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O Yoshida

Publications and source records attributed to O Yoshida.

At least 127 records · Page 7Linked to original sources
PubMed1997

[Poxvirus vectors for gene transfer].

A promising approach to cancer immunotherapy is immunization with modified tumor cells carrying cytokine or immunomodulatory genes. Cytokine genes (tumor necrosis factor-alpha, interleukin 2, interferon gamma) and costimulatory molecule, B7-1, were incorporated into canarypox virus, ALVAC, which does not replicate in infected mammalian cells, and highly attenuated vaccinia virus, NYVAC. We examined the effect of local cytokine production on the growth of the mouse prostate tumor, RM-1, and the mouse bladder tumor, MBT-2. The vectors expressed the high levels of cytokines and B7-1 and the tumor growth of infected cells was significantly inhibited. The mice immunized with irradiated MBT-2 cells infected with ALVAC-interleukin 2 were protected against the subsequent challenge of parental tumor cells. We conclude that poxvirus vectors are useful for gene delivery in immunotherapy studies because of their infection efficiency, their capability of high gene product expression, their safety, and their case of handling.

Animals↗
PubMed1997

Prognostic criteria in patients with prostate cancer: Gleason score versus volume-weighted mean nuclear volume.

Gleason's score (GS) has been reported to be the most valuable prognostic factor in cases of prostate cancer. GS is solely dependent on the histological architecture of the prostate cancer, but, it seems doubtful that histological patterns are sufficient for evaluating the degree of malignancy of prostate cancer. We previously reported that the estimation of volume-weighted mean nuclear volume (MNV) might be a more useful prognosticator for prostate cancer than subjective histological grading. However, the previous study was conducted on patients treated in a single hospital, and the number of subjects was too small to draw a definitive conclusion. In this study, we analyzed a larger number of subjects at another institution using a blinded study design. A retrospective prognostic study of 195 patients with prostate cancer diagnosed between January 1966 and December 1988 at Kyoto University Hospital, and treated by conservative therapy, was conducted. Unbiased estimates of MNV were compared with the clinical stage and histological grading according to GS with regard to the prognostic value. Univariate analysis revealed that estimates of MNV, clinical stage, and GS all correlated significantly with disease-specific survival in cases of prostate cancer. Multivariate analysis of all cases also revealed that all of these factors were significant independent prognosticators of disease-specific survival. However, focusing on clinically localized cases (stages A, B, and C), multivariate analysis revealed that the estimation of MNV was the only powerful prognosticator of prostate cancer. This study indicates that the estimation of MNV is prognostically equal or superior to GS in cases of prostate cancer. We emphasized that the estimates of MNV is a more objective method for histological grading to predict the malignant potential of prostate cancer.

Aged↗
PubMed1996

Overexpression of human mutT homologue gene messenger RNA in renal-cell carcinoma: evidence of persistent oxidative stress in cancer.

Data regarding oxidatively modified DNA bases suggest that cancer cells are more exposed to oxidative stress than adjacent non-tumorous tissue. This novel concept may contribute to the understanding of certain aspects of tumor biology such as activated transcription factors, genetic instability, chemotherapy-resistance and metastasis. We therefore tested this concept in human renal-cell carcinomas (RCCs) by evaluating the expression of hMTH1, an enzyme preventing the misincorporation into DNA of 8-oxo-dGTP (8-oxo-7,8-dihydrodeoxyguanosine triphosphate), an oxidized form of dGTP in the nucleotide pool. The expression of hMTH1 messenger RNA (mRNA) in RCC was significantly higher than that in adjacent non-tumorous kidney. Moreover, advanced-stage tumors showed significantly higher hMTH1 mRNA expression than early-stage tumors, and there was a modest linear correlation between hMTH1 expression and c-myc expression. The results provide logical support for the concept of "persistent oxidative stress in cancer" and suggest a role of hMTH1 mRNA level as a prognostic marker.

Bacterial Proteins↗
PubMed1996

Transurethral microwave thermotherapy for benign prostatic hyperplasia: relation between clinical response and prostate histology.

The effectiveness of transurethral microwave thermotherapy (TUMT) for BPH has been confirmed. To identify the characteristics of the ideal candidate, retrospective analysis and morphometric study of prostatic tissue were performed. Forty-two patients with symptomatic BPH were included in the study; these comprised 10 patients treated for more than 3 months with anti-androgen pre-TUMT (group A) and 32 fresh cases (group B). Subjective and objective responses were evaluated at 2 months post TUMT. In 12 fresh cases who underwent pre-TUMT biopsy of the prostate, the stromal-to-epithelial ratio was determined via quantitative image analysis on a computer-assisted morphometry system. No significant differences in baseline patient characteristics were found between the two groups: age, prostate volume, peak flow rate (PFR), or International Prostate Symptom Score (I-PSS). However, significant differences in treatment outcome were found between the two groups (group A vs. group B, respectively): total energy delivered to the prostate: 96 kJ vs. 125 kJ: I-PSS decrease from baseline: 5.9 vs. 11.6; PFR increase from baseline: 1.1 vs. 4.7 ml/sec. There was a positive correlation between the I-PSS change from baseline and the stromal-to-epithelial ratio of the prostatic tissue (r = 0.4857). The results suggest that microwave interacts poorly with the prostate due to the artificially created "lack" of glandular tissue. The morphometric study also supports the contention that the histological composition of the prostatic tissue plays an important role in terms of microwave thermal interactions and treatment outcome.

Aged↗
PubMed1996

Expression of multidrug resistance-related genes (mdrl, MRP, GST-pi and DNA topoisomerase II) in urothelial cancers.

OBJECTIVE: To characterize the multidrug resistance (MDR) phenotype in human urothelial cancers, the expression levels of four MDR-related genes (multidrug resistance, mdrl; multidrug resistance-associated protein, MRP; glutathione S-transferase-pi, GST-pi; and DNA topoisomerase II, topo II) were analysed in urothelial cancers. MATERIALS AND METHODS: Fifty-two tumour tissue and three normal urothelial mucosa samples were obtained from 44 patients with urothelial cancers. The expression of each gene was analysed with a reverse-transcription polymerase chain reaction (RT-PCR) method using beta 2-microglobulin (b2m) mRNA as an endogenous control. Levels of expression were expressed as the ratio of the specific products of the target gene to those specific to b2m. RESULTS: In primary urothelial cancer tissues, the mean (SD) expression of mdrl, MRP, GST-pi and topo II relative to b2m expression were 0.067 (0.061), 0.27 (0.23), 0.35 (0.31) and 0.12 (0.05), respectively. The mean expressions of MRP and GST-pi were higher than those of mdrl and topo II. The mean ratios of mdrl/b2m, MRP/b2m, GST-pi/b2m and topo II/b2m in normal urothelial mucosa were 0.06 (0.03), 0.12 (0.09), 0.30 (0.32) and 0.14 (0.01), respectively. There was no significant association of the expression of each gene with either the grade or extent of the primary tumour. The level of MRP expression in each sample was correlated significantly with the expression of mdrl and GST-pi in the urothelial cancers (r = 0.637 and 0.537, respectively). Chemotherapy did not markedly influence the induction of expression of the MDR-related genes, except for one case in which mdrl expression was 15 times greater than before chemotherapy. The expression of GST-pi in the patients not receiving chemotherapy was significantly higher than in those that did. CONCLUSIONS: These results suggest that the activation of MRP and GST-pi expression occurs during the tumorigenesis of urothelial cancers and that it may confer de novo and acquired drug resistance on urothelial cancers. These results should provide further insight into the complex role postulated for MDR-related genes in chemotherapy, carcinogenesis and tumour progression.

DNA Topoisomerases, Type II↗
PubMed1996

Impaired production of interferon-alpha in whole-blood cultures from patients with renal cell carcinoma.

OBJECTIVE: To determine the immune status of patients with renal cell carcinoma (RCC) by estimating the production of interferon-alpha (IFN-alpha) in whole-blood cultures from these patients and from healthy subjects. PATIENTS, SUBJECTS AND METHODS: Peripheral blood (2 mL) was collected from 30 untreated patients (23 men and seven women, mean age 59 years, range 35-78) with RCC and 30 healthy subjects (23 men and seven women, mean age 62 years). The patients with RCC comprised 17 with low-stage (stage I, II) and 13 patients with high-stage (stage III, IV) RCC. Sendai virus was added to the samples and incubated at 37 degrees C for 20 h, the supernatants collected and the activity of IFN-alpha determined by a conventional cytopathic-effect inhibition assay performed in microtitre plates with FL cells and challenged with vesicular stomatitis virus. RESULTS: The production of IFN-alpha was suppressed significantly in patients with high-stage RCC compared with that in the control subjects (P < 0.05), but there was no significant difference when compared to patients with low-stage RCC. CONCLUSION: This study demonstrated that the immune status of patients with high-stage RCC was impaired significantly and exogenous IFN-alpha therapy might be beneficial clinically for this group.

Adult↗
PubMed1996

Significance of cytotoxic activity of peripheral blood lymphocytes against autologous tumor cells in patients with bladder cancer.

Cell-mediated immunity is an important and central mechanism of host resistance to cancer. Most reported studies have used cultured tumor cell lines as targets to assess antitumor cell-mediated cytotoxicity. However, it is difficult to translate the data generated from the cytotoxic activity against cultured tumor cell lines to cytotoxicity against autologous tumors. In a recent study, we have reported on the prognostic significance of circulating cytotoxic lymphocytes against autologous tumor cells in patients with bladder cancer. In this study, we examined whether established bladder cancer cell line like T24 or NK-sensitive K562 target cells can be substituted for autologous bladder cancer cells. The cytotoxic activity of peripheral blood lymphocytes (PBL) against freshly isolated autologous tumor cells, the T24 human bladder cancer cell line and the NK-sensitive K562 human myelogenous leukemia cell line was studied in 63 patients with primary initial bladder cancer by a 12-h 51Cr release assay. The mean percent cytotoxic activity of PBL directed against autologous tumor cells, T24 cells and K562 cells were 11.3%, 18.2% and 29.4%, respectively, using an E:T of 40:1. The cytotoxic activity against T24 cells in patients with bladder cancer was higher than that in normal individuals. The anti-K562 and the anti-T24 cytotoxic activities in patients with low-stage or low-grade bladder cancer were relatively higher than those in patients with high-stage or high-grade cancer, but not statistically significant. There was no correlation between the anti-autologous tumor cytotoxic activity and either the histologic grade or stage in patients with bladder cancer. The extent of the anti-autologous tumor cytotoxic activity was not paralleled with that of either the anti-K562 or the anti-T24 cytotoxic activity. In contrast, the anti-K562 cytotoxic activity correlated positively with the anti-T24 cytotoxic activity. Separation of PBL revealed that the anti-K562 and the anti-T24 cytotoxic activities were mediated mainly by the NK cells, whereas the anti-autologous tumor cytotoxic activity was mediated by both the NK cells and the T lymphocytes. These findings demonstrate that cytotoxicity against T24 or K562 cells is not of prognostic value. The magnitude of the anti-autologous tumor cytotoxic activity of PBL derived from bladder cancer patients might represent an independent and important immunological parameter to monitor disease progression.

Adult↗
PubMed1996

Role of IL-7 and KL in activating molecules controlling the G1/S transition of B precursor cells.

While chemically defined conditions for culturing normal tissue have been attained for only a few cell types, the sustained proliferation of B precursor cells expressing IL-7 receptor and c-Kit can be supported under chemically defined conditions containing recombinant IL-7 and the ligand for c-Kit (KL). To understand the biochemical basis of the cell cycle progression of B precursor cells proliferating under these conditions, we investigated the correlation between growth factor stimulation and CDK4 activity. Consistent with our findings that IL-7 regulates the G1/S transition, while KL has only a little role in this process, the kinase activity of CDK4 was related closely with IL-7 stimulation but not KL stimulation. We investigated the mechanism underlying CDK4 activation in the IL-7 stimulated B precursor cells. Our results showed that (i) CDK4 and cyclin D3 are the G1/S regulators in B precursor cells; (ii) their expression levels are unchanged between the cells in G1 arrest and cycling cells; and (iii) they are present in an associated form even when the cell cycle stage is arrested at G1. Thus, the regulation of the expression of CDK4 and cyclin D3 or regulation of their assembly are not the mechanisms for activating CDK4 in the B precursor cells. On the other hand, a number of molecules co-immunoprecipitated with CDK4 were enhanced in the lysate of IL-7-stimulated B precursor cells. Thus, we present a possibility that CDK4 activation might be regulated by molecules associated with the CDK4-cyclin D3 complex in IL-7-dependent manner.

B-Lymphocytes↗
PubMed1996

Bone demineralization following urinary intestinal diversion assessed by urinary pyridinium cross-links and dual energy x-ray absorptiometry.

PURPOSE: We investigated the acid-base balance and bone mineral status in patients with 3 types of urinary intestinal diversion. MATERIALS AND METHODS: Of 46 men with urinary intestinal diversions 20 had a Kock pouch, 15 had an Indiana pouch and 11 had an ileal conduit. Acid-base balance was assessed by arterial blood gas analysis. Bone mineral status was measured by urinary pyridinium cross-links and dual energy x-ray absorptiometry. In addition, urinary deoxypyridinoline was measured in 79 patients. RESULTS: Of the 46 patients 7 (15%) with the Kock pouch (1), Indiana pouch (5) and ileal conduit (1) had metabolic acidosis associated with significantly lower bone mineral densities (p < 0.05) and higher urinary pyridinium cross-links (p < 0.005) than did those with normal acid-base status. No difference was found in metabolic acidosis and bone demineralization among the 3 groups. Additionally, in 79 patients urinary deoxypyridinoline reached the highest level immediately postoperatively and then gradually decreased to the stable level within 1 or 2 years. CONCLUSIONS: Metabolic acidosis following urinary intestinal diversion results in bone demineralization. The types of diversion did not cause differences in metabolic acidosis and bone resorption. Bone has a major role in buffering acid overload in the early postoperative period.

Absorptiometry, Photon↗
PubMed1996

Expression patterns of multidrug-resistance (MDR1), multidrug resistance-associated protein (MRP),glutathione-S-transferase-pi (GST-pi) and DNA topoisomerase II (Topo II) genes in renal cell carcinomas and normal kidney.

PURPOSE: Expression levels of the multidrug-resistance (mdr1), multidrug resistance-associated protein (MRP), glutathione-S-transferase-pi (GST-pi) and DNA topoisomerase II (Topo II) genes in normal kidney and renal cell carcinomas were analyzed to study the complexity of the roles of these genes. MATERIALS AND METHODS: The reverse transcription-polymerase chain reaction (RT-PCR) assay was used with beta 2 microglobulin (beta 2 m) as the internal control. RESULTS: In normal kidneys, the expression levels of the 4 genes in individual normal kidney samples correlated significantly with one another. Comparisons of the expression levels between normal kidneys and renal cell carcinomas showed that only the mean MRP gene expression level was higher in renal cell carcinomas than in normal kidneys (p = 0.018). The expression patterns of the 4 genes in renal cell carcinomas differed markedly for nonpapillary and papillary tumors. The mean MRP/beta 2 m ratio for the papillary type was significantly lower than that for the nonpapillary alveolar type carcinoma (p = 0.004). The 4 genes showed moderate positive correlations with one another in alveolar type renal carcinoma similar to the correlations observed in normal kidneys. In contrast, in papillary type, MRP expression was inversely correlated with mdr1 and Topo II expression. CONCLUSION: Differences in cytogenetic changes, origins and natural histories between papillary and nonpapillary carcinoma may be associated with these distinct expression patterns of the resistance-related genes. Further study is required to clarify whether the differences in the expression patterns between these 2 structural types of carcinoma affect their chemosensitivities and clinical outcomes.

ATP-Binding Cassette Transporters↗
PubMed1996

Assessment of the significance of virulence factors of uropathogenic Escherichia coli in experimental urinary tract infection in mice.

Four Escherichia coli strains, isolated from cystitis patients, belonging to serotype 02:H- and possessing different combinations of urovirulence factors were examined in an experimental pyelonephritis mouse model to assess the relative importance of virulence factors in causation of urinary tract infections (UTI). The results suggest not only that the each virulence factor has a role in causation of UTI but also that the presence of P fimbriae and production of hemolysin significantly reduced the LD50 and ID50 of the strains in the mouse model. The results also demonstrate that the presence of additional virulence factors acts in an additive or synergetic fashion enhancing the cumulative impact of the strain.

Agglutination Tests↗
PubMed1996

A quantitative trait locus in major histocompatibility complex determining latent period of mouse lymphomas.

The effects of two host genes on retrovirus-induced murine lymphoma were evaluated by studying 114 F2 intercross mice between SL/Kh and AKR/Ms mice. Out of 47 T-lymphoma-bearing F2 mice, 45 had the AKR-derived dominant allele at Tism-1. The length of the lymphoma latent period was not related to type of tumor. Instead, it was significantly shortened by a recessive SL/Kh-derived allele at a major histocompatibility complex (MHC)-linked locus on Chr. 17. A quantitative trait analysis of the latent period yielded a maximal logarithm of likelihood ratio for linkage (LOD) score of 7.06 at a class II gene within MHC. The SL/Kh-derived recessive gene was named lla (lymphoma latency acceleration).

Alleles↗
PubMed1996

Immunocytochemical detection of p53 in cultures of exfoliated cells from urine of patients with urothelial cancers.

Early diagnosis of urothelial cancer is critical for successful treatment. Mutation of the p53 gene together with allelic loss of chromosome 17p correlates well with high grade and invasiveness of urothelial cancer. Moreover, this mutation is reported to be an early event for carcinoma in situ of the urothelium. In order to develop a new non-invasive diagnostic method for urothelial cancer, we have established a short-term culture system for urinary exfoliated cells from patients with urothelial cancer. Immunocytochemical detection of p53 in these urine-derived cells was conducted. Short-term cultures of exfoliated cells from 50 ml samples of urine from 52 patients with urothelial cancers were made. Adequate cell growth (> 10(5) cells per flask) was followed by passage onto glass chamber slides for p53 immunocytochemical staining. Successful passage was obtained in 40 of the 52 (76.9%) patients with urothelial cancers studied. The success rate for patients with tumors immunohistochemically positive for p53 nuclear accumulation was 90.5%, and 61.3% for those with tumors negative for p53 (P < 0.05). Results of immunochemical analysis of the p53 in the urine cells and those in the tumor samples were identical in 92.1% of the patients. Culture of exfoliated cells from urine would be a good, non-invasive method for the molecular diagnosis of urothelial cancer that should prove useful for the early detection and follow-up of tumors with p53 mutation.

Adult↗
PubMed1996

Equivalent parental distribution of frequently lost alleles and biallelic expression of the H19 gene in human testicular germ cell tumors.

Epigenetic alterations such as genomic imprinting might play an important role in human tumorigenesis, in addition to specific genetic alterations. To clarify the role of genetic and/or epigenetic alterations in the tumorigenesis of testicular germ cell tumors (GCTs), we analyzed 40 primary and 3 metastatic testicular GCTs with regard to specific chromosomal losses and their parental origin. A high incidence of loss of heterozygosity (LOH) was demonstrated on chromosomes 1p, 3p, 11p, and 17p: 9/19 (47%), 18/39 (46%), 13/40 (33%) and 20/36 (56%), respectively. However, there was no correlation between the frequency of LOH on any chromosome and clinicopathological features. Regarding the parental origin of the lost allele at these chromosomes, preferential loss was not demonstrated in this study. To clarify the imprinting status in GCTs, we analyzed the allele-specific expression of the H19 gene, which is paternally imprinted on chromosome 11p. All of 11 tumors without LOH at this locus showed biallelic expression of H19. Based on previous work demonstrating the biallelic expression of H19 in primordial germ cells and spermatogonia in the mouse germ line, these results suggest that the biallelic expression of H19 in testicular GCTs reflects the characteristics of the original germ cells in which the imprinting marking has been erased and not established, rather than loss of imprinting during tumorigenesis. It is also possible that a failure to re-establish the imprinting might be an initial event which leads to testicular GCTs.

Alleles↗
PubMed1996

Intracorporeal lithotripsy with the Swiss Lithoclast.

BACKGROUND: In addition to currently available modalities of intracorporeal lithotripsy (ultrasonic, electrohydraulic, and laser), a new ballistic lithotriptor known as the Swiss Lithoclast has recently gained attention. This study reports our experience with the Swiss Lithoclast in the endoscopic management of urinary calculi. METHODS: A total of 51 patients with urinary calculi were treated with the Swiss Lithoclast; one patient with a renal calculus, 28 with ureteral calculi, and 22 with lower urinary tract (bladder, urethra and Kock pouch) calculi. RESULTS: The Lithoclast successfully fragmented 94% of the calculi, independent of stone composition. Complete failure of fragmentation was not encountered. In six of the 10 upper ureteral calculi, stone fragments were pushed up into the calyces. Adjunctive extracorporeal shock wave lithotripsy for residual fragments was performed in six cases. The stone-free rate at one and three months was 84% and 88%, respectively. There were no intraoperative or long-term complications directly related to the use of this device. CONCLUSION: The Swiss Lithoclast is a safe and effective means of intracorporeal lithotripsy. Although suitable for mid and lower ureteral stones, the device has a risk of stone push-up in patients with upper ureteral stones.

Adult↗
PubMed1996

Detection of Proteus mirabilis urease gene in urinary calculi by polymerase chain reaction.

BACKGROUND: Urea-splitting microorganisms cannot always be detected by stone or urine culture in patients with infection stones. Detection of genetic elements within the calculi by the polymerase chain reaction (PCR) may be a useful alternative. In this study, we assessed the usefulness of the PCR method in detecting the urease gene specific to Proteus mirabilis in urinary calculi. METHODS: Thirty-eight metabolic stones (calcium oxalate and/or calcium phosphate, uric acid, or cystine) and 49 struvite stones were examined. The PCR was applied with DNA extracted by boiling pulverized stone pieces. RESULTS: Of the 87 stones, PCR demonstrated the presence of the P. mirabilis urease elements ureC1 and ureC2 in 17, all of which were struvite. Stone culture and urine culture had been performed in 22 and 46 struvite stone cases, respectively, and the PCR was positive in all of the 10 culture-positive calculi and also in two calculi from which P. mirabilis was not isolated. CONCLUSION: PCR was reliable and convenient for detecting P. mirabilis in desiccated struvite calculi. Study to detect other species such as Ureaplasma or Corynebacterium would be useful in elucidating the role of bacterial infection in the formation of these stones.

Adult↗
PubMed1996

Simultaneous left renal pelvic and bilateral ureteral tumors producing carbohydrate antigen 19-9.

We report a case of a transitional cell carcinoma of the left renal pelvis and both ureters which secreted carbohydrate antigen 19-9. Aggressive surgery was performed including a left nephroureterectomy including the bladder cuff and a right total ureterectomy with an ileal graft replacement. The patient has had good kidney function and no evidence of disease for one year postoperatively.

Aged↗