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Biomedical subjects

T Seguchi

Publications and source records attributed to T Seguchi.

At least 55 records · Page 3Linked to original sources

[Clinical evaluation of serum basic fetoprotein in patients with urogenital malignancies and renal transplantation].

The serum basic fetoprotein (BFP) in patients with urogenital diseases was measured by enzyme immunoassay (EIA). The positive range of serum BFP was defined to be 75 ng/ml or more. In benign cases except for renal transplantation, the positive rate of serum BFP was 11.1% (5/45), and relatively high (21.4%, 3/14) in benign prostatic hypertrophy. In cases of urogenital cancers before treatment, the positive rate of serum BFP was 29.1% (16/55), and increased with the progression of clinical stage. Eleven of the patients with positive serum BFP before treatment were re-examined after treatment, and all of them exhibited a marked decrease of the titer of serum BFP. In seventeen renal transplant patients, the positive rate of serum BFP was 100% (8/8) in acute rejection, 66.7% (2/3) in chronic rejection and 0% (0/6) in rejection-free condition. We conclude that serum BFP is a clinically beneficial marker for renal transplant rejections and urogenital malignancies.

Genital Neoplasms, Male↗

[Establishment and characterization of new cell lines from human renal cell carcinoma].

We have characterized seven human renal cell carcinoma cell lines established from primary sites of five patients between 1987 and 1989. Two lines, OUR-20P and OUR-20S, were derived from the OUR-20 cells by cloning with a dilution method 3 months after the primary culture. These three cell lines were tumorigenic in athymic nude mice when inoculated subcutaneously. Examined by a dye uptake method, OUR-20 was highly sensitive to interferon-alpha (IFN-alpha); OUR-20P, OUR-20S and OUR-30 showed slight sensitivities, while the other three cell lines were insensitive. All seven cell lines have been maintained for more than 2 years and over 50 passages in vitro. Cytogenetic analyses performed 1.5 to 3 years after the starts of primary cultures indicated that all seven cell lines, which exhibited different morphologies in phase-contrast micrographs, were aneuploid with modal chromosome numbers 41 to 89.

Carcinoma, Renal Cell↗

[Clinical evaluation of the combination of carumonam and cefotiam in the treatment of complicated urinary tract infection].

The combination of carumonam (CRMN) and cefotiam (CTM), expected to have a broader spectrum of coverage in connection with urinary tract infections, was evaluated for its effectiveness and safety at the Department of Urology, Osaka University Hospital and 17 affiliated hospitals. CRMN and CTM were given together to 109 patients with complicated urinary tract infections (UTI), of whom 65 cases satisfied the "Criteria of UTI Committee for the Evaluation of Drug Efficacy in the UTI (3rd Ed.)", which was modified by adopting the midstream urine data for women. CRMN and CTM were administered by drip or one-shot infusion at a total daily dose of 4 g (equally mixed 1 g plus 1 g each, twice a day) for 5 consecutive days or longer. The overall clinical efficacy rate in the 65 cases of complicated UTI was 72%, estimated by the criteria cited above. The efficacy rate according to the infection type groupings was 72% for the 29 patients in the 1st group, 100% for the 1 patient in the 2nd group, 100% for the 7 patients in the 3rd group, 83% for the 6 patients in the 4th group, 50% for the 14 patients in the 5th group and 75% for the 8 patients in the 6th group. The disappearance rate of both urinary Gram positive cocci and Gram negative bacilli was 83.3%. Fifteen strains appeared after the treatment, only 4 of which were Gram positive cocci. Among the 109 patients treated with CRMN+CTM, no subjective side effects were recorded and the abnormalized laboratory findings observed were: eosinophilia in one patient, increases in both GPT and GOT in one patient, and lowered creatinine clearance in one patient. With a broader spectrum and safe regimen, the combination of CRMN/CTM is recommended as the first choice against complicated UTI.

Adult↗

Differential effects of brefeldin A on sialylation of N- and O-linked oligosaccharides in low density lipoprotein receptor and epidermal growth factor receptor.

Low density lipoprotein receptor (LDL-R) is a membrane glycoprotein carrying both N- and O-linked oligosaccharides, processing of which is reflected in conversion from a precursor to mature form during its synthesis and intracellular transport. Treatment with brefeldin A (BFA) of mouse macrophage-like J774 cells, Chinese hamster ovary cells, and two human cancer cell lines (A431 and IMC-2) resulted in production of LDL-R with a molecular size 5-10 kDa smaller than that of the mature form in the control cells. Treatment with sialidase caused apparent reduction in the molecular size of LDL-R synthesized in all BFA-treated J774, Chinese hamster ovary, A431, and IMC-2 cell lines as observed for the mature form of the control cells. Thus, O-linked sugar chains of LDL-R were apparently sialylated in the BFA-treated cells. We also examined the effect of BFA on the processing of another membranous glycoprotein, epidermal growth factor receptor (EGF-R) carrying only N-linked oligosaccharides. EGF-R synthesized in the presence of BFA was found to have no response to sialidase treatment, suggesting that the drug blocks the sialylation of EGF-R. The results indicate that BFA causes different effects on the sialylation of LDL-R and EGF-R depending upon linkage types of their oligosaccharides.

Animals↗

Rapid turnover of low-density lipoprotein receptor by a non-lysosomal pathway in mouse macrophage J774 cells and inhibitory effect of brefeldin A.

The low-density lipoprotein (LDL) receptor of molecular mass 155 kDa was expressed on the cell surface of cultured mouse macrophage J774 cells. The conversion rate of precursor to mature form of LDL receptor in J774 cells was comparable to that in mouse fibroblast L cells. The half-life of the LDL receptor of J774 cells was about 2 h, that of L cells was about 11 h. The rapid degradation of LDL receptor was not significantly inhibited by the lysosomotropic agents, chloroquine and NH4Cl, nor by the thiol-protease inhibitors leupeptin and E-64. By contrast, incubation at 18 degrees C retarded the degradation of LDL receptor. Treatment of J774 cells with brefeldin A, an inhibitor of membrane transport between the endoplasmic reticulum and the Golgi apparatus, inhibited the rapid turnover of the LDL receptor. Even after a 9-h chase in the presence of brefeldin A, LDL receptor 5-10 kDa smaller than the normal mature form was found to be stable. Rapid turnover of the LDL receptor in the macrophages appeared to occur after exit from the Golgi apparatus, possibly during transport of the LDL receptor to the plasma membrane.

Animals↗

[Treatment results and practical dosage of PVB therapy for advanced testicular tumors].

Twenty cases of advanced testicular tumors treated primarily by PVB therapy were reviewed. PVB therapy induced CR in 9 patients (45%). PR in 3 (15%), MR in 3, NC in 3 and PD in 2. The practical doses of the three drugs (cisplatin, vinblastine, bleomycin) were calculated for the initial three courses, and there was very little difference in the mean doses of the drugs per course between good responders (CR + PR, n = 12) and poor responders (MR + NC + PD, n = 8). The interval of each course for good responders was unexpectedly longer than that for poor responders (p less than 0.02). The prognosis based on several clinical factors was studied. The five-year survival rate (Kaplan-Meier) was 100% in stage II (n = 6) and 68.6% in stage III (n = 14) (statistically significant) and 90% in non-bulky cases (n = 10) and 58.3% in bulky cases (n = 10) (statistically insignificant). The two-year survival rate of 5 cases containing choriocarcinoma element was 40.0%, which was statistically worse than that (86.8%) of other histological types (p less than 0.05). These results suggest that the PVB therapy is not sufficient to cure the cases with choriocarcinoma element or bulky metastasis.

Antineoplastic Combined Chemotherapy Protocols↗

[Clinical statistics of germinal testicular cancer].

We experienced a hundred and fifty-six cases of germinal testicular cancer at Osaka University Hospital from 1957 to 1988. Histologically, 114 cases (73.1%) were simple type, and 42 cases (26.9%) were mixed type. Eighty cases (51.3%) were seminoma, and 76 cases (48.7%) were non-seminoma. All patients of seminoma were over 20 years of age, and the mean age was 36.1 years. Non-seminoma cases were distributed as to with two peaks, one in 0 to 4 year-old and another in 20 to 39 year-old, and the mean age was 22.9 years. The seminoma/non-seminoma ratio as to clinical stages were 63 cases/48 cases in Stage 1, 6/9 in Stage 2A, 5/6 in Stage 2B and 6/13 in Stage 3. The five-year survival rate (by Kaplan-Meier's method) was 98.4% for Stage 1 (71 cases), 72.7% for Stage 2A (11 cases), 0% for Stage 2B (4 cases) and 20% for Stage 3 (5 cases) between 1957 and 1978, and 100% for Stage 1 (40 cases), Stage 2A (4 cases), Stage 2B (7 cases) and 26.8% for Stage 3 (14 cases) between 1979 and 1988. The five-year survival rate of 20 advanced cases treated mainly by PVB regimen was 100% for Stage 2 (6 cases) and 68.6% for Stage 3 (14 cases). Five advanced cases containing choriocarcinoma elements were treated by PVB regimen and its two-year survival rate was 40.0%, which was statistically worse than that (86.8%) of other histological types (p less than 0.05).

Adolescent↗

[Leiomyoma of urinary bladder: report of a case].

A case of leiomyoma of the urinary bladder in a 46-year-old woman is reported. The patient was referred to us because of incidental finding of a mass in the bladder. Cystoscopy revealed a protruding tumor covered with normal-appearing urothelium on the right posterior wall of the bladder. The tumor was well-demarcated from adjacent organs on echography and computed tomographic scan. Transurethral biopsy revealed a bladder leiomyoma. Partial cystectomy was performed. The patient is now apparently free of disease 7 months after the operation.

Biopsy↗

Insulin receptor and altered glucose transport in a monensin-resistant mutant of Chinese hamster ovary cell.

A monensin-resistant mutant Monr-31, derived from Chinese hamster ovary (CHO) cell line, has been shown to have a reduced number of insulin receptors and a reduction in glucose uptake in response to insulin. We have further investigated the possibility that altered glucose uptake in Monr-31 cells is related to an alteration in the activity of the insulin receptor. Uptake of glucosamine, 2-deoxy-D-glucose, and 3-O-methyl-D-glucose in Monr-31 cells was one-half to one-third that of CHO cells. The cellular content of the glucose transporter in Monr-31 was reduced to about one-third that of CHO as assayed by use of an antiglucose transporter antibody. After transfection with the human insulin receptor cDNA, we obtained clones CIR-0 from CHO, and MIR-2 and MIR-15 from Monr-31; CIR-0 expressed a tenfold higher level of the insulin-binding activity than did CHO, and MIR-2 and MIR-15 expressed a 20-fold higher level than did Monr-31. Glucose uptake in both CHO and CIR-0 was significantly enhanced by exogenous insulin, but not in Monr-31, MIR-2, and MIR-15. The beta-subunits of insulin receptor in CHO, CIR-0, Monr-31, and MIR-2 were similarly phosphorylated. The decreased glucose transport activity in Monr-31 cells is discussed in relation to the absence or presence of insulin receptor expression.

3-O-Methylglucose↗

[Multidisciplinary treatment of advanced testicular tumors].

Present status and problems of multidisciplinary treatment for advanced testicular tumors were reviewed. In this paper, we presented the treatment results of 69 patients with advanced testicular cancer treated by multidisciplinary treatment. The primary PVB therapy induced a CR in 39 patients (56.5%), and 8 patients of them relapsed. After primary chemotherapy 40 patients, incomplete responders and relapsed cases, underwent salvage therapy. Salvage chemotherapy with CDDP and VM-26 or VP-16 was performed in 19 patients, and induced a CR in 10 (58.5%). Salvage surgery was done in 29, and produced NED in 22 patients (75.9%). As overall results of salvage therapy, 25 of 40 patients are living with NED, 3 are alive with tumors, and 12 patients died of the disease. As final results of the multidisciplinary treatment, of 69 patients with advanced testicular tumors 48 patients are living with NED and 3 patients with tumors, and 18 patients died of the disease. A overall cure rate was 73.9%. The overall 8-year survival rates of the 69 patients was 70.5%. The survival rate of 39 CR-patients, 23 PRs and 7 NRs was 94.9%, 45.7% and 0% at 4 years, respectively. The 8-year survival rates according to clinical stage for the last 10 years were 100% in stage I, 74.0% in stage II, and 70% in stage III. The survival rates for 10 years from 1968 to 1978 were 88.3% in stage I. 60% in stage II, and 33.3% in stage III. The treatment results were so satisfactory. To reach the treatment goal for advanced testicular tumors, importance of aggressive multidisciplinary treatment was emphasized.

Adolescent↗

[Case report of a complete regression of para-aortic lymph node metastasis from bladder cancer by oral administration of UFT].

We report a case in which para-aortic lymphnode metastasis from bladder cancer regressed completely by administration of UFT. The patient was a 72-year-old male who had undergone a total cystectomy for bladder cancer. Since para-aortic node metastasis was recognized in abdominal CT 1 year after the operation, we treated this patient by oral administration of UFT at a dose of 600 mg per day, and the metastatic lesion regressed completely 2 months later. After the complete regression, UFT was administered for one year. At present, 6 months after the discontinuation of UFT, para-aortic lymphnode swelling is not observed. Although adverse effects such as pigmentation and nail degeneration was found, there was no abnormal finding in blood analysis and chemistry. It is suggested that UFT may be effectively used for bladder cancer.

Administration, Oral↗

A new class mutation of low density lipoprotein receptor with altered carbohydrate chains.

In a monensin-resistant mutant (Monr-31) of Chinese hamster ovary cells, the O-linked sugar chains of the low density lipoprotein (LDL) receptor are altered, suggesting a mutation at a Golgi apparatus gene. In a compactin-resistant mutant (MF-2) of Chinese hamster V79 cells, the mature LDL receptor is apparently 5000 daltons smaller; the difference is due to altered glycosylation of O-linked sugar chains. Hybrids between MF-2 and Monr-31 still produced LDL receptor molecules with aberrant sugar chains; thus both mutants are in the same complementation group. Krieger and his colleagues (Krieger, M., Kingsley, D., Sege, R., Hobbie, L., and Kozarsky, K. (1985) Trends. Biochem. Sci. 10, 447-452) have classified Chinese hamster ovary cell mutants with altered LDL receptor structure into four groups: ldlA, ldlB, ldlC, and ldlD. Cell-cell hybrids between their ldl mutants and Monr-31 produced wild type mature LDL receptors with normal molecular sizes, suggesting that these compactin- and monensin-resistant mutants define a new class of LDL receptor mutant. Since both of our mutants are defective in internalization of LDL, we assign them as int mutants. This may imply a further etiology for hypercholesterolemia, and cases can now be examined for such a class.

Animals↗

Novel feature of metabolism of low density lipoprotein receptor in a mouse macrophage-like cell line, J774.1.

Biosynthesis, processing, and degradation of low density lipoprotein (LDL) receptors were studied in a mouse macrophage-like cell line, J774.1, by immunoprecipitation and immunoblotting with an antibody directed against the COOH-terminal 14 amino acids of the LDL receptor. The molecular weight of the mature LDL receptor of J774.1 cells maintained in RPMI medium was 140,000 under nonreducing condition and 160,000 under reducing condition in sodium dodecyl sulfate-polyacrylamide gels. These sizes are 10,000-15,000 daltons larger than those of the receptor in other mouse fibroblastic cells or P388 leucocyte. However, when J774.1 cells were cultured in Dulbecco's modified Eagle's medium, the molecular weight of the mouse cell lines, 123,000 under nonreducing condition and 153,000 under reducing condition. The larger LDL receptor molecules produced by J774.1 cells cultured in RPMI were insensitive to the treatment with end-alpha-N-acetylgalactosaminidase (O-glycanase), suggesting that aberrant serine/threonine-linked (O-linked) glycosylation might account for the apparent large size. Pulse-chase experiments revealed that the rate of processing of the LDL receptor from precursor to mature form in J774.1 was similar to that in other mouse cell lines, but the rate of degradation was much faster: half-life of the LDL receptor of J774.1 was about 2 h. No significant difference in biological function or lifetime was observed between the normal and the larger LDL receptor. This novel character of molecular size and lifetime of the LDL receptor in J774.1 is discussed in relation to altered maturation and/or modification during receptor biosynthesis.

Animals↗

[The clinical value of urinary polyamine analysis in urological disease].

To study the clinical usefulness of the determination of urinary polyamine levels, voluntary urine of several urological diseases including 56 bladder tumor patients was analyzed by high performance liquid chromatography. The obtained values were adjusted by the concentration of urinary creatinine and expressed as the unit of mumol/g creatinine (mumol/g Cr) From the measurement of 8 normal adults, the normal upper limit of each polyamine was decided by mean + 2SD, and the limit for total polyamine was 59.1 mumol/g Cr, putrescine 38.1 mumol/g Cr, spermidine 16.6 mumol/g Cr and spermine 9.2 mumol/g Cr, respectively. In the patients with non-neoplastic benign urological disease, the polyamine levels were statistically not different from those of the normal adults. In the case of bladder tumor, the urinary levels of total polyamine, putrescine and spermine were significantly elevated compared with the control group. The true positive rate of this determination in bladder tumor patients was 26/56 (46%) by total polyamine level, 21/56 (38%), by putrescine level, 11/56 (56%) by spermidine level and 16/56 (29%) by spermine level. Grade or stage of the bladder tumor did not have any significant correlation with the urinary polyamine level. This determination would not be included in routine clinical examinations due to the difficulty of measurement, difference of urine sampling and lack of high sensitivity and specificity.

Biomarkers, Tumor↗

Low binding capacity and altered O-linked glycosylation of low density lipoprotein receptor in a monensin-resistant mutant of Chinese hamster ovary cells.

We have studied function and structure of the low density lipoprotein (LDL) receptors in a monensin-resistant (Monr-31) mutant isolated from Chinese hamster ovary (CHO) cells. To assay the ability of the receptor to bind LDL, we employed three methods, 125I-LDL binding to the cells at 4 degrees C, 125I-LDL binding to the receptor-phospholipid complex (Schneider, W.J., Goldstein, J.L., and Brown, M.S. (1980) J. Biol. Chem. 255, 11442-11447), and ligand blotting (Daniel, T.O., Schneider, W.J., Goldstein, J.L., and Brown, M.S. (1983) J. Biol. Chem. 258, 4606-4611). The LDL receptor number was similar in both CHO and Monr-31, but the binding affinity was reduced in the mutant. The semi-quantitative immunoblotting assay with an antibody directed against the COOH-terminal 14 amino acids and the ligand-blotting assay with LDL also showed that the relative steady-state level of the receptor in Monr-31 was comparable to that in CHO, whereas the binding capacity of the receptor in Monr-31 was lower than that in CHO. The precursor and degradation forms of the LDL receptors produced in the mutant cells were similar in size to those in the parental cells, but the apparent molecular mass of the mature receptor protein in sodium dodecyl sulfate-polyacrylamide gels was reduced about 5000 daltons in the mutant. These results suggest a structural change at the NH2-terminal LDL binding domain. Tests of the effects of tunicamycin, endo-alpha-N-acetylgalactosaminidase (O-glycanase), and sialidase (neuraminidase) on the molecular size of the mature receptors indicated that the reduced size of the receptor in the mutant cells resulted from altered oligosaccharide chain(s) linked to serine/threonine residues in the binding domain. We compared the molecular sizes and binding activity of human LDL receptors in several clones derived from CHO and Monr-31 cells which were transfected with human LDL receptor cDNA. The human LDL receptors produced in the transfected clones of Monr-31 were also smaller in molecular size and lower in binding capacity than those produced in the transfected clones of CHO. These results suggest that both structural and functional alteration of the LDL receptor of Monr-31 is not caused by a mutation in the structural gene of the LDL receptor but by altered processing or maturation of the receptor. The correlation of the decrease in molecular size and reduced binding capacity of the LDL receptor is discussed.

Animals↗

[Combination chemotherapy of urothelial cancer with cisplatin, cyclophosphamide, doxorubicin and peplomycin: treatment of advanced cases and adjuvant chemotherapy after radical operation].

Cisplatin, doxorubicin, cyclophosphamide and peplomycin have been used in combination for urothelial cancer. Doxorubicin 30-40 mg/m2 and cyclophosphamide 300-400 mg/m2 were administered on day 1, cisplatin 12-15 mg/m2 daily for 5 days and peplomycin 4-6 mg/m2/day by continuous infusion for 5 days. Courses were given at 3-4-weekly intervals in principle. Eight patients with measurable locally advanced or metastatic disease were treated with this protocol, and four achieved partial remission (objective response 50%). None of the four patients with locally advanced disease showed any response, (three no change, one progressive disease). Another eight patients were treated with adjuvant chemotherapy after radical surgery. Of the four patients with high-grade (G3) and high-stage (pT3b-pT4) bladder cancer, three relapsed 7-14 months after surgery, leaving one who still remains disease-free after 8 months. These preliminary results seem to indicate that our protocol is insufficient for adjuvant chemotherapy after radical surgery for high-grade and high-stage urothelial cancer.

Aged↗

[Primary malignant melanoma of the female urethra: a case report].

A 76-year-old woman visited us with the chief complaint of a urethral mass on September 11, 1984. There was a thumb-sized, brownish and painless mass in the posterior wall of the urethra. Although excretory urogram revealed nothing remarkable, CT scan suggested metastasis of retroperitoneal lymph nodes. Biopsy of the urethral mass revealed malignant melanoma. She was treated with combined chemotherapy of dimethyltriazenoimidazole carboxamide, peplomycin, and cis-diamine-dichloride platinum, but died of respiratory insufficiency on January 6, 1985. Thirteen cases of primary malignant melanoma of the female urethra, including our own, have been reported in the Japanese literature.

Aged↗