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Biomedical subjects

Y Furuya

Publications and source records attributed to Y Furuya.

At least 55 records · Page 3Linked to original sources

A novel enzyme, L-tryptophan oxidase, from a basidiomycete, Coprinus sp. SF-1: purification and characterization.

A basidiomycete, Coprinus sp. SF-1, was found to produce an L-Trp-oxidizing enzyme by screening from the culture collection of our laboratory. After solubilization by 1 M NaSCN from the particulate fraction of disrupted cells of the strain, the enzyme was purified about 76-fold to essential homogeneity. The enzyme had a molecular mass of about 420 kDa and the subunit molecular mass was 68 kDa. The enzyme contained 1 mol of non-covalently bound FAD per mol of the subunit. It catalyzed the simultaneous reactions of oxidative deamination and oxygenative decarboxylation of L-Trp to form indolepyruvic acid and indole-3-acetamide, the former of which was further oxidized to indole-3-acetic acid. The molar ratio of the respective reaction products was about 9:1. The enzyme specifically oxidized L-Trp, and slightly acted on L-Phe and L-Tyr. The Km for L-Trp was about 0.5 mM in both oxidase and oxygenase reactions. Thus, the enzyme is a novel one and was tentatively designated "L-Trp oxidase (deaminating and decarboxylating)". The optimum pHs of oxidase and oxygenase activities were 7.0 and 9.0, respectively. The optimum temperatures of both activities were 50 degrees C. The enzyme was stable at pH 6.0-10.5 and below 50 degrees C, and at 4 degrees C for 1 year.

Absorption↗

Characteristic changes in carbohydrate profile in the kidneys of hereditary nephrotic mice (ICGN strain).

The ICR-derived glomerulonephritis (ICGN) mice consist of heterozygous and homozygous groups and are considered to be a good model for human idiopathic nephrotic syndrome. To reveal changes in cell-surface carbohydrate construction, 24 lectins were applied to kidney sections of 10-, 30- and 50-week-old male heterozygous and homozygous ICGN mice and age-matched male ICR mice. Bandeiraea simplicifolia lectin-I (BSL-I), which specifically binds to alpha-D-galactopyranosyl groups, showed positive staining in the glomeruli of ICGN mice, but not in those of ICR mice. Positive BSL-I staining was observed only in distal tubules of homozygous ICGN mice. Lectin blotting for BSL-I demonstrated characteristic glycoproteins (45, 58 and 64 kD) in ICGN but not in ICR mice, and the levels of these molecules augmented in homozygous ICGN mice with the progression of renal failure. Moreover, succinylated wheat germ agglutinin, Dolichos biflorus agglutinin, Aleuria aurantia lectin and Ulex europaeus agglutinin-I showed positive staining only in the glomeruli of homozygous ICGN mice, but not in those of heterozygous ICGN or ICR mice. The staining intensities of Ricinus communis agglutinin-I, Phaseolus vulgaris agglutinin-E and -L, Lens culinaris agglutinin and Erythrina cristagalli agglutinin (ECL) in the glomeruli of homozygous ICGN mice were stronger than those of heterozygous ICGN and ICR mice. In conclusion, lectin histochemistry provided useful information for the diagnosis and prognosis of nephrotic lesions. Characteristic BSL-I binding glycoproteins may be pathogenic factors which cause renal disease in ICGN mice and are good tools to investigate the molecular mechanism of renal disorders in ICGN mice.

Animals↗

[A case of gastric cancer with multiple liver metastasis responding to combined chemotherapy with low-dose cisplatin and 5-fluorouracil].

A 68-year-old man who had Borrmann type 4 gastric cancer with multiple liver metastases was admitted to our hospital on October 20, 1998. He was considered nonresectable and placed on neoadjuvant chemotherapy consisting of low-dose CDDP and 5-FU. After 9 weeks of administration, the liver metastases had disappeared on abdominal computed tomography, but the primary lesion had progressed. On May 12, 1999, a total gastrectomy with a partial resection of the transverse colon and resectional biopsy of a white nodule of the liver were performed. This was a non-curative operation because of the peritoneal dissemination. A histopathological examination of the liver nodule revealed that the cancer cells had disappeared. The patient had an uneventful postoperative course and 4 weeks of chemotherapy were added. He remains alive with no symptoms or re-growth of the liver metastatic tumor 4 months after the surgery.

Adenocarcinoma↗

[Two cases of cranial pachymeningitis presenting only severe continuous headache or convulsion].

In cranial pachymeningitis, headache, cranial nerve palsies, and ataxia were the most common clinical manifestations. We reported two rare cases presenting only headache or convulsion as a main symptom. A 66-year-old man was suffering from severe continuous headache for years with no other clinical symptoms. Laboratory data revealed positive RA test and elevated RAPA. With oral steroid therapy, his headache was subsided. A 39-year-old woman visited us with convulsive attacks as only symptom. Biopsy of the thickened dura revealed granulated epithelioid cells without central necrosis. With antituberculosis therapy, hypertrophy of dura, as well as the symptom, was disappeared. It is difficult to diagnose pachymeningitis when patients manifest only headache or convulsion. We suggest to carry out Gd-enhanced MR scan in these cases.

Adult↗

Mapping of metastasis suppressor genes for prostate cancer by microcell-mediated chromosome transfer.

AIM: To identify the metastasis suppressor genes for prostate cancer. METHODS: A copy of human chromosomes was introduced into the highly metastatic Dunning R-3327 rat prostate cancer cells by the use of microcell-mediated chromosome transfer. Relationships between the size of human chromosomes introduced into microcell hybrid clones and the number of lung metastases produced by the clones were analyzed to determine which part of human chromosomes contained the metastasis suppressor gene(s) for prostate cancer. To determine portions of human chromosomes introduced, G-banding chromosomal analysis, fluorescence in situ hybridization analysis, and polymerase chain reaction analysis were performed. RESULTS: Each of microcell hybrid clones containing human chromosomes 7, 8, 10, 11, 12, or 17 showed decreased ability to metastasize to the lung without any loss of tumorigenicity. This demonstrates that these human chromosomes contain metastasis suppressor genes for prostate cancer. Spontaneous deletion of portions of human chromosomes was observed in the human chromosome 7, 10, 11, 12, and 17 studies. In the human chromosome 8 study, irradiated microcell-mediated chromosome transfer was performed to enrich chromosomal arm deletions of human chromosome 8. Molecular and cytogenetic analyses of microcell hybrid clones demonstrated that metastasis suppressor genes on human chromosomes were located on 7q21-22, 7q31.2-32, 8p21-12, 10q11-22, 11p13-11.2, 12p11-q13, 12q24-ter, and 17pter-q23. KAI1 and MKK4/SEKI were identified as metastasis suppressor genes from 11p11.2 and 17p12, respectively. CONCLUSION: This assay system is useful to identify metastasis suppressor gene (s) for prostate cancer.

Animals↗

New Treatment Strategy for Bone Metastases from Breast Cancer.

Breast cancer patients frequently develop bone metastasis. Parathyroid hormone-related protein, an osteoclast activating factor, might be necessary for tumorto erode bone and grow at skeletal site. Bisphosphonates have an affinity for bone and are potent inhibitors of osteoclastic bone resorption. In light of this,53 patients with bone metastasis from breast cancer were treated with chemoendocrine(mainly high-dose medroxyprogesterone acetate as the endocrine therapy) therapy + bisphosphonate (pamidronate, Aredia (R)). During the previous 6 years (median 27 months), 53 breast cancer patients with bone metastasis were treated with pamidronate + chemoendocrine therapy. The regimen consisting of pamidronate + chemoendocrine agent was administered to 27 patients as a post relapse first-line regimen and to the remaining 26 cases, which failed first- or second-line treatment as a second or third line regimen. As a result of the combination therapy, sclerotic changes were observed in the osteolytic lesions in 31 of the 53 patients (59%). The effect on the osteolytic lesions did not correlate with the duration of disease free interval, estrogen receptor (ER) status, presence/absence of previous therapy or number of " hot spot(s) ] on bone scintigraphy. Lessening of pain from the bone metastasis was achieved in 83% of the patients after 3 months of pamidronate administration. Pamidronate + chemoendocrine therapy seems highly promising.

Journal Article↗

Competitive NMDA receptor antagonists disrupt prepulse inhibition without reduction of startle amplitude in a dopamine receptor-independent manner in mice.

Prepulse inhibition is thought to reflect the operation of the sensorimotor gating system in the brain, and is reduced in schizophrenic patients and in animals treated with non-competitive NMDA receptor antagonists such as phencyclidine and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine ((+)-MK-801). Previously, we reported that a competitive NMDA receptor antagonist, cis-4-phosphonomethyl-2-piperidine-carboxylate hydrochloride (CGS 19755), also disrupts prepulse inhibition concomitantly with a marked reduction of startle amplitude elicited by pulse alone in rats. In the present study, the effect of NMDA receptor antagonists on prepulse inhibition was tested in mice. In addition, involvement of the dopaminergic system in CGS 19755-induced disruption of prepulse inhibition was examined. When CGS 19755 was subcutaneously administered at 40 and 80 mg/kg, prepulse inhibition was disrupted without any change in the startle amplitude elicited by pulse alone. Intracerebroventricularly administered CGS 19755 disrupted prepulse inhibition at dosages of 0.1 and 0.2 microg/mouse. The same dosages of R-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (R-CPP), another competitive NMDA receptor antagonist, also decreased prepulse inhibition, while its less active enantiomer, S-CPP, did not affect prepulse inhibition at 0.2 microg/mouse (i.c.v.). A typical neuroleptic, haloperidol, did not significantly improve CGS 19755 (40 mg/kg s.c.)-induced disruption of prepulse inhibition. These results suggest that the disruption of prepulse inhibition by CGS 19755 and R-CPP is NMDA receptor-mediated and dopamine receptor-independent.

Analysis of Variance↗

Inability of bone turnover marker as a strong prognostic indicator in prostate cancer patients with bone metastasis: comparison with the extent of disease (EOD) grade.

BACKGROUND: Although clinical investigations of bone turnover markers in prostate cancer patients have been conducted, the relationships of pretreatment levels of the markers to the prognosis of patients with bone metastasis has not been fully examined. METHODS: The serum levels of carboxy-terminal propeptide of type I procollagen (PICP) and carboxy-terminal telopeptide of type I collagen (ICTP), alkaline phosphatase (ALP), and prostate-specific antigen (PSA) were examined in 48 untreated prostate cancer patients with bone metastasis, and the prognoses of the patients were evaluated using univariate and multivariate analyses. RESULTS: The patients with low PICP or ALP values had significantly better outcomes in terms of cause-specific survival compared to the patients with high PICP or ALP values. There was no significant difference in survival between patients with high and low ICTP or PSA values. The multivariate analysis of PICP, ICTP, ALP, PSA, and extent of disease (EOD) grade revealed that only the EOD grade was an important prognostic indicator for survival. CONCLUSIONS: These results demonstrate that the extent of bone metastasis evaluated by bone scintigrams is a more important prognostic indicator than are the serum biochemical markers of bone turnover.

Aged↗

Interleukin-1alpha concentration in tumors as a risk factor for liver metastasis in gastric cancer.

To investigate the relationship between the concentration of interleukin-1alpha (IL-1alpha) and liver metastasis in gastric cancer, the concentration of IL-1alpha was measured in homogenized tumor samples from 61 patients with gastric cancer. A significantly higher concentration of IL-1alpha was observed in tumors from patients with liver metastasis than in those from patients without liver metastasis; in differentiated type tumors than in undifferentiated type tumors; in tumors associated with moderate to severe venous invasion than in those associated with mild or no invasion; and in tumors with expansive or intermediate growth pattern (INFalpha, INFbeta) than in those with an infiltrative pattern (INFgamma) by Student's t-test. Stepwise logistic regression revealed IL-1alpha, depth of invasion, venous invasion, and tumor size to be associated independently with liver metastasis. These findings led us to conclude that the IL-1alpha concentration was on eof the most useful determinants of liver metastasis among the various clinicopathologic characteristics.

Humans↗

Pattern of progression and survival in hormonally treated metastatic prostate cancer.

BACKGROUND: Patients with prostate cancer generally respond to androgen ablation therapy, but progression to androgen-independence is frequently observed. To further evaluate disease progression, the pattern of progression and survival in hormonally treated metastatic prostate cancer was examined. METHODS: One hundred and ninety-three patients with untreated metastatic prostate cancer (TxNxM ) who received endocrine therapy between 1986 and 1995 were included in the present study. The pattern of progression was evaluated in these patients. RESULTS: One hundred and eighteen of the 193 patients (61.1%) had disease progression: 33 had local progression, 73 had distant progression and 12 had distant with local progression. Patients with only local progression had a longer interval to disease progression and longer survival than those with distant progression. The interval from disease progression to death in patients with local progression was longer than in those with distant progression. The patients whose prostate-specific antigen (PSA) had not been normalized 3 months after the start of endocrine therapy had a tendency to progression either into the prostate or into distant sites. Patients with extent of disease (EOD) scores of 3 and 4 progress, especially to distant sites, after endocrine treatment. CONCLUSIONS: In untreated metastatic prostate cancer, patients with a poor response of PSA levels and patients with a high volume of bone metastasis (i.e. EOD 3, 4) were in the high-risk group for progression, especially to distant sites. Progression into distant sites was a poor prognostic factor for patients with recurrence to endocrine therapy.

Aged↗

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↗

Radiotherapy for local progression in patients with hormone-refractory prostate cancer.

PURPOSE: The aim of the present study was to investigate the effect of radiotherapy on the local progression of hormone-refractory prostate cancer. METHODS: From 1986 to 1995, 38 patients were diagnosed with local progression without distant progression after hormonal therapy at Chiba University Hospital. Eleven cases were treated with irradiation for local progression. External beam irradiation was delivered to the prostate at a dose of 50-66.6 Gy. RESULTS: In patients treated with radiotherapy, the duration from initial treatment to local recurrence was 6-80 months (mean +/- SD: 33.9 +/- 22.9 months). The follow-up period after irradiation was 7-64 months (mean +/- SD; 25.4 +/- 18.8 months). Three and 5 year cause-specific survival rates from radiotherapy were 46.2 and 23.1%, respectively. Radiotherapy had a marked effect on symptoms associated with local progression and no patients suffered from the symptoms after the radiotherapy. Complications of radiotherapy were limited. CONCLUSIONS: In patients with hormone refractory local progression without distant progression, low morbidity, low mortality radiotherapy offers a variable therapy to other palliative treatments because radiotherapy is able to control local symptoms for a long period of time.

Aged↗

Metanephric adenoma of the kidney.

BACKGROUND: Metanephric adenoma is a rare renal neoplasm that is histologically and clinically unique. We found this neoplasm in a 62-year-old female, whose renal tumor was incidentally detected on abdominal ultrasound examination. METHODS/RESULTS: Ultrasound, computed tomography and magnetic resonance imaging were compatible with those of renal cell carcinoma. With a diagnosis of renal cell carcinoma, right partial nephrectomy was performed. This tumor showed histologic similarity to developing metanephric tubular epithelium. It was composed of uniformly small epithelial cells, which formed tubules. CONCLUSIONS: The patient has been well and healthy for 20 months after surgery. The unique features of metanephric adenoma should be clinically and pathologically recognized because of its invariably benign course.

Adenoma↗

Prognosis of patients with T4 prostate carcinoma.

BACKGROUND: The clinical course of patients with T4 prostate carcinoma was examined in order to consider whether there are alternative treatment options besides androgen ablation therapy. METHODS: From 1986 to 1995 at Chiba University Hospital, there were 22 cases of T4 prostate carcinoma. Sixteen cases had no bone metastasis at initial diagnosis. Tumor grade and response of prostate-specific antigen (PSA) to endocrine treatment were evaluated in these 16 cases. RESULTS: Four patients had moderately differentiated and 12 had poorly differentiated adenocarcinoma. For initial treatment, all patients received endocrine therapy. Anti-androgen therapy was effective in 15 cases and the 5 year cause-specific and progression-free survival rates were 72.1 and 38.1%, respectively. Patients with moderately differentiated tumors tended to have a longer disease-free period than those with poorly differentiated tumors (P = 0.047). CONCLUSIONS: Endocrine therapy was effective in patients with T4 tumors. It was suggested that aggressive local treatment (i.e. radiotherapy) in combination with endocrine therapy may be considered if the patients had no distant metastases and had a long life expectancy.

Adenocarcinoma↗

Increased glomerular cytosolic phospholipase A2 activity of OLETF rats with early diabetes.

In view of the potential role of prostaglandins (PGs) in development of glomerular hyperfiltration leading to diabetic nephropathy, we studied the temporal relationship of the activity of cytosolic phospholipase A2 (cPLA2), a rate-limiting enzyme for eicosanoid biosynthesis, with hyperfiltration and the histological changes in glomeruli using OLETF rats, a model for non-insulin-dependent diabetes mellitus (NIDDM). Diabetes mellitus and associated histopathological changes, which developed spontaneously by 30-46 weeks after birth of OLETF rats, were accompanied by approximately 65% increase in glomerular cPLA2 activity that showed significant correlations with elevated plasma glucose levels and creatinine clearance. Moreover, mesangial cells cultured for 5 days with high glucose exhibited approximately 2-fold higher cPLA2 activity than those cultured with physiologic level of glucose. These data suggest that increased glomerular cPLA2 activity leads to production of PGs, which may promote the progression of early diabetic glomerular hyperfiltration and subsequent diabetic nephropathy.

Aging↗

Vitamin D receptor gene polymorphism in Japanese patients with prostate cancer.

Vitamin D receptor gene polymorphism was determined in 66 and 60 Japanese patients with prostate cancer and non cancer controls, respectively. In contrast to previous reports showing an association between vitamin D receptor polymorphism of a TaqI restriction fragment length polymorphism at codon 352 (genotype tt) and prostate cancer in an American population, the frequency of genotype tt is less than one percent in the Japanese population. There was no difference between the patients and the controls in the vitamin D receptor TaqI genotype. In patients with metastatic prostate cancer, genotype TT had a tendency to shorter progression free survival compared to genotype Tt, but the number of patients was limited.

Aged↗