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N Fujimoto

Publications and source records attributed to N Fujimoto.

At least 91 records · Page 5Linked to original sources
PubMed1999

Thrombin stimulates synthesis of type IV collagen and tissue inhibitor of metalloproteinases-1 by cultured human mesangial cells.

Glomerular accumulation of extracellular matrix (ECM) is the common pathologic feature following glomerular injury, and the alteration in the synthesis and degradation of ECM may be involved in the glomerular accumulation of ECM. Glomerular fibrin formation occurs in various forms of human and experimental glomerulonephritis, and it may play an important role in progressive glomerular injury. Thrombin, a multifunctional serine proteinase that is generated at the site of vascular injury, has central functions in hemostasis and it also shows various biologic effects. In this study, it is hypothesized that thrombin may alter the production and the degradation of type IV collagen, which is an important component of ECM in the glomeruli. Human mesangial cells (HMC) were cultured, and the levels of type IV collagen, tissue inhibitor of metalloproteinase-1 (TIMP-1), and matrix metalloproteinase-2 (MMP-2) in the culture supernatants were measured by enzyme immunoassay using specific antibodies. MMP-2 activity was also evaluated by zymography using polyacrylamide/ sodium dodecyl sulfate gel-containing gelatin. Thrombin increased the production of type IV collagen and TIMP-1 in a dose-and time-dependent manner, but it did not increase MMP-2. Thrombin also stimulated the gene expressions of the type IV collagen and TIMP-1 in HMC in a dose- and time-dependent manner. Thrombin treated with diisopropylfluorophosphate, a serine proteinase inhibitor, did not show any of these effects. Hirudin, a natural thrombin inhibitor, and anti-transforming growth factor-beta-neutralizing antibody inhibited the stimulating effect of thrombin. These findings suggest that thrombin may contribute to the excessive accumulation of ECM and progression of glomerulosclerosis through an increase of type IV collagen production and a decreased matrix degradation presumably via a transforming growth factor-beta-dependent mechanism.

Cells, Cultured↗
PubMed1999

[Pick's disease].

Explore the source record for details and available documents.

Dementia↗
PubMed1998

Serum matrix metalloproteinase-2 and its density in men with prostate cancer as a new predictor of disease extension.

We examined whether the serum matrix metalloproteinase-2 (MMP-2) level and MMP-2 density could be predictors of the development and extension of prostate cancer. Serum samples were collected before any clinical treatment from 98 patients with prostate cancer and from 76 patients with benign prostatic hyperplasia (BPH). Control sera were obtained from 70 healthy men. The serum level of MMP-2 was determined by 1-step enzyme immunoassay. A newly defined MMP-2 density parameter was determined by dividing the serum level of MMP-2 by the prostate volume, which was measured by ultrasonography. The mean serum level of MMP-2 in prostate cancer patients was significantly higher than in the control and BPH groups. Furthermore, the serum MMP-2 levels in prostate cancer patients with metastasis were highly elevated compared with those without metastases. The MMP-2 density in pathologically organ-confined prostate cancer was significantly higher than that in BPH. There was a statistically significant difference in the MMP-2 density between pT2N0M0 and pT1N0M0 prostate cancers. Moreover, the serum MMP-2 level correlated well with the clinical course of prostate cancer with bone metastasis. Our results suggest that MMP-2 plays an important role in the development and extension of prostate cancer and that the serum level of MMP-2 and the MMP-2 density indicate prostate cancer extension and are, therefore, useful for the followup of prostate cancer patients.

Aged↗
PubMed1998

Two cases of intrapulmonary lymph node presenting as a peripheral nodular shadow: diagnostic differentiation from lung cancer.

We present two cases of intrapulmonary lymph node. The patients were a 44-year-old woman and a 71-year-old man each with a small peripheral nodule in the lung. On computed tomography (CT) scans, both nodules were spiculated. Since histological diagnosis could not be obtained by bronchoscopic examination or CT-guided needle biopsy, they underwent video-assisted thoracoscopic surgery. Histological examination of the resected material revealed that both nodules were composed of lymph node. Intrapulmonary lymph node has until recently been assigned no clinical significance; however, differential diagnosis of this lesion from lung cancers and other metastatic tumors is now clinically important.

Adult↗
PubMed1998

Induction of thyroid tumours in (C57BL/6N x C3H/N)F1 mice by oral administration of kojic acid.

The tumorigenicity of kojic acid (KA), which is widely used for food and cosmetics in Japan, was examined in B6C3F1 mice. Female and male animals were divided into three groups and given 0, 1.5 and 3.0% KA containing food from the age of 6 weeks. At sacrifice after 20 months, thyroid weights were significantly increased in both sexes of mice receiving KA, especially in the male groups. The enlarged thyroid glands histologically featured diffuse hyperplasia and follicular adenomas, the incidences of the latter being 65% and 87%, respectively in 1.5% and 3.0% KA-treated males, significantly higher than the control value of 2%. In the females, the figures were 2%, 8% and 80% in the 0%, 1.5% and 3.0% KA groups, respectively. The serum free T3 levels in the 3.0% KA animals of both sexes at month 6 were significantly lower than in the controls. On the other hand, their serum TSH levels were higher, although the differences disappeared at later time points. In conclusion, continuous administration of high dose of KA induces thyroid adenomas in male and female B6C3F, mice, presumably by a mechanism involving decrease in serum free T3 levels and increased TSH.

Adenoma↗
PubMed1998

Decreased amplitude of steady state pattern visually evoked cortical potentials in multiple sclerosis.

PURPOSE: We studied the amplitude of steady state (St) PVECP using the amplitude ratio to transient (Tr) PVECP clinically in patients with multiple sclerosis. METHODS: Case report. A 25-year-old woman had multiple sclerosis without optic neuritis. She had normal vision and visual fields. She was followed by both St and TrPVECP. Statistical analysis. Patients with multiple sclerosis and no optic neuritis were retrospectively studied for both Tr and StVECP. RESULTS: Six months later, she showed a decreased ratio in the left eye, corresponding to abnormalities in the center of the visual field. The peak latency of TrPVECP remained normal in both eyes. A decreased ratio was found in 27% of patients with multiple sclerosis and no optic neuritis. CONCLUSIONS: Not only Tr, but StPVECP should be recorded in patients with multiple sclerosis and normal vision to detect abnormalities in the visual pathway.

Adult↗
PubMed1998

Imbalance between serum matrix metalloproteinase-2 and its inhibitor as a predictor of recurrence of urothelial cancer.

Serum levels of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinases-2 (TIMP-2) were evaluated as prognostic indicators of the recurrence of urothelial cancer. Sera were obtained from 127 healthy control subjects and 97 urothelial cancer patients who underwent complete resection and were measured for MMP-2 and TIMP-2 using a one-step enzyme immunoassay. The relationship between the serum MMP-2/TIMP-2 ratio and the recurrence of urothelial cancer was examined. The mean serum MMP-2/TIMP-2 ratio in the 31 advanced urothelial cancer patients with recurrence was significantly higher than that in the 22 patients without recurrence (P = 0.0029) and in the 44 superficial bladder cancer patients (P < 0.0001). The 1- and 3-year disease-free survival rates in the patients with high MMP-2/TIMP-2 ratios (50% and 12%) were significantly poorer than those of the patients with normal ratios (82% and 56%) (P = 0.0152). Univariate and multivariate analyses of recurrence demonstrated that the serum MMP-2/TIMP-2 ratio is a significant independent indicator of advanced urothelial cancer. Our results indicate that an imbalance between the serum levels of MMP-2 and TIMP-2 could be a new predictor of recurrence in advanced urothelial cancer patients.

Adult↗
PubMed1998

Measurement and evaluation of serum anti-p53 antibody levels in patients with lung cancer at its initial presentation: a prospective study.

Anti-p53 antibodies in sera are known to be products of the host immune response to mutated p53 protein, and are present in some patients with various types of cancer. In this study, we measured serum anti-p53 antibody levels in 52 patients with lung cancer and 63 normal volunteers to determine the relationship between anti-p53 antibody level and clinical features of lung cancer patients. Anti-p53 antibody level was measured by an enzyme-linked immunosorbent assay and expressed as an anti-p53 antibody index, defined as the ratio of absorption of serum sample to that of p53-positive serum. The median anti-p53 antibody index was 6.6 for lung cancer patients, and higher than that in normal volunteers (1.7) (P = 0.0000). For lung cancer patients, significant differences in index levels were found by histology (4.3, n = 25, adenocarcinoma vs 8.7, n = 18, squamous cell carcinoma vs 64.8, n = 2, large-cell carcinoma vs 9.8, n = 7, small-cell carcinoma; P = 0.0109). High anti-p53 antibody index levels were observed for both large-cell carcinoma and small-cell carcinoma. When the cut-off level was set at 7.2, determined using the twice 95% specificity level for normal volunteers, the sensitivities of anti-p53 antibodies were 46.1% for all lung cancers, 28.0% for adenocarcinoma, 55.6% for squamous cell carcinoma, 100% for large-cell carcinoma and 71.4% for small-cell carcinoma. However, there were no significant differences in index level by gender, age, smoking index, presence of previous or concomitant cancer or disease stage. Multivariate analysis using a logistic regression model demonstrated that histological type of tumour was a dominant factor associated with elevation of anti-p53 antibody index level (P = 0.0184). These findings suggest that serum anti-p53 antibody index level might be independent of tumour burden and the presence of previous or concomitant cancer in our series of lung cancer patients, but is clearly strongly correlated with tumour histological type.

Adenocarcinoma↗
PubMed1998

Oral administration of tritiated water (HTO) in mouse. III: Low dose-rate irradiation and threshold dose-rate for radiation risk.

PURPOSE: To investigate the biological effect of tritium on mouse at low dose-rates. MATERIALS AND METHODS: Mice ([C57BL/6N x C3H/He]F1) were exposed to beta-rays by continuous administration of tritiated drinking water throughout their lives at low dose-rates of 3.6, 0.9, and 0.2 mG/day. RESULTS: Including the previous study, the tumour frequency was 70 to approximately 80% for exposure in the range 240 mGy/day to 9.6 mGy/day. Frequency of tumours decreased with decrease of dose-rate to 50% comparable to the controls. Restricting to thymic lymphomas, a linear relationship in a semi-log plot was found between the frequency and the dose-rate above a threshold dose-rate of 12 mGy/day. There was a 'tail' to this relationship down to 0.9 mGy/day. A similar pattern resulted for the relationship between the life-shortening and the dose-rate. The threshold dose-rate of 3H beta-rays, 2 mGy/day (with a tail down to 0.2 mGy/day), was much lower than that of gamma-rays, 20 mGy/day (tail down to 2 mGy/day) derived from other studies. CONCLUSIONS: These studies suggest that there exists the threshold dose-rate in the biological effects of radiation, and that the threshold dose-rate for 60Co gamma-irradiation is higher than that for 3H beta-irradiation.

Administration, Oral↗
PubMed1998

Effect of cAMP- and cGMP-related drugs on porcine cultured ciliary muscle.

We studied in this work the compounds which affect the contraction of ciliary muscle and are potential ocular hypotensive drugs, and second messengers produced by the compounds. Using second-passaged porcine cultured ciliary muscle, single cell contraction was used for assay. Cell contraction by carbachol was affected by isobutyl methylxanthine, forskolin, dibutyryl cGMP and sodium nitroprusside (SNP). Forskolin increased intracellular cAMP while SNP stimulated cGMP formation. The results indicate that these cAMP- or cGMP-related compounds could affect the contraction of ciliary muscle like prostaglandins and could therefore have a potential to reduce intraocular pressure.

1-Methyl-3-isobutylxanthine↗
PubMed1998

Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in HTLV-I-associated myelopathy.

Matrix metalloproteinases (MMPs) have been reported to be involved in inflammatory disorders of the central nervous system (CNS). However, little is known about the role of MMPs in the pathogenesis of HTLV-I-associated myelopathy (HAM)/Tropical spastic paraparesis (TSP). To address this issue, we examined the tissue expression and localization of MMPs and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs) in the spinal cord lesions of HAM/TSP using immunohistochemistry. In addition, the blood and cerebrospinal fluid (CSF) levels of MMPs and TIMPs of the patients with HAM/TSP were determined using sandwich enzyme immunoassays (SIA) and gelatin zymography. Immunohistochemical studies revealed that collagen IV and decorin immunoreactivity on the basement membrane of CNS parenchymal vessels was partially disrupted where inflammatory mononuclear cells infiltrated in active-chronic lesions of HAM/TSP. In these lesions, MMP-2 (gelatinase A) was immunostained mainly on the surface of foamy macrophages and lymphocytes, whereas MMP-9 (gelatinase B) expression was positive in the intravascular and perivascular mononuclear cells but not on foamy macrophages. In contrast, inactive chronic lesions of the spinal cords of the HAM/TSP contained fewer MMP-2-positive or MMP-9-positive mononuclear cells than active-chronic lesions. Many parenchymal vessels had thickened vascular walls which showed increased immunoreactivity to decorin. SIA revealed that production levels of MMP-2 and MMP-9 in both blood and CSF were higher in the patients with HAM/TSP than those in non-inflammatory other neurological disease controls (ONDs). Using zymography, proMMP-9 was detected more frequently in the CSF of patients with HAM/TSP than those in ONDs. Taken together, our data indicate that MMP-2 and MMP-9 may play an important role in the blood-brain barrier breakdown and tissue remodeling in the CNS of HAM/TSP.

Aged↗
PubMed1998

A pediatric case of atypical Mycobacterium avium infection of the skin.

We report a case of cutaneous atypical mycobacteriosis in a 12-year-old healthy girl due to Mycobacterium avium. The cutaneous symptoms were three well-defined subcutaneous nodules on both buttocks and on the posterior surface of the left thigh. One had a fistulous opening on the skin surface. Histopathological examination revealed epithelioid cell granulomas surrounded by dense lymphocytic infiltration and acid-fast bacteria were seen with modified periodic acid-carbol fuchsin staining. Using Ogawa's medium at 37 degrees C, acid-fast bacteria were isolated from the biopsied specimen and identified by the DNA-DNA hybridization method as Mycobacterium avium. In drug susceptibility test, these were resistant to all antituberculous drugs. Oral administration of minocycline 100 mg/day for two months had little effect on the two remaining lesions, which were therefore excised. Based upon reported cases of Mycobacterium avium complex, we considered that our pediatric patient with multiple intradermal or subcutaneous nodules on the buttocks and the thigh exhibited the characteristic symptoms of M. avium infection.

Administration, Oral↗
PubMed1997

Risk factors for development of radiation pneumonitis following radiation therapy with or without chemotherapy for lung cancer.

PURPOSE: To determine the risk factors contributing to development of radiation pneumonitis (RP) in patients with lung cancer who undergo radiation therapy to the thorax. METHODS AND MATERIALS: Development and severity of RP were retrospectively analyzed for 89 patients with lung cancer who underwent radiation therapy with or without chemotherapy at the National Shikoku Cancer Center Hospital between 1991 and 1995. The severity of RP was determined using a modified grading scale based on that of the Radiation Therapy Oncology Group and the European Organization for the Research and Treatment of Cancer. RESULTS: Fifty-two (58%) patients developed RP: 34 patients with Grade 1, 5 with Grade 2, 8 with Grade 3, and 5 with Grade 5 RP. Severe RP tended to develop earlier than less severe RP, but not to a significant extent (p = 0.151). On logistic regression analysis including both patient condition and treatment factors, development of Grade 1 or more severe RP was most frequently observed for Stage I-II disease (p = 0.011). The use of chemotherapy, large daily radiation dose, and once-daily fractionation (vs. twice-daily fractionation) were possibly related to the development of RP (p = 0.057, p = 0.069, and p = 0.092, respectively). For the group of 48 patients who underwent chemoradiation therapy, the use of large daily radiation dose was a significant risk factor for RP (p = 0.014). In addition, the use of once-daily fractionation was a marginally significant risk factor (p = 0.052). Among chemotherapy drugs administered, cisplatin was a favorable factor (p = 0.011), while adriamycin was a risk factor (p = 0.061). CONCLUSIONS: In radiation therapy for lung cancer, administration of a large daily dose should be avoided in order to prevent RP, particularly when radiation therapy is combined with chemotherapy.

Adult↗
PubMed1997

Strain differences in the induction of intestinal metaplasia by X-irradiation in rats.

Strain differences in the susceptibility of rats to induction of intestinal metaplasia by X-irradiation were examined. The gastric regions of 5-week-old males of five inbred strains of rats (F344/NSlc, Copenhagen, Buffalo/NacJcl, and ACI/NHos) and three strains of randomly bred rats (HOS:Donryu, Slc:Wistar, Slc:SD) were irradiated with a total dose of 20 Gy X-ray given in two equal fractions at 3-day interrals. When examined after the rats were killed, 6 months after the last irradiation, the number of intestinal metaplastic crypts positive for alkaline phosphatase (ALP) was highest in the Donryu and lowest in the Copenhagen rats. Morphologically, the number of crypts with intestinal metaplasia in the glandular stomachs of Donryu, Wistar, SD, and Buffalo rats was higher than the number in ACI, F344, and Copenhagen rats. Intestinal metaplasia was more frequently observed in the pyloric than in the fundic glands. These results demonstrate that the induction of intestinal metaplasia by X-irradiation in rats is greatly influenced by the rat strain.

Animals↗