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Biomedical subjects

T Masumoto

Publications and source records attributed to T Masumoto.

At least 37 records · Page 2Linked to original sources

Relationship between the effect of interferon therapy and the change of hepatitis C virus non-structural 5B gene.

BACKGROUND: Hepatitis C virus (HCV)-RNA titre has been regarded as a factor affecting the response to interferon (IFN) therapy of patients with chronic hepatitis C (CHC). The focus of our study is the investigation of the nucleotide sequence of HCV-RNA NS5B, which may code RNA-dependent RNA polymerase and NS5A in the sera of 33 patients with CHC prior to IFN therapy. METHODS: Hepatitis C virus genotype and HCV-RNA titre were examined by polymerase chain reaction (PCR) and competitive reverse transcriptase-PCR. RESULTS: The sequence for HCV-RNA NS5B (nt 8331-8600 in 1b and 8410-8679 in 2a) was determined by direct sequencing. The changes of the predicted amino acids in the genotype-specific sites of HCV-J, HCV-BK, HC-J4/83, HCV-JT, HCV-N, HC-J6 and HCV-K2a were examined, and the mutation was defined when changes of amino acids in sites specific to different reported genotypes were revealed. The mutations were observed in 6/19 (32%) in genotype 1b and 9/14 (64%) in 2a. In the 1b group, complete response (CR) was achieved in 5/6 of the mutant and in 2/13 of the wild type groups (P < 0.05). No relationship was observed between IFN effectiveness and HCV-RNA titre in the 1b wild type group. In the 2a group, CR was achieved in 4/9 of the mutant and in 4/5 of the wild type groups. An inverse relationship between IFN responsiveness and HCV-RNA titre was apparent in 1b mutant, 2a wild and 2a mutant. CONCLUSIONS: These data suggest the possible relationship between changes in the HCV-NS5B gene and the effect of IFN therapy in CHC patients with genotype 1b.

Amino Acid Sequence↗

Early diagnosis of central nervous system aspergillosis with combination use of cerebral diffusion-weighted echo-planar magnetic resonance image and polymerase chain reaction of cerebrospinal fluid.

We treated a patient diagnosed as central nervous system (CNS) aspergillosis with the combined use of cerebral diffusion-weighted echo-planar magnetic resonance imaging (DWI) and polymerase chain reaction of the cerebrospinal fluid (CSF-PCR). DWI, a cutting-edge imaging modality to reveal the earliest changes of cerebral infarction, detected cerebral fungal embolization when the conventional computed tomographic scan and magnetic resonance imaging failed to reveal it. CSF-PCR demonstrated the presence of Aspergillus-specific DNA in the specimen, when the conventional examination and culture of CSF were nonspecific or negative. These diagnostic methods could be useful in the early diagnosis of CNS aspergillosis.

Aspergillosis↗

Three patients with autoimmune cholangiopathy treated with prednisolone.

We describe three patients with autoimmune cholangiopathy, i.e., anti-mitochondrial antibody-negative and anti-nuclear antibody-positive primary biliary cirrhosis, who were treated with prednisolone. Serum anti-mitochondrial antibody and anti-pyruvate dehydrogenase-E2 component antibody were determined by immunofluorescence of frozen sections and enzyme-linked immunosorbent assay, respectively. Immunoblotting using mitochondria prepared from rat liver was performed to analyze anti-mitochondrial antibody in detail. Serum from one patient reacted with a 48-kilodalton protein, but sera from the other two patients failed to react with the mitochondrial proteins. There was a marked improvement in liver function test results after prednisolone treatment. Before treatment, liver biopsy in all three patients showed histological features of primary biliary cirrhosis with hepatocellular necrosis. Repeat biopsy during treatment showed marked amelioration of hepatocellular damage in all three patients, although bile duct involvement persisted in two patients. These findings suggest that prednisolone is an effective treatment for hepatocellular damage in patients with autoimmune cholangiopathy, but has little impact on the bile duct involvement.

Anti-Inflammatory Agents↗

Increased nitric oxide (NO) production by antigen-presenting dendritic cells is responsible for low allogeneic mixed leucocyte reaction (MLR) in primary biliary cirrhosis (PBC).

The levels of blastogenesis in allogeneic MLR containing T cells from one normal volunteer and irradiated dendritic cells from 29 patients with PBC, 17 patients with chronic hepatitis type C (CH-C) and 22 allogeneic normal controls were compared to see if there is any role of antigen-presenting cells (APC) in the pathogenesis of PBC. The stimulatory capacity of dendritic cells from PBC was significantly lower compared with that of dendritic cells from CH-C (P < 0.05) and normal controls (P < 0.05), which could not be attributable either to the levels of expression of surface molecules, such as HLA-DR and CD86 on dendritic cells, or to the levels of cytokines, such as IL-10 and IL-12. Significantly higher levels of NO were seen in the allogeneic MLR supernatants containing dendritic cells from PBC compared with the supernatants from cultures containing dendritic cells from CH-C (P < 0.001) or normal controls (P < 0.001). Moreover, dendritic cells from PBC produced 10 times more NO compared with dendritic cells from CH-C and normal controls (21.9 +/- 2.8 microM versus 1.6 +/- 0.3 microM and 1.6 +/- 0.3 microM, respectively; P < 0.001). The addition of N(G)-monomethyl-L-arginine monoacetate (L-NMMA), a known inhibitor of NO in allogeneic MLR containing dendritic cells from PBC, resulted in a significant decrease of NO and increase of blastogenesis. The selective impairment of dendritic cell function, increased production of NO by dendritic cells and restoration of blastogenesis using NO inhibitor in PBC have suggested a role for NO and dysfunction of dendritic cells in the pathogenesis of PBC. This inspires optimism that modulating the function of dendritic cells and controlling NO production, an improved therapeutic approach, might be planned for PBC.

Adult↗

Induction of CINC (interleukin-8) production in rat liver by non-parenchymal cells.

The production of interleukin-8 (CINC: cytokine-induced neutrophil chemo-attractant) from different cell populations in the rat liver was studied and cells related to the initiation of CINC production in lipopolysaccharide (LPS)-injected endotoxaemic rats were characterized. Sinusoidal endothelial cells (16.4 +/- 10.6 ng/mL) produced significantly higher amounts of CINC in 24 h primary cultures compared with hepatocytes (0.9 +/- 0.9 ng/mL; P < 0.05) and Kupffer cells (6.5 +/- 5.1 ng/mL; P < 0.05). Lipopolysaccharide, tumour necrosis factor-alpha (TNF-alpha), and interleukin-1 alpha (IL-1 alpha) stimulated different liver cell populations to produce CINC; LPS mainly stimulated Kupffer cells. TNF-alpha stimulated hepatocytes and IL-1 alpha stimulated all three types of cells. Intraperitoneal injection of LPS (4 mg/kg) caused CINC accumulation in non-parenchymal cells of the rat liver within 1 h of injection, as shown by immunohistochemical staining. In contrast, CINC-positive hepatocytes were not seen until 3 h after injection of LPS. Ethanol was not a direct inducer of CINC production by rat hepatocytes in vitro. These findings strongly suggest that non-parenchymal liver cells, including sinusoidal endothelial cells, are the main source of CINC. Our data also suggest that during endotoxaemia, CINC production is initiated by non-parenchymal cells and this is followed by production from hepatocytes.

Animals↗

Placebo-controlled trial of vaccination with hepatitis B virus surface antigen in hepatitis B virus transgenic mice.

BACKGROUND/AIMS: Treatment of hepatitis B virus carriers by vaccine containing hepatitis B surface antigen with Pre-S protein and HBsAg/ anti-HBs complex has been reported and these studies have constituted a new and promising concept for the treatment of HBV-carriers. The present communication, a placebo-controlled trial of vaccination in HBV-transgenic mice, was designed to examine the impact of vaccination using a high dose of HBsAg for a duration of 12 months to achieve further insights about the dose, duration and effectiveness of vaccine therapy. Another aim of this study was to analyse the mechanism underlying the antiviral and immunomodulatory potentiality of vaccine therapy in HBV-transgenic mice. METHODS: HBV-transgenic mice positive for HBV DNA, hepatitis B surface antigen and hepatitis B e antigen in sera received either HBV-vaccine containing HBsAg in complete Freund's adjuvant (CFA), intraperitoneally, once a month for 12 consecutive months (vaccine recipients), or only CFA, intraperitoneally once in a month for 12 consecutive months (placebo recipients). Thirty-two vaccine-recipient and 16 placebo-recipient HBV-transgenic mice were injected, checked and followed on a monthly basis for the entire duration of 12 months. RESULTS: Of the 32 transgenic mice from the vaccine-recipient group, 25 became completely negative for HBsAg and 30 for HBeAg. Five mice developed anti-HBs in sera after the observation period of 12 months. Semiquantitative estimation of HBV DNA by polymerase chain reaction showed that vaccination resulted in a decrease of HBV DNA in sera. Placebo-recipient transgenic mice did not show any significant change in the titres of HBV markers after receiving 12 monthly injections of CFA. Interleukin-2 could be detected in sera from vaccine-recipient transgenic mice, but not in placebo-recipient transgenic mice. CONCLUSIONS: Vaccination with a high dose of HBsAg in adjuvant over a long period had a significant antiviral as well as immunomodulatory potential in HBV-transgenic mice. This inspires optimism that vaccine alone or in combination with antiviral agents can be used successfully for the treatment of human HBV-carriers.

Adjuvants, Immunologic↗

[A case of hemophagocytic syndrome with severe liver injury manifestating adult Still's disease].

In April 1988, a 23 year-old woman developed high fever, arthralgia, eruptions and splenomegaly. She was treated with non Steroid anti-inflammatory drugs, and the symptoms disappeared. In June 1991, she was diagnosed as adult Still's disease and treated with prednisolone. In July 1994, she was treated with pulse therapy methylprednisolone due to high fever, eruptions, arthralgia and the high levels of ferritin. However, due to the marked increase of serum transaminase and bilirubin levels, she was referred to University hospital. She developed hepatic failure after admission Bone-marrow puncture revealed hemophagocytosis. She died ten days after admission. She was diagnosed as hemophagocytic syndrome combined with acute hepatic failure.

Adult↗

Effects of work-related stress reduction on depressive symptoms among Japanese blue-collar workers.

OBJECTIVES: The effects of a stress reduction program on Japanese blue-collar workers were investigated using a controlled trial design. METHODS: Two blue-collar worksites that showed higher depression scores (Zung self-rating depression score) were selected for the intervention group, after a survey of a large electric company in 1985. Three blue-collar worksites were selected as a reference group whose workers were matched with the workers of the interventive worksites by mean age, worksite size and mean depression scores. A 1-year stress reduction program was conducted in the intervention group from 1986 to 1987 by worksite supervisors. Effects of the stress reduction program were assessed by comparing the initial depression scores, length of sick leave, and systolic and diastolic blood pressures with those after the follow-up. RESULTS: The depression scores decreased during the follow-up in the intervention group, while the scores were almost the same in the reference group. An analysis of covariance with repeated measurements indicated a statistically significant intervention (group x time interaction) effect after control for gender and age (P = 0.035). Sick leave in the past year decreased in 1988 only in the intervention group; generalized logit analysis with repeated measurements indicated a statistically significant intervention effect after control for gender and age (P = 0.034). No statistically significant intervention effects were observed on systolic and diastolic blood pressures or selected work stressors. CONCLUSIONS: A stress reduction program directed towards worksite supervisors can be used to reduce depressive symptoms and sick leave among Japanese blue-collar workers.

Absenteeism↗

[Association of participation in health checkups with medical service utilization in a rural town].

Association of participation in health checkups in 1983-94 with medical service utilization in 1989-94 was studied. The study subjects consisted of 1,198 males and 1,247 females aged 30 years or over, who were members of the National Health Insurance in a rural town in Kyoto prefecture. One hundred and four males and 95 females died during 1989-94. Cumulative death rates were higher among both males and females with less participation in checkups than among those with higher participation, however, there was no difference seen for medical service utilization. Regarding subjects alive in 1994, both males and females who participated frequently in checking in 1983-88 also visited medical facilities more frequently and had higher medical costs in 1989-94 than those with less frequent participation. Similar analysis for checkups in 1989-94, showed that only females had that tendency. Among participants in checkups in 1989-94, there were smaller numbers of hypertensives, current smokers, and current drinkers than among non-participants, therefore, the participants are thought to have decreased their risk for chronic diseases. In conclusion, frequent participation in health checkups are thought to increase medical utilization even with a lower prevalence or risk of chronic diseases.

Adult↗

Response to interferon in chronic hepatitis C due to mixed genotype infection.

We examined the response to interferon (IFN) in patients with chronic hepatitis C (CHC) due to two different genotypes of hepatitis C virus (HCV) infection. Among 64 CHC patients studied, one (2%) had HCV-RNA genotype I, 36 (56%) had genotype II, 19 (30%) had genotype III, 2 (3%) had genotype IV and 6 (9%) had both genotypes II and III. There was no significant difference in age, sex, history of blood transfusion and liver histology among patients with genotypes II, III and II + III. The HCV-RNA titre of genotype II patients was significantly higher than that of genotype III patients (P < 0.05). However, there was no significant difference in the HCV-RNA titre between genotype II + III and the other groups. The complete response rate achieved with IFN therapy was significantly higher in genotype III patients (74%) than in genotype II patients (17%; P < 0.01). Of the six patients with genotype II + III, a complete response to IFN was only achieved by two patients (33%), both of whom had a low HCV-RNA titre ( < or = 10(4.5) copies/mL) and HCV serotype 2. The remaining four patients had HCV serotype 1 and three of the patients had a high HCV-RNA titre ( > or = 10(5) copies/mL). The HCV genotype III was lost in two patients after IFN therapy. These data suggest that HCV-RNA titre and HCV serotype are important factors for predicting the efficacy of IFN therapy in patients with mixed genotype infection and show direct evidence of higher susceptibility towards CHC of patients with genotype III than genotype II.

Adolescent↗

Effects of mood states, smoking and urinary catecholamine excretion on hemoglobin A1c in male Japanese workers.

To know the association between psychological strain and glycosylated hemoglobin (HbA1c) and to examine roles of smoking and catecholamine excretion as a possible mediator in the association, we measured mood states (Profile of Mood States, POMS), urinary catecholamines (adrenalin, noradrenaline and dopamine) from urine sample in early morning, HbA1c and fasting plasma glucose (FPG) of 63 male employees on a rest day. After excluding 12 subjects who had diabetes or impaired glucose tolerance or had missing response to the questionnaire, data from 51 subjects were analyzed. The POMS anger-hostility score significantly and positively correlated with HbA1c (p < 0.05), while other scale scores did not (p > 0.05). Number of cigarettes smoked per day significantly and positively correlated with HbA1c (p < 0.05). Urinary excretion rate of any catecholamine did not significantly correlate with HbA1c (p > 0.05). Multiple linear regression analysis indicated that the anger-hostility score significantly correlated with HbA1c after controlling for number of cigarettes per day (p < 0.05). It is suggested that, among mood states, anger-hostility is associated with increased HbA1c. However, our study failed to find a mediating role of urinary catecholamines or smoking on the association between the mood and HbA1c.

Adult↗

[Characteristics of smoking, drinking, dietary habits, and physical exercise in health behavioral models].

Various kinds of preventive health behaviors are promoted by health education. The extent of behavioral modification achieved, however, obviously differs from individual to individual according to habits, one of the reasons being the characteristics of various health habits are perceived differently. This cross-sectional study examined the association of indices representing health behavior models with smoking, drinking, dietary habits, and physical exercise. The indices and their meaning were as follows; health locus of control (HLC) and saliency of health are thought to cause the most active behavioral change, health norm relatively passive change, and vulnerability to illness the most passive change. The indices and lifestyle (health related practices) were surveyed by a self-administered questionnaire in a rural town in March 1994. The study sample consisted of 1,010 males and 1,055 females aged 20 years or older who responded to all questions related to the indices. Results are as follows: 1) Smoking and alcohol drinking were associated with vulnerability to illness, suggesting that people who quit smoking or alcohol drinking do so because of perception of their association with illness. Alcohol drinking seemed to have a higher magnitude of being associated with becoming ill or with fear of illness than smoking. 2) Consuming green-yellow vegetables and fresh fish, and physical fitness were associated with internal HLC, saliency of health, and health norm. These habits appeared to be easy to modify by active personal behavior choice. 3) Consuming milk, yogurt, boiled beans, tofu, oranges, and other fruits were associated with saliency of health. These habits seemed to relate to personal sense of being "healthy". 4) It seemed that younger people more likely changed their behavior by active self-management, while, older people changed due to their sense of value or norm. While it is important for health education to promote "self-management of health" by active behavioral change, certain habits are more resistant to change despite educational efforts possibly because of their characteristics in health behavioral models. For cases such as these, techniques promoting passive behavioral change should be considered.

Adult↗

Soluble intercellular adhesion molecule-1 in serum in chronic hepatitis B and C.

Intercellular adhesion molecule-1 (ICAM-1) is expressed on the hepatocyte membrane in patients with chronic hepatitis B and C. We assayed levels of the soluble form of this molecule (sICAM-1) in serum by an enzyme-linked immunosorbent assay method; we then analyzed the results in relation to hepatitis activity. Fifty-one patients with chronic hepatitis (22 with type B and 29 with type C) and 10 normal controls were examined. The serum levels of sICAM-1 in hepatitis B and C were significantly higher (P < 0.01) than in normal controls. The serum level of sICAM-1 was correlated with serum glutamic-pyruvic transaminase level (P < 0.01), and the level of sICAM-1 in patients in whom exacerbation was seen was significantly higher (P < 0.05) than that in patients in a remission. There was no relationship between the serum level of sICAM-1 and the degree of ICAM-1 expression on the hepatocyte membrane. These results suggest that the serum level of sICAM-1 reflects the degree of activity of chronic hepatitis B and C.

Adult↗

Pantothenic acid deficiency detection in rainbow trout (Oncorhynchus mykiss).

Rainbow trout averaging 150 g were fed semipurified diets supplemented or not supplemented with pantothenic acid. After 16 wk of feeding, fish fed the deficient diet had reduced feed intake. At 28 wk, supplemented fish weighed > 600 g, whereas deficient fish weighed 425 g. Deficient fish became anorectic and listless at 25 wk and began to die at 28 wk. Histological examination of gill tissue revealed fused gill lamellae in the deficient fish, confirming pantothenic acid deficiency. At 4-wk intervals, samples of fish were taken from each group for determination of free and total concentrations of pantothenic acid in gills, liver, heart and erythrocytes by RIA. Concentrations of bound pantothenic acid, calculated by difference, did not differ between dietary treatment groups except in gills. Free pantothenic acid concentration in gills and heart were significantly lower in fish fed the deficient diet than in those fed the complete diet after 4 wk of feeding and remained so thereafter. Free pantothenic acid concentrations in the livers of deficient fish were significantly different from those in sufficient fish after 16 wk of feeding. Erythrocyte free pantothenic acid concentrations of deficient fish were significantly different from initial values at 8 wk and beyond. Using free pantothenic acid concentrations in erythrocytes allows detection of pantothenic acid deficiency in fish that are too valuable to permit destructive sampling techniques, such as broodstock and threatened or endangered species.

Animals↗