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Biomedical subjects

O Yoshida

Publications and source records attributed to O Yoshida.

At least 235 records · Page 13Linked to original sources

Efficacy of a novel injectable cephalosporin, Cefclidin, on the experimental complicated urinary tract infections with urinary stones caused by Pseudomonas aeruginosa and Proteus mirabilis.

We evaluated the effects of a novel cephalosporin, cefclidin (CFCL) and imipenem (IPM), on the eradication of bacteria from the urine, bladder stones and the kidneys, and also on the prevention of the infection stone formations, in our polymicrobial urinary tract infection model of rats associated with bladder stones using IMP-sensitive or IPM-resistant Pseudomonas aeruginosa and Proteus mirabilis as a causative pathogen. CFCL completely eradicated P. mirabilis from the urine and the stone in the short-term regimen (5 days). CFCL completely eradicated both IPM-sensitive P. aeruginosa and P. mirabilis from the urine, the stones and the kidneys as compared to IPM in the long-term regimen (11 days), reflecting the superior antibacterial activity of CFCL. CFCL also significantly prevented the development of infection stones as compared to IPM in the long-term regimen. There was no significant difference in the blood urea nitrogen (BUN) values between the CFCL or IPM-treated and the non-treated groups. The cumulative recovery rate of unchanged CFCL reached 47.3% of the total dosage (20 mg/kg) within 8 hours.

Animals↗

Induction of specific anti-tumour immunity by interferon-gamma gene-transferred murine bladder carcinoma MBT-2.

Tumour cell-targeted cytokine gene therapy of cancer has been proposed using various cytokine genes including interferon (IFN)-gamma gene. In the course of the experimental approach using IFN-gamma gene, we established two IFN-gamma gene-transferred clonal sublines, IFN-gamma producer and non-producer, from a murine bladder tumour line MBT-2 via retroviral transfer of mouse IFN-gamma cDNA, and studied the influence of local secretion of IFN-gamma on tumour progression. While cell growth in vitro was not affected by gene transfer, expression of major histocompatibility complex (MHC) class I antigens was increased in both sublines. The IFN-gamma producing cells injected subcutaneously into syngeneic mice could not induce tumours but the non-producing cells tended to induce tumours. Thus the increase in MHC class I expression was not enough to cause tumour regression, and IFN-gamma secretion over a certain amount was needed for tumour suppression, probably in addition to MHC class I expression. Mice that rejected IFN-gamma producers established a specific anti-tumour immunity and spleen cells derived from the mice contained populations of CD8+ effector T cells against MBT-2 cells. These results supported previous reports that IFN-gamma gene transfer into tumour cells apparently abrogated the tumorigenicity by augmenting the host anti-tumour immunity, and were encouraging for a promising execution of the tumour cell-targeted IFN-gamma gene therapy against human bladder cancers.

Animals↗

Effect of erythropoietin (rHuEPO) on trace elements and quality of life (Qol) in chronic hemodialysis patients.

In 30 patients undergoing chronic hemodialysis and whose hematocrit levels had been maintained at 30-50% for 2 years with recombinant human erythropoietin (rHuEPO) administration, changes of serum proteins, serum albumin levels, improvement of trace elements such as zinc (Zn), nickel (Ni) and manganese (Mn), and quality of life (Qol) were examined for 2 years. rHuEPO therapy significantly improved the protein nutritional status, as well as serum Zn, Ni and Mn levels; the concentrations of Zn ion (Zn++), Ni ion (Ni++) and Mn ion (Mn++) in serum were significantly elevated. Objective and subjective Qol of 30 patients showed significant improvement with rHuEPO therapy for 2 years.

Adult↗

[Intraarterial chemotherapy for metastatic renal cell carcinomas: combination with MDR-overcoming agents].

We analyzed the sensitizing activity of five agents, which have been assumed to be MDR-overcoming drugs, in two human renal cell carcinoma cell lines expressing the MDR1 gene at high levels. In addition, we studied the sensitizing activity of cepharanthin, an MDR-overcoming agents, to vinblastine, adriamycin, epirubicin, cisplatin, mitomycin C and etoposide. Based on the results, we treated 6 patients with metastatic renal cell carcinomas (4: bones, 2: contralateral kidneys) by intraarterial injection of vinblastine and adriamycin (or epirubicin) in combination with cepharanthin. Two of the 4 bone metastasis cases responded markedly to the treatment. Renal tubular impairment was observed in one patient who was treated for the contralateral kidney metastasis.

Alkaloids↗

[A case of incidental renal leiomyosarcoma].

A 68-year-old man visited his home doctor with the chief complaint of left flank pain. Abdominal ultrasonography revealed left hydronephrosis and space occupying lesion in the right kidney. He was referred to our hospital because of suspected left ureteral stone and for further examination. Drip infusion pyelography revealed a left ureteral stone and retrograde pyelography showed extrinsic compression and deformation of the right pyelogram. A computed tomography showed a heterogeneous solid mass, 7 x 4 cm in size, compressing the pelvicocalyceal system and growing out of the kidney. Right radical nephrectomy was performed under the diagnosis of renal cell carcinoma. The pathological diagnosis was leiomyosarcoma. Seventy-five cases of renal leiomyosarcoma have been reported in the Japanese literature and this is the third case as an incidental tumor. Because of the absence of the characteristic diagnostic signs, this malignant tumor can present diagnostic difficulty. The diagnostic problems and clinical features of renal leiomyosarcoma are discussed.

Aged↗

A prospective randomized trial for treating stages B2 and C prostate cancer: radical surgery or irradiation with neoadjuvant endocrine therapy.

A randomized clinical trial of neoadjuvant endocrine therapy followed by either surgery or irradiation and a resumption of endocrine therapy for stages B2 and C prostate cancer has been in progress since 1989. A hundred patients entered the trial between 1989 and 1993, and 95 cases were evaluated. Forty-six patients received surgery and 49 were treated with irradiation. Neoadjuvant endocrine therapy for two months resulted in prostate shrinkage and prostate specific antigen lowering. Except for two patients, one dying of a progression of disease and the other of another concurrent cancer, all are alive with an average follow-up term of 25 (range 3-53) months. The good prognostic results obtained from both treatment groups at present seem to be due in part to the neoadjuvant endocrine therapy; but in order to reach a final conclusion further comparisons need to be made.

Aged↗

[Single agent carboplatin therapy for advanced seminoma].

Between May 1990 and August 1992, 5 patients with advanced seminoma were treated with single agent carboplatin at Kyoto University. The mean follow-up period of all patients was 23 months. The clinical stage was IIA: 1, IIB: 1, IIIA: 2, IIIB1: 1. Three to 4 courses of carboplatin at 400 mg/m2, were administered intravenously over 1 hour without hydration every 3 to 4 weeks. One patient achieved complete response (CR). Four patients with a residual mass were observed, in two of them the mass disappeared and they remained free of disease. Two of the 4 patients with a residual mass relapsed 11 and 19 months after the start of treatment, and were successfully salvaged with surgery and adjuvant EP (etoposide and cisplatin) therapy. Subsequently, the overall CR rate was 60% and overall survival rate was 100%. The side effects of carboplatin were compared with those of VAB6 (vinblastine, actinomycin-D, bleomycin, cisplatin and cyclophosphamide), with which another 5 patients were previously treated at our hospital. Leukopenia and alopecia were observed in the VAB6 group with a significant difference (p < 0.05). Severe thrombocytopenia, dyspnea, skin rash, tinnitus and numbness were observed in 4 patients in the VAB6 group. However, no other symptoms but nausea and vomiting were observed in the carboplatin group. It was concluded that single agent carboplatin therapy for advanced seminoma was effective and less toxic, and it would be beneficial for the quality of life of patients, but the residual mass should be treated with surgery, cisplatin-based chemotherapy, or radiotherapy because it possibly has a recurrent potential; otherwise it should be carefully observed.

Adult↗

Quantitative evaluation of intraarterial lymphocyte injection therapy for lymph edema using MR imaging.

Five patients with unilateral leg lymph edema had intraarterial injections of lymphocytes in the affected leg with consequent improvement in 3. To assess the degree of lymph edema, T2 and intensity ratio between the 2 legs in STIR images were used. Mean and SD of T2 values in the subcutaneous tissue were measured using a triple echo sequence and found larger on the edematous side than in the opposite extremity. The mean T2 shortening obtained after the lymphocyte therapy correlated well with the reduction of limb circumference. Mean T2 reflects the fluid content, and SD of T2 the fluid distribution in the subcutaneous tissue. The degree of lymph edema and the effect of therapy can be evaluated quantitatively by measuring the value of the T2 relaxation time.

Adult↗

[A case of adrenal myelolipoma consisting of two masses with different red and yellow colors].

A 52-year-old woman with asymptomatic gross hematuria visited a hospital, where computed tomography and ultrasonography revealed a left suprarenal mass, which was diagnosed as adrenal myelolipoma. After two years observation, she was admitted to our hospital due to enlargement of the tumor, and left adrenalectomy was performed. The tumor consisted of two separate masses with different macroscopic appearances. One was type I, while the other was type II according to Soos' classification. We found no similar case in the literature. We added a review of 119 cases of surgically resected adrenal myelolipoma in Japan.

Adrenal Gland Neoplasms↗

Qualitative and quantitative histopathology in transitional cell carcinomas of the urinary bladder. An international investigation of intra- and interobserver reproducibility.

BACKGROUND: Histopathologic, prognosis-related grading of malignancy by means of morphologic examination in transitional cell carcinomas of the urinary bladder (TCC) may be subject to observer variation, resulting in a reduced level of reproducibility. This may confound comparisons of treatment results. Using objective, unbiased stereologic techniques and ordinary histomorphometry, such problems may be solved. EXPERIMENTAL DESIGN: A study of 110 patients with papillary or solid transitional cell carcinomas of the urinary bladder in stage Ta through T4 was carried out, addressing reproducibility of both qualitative and quantitative grading methods. Grading of malignancy was performed by one observer in Japan (using the World Health Organization scheme), and by two observers in Denmark (using the Bergkvist system). A "translation" between the systems, grade for grade, and kappa statistics were used in evaluating the reproducibility. Unbiased estimates of nuclear mean volume, nuclear mean profile area, nuclear volume fraction, nuclear profile density index, and mitotic profile density index were obtained twice in 55 of the studied cases by one observer in Japan and one in Denmark, using a random, systematic sampling scheme. RESULTS: The results were compared by bivariate correlation analyses and Kendall's tau. The international interobserver reproducibility of qualitative gradings was rather poor (kappa = 0.51), especially for grade 2 tumors (kappa = 0.28). Likewise, the interobserver agreement on the Bergkvist scheme was poor (kappa = 0.43). On the other hand was the interobserver agreement on invasion high (kappa = 0.75). The intraobserver reproducibility of the quantitative histopathologic variables was excellent in both Japan and Denmark for estimates of nuclear mean volume (r = 0.93), for nuclear mean profile area (0.78 < r < 0.83), and for nuclear profile density index (0.85 < r < 0.89), whereas the reproducibility for nuclear volume fraction was somewhat poorer (0.68 < r < 0.64). The slopes of the correlation lines were not significantly different from unity. Estimates of mitotic profile density index also showed acceptable intraobserver reproducibility (Kendall's tau > 0.53). CONCLUSIONS: The international, interobserver reproducibility of the quantitative estimators yielded similar results for all histopathologic variables investigated, except for nuclear volume fraction (r = 0.54). This can probably be related to the manual design of the sampling scheme and may be solved by introducing a motorized object stage in the systematic selection of fields of vision for quantitative measurements. However, the nuclear mean size estimators are unaffected by such sampling variability. The results obtained in this study stress the need for objective, quantitative histopathologic techniques substituting qualitative, subjective methods in prognosis-related grading of malignancy.

Adult↗

Metachronous multifocal development of urothelial cancers by intraluminal seeding.

To investigate the clonal origin of multifocal urothelial tumours, we analysed the p53 tumour-suppressor gene in 3 cases with bladder tumours developing after treatment for a renal pelvic or ureteral tumour and in 1 case with a ureteral tumour after treatment for a bladder tumour. For each case, identical p53 gene mutations were detected in all primary and recurrent tumours. The results suggest that heterotopic recurrence by intraluminal seeding from the original tumour is common in urothelial cancer. The data also support the view that multifocal urothelial tumours are derived from a single progenitor cell.

Female↗

Quantitative histopathology in the prognostic evaluation of patients with transitional cell carcinoma of the urinary bladder.

BACKGROUND: Morphologic grading of malignancy is considered to be of prognostic value in patients with transitional cell carcinomas of the urinary bladder (TCC). This qualitative approach is, however, associated with low reproducibility. Grading of malignancy can be carried out on a reproducible, quantitative scale. METHODS: A retrospective, prognostic study of 110 patients treated for TCC in clinical Stages Ta-T4 (median follow-up time, 6 years) was performed, evaluating various grading techniques. Unbiased estimates of the volume-weighted mean nuclear volume (nuclear vV), nuclear volume fraction, estimates of nuclear mean profile area (aH(nuc)), nuclear profile density index (NI), and mitotic profile density index (MI) were obtained by stereologic and morphometric techniques. RESULTS: The T-stage and morphologic grade of malignancy were closely cross-correlated (+0.63 < Kendall tau < +0.71, 2P < 6.7 x 10(-16)). The estimation of nuclear vV was highly efficient, with more than 85% of the associated variation attributable to differences between tumors. A positive significant correlation between estimates of nuclear vV and aH(nuc) was detected (r = +0.79), whereas an inverse correlation was documented between nuclear vV and NI (r = -0.63). Estimates of nuclear volume fraction showed no correlation with nuclear vV. Comparisons between categorical and quantitative data revealed the following: a decrease in averaged estimates of NI for tumors in advanced T-stage and malignancy grade (2P < 0.0008); and nuclear vV and aH(nuc) increased on average, in tumors of high T-stage and malignancy grade. Estimates of MI were also positively correlated with the T-stage and the malignancy grade (+0.42 < Kendall tau < +0.49). Single-factor analyses showed prognostic effect of T-stage, grade of malignancy, and, apart from nuclear volume fraction, all quantitative histopathologic variables with regard to overall survival (2P < 0.03). None of the morphometric and stereologic parameters were of prognostic values with regard to recurrence-free survival (2P > 0.26). Multiple hazards regression analysis (Cox models) revealed that clinical stage of disease was the sole independent prognostic variable. Only estimates of nuclear vV added significant independent prognostic prediction with regard to recurrence-free survival in the 48 patients with Ta tumors (2P = 0.03). CONCLUSIONS: The results suggested that estimates of nuclear vV are prognostically superior to morphologic grading of malignancy in noninvasive TCC, whereas both morphologically and quantitatively based malignancy grading are without prognostic value in invasive TCC.

Adult↗

Accumulated allelic losses in the development of invasive urothelial cancer.

To investigate the roles of allelic loss in the development of urothelial cancer, loss of heterozygosity was examined on 7 chromosomal arms in 49 cases of urothelial cancer of various grades and stages. Loss of heterozygosity was found in alleles in order of frequency as follows: 9q (21/38, 55%), 11p (20/44, 45%), 17p (18/42, 43%), 13q (10/39, 26%), 3p (8/41, 20%), 10q (2/29, 7%), and 1p (1/36, 3%). Invasive (high-grade or > or = pT2) tumors showed the loss of 17p (13/16, 81%) and the loss of 13q (7/16, 44%) with significantly higher frequencies than non-invasive (grade 1-2 < or = pT1) tumors. Although the loss of 3p and the loss of 11p were also more frequently associated with the invasive phenotypes, the loss of 11p was detected in a considerable number (9 of 26, 35%) of non-invasive tumors. Our results indicate that the loss of 11p might generally occur at an earlier stage before the loss of 3p, 13q or 17p in tumor progression. Since no correlation was found between the loss of 9q and the tumor grade or stage, this genetic alteration appears to be unrelated to invasiveness, and could be one of the initial events in tumorigenesis. Although accumulated allelic losses of 3p, 11p, 13q and 17p are considered to be involved in the development of the invasive type of urothelial cancers, these multiple genetic alterations may have already occurred in some pathologically non-invasive urothelial cancers. Furthermore, there appears to be some variation in the pattern of cumulative allelic loss.

Alleles↗

Enhanced susceptibility of cis-diamminedichloroplatinum-treated K562 cells to lysis by peripheral blood lymphocytes and lymphokine activated killer cells.

BACKGROUND: Previous studies have reported that cis-diamminedichloroplatinum (II) (CDDP) exhibits various immunomodulating activities. The current study investigates the effect of CDDP on the susceptibility of K562 cells to lysis by peripheral blood lymphocytes (PBL), natural killer (NK) cells, and lymphokine activated killer (LAK) cells. METHODS: Cytotoxicity was determined by the 51Cr release assay. RESULTS: Treatment of K562 cells with CDDP at 10 micrograms/ml or more for 3 hours or more enhanced their susceptibility to lysis by PBL. This CDDP-mediated enhancement of lysis was observed by PBL derived from healthy donors and from patients with urinary bladder tumor or with other malignant and nonmalignant urologic diseases. The CDDP-induced enhancement of K562 cell susceptibility to lysis by PBL also was observed when purified NK cells and LAK cells were used as effector cells. The CDDP analog, carboplatin, enhanced the susceptibility of K562 cells to lysis by PBL, but treatment with transdiamminedichloroplatinum (II) had no effect. Several experiments were done to investigate the mechanism of the enhanced susceptibility of CDDP-treated K562 cells to lysis by PBL. Treatment of K562 cells with CDDP had no effect on the expression of major histocompatibility complex (MHC) Class I, MHC Class II, neural cellular adhesion molecule, and leukocyte function antigen-1 on the tumor cells. The frequency of target cell conjugates to PBL was not changed by CDDP-treated K562 cells. Pretreatment of K562 cells with CDDP and lysosomotrophic agents (L-leucine-methyl-ester or chloroquine) abrogated their enhanced susceptibility to lysis by PBL. CDDP treatment of K562 cells did not augment their sensitivity to alpha-interferon, gamma-interferon, tumor necrosis factor alpha, or natural killer cytotoxic factor (NKCF). Treatment of effector cells with CDDP had no effect on their cytotoxic function. CONCLUSIONS: These results demonstrate that CDDP has a direct effect on the K562 target cells, rendering them more susceptible to lysis by PBL, NK cells, and LAK cells. In addition, the result suggest that CDDP-mediated enhancement of target cell lysis is not attributable to changes of surface membrane antigen expression or recruitment of precursor cells but to processing of CDDP by the cells. The possible mechanisms of the effect of CDDP on K562 cells and clinical implications are discussed.

Aged↗

Relationship between the incidence infection stones and the magnesium-calcium ratio of tap water.

In a previous study we showed that the magnesium-calcium ratio of tap water is negatively correlated with the incidence of calcium-containing urinary stones. In this study we examined the relationship between the incidence of struvite stones, water hardness and the regional geological features on the basis of our previous study and an epidemiological study of urolithiasis performed in Japan. The magnesium-calcium ratio of tap water was found to correlate positively with the incidence of struvite stones. The tap water magnesium-calcium ratio was high in regions of basalt and sedimentary rock and was low in granite and limestone areas. The incidence of struvite stones in the regions of basalt and sedimentary rock was higher than that in the granite and limestone areas. Thus, this study suggested that the incidence of struvite stones is related to the magnesium-calcium ratio of tap water and to the regional geology, as is the case for calcium-containing stones.

Calcium↗

Application of polymerase chain reaction-single strand conformation polymorphism analysis to the diagnosis and screening of adenine phosphoribosyltransferase deficiency.

Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis is a rapid and sensitive method used to identify point mutations in a given sequence of genomic DNA. We applied this method to the diagnosis of adenine phosphoribosyltransferase (APRT) deficiency, which is an autosomal recessive hereditary disease leading to 2,8-dihydroxyadenine urolithiasis. Genomic APRT genes were amplified and labeled simultaneously with [alpha-32P]dCTP (cytidine triphosphate) by PCR. When run in a 6% polyacrylamide gel containing 10% glycerol, two types of mutant genes-APRT*QO and APRT*J-gave bands clearly distinct from those of the equivalent normal APRT genes. Using this method we diagnosed both homozygotes and heterozygotes for defective APRT genes. On screening 80 Japanese individuals for polymorphism or mutations by PCR-SSCP we did not find any alterations leading to a false positive diagnosis. These findings suggest that PCR-SSCP, in addition to being rapid and sensitive, is a useful diagnostic method which is highly specific in detecting mutant APRT genes in the Japanese population.

Adenine↗

The dopamine D1 receptor agonist SKF 38393 suppresses detrusor hyperreflexia in the monkey with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

A pharmacological study using monkeys, in which parkinsonism was induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), was undertaken to elucidate the mechanism underlying urinary bladder dysfunctions in Parkinson's disease. Under ketamine anesthesia, cystometrograms showed that, in MPTP-treated monkeys, a contraction of the urinary bladder was induced with smaller bladder volume than that in normal monkeys. In MPTP-treated monkeys, subcutaneously injected SKF 38393, a dopamine D1 receptor agonist, significantly increased the bladder volume and pressure thresholds for inducing the micturition reflex without affecting those in normal monkeys. In contrast, subcutaneous injections of quinpirole, a dopamine D2 receptor agonist, and apomorphine, a dopamine D1 and D2 receptor agonist, slightly, but significantly reduced the volume threshold of the bladder for the micturition reflex in both normal and MPTP-treated groups. These results indicate that, in parkinsonism, the degeneration of dopaminergic neurons in the substantia nigra leads to the detrusor hyperreflexia, probably due to a failure of activation of dopamine D1 receptors.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗