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Biomedical subjects

O Yoshida

Publications and source records attributed to O Yoshida.

At least 343 records · Page 19Linked to original sources

Allelic loss at chromosome 3p characterizes clear cell phenotype of renal cell carcinoma.

Incidence of the loss of heterozygosity on chromosome 3p was evaluated using 7 polymorphic probes in 35 Japanese patients with sporadic renal cell carcinoma (RCC). Overall frequency of the loss of heterozygosity on 3p was 53%, representing 16 of 30 informative cases. Examination of the relationship between histopathological phenotypes of RCC and incidence of the 3p loss revealed that the loss of heterozygosity in clear cell type tumors (75%, 12 of 16) was significantly (P less than 0.01) more frequent than that in granular cell type tumors (14%, 1 of 7). In addition, three mixed cell type tumors, consisting predominantly of granular cell components, showed no loss of chromosome 3p loci. These findings may support the notion that the loss of heterozygosity on chromosome 3p is a nonrandom event in the tumorigenesis of sporadic RCC, and suggest that this type of chromosomal rearrangement is specific to the clear cell phenotype of RCC.

Carcinoma, Renal Cell↗

Adhesion of mouse mast cells to fibroblasts: adverse effects of steel (Sl) mutation.

Mouse bone marrow-derived cultured mast cells proliferate on +/+ mouse embryo-derived 3T3 fibroblasts, but not on Sl/Sld mouse embryo-derived 3T3 fibroblasts, in the absence of IL-3 and IL-4 (Fujita et al: Proc. Natl. Acad. Sci. U.S.A. 86:2888-2891, 1989). To further characterize the mast cell-fibroblast interactions and the effects of Sl mutation, we tried to analyze the adhesion of cultured mast cells to 3T3 fibroblasts in vitro. Mast cells plated onto NIH/3T3 fibroblasts showed marked adhesion within 30 min, which reached a plateau after 3 h. The numbers of adhered mast cells were linear over the range of 10(3) to 5 x 10(5) cells inoculated into each (2 cm2) of 24 multiwells. Adhesion required active energy production and the presence of divalent cations. It was not inhibited by an RGD-containing peptide, an anti-LFA-1 antibody, or asialofetuin. Mast cells adhered efficiently to the eight 3T3 cell lines derived from +/+ mouse embryos, but not to the eight 3T3 cell lines derived from Sl/Sld mouse embryos. Adhesion to +/+ mouse spleen-derived fibroblasts lacking mast cell-supporting activity was comparable to that to Sl/Sld/3T3 cells. The failure of mast cells to adhere to fibroblasts with the Sl mutations was not due to a production of a diffusible inhibitor by the latter. These results indicate that production of wild type Sl gene product by fibroblasts is mandatory for adhesion/migration, as well as for proliferation of mast cells on them, and that the coculture system should be useful for the biochemical and molecular analysis of these interactions.

Animals↗

Evaluation of anti-human immunodeficiency virus effect of recombinant CD4-immunoglobulin in vitro: a good candidate for AIDS treatment.

CD4 molecule, a surface marker of helper T lymphocytes, interacts with gp120 of human immunodeficiency virus (HIV) with a high affinity and, hence, serves as a virus receptor. Soluble chimeric CD4-immunoglobulin (Ig) possesses anti-HIV activity due to its binding activity to gp120. Furthermore, this recombinant molecule has unique Ig-like properties representing Fc receptor-binding activity and a long half-life in vivo. In this report we have thoroughly evaluated the effect of this compound on HIV infection using different in vitro systems. Treatment with 4 micrograms/ml of recombinant CD4-Ig after infection completely blocked the HIV-specific cytopathic effect, antigen expression, and virus release in MT-4 cells, a human T cell line which is highly susceptible to HIV. Similarly, this molecule blocked the HTLV-III/B and YU-1 strains of HIV infection in peripheral blood mononuclear cells even at 1 microgram/ml. Pretreatment of the Fc receptor-positive cell line U937 with this reagent resulted not in enhancement but again in blocking of HIV infection. About 95% of HIV infection was inhibited in U937 cells when cells were treated with this compound at the time of exposure to HIV. Recombinant-CD4-Ig also completely inhibited HIV-induced syncytia formation between MOLT-4 and MOLT-4/HIV and resulting virus release at 8 and 2 micrograms/ml, respectively. Due to its stability and long half-life, this compound could be a promising therapeutic agent against HIV infection.

Acquired Immunodeficiency Syndrome↗

Impaired interferon-alpha production in whole-blood cultures from bladder cancer patients.

Interferon-alpha (IFN-alpha) production was investigated in whole-blood cultures of 66 bladder cancer patients and 65 control subjects. IFN synthesis was induced with Sendai virus, and IFN activity was assayed in FL cells challenged with vesicular stomatitis virus (VSV). The mean levels of the IFN-alpha produced were 5,724 +/- 2,288 IU/ml in the control subjects and 4,800 +/- 2,353 IU/ml in the bladder cancer patients. IFN-alpha production was significantly suppressed in the bladder cancer patients compared with that in the control subjects (P less than 0.05). The impairment in IFN-alpha production correlated with the tumor grade, and it was shown that the tendency toward decreased IFN-alpha production was closely associated with the advancement of the tumor stage. Our results suggested that the decreased IFN-alpha production may contribute to the disordered immunoregulation in bladder cancer patients.

Aged↗

Effects of dietary calcium, magnesium and phosphorus on the formation of struvite stones in the urinary tract of rats.

After feeding various diets we studied the effects of dietary calcium, magnesium and phosphorus on the formation of struvite stones in rats with urinary tract infections, and also studied the effects of the administration of vitamin D3 and aluminium gel on stone formation. A low-magnesium diet decreased urinary magnesium and prevented stone formation, but a medium-calcium diet did not significantly decrease stone weight. A high-calcium diet decreased urinary phosphorus and inhibited stone formation. A high-calcium and high-phosphorus diet decreased urinary excretion of magnesium and inhibited stone formation. Although the administration of vitamin D3 did not inhibit stone formation, aluminium gel decreased the urinary level of phosphorus and prevented stone formation. A marked decrease in urinary magnesium and/or phosphorus may prevent struvite stone formation in rats with urinary tract infections.

Aluminum↗

Does a gonadotropin-releasing hormone analogue prevent cisplatin-induced spermatogenic impairment? An experimental study in the mouse.

The cytotoxic effect of cis-diamminedichloroplatinum II (cisplatin, CDDP) on spermatogenesis in BALB/C mice, and possible protection of the testes by leuprolide acetate (D-Leu-6 LHRH(1-9)-ethylamide, TAP-144, leuprolide), a synthetic gonadotropin-releasing hormone analogue, were examined. Temporary interruption of the pituitary-gonadal axis by the analogue and amelioration of the gonadal toxicity of cisplatin by reducing the cell division rate in spermatogenesis were expected. The results showed cisplatin to have a cytotoxic effect on spermatogenic cells in BALB/C mice. The administration of leuprolide had no effect on testicular weight or histological findings in the mouse testes. Pretreatment and simultaneous administration of leuprolide did not reduce the damaging effect of cisplatin on the testes in mice. This is at variance with a previously published report.

Animals↗

Vanadium transfer during haemodialysis.

The authors examined transport of vanadium (V) in 100 chronic haemodialysis (HD) patients. Serum V levels were different at the inflow and the outflow site. Vanadium was transferred from blood to dialysate through the membrane. Serum V levels decreased in the course of haemodialysis.

Dialysis Solutions↗

Removal of silicon, aluminum and beta 2-microglobulin in chronic haemodialysis patients.

One hundred outpatients on chronic haemodialysis with polymethylmethacrylate (PMMA) membrane dialyzer were randomly chosen. A control group of 100 likewise randomly chosen outpatients were treated with cuprophane membrane dialyzer. In both groups the treatments lasted for one year. Comparison of the test results revealed that Si, Al and beta 2-M.G levels could be reduced in patients on chronic HD with PMMA.

Aluminum↗

Afferent nipple valve malfunction caused by anchoring collar: an unexpected late complication of the Kock continent ileal reservoir.

In the construction of a Kock continent ileal reservoir for urinary diversion, significantly high rates of late postoperative complications regarding nipple valves, the efferent limb in particular, have been reported. There are only a few reports on afferent nipple valve malfunction. A total of 42 patients who underwent a Kock pouch operation and were observed for more than 12 months (mean 38 months) was evaluated in terms of afferent nipple valve malfunction. Late afferent nipple valve complications were observed in 10 of the 42 patients (24%). These complications included erosion of the polyester fiber fabric used as a collar (5 patients), stenosis of the afferent limb (2) and obstruction of the afferent nipple by a mucous plug or fungus ball (3). The latter 2 complications were due to mechanical or dynamic obstruction of urine flow caused by a nonabsorbable collar. None of the 10 patients had problems with efferent nipple valve function. Our results suggest that the peristaltic direction of the intestine and the use of nonabsorbable material as a collar are primarily responsible for the late afferent nipple valve complications. Further modifications are needed to produce a stable nipple valve. Otherwise, simpler and more reliable alternative techniques of antireflux anastomosis should be considered.

Adult↗

Activation by the protein-bound polysaccharide PSK (krestin) of cytotoxic lymphocytes that act on fresh autologous tumor cells and T24 human urinary bladder transitional carcinoma cell line in patients with urinary bladder cancer.

PSK, a protein-bound polysaccharide Kureha, was tested for its ability to modulate the cytotoxicity of lymphocytes that act on autologous tumor cells and T24 human urinary bladder tumor cells in urinary bladder cancer patients in a 6-h 51Cr release assay. In vitro treatment of peripheral blood lymphocytes (PBL) with PSK for 18 hours resulted in an augmentation or induction of cytotoxicity against relatively resistant T24 cells in previously reactive and nonreactive cases, respectively. The PSK-treated PBL were able to kill more effectively tumor cells that were freshly isolated from the same cancer patients than non-treated PBL. The effects of PSK were noted with PBL as well as tumor infiltrating lymphocytes (TIL) and with PSK at concentrations of 10 to 100 micrograms./ml., while PSK at higher doses reduced their lytic activities. The addition of PSK to the assay at the same concentrations also enhanced the cytotoxicities. Autologous tumor killing (ATK) activities of both large granular lymphocytes (LGL) and T lymphocytes were enhanced by PSK. Treatment of PBL with PSK did not effect on the proportion of PBL binding to the tumor cells, while it augmented the cytotoxic activity. Cell-free supernatant of PSK-stimulated lymphocyte culture did not contain any detectable amounts of interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma) and interleukin-2 (IL-2). In addition, anti-IFN-alpha monoclonal antibody (MAb), anti-IFN-gamma MAb and anti-IL-2 MAb did not inhibit PSK-induced augmentation of cytotoxicity against T24. Oral administration of PSK (three gm./day) to patients with urinary bladder cancer daily for seven days before operation resulted in an augmentation of the cytotoxicity against T24 cells in five out of 10 patients and no change of the cytotoxicity in the other five patients. ATK activity was also enhanced by oral administration of PSK in three out of five patients. These results indicate that the antitumor activity of PSK may be in part mediated through activation of tumor killing system independent of IFN-alpha, IFN-gamma and IL-2.

Adjuvants, Immunologic↗

Epstein-Barr virus activating principle in husbands' semen of cervical cancer patients.

A short-term in vitro assay for detecting tumor promoter activity has been cultivated utilizing the induction of Epstein-Barr virus early antigen (EBV-EA) in EBV genome-carrying human lymphoblastoid cell line (Raji cell) system. By using this system, we found that some of human semen samples possessed a marked capacity to induce EBV-EA, suggesting possible tumor promotor activity of semen. In the present study, 60 semen samples obtained from husbands of cervical cancer patients and 90 control samples were incubated with Raji cells for 48 h, and EBV-EA-expressing cells detected by indirect immunofluorescence were counted. The percentages of EBV-EA-positive cells treated with semen of cervical cancer patients' husbands (8.17 +/- 5.43%) were significantly higher than those of controls (5.23 +/- 5.91%). Since most of EBV-EA expressing effect on Raji cells show overlapping with tumor promotor activities, our present results implies the circumstantial association of seminal EBV-EA inducing activity with occurrence of human cervical cancer.

Adult↗

Evidence for insertion sequence-mediated spread of the thermostable direct hemolysin gene among Vibrio species.

The tdh gene of Vibrio parahaemolyticus which encodes the thermostable direct hemolysin has been found in some strains of other Vibrio species. Analysis of seven tdh genes cloned from V. parahaemolyticus, Vibrio mimicus, and non-O1 Vibrio cholerae revealed that all tdh genes were flanked by insertion sequence-like elements (collectively named ISVs) or related sequences derived from genetic rearrangement of ISVs. The ISVs possessed 18-bp terminal inverted repeats highly homologous to those of IS903 (2- to 4-bp mismatch) and were 881 to 1,058 bp long with less than 33.6% sequence divergence. These features and nucleotide sequence similarities among ISVs and IS903 (overall homologies between ISVs and IS903, ca. 50%) strongly suggest that they were derived from a common ancestral sequence. A family of ISVs were widely distributed in Vibrio species, often regardless of the possession of the tdh genes, and one to several copies of the ISVs per organism were detected. A strain of V. mimicus possessed two copies of the ISVs flanking the tdh gene and three copies unrelated to the tdh gene. However, the transposition activity of the ISVs could not be demonstrated, probably because they had suffered from base changes and insertions and deletions within the transposase gene. The possible mode of ISV-mediated spread of the tdh gene is discussed from an evolutionary standpoint.

Bacterial Toxins↗

VAB-6 chemotherapy causes spurious elevation of alpha-fetoprotein associated with liver dysfunctions.

In order to elucidate the mechanism of elevation of alpha-fetoprotein (AFP) which we often observed during VAB-6 chemotherapy, we analyzed sequential changes of AFP, liver enzymes and bilirubin in 10 patients with evaluable disseminated testicular cancer who were treated with VAB-6 chemotherapy. None of the patients had previous liver disease or hepatic involvement. During the early phase of each course of chemotherapy, AFP showed a temporary elevation associated with reversible increase in liver enzymes and bilirubin. These changes returned to normal before the next course of chemotherapy. In each patient, marked tumor regression occurred as a result of VAB-6 chemotherapy. Nine of the 10 patients remain free of disease after treatment. We conclude that during VAB-6 chemotherapy, a temporary elevation of AFP is common, associated with reversible liver dysfunctions, and that this spurious elevation of the tumor marker, most likely caused by a heavy dose of cisplatin, should not be interpreted as related treatment failure.

Adult↗

Young's syndrome: report of two Japanese cases.

Young's syndrome is characterized by azoospermia due to bilateral epididymal obstruction associated with chronic sinobronchial disease. We report two Japanese cases of Young's syndrome who were treated with microsurgical epididymovasostomy. The histopathology of the caput epididymis showed an obstruction at the most distal region of the ductuli efferentes. The incidence of Young's syndrome in patients with obstructive azoospermia was much lower for mongoloids than for Caucasians.

Adult↗

Urologic oncology in Japan: current status and future direction.

In Japan, there has been a substantial increase in urologic cancer, and it can be argued that the establishment and expansion of urologic oncology demands the integration of basic and clinical sciences. Some of the recent studies and future direction of urologic oncology in Japan are described.

Female↗

Restriction fragment length polymorphism of the L-myc gene and susceptibility to metastasis in genitourinary cancers.

We examined Southern blot analysis of genomic DNAs from 70 patients with sporadic renal cell carcinoma, using the human L-myc oncogene fragment as a hybridization probe. Our purpose was to study the relationship between the restriction fragment length polymorphism (RFLP) of the L-myc and the frequencies of metastasis. The patients were classified into 3 genotypes according to the polymorphic patterns defined by two alleles (L-L:17, L-S:31, S-S:22). The relative ratios of the 3 genotypes in the renal cancer patients were similar to those seen in healthy Japanese. However, of 20 patients who exhibited distant metastases at diagnosis, only 2 belonged to the L-L type. The incidence of distant metastasis in L-L type patients was significantly lower than that in L-S and S-S patients (p = 0.068, by Fisher's exact probability test). These results basically correspond to the previous findings in the lung cancer patients [Kawashima et al.: Proc. natn. Acad. Sci. USA 85: 2353-2356, 1988]. On the other hand, L-myc RFLP analysis in 50 prostatic cancer patients revealed that the incidence of metastasis at diagnosis did not correlate with L-myc genotypes. L-myc RFLP seems to be less promising in prostatic cancer than in lung or kidney cancer.

Blotting, Southern↗

Multidisciplinary treatment of invasive bladder cancer.

To improve cure rates of locally invasive bladder cancer patients, we have performed radiation therapy prior to radical cystectomy in 88 patients since 1980. Until 1984, a total dose of 40 Gy for 4 weeks had been irradiated to the pelvic cavity of 46 patients, while 24 Gy with or without hyperthermia for 2 weeks has been applied to 42 patients since 1985. The treatment efficacy was assessed histopathologically according to the evaluation system proposed by Shimosato et al. in 1971. Approximately 50% of the patients responded well to this preoperative therapy. Among these patients, those with pT3 lesion showed significantly favorable prognoses as compared with the same stage patients who did not respond to the radiation therapy. However, the survival rates of the other pT stage patients did not correlate with the responsiveness to radiation. These results suggest that pT3 stage patients are the best candidates for preoperative radiation therapy, while radical cystectomy alone is adequate for those with superficially invasive lesions. Systemic chemotherapy should be properly built into the treatment strategy for those with locally far-advanced bladder cancer.

Carcinoma, Transitional Cell↗