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Biomedical subjects

S Murakami

Publications and source records attributed to S Murakami.

At least 181 records · Page 10Linked to original sources

Identification and cloning of rat galectin-2: expression is predominantly in epithelial cells of the stomach.

A complementary DNA clone preferentially expressed in the gastrointestinal tract was obtained from a rat stomach library. The protein coded by the clone had a single carbohydrate recognition domain having conserved motifs for beta-galactoside binding and showed 67% amino acid identity with human galectin-2. The recombinant protein synthesized in Escherichia coli could bind to an asialofetuin column and was eluted with beta-galactopyranoside. From these observations, we named the protein rat galectin-2 coded by the cDNA. The rat galectin-2 was predominantly expressed in the epithelial cells of stomach. Thus this protein may form a mucin layer cross-linking with the beta-galactoside moiety of glycoproteins.

Amino Acid Sequence↗

Human hepatitis B virus X protein augments the DNA binding of nuclear factor for IL-6 through its basic-leucine zipper domain.

The X gene product of human hepatitis B virus, HBx, transactivates the expression of viral and cellular genes through a wide variety of cis elements, including the nuclear factor for IL-6 (NF-IL6) binding sites, although HBx does not appear to bind DNA directly. We previously reported that HBx transactivated the interleukin 8 promoter through NF-kappaB binding site and C/EBP-like binding site (NF-IL6 binding site). In this study, the interactions were examined between NF-IL6 and HBx using recombinant proteins. In a DNA-protein binding assay, the formation of a specific complex between NF-IL6 and a DNA probe harboring an NF-IL6 binding site was increased by the addition of either the full or the C-terminal 104 amino acids of HBx. A direct protein-protein binding assay (far-Western blot) revealed the direct interaction between the C-terminal 104 amino acids of HBx and the basic region-leucine zipper domain of NF-IL6. These results indicate that HBx alters the DNA-binding affinity of NF-IL6 through the direct interaction between the C-terminal domain of HBx and the basic region-leucine zipper domain of NF-IL6.

Binding Sites↗

Effects of basic fibroblast growth factor (bFGF)-neutralizing antibody and platelet factor 4 on facial nerve regeneration.

Exogenous basic fibroblast growth factor (bFGF) has been shown to prevent death of injured cholinergic neurons and stimulate neurite outgrowth from the proximal stump of the transected sciatic nerve. The present study was designed to examine the role of endogenous bFGF, rather than exogenous bFGF in the regenerative process of the transected facial nerve of guinea pig, by using the so-called silicone tubulization model which enabled us to bridge the transected facial nerve with a silicone tube and to inject into the tube bFGF-neutralizing antibody, normal IgG, saline, or platelet factor 4 (an antagonist for bFGF receptor). Under light microscopy, treatment with bFGF-neutralizing antibody caused significant decreases in vascular number, vascular area, and regenerating axons in the middle point of regeneration chambers at the third week after facial nerve transection, even though electron microscopy revealed that the bFGF-neutralizing antibody increased the number of thin axons with caliber smaller than 1 micrometer. Treatment with platelet factor 4 exhibited similar but more conspicuous effects on facial nerve regeneration. These findings suggest that endogenous bFGF not only facilitates angiogenesis within the transected facial nerve but also acts as a neurotrophic agent during facial nerve regeneration; it appears that endogenous bFGF contributes to the enlargement of axon caliber and increases the number of relatively large caliber axons.

Animals↗

Sequential MRI, SPECT and PET in respiratory syncytial virus encephalitis.

We report on a 3-year-old girl with respiratory syncytial virus (RSV) encephalitis manifested by disturbance of consciousness, conjugate eye deviation, anuria, truncal ataxia and intention tremor. T2-weighted magnetic resonance imaging (MRI) showed hyperintense areas in the cerebellar cortex. No lesion was detected in the cerebral cortex, pons or spinal cord. The hyperintense areas in the cerebellar cortex diminished with recovery from the clinical manifestations and had resolved 2 months after onset. The MRI lesions in the cerebellum were considered to be due to oedema. SPECT and positron emission tomography (PET), performed 3 months after onset, disclosed areas of hypoperfusion and hypometabolism at the same sites. One year after onset, MRI showed mild atrophy of the cerebellum. Hypoperfusion on SPECT and hypometabolism on PET remained. Neuroimaging showed that ataxia and tremor in this case were the result of cerebellitis. The patient has no neurological deficit except for mild truncal ataxia. This patient is a rare example of RSV encephalitis.

Brain↗

Estimation of glycogen levels in human colorectal cancer tissue: relationship with cell cycle and tumor outgrowth.

In this study, we quantitatively measured glycogen levels in tissue samples obtained from tumors, regions adjacent to tumor, and regions of normal colorectum to determine whether the levels were related to cell cycle and cancer growth. Glycogen levels were analyzed in relation to histopathological factors, (tumor size and stage of disease) and cell cycle progression. The glycogen level was found to be highest in the cancer tissue, lower in normal tissue, and lowest in the adjacent tissue. The difference in glycogen level between the cancer tissue and the other two regions was significant (P < 0.05). There was a negative correlation between glycogen level and tumor size, but it was not significant. The level of glycogen in cancer tissues decreased as the stage of the disease progressed, but a significant difference was not found between stages. There was a negative correlation between the glycogen level and the proliferation index. There was a positive correlation between the glycogen level and the proportion of cancer cells in G1 phase, while there was a negative correlation with S and G2M phases. Glycogen levels were highest in cancers with a high proportion of cells in G1, and decreased with progression to S phase. It may be that glycogen is utilized in the progression to S phase, and the cancer tissues are supplied with glycogen from the tumors themselves as well as their adjacent tissues. Cancer growth may be inhibited by artificial control of the glycogen level in the G1 phase of cancer cells.

Adenocarcinoma↗

Tumor angiogenesis and recurrence in stage I non-small cell lung cancer.

BACKGROUND: Tumor angiogenesis appears to relate to recurrence after an operation as a route for distant metastasis. We assessed the association of vascular endothelial growth factor (VEGF) expression and intratumoral microvessel density (MD) with recurrence in primary lung cancer. METHODS: Samples were randomly obtained from 104 stage I lung cancer patients who underwent curative operations (43 recurrent, 61 nonrecurrent patients). Microvessels were highlighted by staining endothelial cells for factor VIII and VEGF antigen was detected using a polyclonal antibody. RESULTS: VEGF antigen was detected in large amounts in both recurrent (100%) and nonrecurrent tumors (73.8%). The percentages of patients with the strongest VEGF stain (more than 50% of staining area in tumor cells) were 46.5% in tumors with recurrence and 11.5% in tumors without recurrence. The mean MD in recurrent and nonrecurrent tumors were 18.2+/-10.5 and 8.5+/-5.0, respectively, resulting in a significantly greater value in tumors with recurrence (p<0.0001). Although there were no significant differences in mean MD according to pathological types, in adenocarcinoma and adenosquamous carcinoma, the mean value in the recurrent group was significantly greater than that in the nonrecurrent one. CONCLUSIONS: An evaluation of VEGF expression and MD in tumors may contribute to the estimation of the risk of recurrence of non-small cell lung cancer in early stages.

Adult↗

Up-regulation of low density lipoprotein receptor by a novel isobenzofranone derivative, MD-700.

Stimulatory effects of a novel isobenzofranone, MD-700, on low density lipoprotein (LDL) receptor activity were investigated in vitro and in vivo. MD-700 at 0.03 microg/ml elevated the expression of LDL receptor in HepG2 cells within 4 h. Corresponding to this, uptake of fluorescent labeled-LDL (3,3'-dioctadecylindocarbocyanine-LDL) by the cells increased linearly in time- and dose-dependent manner by MD-700 for up to 12 h. In the experiment using HepG2 cells transiently transfected with promoter-luciferase gene constructs, MD-700 increased luciferase activity in a dose-dependent manner from 0.03 to 0.1 microg/ml. In contrast, luciferase activity was not stimulated by MD-700 in construct with a deleted sterol regulatory element (SRE)-1, suggesting importance of SRE-1 in stimulation of the LDL receptor gene promoter by MD-700. Binding experiments on liver membranes from MD-700-treated hamsters showed about a 60% increase in 125I-labeled LDL binding. A Scatchard plot revealed that MD-700 increased the maximal binding without affecting binding affinity. In contrast to findings with an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, pravastatin, MD-700 had no effect on the sterol synthesis in hamster liver homogenates. These results suggest that MD-700 stimulates the expression of LDL receptor, presumably in a manner independent of change in sterol metabolism, and thereby promotes LDL clearance. Hypocholesterolemic actions of MD-700 in hamsters were then examined. MD-700 lowered serum cholesterol levels in hamsters fed normal chow or a high-fat diet. Fractionation of serum lipoproteins demonstrated that MD-700 selectively decreased LDL and very low density lipoprotein cholesterol. Dose-dependent decrease in serum cholesterol was also seen in hypercholesterolemic rats. Thus, the hypocholesterolemic action of MD-700 may be attributed to up-regulation of the LDL receptor, based on stimulation of the transcription of the LDL receptor gene. Although pravastatin stimulates LDL uptake and lowers serum cholesterol in a manner similar to that seen with MD-700, the mechanism responsible for hypocholesterolemic action appears to differ.

Animals↗

Improvement in cholesterol metabolism in mice given chronic treatment of taurine and fed a high-fat diet.

The effects of chronic treatment of taurine on hypercholesterolemia and atherosclerosis were examined in C57BL/6J mice fed a high-fat diet containing 15% fat and 1.25% cholesterol. Taurine was dissolved in drinking water at 1% (w/v) and was given to mice ad libitum during 6 months-feeding of a high-fat diet. Hypercholesterolemia occurred and lipid accumulation on the aortic valve was evident. Taurine treatment lowered serum LDL + VLDL cholesterol by 44% in mice fed a high-fat diet, while it elevated serum HDL cholesterol by 25%. As a result, the atherogenic index, the ratio of HDL to LDL + VLDL was markedly improved. Cholesterol content in the liver also decreased by 19% with taurine. Similar tendencies were seen in mice fed regular chow, but the changes were not significant. The area of aortic lipid accumulation, which served as an index of atherosclerosis, was reduced by 20% with taurine. In the liver, taurine doubled the activity of cholesterol 7alpha-hydroxylase. These observations, together with prior findings, suggest that the cholesterol-lowering action of taurine may relate to the increased conversion of cholesterol to bile acids via stimulation of cholesterol 7a-hydroxylase activity. Thus, chronic treatment of high-fat mice with taurine improves the abnormal profile of the serum lipoproteins, and thereby retards the progression of atherosclerosis.

Animals↗

Incidence of hepatocellular carcinoma in transgenic mice expressing the hepatitis B virus X-protein.

BACKGROUND/AIMS: Chronic infection with hepatitis B virus is a high-risk factor for hepatocellular carcinoma in humans. The HBV X-protein, a multi-functional viral regulator, has been suspected to play a positive role in hepatocarcinogenesis, as demonstrated by the high incidence of hepatocellular carcinoma in HBx-expressing transgenic mice, although it is still controversial. The aim of this study was to generate transgenic mice expressing the HBV X-gene under authentic promoter control and to test whether the gene products can cause hepatic tumors. METHODS: Three transgenic mouse lines were generated by microinjecting the X-gene construct into hybrid (C57BL/6 x DBA) eggs. Gene expression was tested by protein and mRNA analyses. During an observation period of 18 months, mice were sacrificed and organs subjected to histologic examinations. RESULTS: Grossly defined hepatocellular carcinomas reproducibly were observed in mice expressing the X-protein, which were investigated through six generations from the age of 11 to 18 months. Among 14 transgenic mice investigated from the age of 11 to 18 months, 12 were found to have hepatocellular carcinoma, grossly or microscopically. The lesion of the hepatocellular carcinoma disclosed a significant increase in the proliferating cell nuclear antigen in the nuclei. CONCLUSION: The incidence of hepatocellular carcinoma (86%) in our HBV X transgenic mice may be highly significant, since, except for one case, HBV X-gene transgenic mice produced in other laboratories did not develop liver tumor or any other pathologic phenomena.

Animals↗

Lack of correlation between timing of surgery in relation to the menstrual cycle and prognosis of premenopausal patients with early breast cancer.

In a retrospective cohort of a randomised study of adjuvant endocrine, chemotherapy and chemoendocrine therapy, we investigated the correlation between timing of mastectomy and relapse-free survival (RFS) and overall survival (OS) in 721 premenopausal patients with early breast cancer. The median follow-up was 10.1 years (range: 6.1-19.1 years). We grouped the patients by three kinds of classification according to Badwe, Senie, and Hrushesky. The logrank test after the Kaplan-Meier curves showed that there were no significant differences between the categorised menstrual phase in cycle and RFS or OS, except for RFS using Badwe's classification, where the patients whose timing of operation was in the follicular phase had a better RFS compared with those in the luteal phase. These were confirmed by the Cox proportional hazard model. These results suggest that a positive result might be a chance finding, dependent upon the cut-off levels in the menstrual cycle.

Adult↗

Experimental actinomycosis caused by Actinomyces-like bacteria in mice and a sow.

The present experiment was performed to test the pathogenicity of Actinomyces-like bacteria in experimental animals and swine. Two rough (R) strains of Actinomyces-like bacteria isolated from a site of arthritis and from the tonsil in pigs were used as inocula. To investigate their susceptibility to Actinomyces-like bacteria, BALB/c, SS and ddY mice and guinea-pigs were inoculated intraperitoneally with the strains of Actinomyces-like bacteria. The ddY mice were used for the long-term observation of Actinomyces-like bacteria lesions and the mammary tissue of a sow was inoculated with Actinomyces-like bacteria isolated from swine tonsil. Macroscopic observation revealed many abscesses on the surfaces of the abdominal and/or thoracic organs in the mice, but not on those of the guinea-pigs. The sow developed firm nodules at the inoculation site in the mammary glands. Histopathologically, the lesions in the mice were characterized as actinomycotic abscesses in the early stage and as pus-forming granuloma (PFG) in the advanced stage; the lesions were accompanied by crystalloid particles. Actinomyces-like bacteria induced granulomatous mastitis in the sow, and the lesion was characterized as PFG. The characteristic actinomycotic lesions in swine mammary glands were reproduced by experimental infection.

Actinomyces↗

Evaluation of functional bladder capacity in Japanese children.

BACKGROUND: Functional bladder capacity is a very important factor in the diagnosis of children with voiding disorders. Because Japanese children are thought to have somewhat smaller functional bladder capacity compared with Western children, the convenient formula (so-called Koff formula) bladder capacity (in ounces) = age (in years)+ 2 is not suitable for use in Japanese children. METHODS: We measured the bladder capacities of 131 Japanese children aged 5-15 years without clinical voiding pattern abnormalities to develop a practical guideline for the prediction of normal bladder capacity for age. RESULTS: An approximate formula relates age and bladder capacity as: bladder capacity (mL) = 25 x (age (years) + 2). CONCLUSIONS: The formula presented is thought to be a useful guide for the diagnosis of small, normal or large bladder capacity and offers information on voiding disorders in Japanese children.

Adolescent↗

External beam radiation monotherapy for prostate cancer.

BACKGROUND: To clarify the implications and limitations of external beam radiation monotherapy for localized prostate cancer, the long-term outcomes and prognostic factors were investigated. METHODS: Between 1976 and 1994, 91 patients with untreated prostate cancer were treated with external beam radiation therapy alone. Thirty-two were classified as T1b, eight were T2a, four were T2b and 47 were T3. Pelvic lymphadenectomy was carried out in 69 cases; 57 were staged as pN0, eight were pN1, four were pN2 and 22 were pNX. Linac X-rays were used in 55 cases, fast neutron in 15 and a combination of the two in 21. No other therapy was given until relapse and when relapse was evident endocrine therapy was started. RESULTS: The observation period ranged from 3 to 206 months with a median of 78 months. Local control rate and disease-free, cause-specific and overall survivals at 10 years were 74.0, 49.6, 74.2 and 39.2%, respectively. By univariate analysis, T category, pN category and histologic grade were significant prognostic indicators for disease-free survival. Multivariate analysis revealed that T category was an independent prognostic factor. In T2b and T3 diseases, pN0/1 patients demonstrated significantly better disease-free survival than pNX. CONCLUSIONS: A favorable long-term outcome was achieved by external beam radiation monotherapy in patients with minimally extended prostate cancer (T1b and T2a). For locally advanced disease (T2b and T3), staging pelvic lymphadenectomy would be useful for the selection of patients.

Adenocarcinoma↗

Immunohistochemical finding of alpha-1-antichymotrypsin in tissues of benign prostatic hyperplasia and prostate cancer.

BACKGROUND: Ratio of free to total (F/T) prostate-specific antigen (PSA) is higher in the blood of patients with benign prostatic hyperplasia than those with prostate cancer. To clarify the difference between ratios in these two, alpha-1-antichymotrypsin, the major component of the bound PSA in the blood, was immunohistochemically examined. METHODS: Tissues were obtained surgically via a retropubic approach from patients with benign prostatic hyperplasia (nine cases) and prostate cancer (27 cases). These samples were processed in paraffin blocks, cut into 5 mm sections and stained with antibodies against alpha-1-antichymotrypsin and PSA. RESULTS: The percentage of alpha-1-antichymotrypsin-stained cells in prostate cancer was higher than that in benign prostatic hyperplasia (P<0.05). Almost all of glandular and cancer cells were stained with PSA antibody. The percentage of alpha-1-antichymotrypsin-stained cells in prostate cancer did not correlate to histologic grade, although alpha-1-antichymotrypsin-stained cells were more widely scattered in high grade tissues. No correlation was found between alpha-1-antichymotrypsin-stained cells and ratio of F/T in the blood of cancer patients. In about 20% of cancer tissues, histiocytes with positive alpha-1-antichymotrypsin staining were found in stroma but not in that of benign prostatic hyperplasia. CONCLUSIONS: Prostate cancer tissues are shown to have a richer environment of alpha-1-antichymotrypsin than those of benign prostatic hyperplasia. Some cancer tissues contained alpha-1-antichymotrypsin-stained histiocytes. These local events may correlate to a high amount of the bound form among total PSA in the blood of prostate cancer patients.

Aged↗

The utility of endoscopic screening for patients with esophageal or head and neck cancer.

In a series of 378 patients with esophageal carcinoma, 43 patients with head and neck carcinoma were divided into two groups: 30 patients without symptoms whose esophageal or head and neck second primary carcinomas were incidentally detected by an endoscopic examination for the second carcinoma (group 1) and 13 patients with symptoms whose esophageal or head and neck second primary carcinomas were detected by routine examinations (group 2). Regarding the second primary carcinomas, the incidence of stage 0-I and curability were significantly higher in group 1 than in group 2 (p < 0.001 and p < 0.05 respectively). The 5-year overall survival rates of patients with the second primary carcinomas were significantly higher in group 1 (60.4%) than in group 2 (0%) (p < 0.01). We suggest that a routine endoscopic screening of the upper aerodigestive tract in patients with esophageal carcinoma or head and neck carcinoma contributes to the improvement of the prognosis and the patient's quality of life.

Adult↗

Mortality in relation to urinary and faecal incontinence in elderly people living at home.

OBJECTIVE: To examine the relationship between incontinence and mortality in elderly people living at home. DESIGN: Of the randomly selected people aged 65 years and older living in Settsu city, Osaka in October 1992, 1405 were contacted and constituted the study cohort. Follow-up for 42 months was completed for 1318 (93.8%; 1129 alive, 189 dead). MEASURES: Data on general health status, history of health management, psychosocial conditions and urinary and faecal incontinence were collected by interview during home visits at the time of enrolment. RESULTS: From the Kaplan-Meier analysis, the estimated survival rates decreased with a decline in continence in both the 65-74 and 75 years and older age groups. From the Cox proportional hazards model, unadjusted hazard ratios of minor, moderate and severe incontinence for mortality, compared with continence, were 2.27, 2.96 and 5.94, respectively. Multivariate analysis yielded adjusted hazard ratios of minor, moderate and severe incontinence of 0.99, 1.17 and 1.91, respectively, leaving severe incontinence as the significant factor, when other indicators are controlled. CONCLUSIONS: Incontinence is related to mortality and severe incontinence represents an increased risk factor for mortality in elderly people living at home.

Activities of Daily Living↗

B-cell lymphoma associated with haemophagocytic syndrome: a clinical, immunological and cytogenetic study.

B-cell lymphoma associated with haemophagocytic syndrome (HPS) is extremely rare in Western countries but has recently been increasingly reported in Asian countries. We describe seven patients with B-cell lymphoma associated with HPS, six males and one female, age range 41-82 years (median 63 years). All patients had fever and splenomegaly, and six of the seven patients had hepatomegaly with no associated lymphadenopathy. The bone marrow showed haemophagocytosis and an infiltration of lymphoma cells. All patients showed increased levels of lactate dehydrogenase, C-reactive protein, ferritin and soluble interleukin-2 receptor. Lymphoma cells were positive for CD19. CD20 and surface immunoglobulin in all patients examined, and positive for CD5 in four of seven patients. Cytogenetic analyses of bone marrow cells showed a complex structural abnormality including chromosome 14q32 in two patients, 19q13 in three patients and deletion of the terminal part of 8p21 in six patients. The prognosis was poor; only two of the seven patients have survived in complete remission with a median survival of 11 months. These data suggested that B-cell lymphoma associated with HPS might constitute a distinct biological and clinical disease entity. Abnormality of chromosome 19q13 and loss of 8p21 might be involved in the pathogenesis of this disease.

Adult↗