Biomedical subjects
Publications and source records attributed to N Kinukawa.
We searched literature databases regarding the four Japanese universities that published the highest number of life science papers. The databases used in this study were MEDLINE and EMBASE. As a result, there was a 30% difference in the number of papers among the four universities.
We have developed a visual field quantification system that can accurately quantify the measurement results by the Goldmann Perimeter (GP). This system calculates the plural indexes introduced in published papers. In recent years, several isopter quantification methods have been proposed. In these methods, the isopters are digitized and the data are input into a computer, after which a computer program evaluates the changes in the isopters quantitatively. However, each program is only able to evaluate private indexes. We have developed a system that quantifies data using multiple methods. This system used five methods that have been introduced in published papers. With this system, a physician can analyze GP data with multiple methods and can diagnose diseases accurately. We have already input about 2500 GP recording papers into the computer by this system. We then calculated the plural indexes, and visualized the temporal changes in the perimetry.
In literature database searching, we show that it is necessary to use plural databases for a more improved search. We also compare the results of a single database search with that of multiple database search in the domain of Japanese life sciences. We searched the MEDLINE and EMBASE using the same search terms. There were some differences in the results, owing to differences in the journals and recording methods. We herein show some of the differences in the journals contained in both databases. Furthermore, we show the differences in the number of papers derived from the same journal. Next, as an example of a practical search, we selected some universities in Japan, searched both databases regarding papers published from these universities and then merged the results by hand. According to our results, only 63% of all papers were common to both databases.
Abnormal expansion of large granular lymphocytes (LGLs) was observed in peripheral blood and bone marrow in a 28-year-old man. He had general lymphadenopathy and splenomegaly. Surface phenotypical analysis of LGLs showed that these LGLs express CD 2, Ia and NKH-1 but not express CD 3, CD 4, CD 8 and Leu 7. Cytochemical analysis of these LGLs revealed positive acid phosphatase and beta-glucuronidase reaction but negative alpha-naphthyl acetate esterase reaction. These LGLs showed very weak NK activity against only MOLT-4 but showed no cytotoxic activity against K 562. An beta-receptor gene rearrangement of human T-cell receptor was not found by Southern blot analysis. Rapid and fetal clinical course with the results of theses analytical studies showed that this case is highly suggestive of acute leukemia of LGLs which is committed to NK cell lineage.
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We examined changes in the plasma levels of estradiol (E2), insulin-like growth factor-1 (IGF-1), ACTH, cortisol and catecholamines accompanying various kinds of hypothalamically elicited emotional behaviors in female cats. The emotional behaviors consisting of restlessness, threat and searching-biting (S-B) were elicited intermittently for 6 h by electrical stimulation of the anterior hypothalamus (AH), ventromedial hypothalamus (VMH) and lateral hypothalamus (LH), respectively, in awake and free-moving conditions. The blood was sampled three times immediately before, 1 h after and 6 h after the start of stimulation. The plasma levels of ACTH, cortisol and catecholamines significantly increased in both restlessness and threat behaviors, whereas in the S-B behavior, the ACTH level significantly increased, while the cortisol level showed a slight nonsignificant increase. No changes were observed in the plasma catecholamine levels in the S-B behavior. The plasma E2 level significantly increased in threat behavior after 1 and 6 h of stimulation compared to the prestimulation levels, and the level also increased in comparison to the control group after 1 h. In contrast, the restlessness and S-B behaviors had little or no effect on the E2 level. No significant changes were observed in the plasma levels of IGF-1 in all behavior groups. These findings suggest that various hypothalamically elicited emotional behaviors have differential effects on the plasma E2, but not on the IGF-1 levels. Therefore, E2 and IGF-1 are regulated independently of each other.
To understand the role of vascular endothelial growth factor (VEGF) in placental development, we examined immunohistochemically 56 placentae ranging from 6--41-weeks gestation using rabbit antibody to a synthetic multiple antigen peptide (MAP), composed of N-terminal amino acid residues 1--20 of human VEGF. In the present study, syncytiotrophoblast and invading extravillous trophoblasts ubiquitously expressed VEGF throughout gestation. However, the expression of VEGF in syncytiotrophoblasts was uneven in the first trimester and most intense at the sprouting sites. In addition, some stromal cells in the villi and decidual cells were also positive in the first trimester. A morphometrical analysis of the ratio of the VEGF-positive cell area to the capillary area in the terminal villi statistically revealed a critical point of change at 16 weeks' gestation. These results provide further evidence to support the hypothesis that VEGF, locally expressed by trophoblasts, stromal cells in villi and decidual cells, may play an important role in the physiological growth and function of the vascular system in the villous stroma and basal plate during placental development and maturation.
The relationships of hypothalamically elicited emotional behaviors to their accompanying pathophysiological effects were examined as a model of how complex "emotional behaviors" may be related to fundamental psychosomatic disorders. Twenty-two unanesthetized adult cats were studied. EKG alterations and histological changes in the heart, stomach, adrenal glands, and thymus were related to the specific stereotypical emotional behaviors that could be elicited by hypothalamic stimulation in tamed subjects. Restlessness, threat, and searching-biting behaviors were evoked by electrical stimulation of the anteromedial, ventromedial, and lateral hypothalamus, respectively. The occurrence of cardiac arrhythmias, ST and/or T (ST-T) changes in the EKG, histological damage to myocardium, gastric erosion, and adrenal hyperplasia were generally observed in the restlessness and threat groups but not in the searching-biting group. The pathophysiological effects were similar in the restlessness and threat groups with no specific EKG change or organ effect attributable to either site of stimulation. Hypothalamically elicited restlessness or threat behaviors in cats are each associated with cardiac, gastric, and adrenal pathophysiologies.
OBJECTIVE: In this study, we attempted to identify which background factors were the most important indicators regarding such psychological problems as depression and anxiety in female rheumatoid arthritis (RA) patients. METHODS: Among female RA patients aged 20 and older, who visited the outpatient clinic, and who met the Revised Criteria of the American Rheumatism Association for RA (ARA1987), 101 Class I and II patients were selected as subjects for the present study. Specially designed questionnaires and psychological tests were given to those subjects who had given their written consent for such testing, and a stepwise multiple logistic regression analysis was carried out on the 85 patients who returned all written forms. Those factors affecting psychological problems at a significance level of 5% or less were identified. RESULTS: It was shown that among sociodemographic factors, "a decrease in the frequency of going out socially after having RA" and "a higher education" worked as significantly associated variables for depression, while "a decrease in the number of friends after having RA" served as a significantly associated variable for trait anxiety. Significantly associated variables for state anxiety included "a decrease in the frequency of going out socially after having RA" and "a willingness to join an RA study group". CONCLUSION: The present study demonstrated that factors related to social interactions were significantly associated with depression and anxiety in Class I and II female RA outpatients.
INTRODUCTION: Several pretreatment factors have been reported to be useful in predicting patients with a high probability for a sustained response to IFN-alpha treatment, however, predictors of the efficacy of interferon-beta treatment in chronic hepatitis C have not been fully assessed. MATERIAL AND METHODS: To clarify this issue, a prospective study of 52 patients with chronic hepatitis C was conducted. Patients were treated with human natural interferon-beta by drip infusion at doses of 6 MU/day for 8 weeks. The following characteristics were compared between patients with sustained response (SR) and no response (NR): gender, age, source of HCV infection, mean pretreatment serum ALT levels, liver histology, pretreatment serum HCV-RNA levels and HCV genotype. RESULTS: Seventeen of 52 patients (32.7%) demonstrated SR. The proportion of patients with undetectable HCV-RNA levels determined by branched DNA assay (< 0.5 x 10(6) eq/ml) was higher in patients with SR than in those with NR (88.2% vs. 22.9%; p = 0.0001). Pretreatment HCV RNA levels determined by multicyclic reverse transcriptase polymerase chain reaction were lower in patients with SR than in those with NR (10(5.1 +/- 1.5) vs. 10(7.1 +/- 1.3) copies/ml; p = 0.0001). The rate of SR was higher in patients with genotype 2a or 2b than in genotype 1b (43.8% vs. 15.0%; p = 0.0382). Multivariate stepwise logistic regression analysis showed that a younger age and low pretreatment serum levels of HCV RNA were independent predictors of SR to treatment. This prospective study demonstrated that a younger age, low pretreatment viral load and HCV genotype 2a or 2b were factors influencing the SR to interferon-beta treatment, but a younger age and low pretreatment viral load were most important predictors of the efficacy of the treatment.
Low density lipoprotein receptor (LDLR) has been proposed as a candidate receptor for hepatitis C virus (HCV). According to previous reports, free beta-lipoproteins in a human serum may regulate the rate of hepatocyte infection by competing with the virus. Therefore, serum HCV levels should be regulated by the rise and fall of serum beta-lipoproteins since the infection rate of virions influences HCV replication in hepatocytes and release of virions by hepatocytes. In this study, we examined the relationship between serum beta-lipoproteins and HCV-antigen (Ag) levels in patients with chronic type C hepatitis. Patients were selected based on strict criteria to eliminate other factors that might influence serum HCV levels. Serum concentrations of beta-lipoproteins and HCV-Ag were measured two or more times within 3 months for each patient. The result showed that HCV-Ag levels were negatively correlated with the increased beta-lipoproteins. The results support the concept that LDLR is a HCV receptor and that beta-lipoproteins competitively inhibit the infection of hepatocytes with HCV through the LDLR.
BACKGROUND/AIMS: The elevated serum leptin level of patients with alcoholic cirrhosis has been reported, however, the precise mechanism is still unknown. Leptin expression and protein synthesis have also been detected in activated hepatic stellate cells in cell cultures, which play a major role in hepatic fibrosis. We evaluated the serum leptin levels of patients with nonalcoholic liver diseases including cirrhosis and chronic hepatitis. We also investigated the hepatic clearance of leptin by determining the serum leptin level in blood samples obtained from the portal and hepatic veins. METHODOLOGY: The serum leptin level of 44 patients with nonalcoholic chronic liver disease (male/female = 21/23, cirrhosis/chronic hepatitis = 30/14) and 40 control subjects (male/female = 20/20) was determined in blood samples obtained from the antecubital vein by enzyme-linked immunosorbent assay. We also assessed the relationship between the leptin level and various biochemical tests of liver function. Additionally, we determined the leptin levels in the portal and the hepatic venous blood (nonalcoholic cirrhosis = 10, nonhepatic disease = 4). RESULTS: There were positive correlations between the serum leptin level and body mass index among males and among females in the liver disease group and in the control group. However, the serum leptin level of the liver disease group and control group did not differ significantly. Among the 44 liver disease patients, only the serum cholesterol level was significantly correlated with the serum leptin level after adjusting for sex and body mass index by multiple regression analysis. Furthermore, the leptin level in hepatic venous blood was significantly lower than that in portal venous blood. However, the ratio of [leptin level in hepatic venous blood]/[leptin level in portal venous blood] in the cirrhosis group, and that in the nonhepatic disease group, did not significantly differ. CONCLUSIONS: The serum leptin level of patients with nonalcoholic liver diseases is not elevated. On the other hand, the serum leptin level of patients with alcoholic cirrhosis has been reported to be elevated. The difference in the serum leptin level of patients with nonalcoholic liver disease and that of patients with alcoholic cirrhosis may be due to a difference in factors such as the levels of cytokines or sex steroids, and/or nutrition. Furthermore, it is likely that leptin is cleared in part by the portosystemic circulation through the liver.
The purpose of this study was to determine the distribution and the expression of vascular endothelial growth factor (VEGF) in human placentas obtained from 22 cases of nonimmunologic hydrops fetalis (NIHF), ranging from 25 to 41 weeks of gestation, as compared with those in 75 normal placentas. The terminal villi were examined immunohistochemically using rabbit anti-human VEGF immunoglobulin G. The expression of VEGF in the terminal villi was assessed by the ratio of the VEGF-positive area to the capillary area. Among the 22 placentas, 18 placentas were hydropic and appeared to be histologically immature, and the other 4 placentas, whose fetuses eventually recovered before their deliveries, were nonhydropic. In both the HF and normal placentas, syncytiotrophoblasts expressed VEGF in the villi throughout gestation. VEGF was also expressed by stromal cells in the terminal villi of normal placentas in only the first trimester, whereas its expression continued until the term of pregnancy in 12 of 18 HF placentas. The ratio of the VEGF-positive area to the capillary area was significantly higher in the terminal villi of all hydropic HF placentas than in those of the normal placentas but was entirely the same in the four nonhydropic placentas as in the normal control placentas. These results suggest that the persistent expression of VEGF by stromal cells in the hydropic villi of NIHF, in addition to the VEGF expression by syncytioptrophoblasts, seems to be a reaction to poor villous vascular development and to participate in the regulatory mechanisms of vascular function including angiogenesis and permeability.