectively. The seroreversion rate per year was 1.8% for children and 1.5% for adults. The cohort study was confirmed by the two cross-sectional studies. H. pylori prevalence fell in all age groups in both children (odds ratio [OR] = 0.5, 95% confidence interval [CI] = 0.2-1.0, P = .05) and adults (OR = 0.4, 95% CI = 0.3-0.6, P = .001). The rate of loss of H. pylori infection was greater than the acquisition. Data regarding acquisition and loss of H. pylori infection are critical to understanding the epidemiology of the infection and to developing treatment and vaccination strategies.

Adolescent↗
PubMed1998

Preoperative nocturnal desaturations as a risk factor for late postoperative nocturnal desaturations.

Severe postoperative hypoxaemia during sleep may increase the risk of postoperative cardiovascular complications. We hypothesized that the severity of hypoxic episodes after surgery are related to the presence of preoperative sleep-disordered breathing (SDB). We tested this hypothesis in a multicentre study designed to elucidate the major risk factors for development of postoperative nocturnal desaturations. We performed overnight oximetry before operation and for one night between the second and fourth day after operation in 80 patients undergoing major surgery. We calculated oximetry variables such as oxygen desaturation index (ODI), defined as the number of oxygen desaturations exceeding 4% below baseline, percentage time spent at SpO2 < 90% (CT90, %) and lowest SpO2 value. After operation, although the change in ODI was not significant (P = 0.34), deterioration in CT90 and lowest SpO2 values were significant (P = 0.036 and P = 0.007, respectively). Multivariate analysis of possible risk factors for postoperative desaturations revealed that preoperative hypoxaemia and apnoea witnessed by others were highly correlated with postoperative hypoxaemia.

Adult↗
PubMed1998

Identification and characterization of a constitutively active STAT5 mutant that promotes cell proliferation.

STAT (signal transducers and activators of transcription) proteins are transcription factors which are activated by phosphorylation on tyrosine residues upon stimulation by cytokines. Seven members of the STAT family are known, including the closely related STAT5A and STAT5B, which are activated by various cytokines. Except for prolactin-dependent beta-casein production in mammary gland cells, the biological consequences of STAT5 activation in various systems are not clear. We applied PCR-driven random mutagenesis and a retrovirus-mediated expression screening system to identify constitutively active forms of STAT5. By this strategy, we have identified a constitutively active STAT5 mutant which has two amino acid substitutions; one is located upstream of the putative DNA binding domain (H299R), and the other is located in the transactivation domain (S711F). The mutant STAT5 was constitutively phosphorylated on tyrosine residues, localized in the nucleus, and was transcriptionally active. Expression of the mutant STAT5 partially dispenses with interleukin 3 (IL-3) as a growth stimulant of IL-3-dependent cell lines. Further analyses of the mutant STAT5 have demonstrated that both of the mutations are required for nuclear localization, efficient transcriptional activation, and induction of IL-3-independent growth of an IL-3-dependent cell line, Ba/F3, and have indicated that a molecular basis for the constitutive activation is the stability of the phosphorylated form of the mutant STAT5.

Animals↗
PubMed1998

The amount and pattern of DNA polymorphism under the neutral mutation hypothesis.

The amount and pattern of DNA polymorphism can give useful information on the maintenance mechanism of genetic variation at the DNA level. In this note we have shown the amount and pattern of DNA polymorphism expected under the neutral theory. The amount of DNA polymorphism can be estimated from the average number of nucleotide differences per site, the proportion of segregating sites, and so on. We have shown how to estimate theta from these quantities, where theta = 4Nv, N is the effective population size and v is the mutation rate per site per generation. We have also shown the expectations of the nucleotide variation within and between allelic classes.

Base Sequence↗
PubMed1997

Tacrolimus (FK506) down-regulates free radical tissue levels, serum cytokines, and neutrophil infiltration after severe liver ischemia.

BACKGROUND: Liver ischemia and reperfusion injury is associated with activation of multiple inflammatory pathways, including free radicals, cytokines, and neutrophil-mediated tissue damage among others. Tacrolimus (FK506) has shown important regulatory effects on some inflammatory pathways, such as cytokines, neutrophils, and adhesion molecules. In this study, we explored a new potential protective mechanism for tacrolimus in the liver inflammatory response after ischemia and reperfusion, specifically its effect on liver tissue free radicals. METHODS: Total hepatic ischemia was produced in the rat for 90 min with an extracorporeal portosystemic shunt. Animals (n=96) were divided into four groups: group 1 comprised normal rats for reference values; group 2 comprised sham operated rats; in group 3, ischemic control rats received only the vehicle; and the experimental treatment group, group 4, received tacrolimus at a dose of 0.3 mg/kg, 4 hr before ischemia. Animal survival was followed up to 7 days. Liver function tests were performed and liver tissue free radicals and myeloperoxidase, serum cytokines (interleukin 1, tumor necrosis factor-alpha), and liver histology were measured 4 hr after reperfusion. RESULTS: Seven-day survival was significantly improved from only 20% in the control group to 55% in the tacrolimus group (P<0.01). Liver function tests, histology, and myeloperoxidase tissue values were significantly improved (P<0.05) with tacrolimus pretreatment. Furthermore, a significant (P<0.05) down-regulation of serum cytokines and liver tissue free radicals was observed. CONCLUSIONS: These data indicate a new and different protective mechanism for FK506 in regard to its ability to down-regulate free radical levels in livers subjected to severe ischemia and reperfusion. Tacrolimus, also confirmed to be a potent suppressor of the cytokine response, specifically interleukin 1 and tumor necrosis, decreased neutrophil tissue migration as well.

Animals↗
PubMed1997

Estimation of the amount of DNA polymorphism when the neutral mutation rate varies among sites.

Knowing the amount of DNA polymorphism is essential to understand the mechanism of maintaining DNA polymorphism in a natural population. The amount of DNA polymorphism can be measured by the average number of nucleotide differences per site (pi), the proportion of segregating (polymorphic) site (s) and the minimum number of mutations per site (s*). Since the latter two quantities depend on the sample size, theta is often used as a measure of the amount of DNA polymorphism, where theta = 4Nmu, N is the effective population size and mu is the neutral mutation rate per site per generation. It is known that theta estimated from pi, s and s* under the infinite site model can be biased when the mutation rate varies among sites. We have therefore developed new methods for estimating theta under the finite site model. Using computer simulations, it has been shown that the new methods give almost unbiased estimates even when the mutation rate varies among sites substantially. Furthermore, we have also developed new statistics for testing neutrality by modifying Tajima's D statistic. Computer simulations suggest that the new test statistics can be used even when the mutation rate varies among sites.

DNA↗
PubMed1997

Quantitative evaluation of the rate of myocardial interstitial fibrosis using a personal computer.

We investigated the reliability and reproducibility of an image-analyzing system run on a personal computer for measurement of myocardial interstitial fibrosis. Measurements of myocardial interstitial fibrosis in right ventricular endomyocardial biopsies obtained from patients with hypertrophic cardiomyopathy determined by this image-analyzing system were compared with measurements determined by the point-counting method. We also investigated the correlation between measurements of interstitial fibrosis obtained by image analysis and biochemical measurements of myocardial levels of hydroxyproline in normal and cardiomyopathic hamsters. The intra- and interobserver variability were significantly lower for measurements obtained by the image-analyzing system than for measurements obtained by the point-counting system. Reproducibility was superior with the image-analyzing method. The rate of myocardial interstitial fibrosis determined by the computer image-analyzing method was positively correlated with the hydroxyproline measurement (r = 0.89). Our results suggest that an image-analyzing system using a personal computer provides reproducible results with a high level of reliability.

Adult↗
PubMed1997

Effect of blood collection imitating toxicokinetic study on rat hematological parameters.

The effect of blood collection imitating a one-month toxicokinetic study on hematological parameters was studied in male rats (6 weeks of age at the beginning of the experiment). Three groups were established according to blood sampling points per day; Group I (3 points), Group II (5 points) and Group III (10 points). These repeated blood samplings were carried out on the first and last days of this study, and one-point blood sampling was also done every week during the experiment. In each sampling, 0.3 ml of blood was collected from the jugular vein. There were no changes in Group I, but in other groups, especially in Group III, red blood cell counts, hematocrit and hemoglobin concentration decreased during repeated blood sampling. On the other hand, white blood cell counts also decreased, but recovered within 24 hr. Platelet counts did not show any decrement. From the present result, less than 0.9 ml of blood per day is conceivable as the volume without causing changes in hematological parameters. The baseline of the sampling volume can become one reference for toxicokinetic and toxicological studies.

Animals↗
PubMed1996

Tranilast antagonizes angiotensin II and inhibits its biological effects in vascular smooth muscle cells.

Recent studies have been reported indicating that angiotensin II may potentiate neointimal formation. In the present study, we examined the antagonistic effect of tranilast on angiotensin II. Losartan was used as the reference compound. First, tranilast inhibited the angiotensin II-induced contraction of rabbit aortic strips in a noncompetitive manner (pD'(2) = 3.7), whereas it had little effect on the contraction induced by noradrenaline or endothelin-l. Second, tranilast inhibited the binding of (125)I-labeled angiotensin II to angiotensin AT1 receptors in rat liver membranes with an IC(50) value of 289 mu M. Finally, functional antagonism of tranilast (100 and 300 mu M) was demonstrated by its blockade of angiotensin II (10(-8)M)-induced (45)Ca(2+) -efflux from human vascular smooth muscle cells (VSMC). However, tranilast (30-300 mu M) exerted no influence on PDGF-induced formation of inositol triphosphates which cause an increase in [Ca(2+)]i in human VSMC. The antagonistic activity of tranilast towards angiotensin II may be involved in part in preventing restenosis after percutaneous transluminal coronary angioplasty (PTCA).

Angiotensin II↗
PubMed1996

21-Aminosteroids block neutrophil infiltration and provide liver protection independent of NO2-/NO3- levels.

21-Aminosteroids are antioxidant compounds that prevent iron-dependent lipid peroxidation and improve cell viability. In this work we attempt to define the role of 21-aminosteroids in liver ischemia and reperfusion and assess their possible mode of action, specifically their effect on neutrophil infiltration and nitrite/nitrate levels. Total liver ischemia for 90 min was produced in the rat with the use of a portosystemic shunt. Three groups of animals were studied. One group received the 21-aminosteroid U-74389G (10 mg/ kg) divided into two equal doses 10 min prior to ischemia (7 mg/kg) and 10 min before reperfusion (3 mg/ kg). The two other groups included the sham and the control animals. We studied survival at 7 days and serum liver enzymes, liver myeloperoxidase, plasma nitrites, nitrates, and liver histology at 6 hr postreperfusion. Animal survival improved from 13% in the ischemic control to 52% in the lazaroid treated group (P < 0.05). We observed significant improvements in liver function tests, liver myeloperoxidase levels, as well as in the liver histology (P < 0.05). We could not find statistical difference in plasma nitrite/nitrate (P > 0.1). The 21-aminosteroids significantly improved animal survival after total liver ischemia, through a mechanism that includes blocking neutrophil infiltration which is independent from nitrite/nitrate levels.

Animals↗