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M Ishizaki

Publications and source records attributed to M Ishizaki.

At least 19 recordsLinked to original sources

A cross-sectional study on association of calcium intake with blood pressure in Japanese population.

To investigate the association of calcium intake independently of other nutrients already known as predictors of hypertension, a cross-sectional study was carried out on the same population in Japan as used for the INTERSALT study. Dietary calcium intake was estimated from a 1-day 24-h recall. Sodium and potassium intakes were evaluated by 24-h urinary excretion. Data from 476 subjects aged 20-59 years, 230 men and 246 women, were analysed. The mean dietary calcium intake ranged from 557 to 608 mg/day among men, and from 528 to 639 mg/day among women. Among men, the pooled estimate of the regression coefficients of blood pressure (mm Hg) per 100 mg increase of calcium intake, adjusted for age and body mass index (BMI), were -0.42 mm Hg for systolic blood pressure (SBP) and -0.35 mm Hg for diastolic blood pressure (DBP), but there was no statistical significance. Among women, the pooled estimates of regression coefficients adjusted for age and BMI were -0.92 mm Hg for SBP and -0.83 mm Hg for DBP with statistical significance. After adjustment for age, BMI, alcohol intake and urinary excretion of sodium and potassium, the pooled estimate of calcium intake was -0.66 mm Hg for DBP with statistical significance and -0.70 mm Hg for SBP. A significant negative association of calcium intake with blood pressure was observed among the subjects in Osaka. Our study suggests that increased calcium intake may provide a benefit of lowering blood pressure independently of other minerals such as sodium and potassium.

Adult↗

Amperometric recording of gonadotropin-releasing hormone release activity in the pituitary of the dwarf gourami (teleost) [correction of (teleosat)] brain-pituitary slices.

We developed a method for real-time electrochemical recording of gonadotropin-releasing hormone (GnRH) release using carbon fiber electrodes (CFE). The oxidation current of GnRH was measured by amperometry. We recorded the release activity in the pituitary of the teleost brain-pituitary slice. The CFE was located in the part of the pituitary that receives dense innervation from GnRH neurons in the preoptic area. A bulk amperometric current was recorded in response to high K+(o) stimulation in a dose dependent manner. Decreasing the holding potential to below the oxidation potential of GnRH resulted in the loss of amperometric currents. Thus, it is suggested that the amperometric currents are mainly attributed to the oxidation currents of GnRH and reflect the GnRH release activity.

Animals↗

Two cases of cholesterol granuloma of the breast.

We report two cases of cholesterol granuloma of the breast clinically diagnosed as malignant and describe the features. The first patient was a 74-year-old woman who complained of a lump in the left breast. The mammography and ultrasonography suggested a malignant mass. Fine needle aspiration showed multinucleated giant cells. We suspected breast cancer, but cholesterol granuloma was diagnosed on excisional biopsy. The second case was a 51-year-old woman who was found to have a breast tumor on a screening mammography. The mammography and ultrasonography suggested carcinoma, but excisional biopsy revealed cholesterol granuloma. Reports of cholesterol granuloma of the breast are very rare. Cholesterol granuloma should be considered in the differential diagnosis of breast carcinoma.

Aged↗

The formation of capsule and septum in human hepatocellular carcinoma.

The formation of fibrous capsule around the cancer nodule and of the septum in the tumor is frequently observed with the development of hepatocellular carcinoma (HCC). We aimed to clarify how the capsule and septum were formed during the growth of HCC. Liver samples surgically resected from 25 patients with HCC were studied with in situ hybridization for type-I, -III, and -IV procollagen. Type-I and -III procollagen-expressing cells, mostly alpha-smooth muscle actin (SMA)-positive, were increased in the fibrous capsule and in the septum between HCC nodules. These cells were also found at the invasion front of HCC and around the necrotic cancer tissues. Type-IV procollagen gene expression was mainly observed in mesenchymal cells localized in both HCCs and non-cancerous liver. Cancer cells or hepatocytes did not express any of these procollagen genes. The present study reveals that the capsule and septum are mainly formed by alpha-SMA-positive mesenchymal cells at the interface between two different tissues (e.g., cancer nodule vs non-cancerous liver or another cancer nodule). The wound healing occurs even in HCC. The capsule formation may result from interaction between tumor and host liver and interfere the growth and invasion of HCC.

Actins↗

Vascular endothelial growth factor enhances glomerular capillary repair and accelerates resolution of experimentally induced glomerulonephritis.

Vascular endothelial growth factor (VEGF) regulates angiogenesis through endothelial cell proliferation and plays an important role in capillary repair in damaged glomeruli. We tested the hypothesis that VEGF might be beneficial in rats with severe glomerular injury in glomerulonephritis (GN) based on its angiogenic and vascular remodeling properties. Acute GN with severe glomerular destruction was induced in rats by injection of anti-Thy-1.1 antibody (day 0) and Habu-snake venom (day 1). Rats were intraperitoneally injected with recombinant human VEGF(165) (10 microg/100 g body wt/day) or vehicle from day 2 to day 9, and monitored changes in glomerular capillaries, development of glomerular inflammation, and progression to glomerular sclerosis after acute glomerular destruction in both groups. Rats that received anti-Thy-1.1 antibody and Habu-snake venom showed severe mesangiolysis and marked destruction of capillary network on day 2. VEGF was expressed on glomerular epithelial cells, proliferating mesangial cells, and some infiltrating leukocytes, and VEGF(165) protein levels increased in damaged glomeruli during day 5 to day 7. Normal, damaged, and regenerating glomerular endothelial cells expressed VEGF receptor flk-1. However, endothelial cell proliferation and capillary repair was rare in vehicle-treated rats with severe glomerular damage, which progressed to global sclerosis and chronic renal failure by week 8. In contrast, in the VEGF-treated group, VEGF(165) significantly enhanced endothelial cell proliferation and capillary repair in glomeruli by day 9 (proliferating endothelial cells: VEGF(165), 4.3 +/- 1.1; control, 2.2 +/- 0.9 cells on day 7, P < 0.001; and glomerular capillaries: VEGF(165), 24.6 +/- 4.8; control, 16.9 +/- 3.4 capillaries on day 7, P < 0.01). Thereafter, damaged glomeruli gradually recovered after development of capillary network by week 8, and significant improvement of renal function was evident in the VEGF-treated group during week 8 (creatinine: VEGF(165), 0.3 +/- 0.1; control, 2.6 +/- 0.9 mg/dl, P < 0.001; proteinuria: VEGF(165), 54 +/- 15; control, 318 +/- 60 mg/day, P < 0.001). We conclude that the beneficial effect of VEGF(165) in severe glomerular injury in GN emphasizes the importance of capillary repair in the resolution of GN, and may allow the design of new therapeutic strategies against severe GN.

Animals↗

Role of MMP-2 in alveolar epithelial cell repair after bleomycin administration in rabbits.

Matrix metalloproteinases (MMPs) have been implicated in the pathological processes of interstitial lung diseases. However, underlying mechanisms, particularly for activity levels and distribution of activated MMP-2 in the disease process, are yet to be elucidated. The present study investigated the immunolocalization of MMP-2, membrane type 1-matrix metalloproteinase (MT1-MMP), tissue inhibitor of metalloproteinase (TIMP)-2, p53, and Ki-67 in a rabbit model of bleomycin-induced pulmonary fibrosis. Gelatin zymography and in situ zymography were used to examine the activity and the localization of MMP-2. Furthermore, we performed Western blot and in situ hybridization for MT1-MMP, an activator for MMP-2. The total MMP-2 level estimated by gelatin zymography increased significantly at 3, 7, and 14 days after bleomycin administration, compared with controls. In the immunohistochemical study, immunoreaction for MMP-2 was strongest in alveolar epithelial cells among the cell populations. Swollen and/or elongated type II alveolar epithelial cells showed strong immunoreactions for MMP-2, MT1-MMP, and TIMP-2. After bleomycin administration, immunoreaction for p53 was observed in bronchiolar and alveolar epithelial cells. The proportion of p53-positive cells was high in epithelial cells from 1 to 14 days as MMP-2 levels were increased, suggesting that p53 may be responsible, at least in part, for the increase of MMP-2. The ratio of activated MMP-2 to total MMP-2 estimated by gelatin zymography increased significantly at 3, 7, 14, and 28 days after bleomycin treatment. In situ zymography revealed that type II alveolar epithelial cells degraded gelatin. An increased expression of MT1-MMP protein was observed by Western blot following administration of bleomycin. In situ hybridization demonstrated that type II alveolar epithelial cells gave intense signal for MT1-MMP mRNA. These results suggest that type II alveolar epithelial cells express MT1-MMP and activate MMP-2 on their cell surfaces, which may lead to the elongation and migration of alveolar epithelial cells in the repair process of bleomycin-induced pulmonary fibrosis.

Animals↗

Socioeconomic differences in behavioural and biological risk factors: a comparison of a Japanese and an English cohort of employed men.

BACKGROUND: To compare socioeconomic differences in behavioural and biological risk factors in Japanese and English 39-59-year-old employed men. METHODS: We measured systolic and diastolic blood pressure, total and high density lipoprotein (HDL) cholesterol, body mass index (BMI), waist-to-hip ratio and fibrinogen at medical screenings and smoking and alcohol consumption in health questionnaires among Japanese non-manual and manual employees of a steel products company and among English non-manual employees working in Civil Service departments. RESULTS: In England, higher employment grades were advantaged with regard to most risk factors studied. In Japan the picture was different in that higher grades had higher BMI, waist-to-hip-ratio and lower HDL cholesterol. In Japan employment grade differences in these three risk factors are clearly larger among younger men than among older men, while in England age differentials in the grade differences are small. Similar results were obtained for education. CONCLUSIONS: Important differences in the social patterning of risk factors were observed in our cohorts of employed Japanese and English men. The contribution that these risk factors make in explaining social differences in health may vary accordingly. Studies that identify the common and unique determinants of socioeconomic health differences in different populations are needed.

Adult↗

Breast biopsy for mammographically detected non-palpable lesions using a vacuum-assisted biopsy device (Mammotome) and an upright-type stereotactic mammography unit.

BACKGROUND: It is planned to start screening mammography throughout Japan in the near future. However, a minimally invasive biopsy procedure for mammographically detected non-palpable breast lesions is not available in almost all Japanese hospitals. It is crucial to develop a useful minimally invasive biopsy method which can be applied without difficulty. METHODS: Eighty-nine biopsies for 88 mammographically detected non-palpable breast lesions, consisting of 70 lesions with microcalcifications alone, eight masses without calcifications and 10 with both masses and microcalcifications, were performed using the combination of a vacuum-assisted biopsy device (Mammotome) and an upright-type stereotactic mammography unit. RESULTS: Microcalcifications were confirmed radiographically in the tissue obtained from 78 biopsies among 81 biopsies for the lesions with microcalcifications (96.3%). All the lesions without calcifications were considered to be biopsied successfully. Five patients complained of nausea or fainted during the localization or biopsy procedure and an additional patient suffered from hyperventilation syndrome. Five cases experienced mild subcutaneous bleeding in the breasts. CONCLUSIONS: The biopsy technique using the combination of a vacuum-assisted biopsy device and an upright-type stereotactic mammography unit is a cost-effective, safe and very useful method for mammographically detected non-palpable breast lesions. It is expected to be a standard method of biopsy for such lesions in many developed countries other than the USA. However, it is important to make the patients relaxed during the biopsy to prevent mental strain.

Adult↗

Apoptosis mediates decrease in cellularity during the regression of Arthus reaction in cornea.

BACKGROUND/AIMS: The Arthus type allergic reaction is characterised by inflammatory cell infiltration and marked neovascularisation in the cornea. During the healing stages, inflammatory cells and newly formed microvessels gradually disappear. The aim was to establish whether apoptosis affected the regression of inflammatory cells and newly formed microvessels, in order to define more clearly the cellular mechanisms involved in the pathobiology of corneal diseases. METHODS: Albino male rabbits were injected subcutaneously with 5 mg/ml bovine serum albumin (BSA) incorporated in Freund's complete adjuvant twice weekly. Under the anaesthesia, 30 microl of a 0.5 mg/ml BSA solution was injected into the central corneal stroma to induce an Arthus type allergic reaction. The injured corneas were collected at various time points ranging from 3 to 20 days. Apoptotic cells were identified by both light microscopy using in situ TdT-dUTP nick end labelling (TUNEL) method and electron microscopy. RESULTS: With increasing time after induction of the Arthus reaction, marked neovascularisation and infiltrated inflammatory cells such as polymorphonuclear cells (PMNs) and plasma cells were observed in the cornea. Thereafter, the inflammatory cells and newly formed microvessels gradually disappeared. Coincidently, the numbers of microvessel endothelial cells and infiltrated inflammatory cells undergoing apoptosis were increased. Apoptotic bodies were taken up by macrophages, PMNs, as well as myofibroblasts derived presumably from transformation of migrated keratocytes. CONCLUSIONS: These data demonstrate that regression of the cellular infiltrates and microvessel endothelial cells associated with the Arthus reaction in the cornea occurs via apoptosis. This finding adds insights into the cellular mechanisms regulating the pathobiology of corneal diseases.

Animals↗

Dermoid cyst of the colon.

Dermoid cysts are benign cystic teratomas lined by skin and epidermal appendages. We report a dermoid cyst occurring in a 26-year-old female whose chief complaint was irregular vaginal bleeding. Abdominal magnetic resonance image demonstrated a space-occupying lesion in the right lower abdomen. The mass showed hyperintensity on the T2 image and the signal was homogeneous for the interior. During abdominal surgery we made the diagnosis of subserous tumor of the colon and resected the ileocecal portion of the colon. The tumor measured 5.4 x 4.8 x 3.5 cm and was soft and elastic. On cross section, a unilocular cyst filled with atheromatous material was found. Pathological examination revealed a dermoid cyst. In the view of this diagnosis, a simple excision would have been an adequate treatment.

Adult↗

Socioeconomic status, workplace characteristics and plasma fibrinogen level of Japanese male employees.

OBJECTIVES: This study examined the relationships between workplace characteristics and plasma fibrinogen level and assessed the possibility of socioeconomic differences in plasma fibrinogen level being accounted for by workplace characteristics. METHODS: Cross-sectional questionnaire data from 4343 Japanese male employees were examined with Karasek's demand-control model, as was sedentary job and overtime work. RESULTS: Less overtime work, a less sedentary job, and to a less extent, lower job control and low worksite support were related to increased plasma fibrinogen levels. Adjusting for employment grade strongly attenuated or eliminated these relationships. The association of job demands or job strain with plasma fibrinogen level was weak. High plasma fibrinogen in lower socioeconomic groups remained largely unchanged after adjustment for workplace characteristics. CONCLUSIONS: Workplace characteristics are not significantly related to the plasma fibrinogen levels of male Japanese employees after adjustment for socioeconomic status, and they do not explain socioeconomic differences in plasma fibrinogen levels among these employees.

Adult↗

[Long-term survival of a patient with postoperative liver metastasis of stage IVa gallbladder cancer responding to hepatic arterial infusion chemotherapy].

A 58-year-old man was diagnosed as having advanced gallbladder cancer (T4, P0, H0, N0, stage IVa) with direct invasion to the liver, transverse colon and duodenum. Therefore, extended cholecystectomy and bile duct resection with a partial resection of the transverse colon and the duodenum were performed in March 1992. Histopathological examination revealed moderately differentiated tubular adenocarcinoma of si, ly1, v1, hinf3, binf3, n0. Three years and eight months after the operation, multiple liver metastases were diagnosed by abdominal CT. Repeated hepatic arterial infusion chemotherapy with 5-FU 500 mg/body/w, MMC 4 mg/body/2w and EPI 40 mg/body/4w was performed starting in January 1996. Four months later, the lesions in the liver were reduced in size, and abdominal CT 10 months after the chemotherapy showed a partial response. However, the liver metastasis of the right lobe was enlarged on an abdominal CT in August 1997. Repeated hepatic arterial infusion chemotherapy with the same regimen was performed again starting in March 1998. Ten months later, the liver metastasis was slightly enlarged, but the greater part of the metastasis showed necrosis on an abdominal CT in January 1999. However, peritonitis carcinomatosa was observed later and the patient died 8 years after the operation.

Adenocarcinoma↗

The relationship between employment grade and plasma fibrinogen level among Japanese male employees. YKKJ Research Group.

Plasma fibrinogen is an important risk factor for cardiovascular disease, and is associated with socioeconomic status in Europe and the United States. We evaluated whether the relationship between socioeconomic status and plasma fibrinogen level exists in Japanese male employees, and whether this relationship is independent of other correlates of plasma fibrinogen. This cross-sectional study was conducted on full-time male employees aged 20-58 in a metal-products factory between April 1996 and March 1997. Altogether 4375 employees (92.9%) participated. Low employment grade and low educational background were associated with increased age-adjusted plasma fibrinogen level. Adjusting for body mass index, waist to hip ratio, height, smoking habit, alcohol consumption, physical activity at leisure and systolic blood pressure did not attenuate these associations much. Adjusting for white blood cell count and hemoglobin Alc reduced the associations of both employment grade and educational background with plasma fibrinogen level, nevertheless these relationships remained significant.

Adult↗

Expression of MAGE, GAGE and BAGE genes in human liver diseases: utility as molecular markers for hepatocellular carcinoma.

BACKGROUND/AIMS: The MAGE, GAGE and BAGE genes encode tumor antigens recognized by autologous cytotoxic T lymphocytes. The aim of this study was to evaluate the possibility of using these genes as molecular markers and as the targets of specific immunotherapy for human hepatocellular carcinoma (HCC). METHODS: The expressions of MAGE-1, MAGE-3, GAGE1-6, GAGE1-2 and BAGE mRNA in 33 surgically resected HCC samples and 26 of their corresponding non-cancerous samples (11 liver cirrhosis and 15 chronic hepatitis) were studied by a reverse-transcription polymerase chain reaction, and were compared with clinicopathological parameters. The expression of MAGE-1 was also examined in 16 biopsied HCC samples. RESULTS: MAGE-1, MAGE-3, GAGE1-6, GAGE1-2 and BAGE mRNA were expressed in 67%, 39%, 36%, 30%, and 21% of the HCC, respectively. At least one transcript was detected in 88% of the HCC, while no expression was observed in the non-cancerous livers. There was no significant correlation between the expression of any of the tumor antigens examined and the differentiation stage or size of the HCC. Especially, MAGE-1 was highly expressed in small HCC with a diameter of less than 2 cm and in well-differentiated HCC (81% and 70%, respectively), and was also expressed even in alpha-fetoprotein-negative and PIVKA-II-negative HCC (58% and 76%, respectively). The MAGE-1 expression was detected in 69% of biopsied HCC samples and the expression was high in both small and well-differentiated HCC. CONCLUSIONS: These tumor-specific antigens can be useful as molecular markers and as the possible target molecules for the specific immunotherapy of human HCC.

Adult↗

Job strain, social support in the workplace, and haemoglobin A1c in Japanese men.

OBJECTIVES: To examine the association between job strain (defined in the model of job demands and job control) and social support at the workplace with levels of glycosylated haemoglobin A1c (HbA1c) METHODS: All male employees aged 40-60 in a manufacturing firm, Japan, were invited to take part in the study. A blood sample was taken from the participants and HbA1c (%) was measured. Job strain and social support at the workplace were assessed with the job content questionnaire (JCQ). After excluding those who had a history of diabetes mellitus or other chronic diseases, data from 268 male day workers were analyzed. RESULTS: Age adjusted average concentrations of HbA1c were significantly higher in the highest quartile group of job strain or the lowest quartile group of social support at the workplace (p<0.05). Multiple linear regression analysis indicated that job strain was significantly and positively related to HbA1c (p<0.05), whereas social support at the workplace was significantly and negatively related to HbA1c (p<0.05), both after controlling for other covariates. CONCLUSIONS: Greater job strain and lower social support at the workplace may be associated with increased concentrations of HbA1c. Increased blood glucose may be a physiological mediator between job strain or social support at the workplace and coronary heart disease.

Adult↗

Matrix metalloproteinases and tissue inhibitor of metalloproteinase-2 in fetal rabbit lung.

Cell-extracellular matrix interaction and extracellular matrix remodeling are known to be important in fetal lung development. We investigated the localization of matrix metalloproteinases (MMPs) in fetal rabbit lungs. Immunohistochemistry for type IV collagen, MMP-1, MMP-2, MMP-9, membrane type (MT) 1 MMP, and tissue inhibitor of metalloproteinase (TIMP)-2 and in situ hybridization for MMP-9 mRNA were performed. Gelatin zymography and Western blotting for MT1-MMP in lung tissue homogenates were also studied. MMP-1 and MT1-MMP were detected in epithelial cells, and MMP-2 and TIMP-2 were detected in epithelial cells and some mesenchymal cells in each stage. MMP-9 was found in epithelial cells mainly in the late stage. Gelatin zymography revealed that the ratio of active MMP-2 to latent MMP-2 increased dramatically during the course of development. MT1-MMP was detected in tissue homogenates, especially predominant in the late stage. These findings suggest that MMPs and their inhibitors may contribute to the formation of airways and alveoli in fetal lung development and that activated MMP-2 of alveolar epithelial cells may function to provide an extremely wide alveolar surface.

Animals↗

Complement-mediated killing of mesangial cells in experimental glomerulonephritis: cell death by a combination of apoptosis and necrosis.

Immune system mediated, particularly antibody- and complement-mediated, glomerular injury triggers glomerulonephritis (GN). To characterize complement-mediated cytotoxicity in GN, we assessed the process of mesangial cell death induced by C5b-9 attack in Thy-1 GN. Cell injury was recognized morphologically, and nuclear DNA breaks were confirmed by the DNA nick end labeling (TUNEL) method as well as DNA gel electrophoresis. Thy-1 GN was induced in rats with anti-Thy-1.1 antibody injection. Mouse IgG (administered antibody) and rat C3 were detected in all glomeruli within 5 min after antibody injection. Damaged mesangial cells with condensed as well as TUNEL-positive nuclei could be observed at 20 min and became prominent at 40-60 min. Ultrastructurally, damaged mesangial cells contained condensed apoptotic nuclei from 40 to 60 min, whereas the cytoplasm showed necrotic degeneration. This was followed by progressive lysis of both nuclei and cytoplasm. The DNA 'ladder' pattern was observed by gel electrophoresis of extracted DNA between 40 and 60 min and correlated with the increased number of TUNEL-positive damaged mesangial cells. To examine the role of complement in this form of cell death, complement depletion was induced in rats by cobra venom factor. Complement-depleted rats showed no rat C3 deposition, rare TUNEL-positive mesangial cells, rare ultrastructural degenerated mesangial cells with apoptotic nuclei and necrotic cytoplasm, and no DNA 'ladder' pattern on gel electrophoresis at 40 min, although prominent mouse IgG was seen in glomeruli. To analyze milder forms of complement injury, a low dose of the antibody was administered to rats with a normal complement level. A few TUNEL-positive mesangial cells were detected in the glomeruli which contained apoptotic nuclei and necrotic cytoplasm. Our results indicate that an apoptotic death mechanism accompanies cell necrosis in complement-mediated mesangial cell destruction in GN and that this unusual form of cell death may represent a combination of apoptosis-necrosis within the same cell. Complement injury activates a 'death program' which in turn leads to irreversible damage of mesangial cells and which may contribute to initiation and development of GN.

Animals↗

Increased expression of epimorphin in bleomycin-induced pulmonary fibrosis in mice.

Epimorphin was originally identified as a mesenchymal, cell surface-associated protein that modulates epithelial morphogenesis in embryonic organs, whereas pulmonary fibrosis is a process of wound healing, which in part mimics the process of fetal lung development. We investigated the temporal and spatial changes in the distribution of epimorphin protein and expression of its messenger RNA (mRNA) in bleomycin-induced pulmonary fibrosis in mice. Immunohistochemical analysis showed that low levels of epimorphin were present in the bronchiolar, alveolar, and vascular walls of normal adult lungs. However, from Day 7 until Day 28 after bleomycin treatment, increasing levels of epimorphin immunoreactivity were detected in the mesenchymal cells and in the extracellular matrix within intra-alveolar fibrotic lesions. Moreover, Northern blots showed corresponding increases in epimorphin mRNA expression. Re-epithelialization of epimorphin-rich intra-alveolar fibrosis was complete by Day 28 after bleomycin, and by Day 56, epimorphin immunoreactivity had declined. In situ hybridization and confocal microscopic studies confirmed expression of epimorphin mRNA by mesenchymal cells situated within early fibrotic lesions, whereas immunoelectron microscopy localized the epimorphin to the endoplasmic reticulum of the mesenchymal cells and to the basement membrane and collagen fibrils in the area. These results suggest that epimorphin may contribute to the remodeling of pulmonary fibrosis via epithelial-mesenchymal interactions.

Animals↗