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Biomedical subjects

S Kamidono

Publications and source records attributed to S Kamidono.

At least 163 records · Page 9Linked to original sources

Percutaneous treatment of transitional cell carcinoma of the upper urinary tract.

BACKGROUND: We evaluated the long-term effect of percutaneous resection in 2 Japanese patients with transitional cell carcinoma of the renal pelvis, and reviewed the medical literature on similar patients, to determine the appropriate indications for percutaneous treatment of transitional cell carcinoma in the upper urinary tract. RESULTS: Indications for endoscopic resection in the 2 patients were renal insufficiency and unsuitability for major open surgery. The patients had no recurrence during follow-up. Seven previous reports described percutaneous resection of upper urinary tract transitional cell carcinoma in 82 patients. Although 72.6% of the patients were successfully treated by percutaneous resection, half of the patients with grade 3 carcinoma developed recurrence. CONCLUSION: These results, together with those of the 7 published reports, suggest that percutaneous resection should be limited to selected patients with low-grade transitional cell carcinoma.

Aged↗

Y chromosome (Yq11) microdeletions in idiopathic azoospermia.

BACKGROUND: Cytogenetic anomalies and molecular deletions of the Y chromosome in idiopathically sterile men suggest that genetic factor(s) controlling spermatogenesis are located in the distal portion of Yq11. We studied Y chromosome microdeletions in the Yq11.23 region in idiopathic azoospermia. METHODS: We studied 25 azoospermic male patients with a cytogenetically normal 46XY karyotype; 13 exhibited Sertoli-cell-only syndrome and 12 exhibited maturation arrest. Microdeletions in the Yq11 region were examined using the PCR technique with 4 pairs of primers from DNA loci in Yq11.23. RESULTS: Microdeletions in Yq11.23 were detected in 4 of the 25 azoospermic men. The most common deletion was of the Y6HP52pr sequence, which was detected in 3 of 13 men with Sertoli-cell-only syndrome but in only 1 of 12 with maturation arrest. CONCLUSION: Detection of microdeletions within the Yq11 sequence is an important clue to the genetic factor(s) underlying azoospermia.

Adult↗

Treatment of crush syndrome patients following the great Hanshin earthquake.

Five of 8 patients with rhabdomyolysis treated at our hospital following the Great Hanshin Earthquake were diagnosed with crush syndrome. One patient with crush syndrome and 3 patients with rhabdomyolysis and no renal dysfunction recovered with conservative therapy, while 1 crush syndrome patient recovered with peritoneal dialysis (PD). Of the 3 patients who died, 2 had undergone continuous arterio-venous hemofiltration (CAVH). We examined the laboratory data to identify any factors that may be prognostic for crush syndrome. The serum amylase levels were significantly higher and the levels of aspartate transaminase (AST) and lactic dehydrogenase (LDH) tended to be higher from the patients who died. Examination of the serum amylase, AST and LDH levels may be useful for assessing the prognosis in patients with crush syndrome.

Aged↗

Enzymes involved in DNA synthesis in the testes are regulated by temperature in vitro.

OBJECTIVE: Temperature is considered to be an important local regulating factor of testicular function. We investigated whether a high temperature would affect the activity of DNA polymerases alpha, beta, and gamma (EC2.7.7.7) and DNA topoisomerase I in the testes which are required for germ cell differentiation. METHODS: An in vitro rat testis tissue culture system was used to evaluate the activity of DNA polymerases alpha, beta, and gamma and DNA topoisomerase I after incubation at 31 and 37 degrees C. The expression of proliferating cell nuclear antigen was evaluated immunohistochemically in the testis. RESULTS: Incubation at 37 degrees C significantly reduced the activity of all four enzymes as compared with incubation at 31 degrees C. Reducing the temperature to 31 degrees C after prior incubation at 37 degrees C partially restored DNA polymerase alpha activity. Expression of proliferating cell nuclear antigen demonstrated a reduction in DNA synthesis in the seminiferous tubules after incubation at 37 degrees C CONCLUSION: These findings indicate that a high temperature of 37 degrees C reduces the activity of the enzymes involved in the testicular synthesis of DNA which may cause the impairment of spermatogenesis.

Animals↗

Nitric oxide production by cultured rat Leydig cells.

Nitric oxide (NO) has emerged as an intracellular and intercellular messenger in a number of biological systems. In the present study, we demonstrated that NO was produced by cultured rat Leydig cells, and that inducible nitric oxide synthase (iNOS) messenger RNA (mRNA) was expressed in Leydig cells. NO was measured as nitrite with the method of Griess. Although unstimulated Leydig cells produce little NO, interleukin-1 beta (IL-1 beta) markedly increased NO production. NO production was inhibited by the NOS inhibitor, NG-monomethyl-L-arginine. Northern blot analysis showed that iNOS mRNA was little expressed in freshly isolated immature Leydig cells, but that iNOS mRNA levels were increased by the addition of IL-1 beta in a dose-dependent manner at the concentration up to 10 ng/ml. The levels of iNOS mRNA were increased as early as 3 h after the addition of IL-1 beta and persisted for up to 24 h. In adult Leydig cells, IL-1 beta stimulated iNOS mRNA expression. Immunocytochemical analysis demonstrated iNOS-like immunoreactivity in the cytoplasm of Leydig cells. These results indicate that NO is produced in Leydig cells and suggest that NO might be involved in the physiological function of Leydig cells.

Animals↗

Formation of reactive oxygen species by spermatozoa from asthenospermic patients: response to treatment with pentoxifylline.

PURPOSE: We determined the incidence of reactive oxygen species formation by spermatozoa from asthenospermic patients, and the relationship between reactive oxygen species formation and sperm motion parameters. We also assessed the efficacy of in vitro and in vivo pentoxifylline treatment of asthenospermic patients whose spermatozoa generated high reactive oxygen species levels. MATERIALS AND METHODS: Reactive oxygen species formation by spermatozoa from asthenospermic patients and fertile volunteers was measured by chemoluminescence. Reactive oxygen species formation by the sperm preparations was investigated without stimulation (steady state), or after stimulation with N-formyl-methionyl-leucyl-phenylalanine (f-MLP) or phorbol-12-myristate-13-acetate. Spermatozoa from 15 asthenospermic patients whose spermatozoa produced high levels of reactive oxygen species at steady state were treated in vitro with pentoxifylline to determine its effect on reactive oxygen species generation and sperm motion parameters. These same 15 patients and 18 with asthenospermia whose spermatozoa did not produce reactive oxygen species at steady state were treated with pentoxifylline at 2 different dosages (300 and 1,200 mg. daily) to determine its effect on reactive oxygen species generation, sperm motion parameters and sperm fertilizing ability in vivo. RESULTS: When reactive oxygen species formation was detected in the steady state that was not stimulated by f-MLP, the source of reactive oxygen species could be attributed to the spermatozoa themselves. Spermatozoa from 15 of 71 asthenospermic patients generated reactive oxygen species at steady state. Pentoxifylline decreased reactive oxygen species generation by spermatozoa in these patients, and preserved the decrease of curvilinear velocity and beat cross frequency for 6 hours in vitro. For these patients orally administered pentoxifylline failed to decrease reactive oxygen species generation by spermatozoa, and had no effect on sperm motility, sperm motion parameters and sperm fertilizing ability at low dosage (300 mg. daily). However, it increased motility and beat cross frequency at high dosage (1,200 mg. daily) but it had no effect on sperm fertilizing ability. CONCLUSIONS: Stimulation of sperm preparations with f-MLP can identify the source of reactive oxygen species generated at steady state. Among asthenospermic patients there were some whose spermatozoa produced detectable steady state levels of reactive oxygen species. In this group pentoxifylline appeared to be effective for decreasing reactive oxygen species formation and preserving sperm motion parameters in vitro. Orally administered pentoxifylline had no effect at low dosage but it increased sperm motility and some sperm motion parameters without altering sperm fertilizing ability at high dosage.

Fertilization↗

Basic fibroblast growth factor regulates matrix metalloproteinases production and in vitro invasiveness in human bladder cancer cell lines.

PURPOSE: This study was designed to investigate the effect of endogenous basic fibroblast growth factor (FGF-2) on matrix metalloproteinases (MMPs) production and in vitro invasive potential of human bladder cancer cell lines. MATERIALS AND METHODS: The human bladder cancer cell lines, HT1376 and KoTCC-1, were used in this study. The mRNA for FGF receptor has been shown to be expressed in both cell lines; the mRNA for FGF-2 is expressed in only KoTCC-1. The effects of FGF-2 expression on HT1376 by gene transfection and those of FGF-2 antisense oligonucleotides treatment on KoTCC-1 were analyzed by zymography and in vitro tumor cell invasion assay. RESULTS: The introduction of human FGF-2 gene into HT1376 cells markedly enhanced both the MMP-2 and MMP-9 production, and the in vitro invasive potential was also increased. In contrast, the exposure of KoTCC-1 cells to FGF-2 specific antisense oligonucleotides decreased the MMP-2 production and in vitro invasive potential, but the exposure to FGF-2 sense oligonucleotides did not. CONCLUSIONS: These findings suggest that FGF-2 plays an important role in the invasive process of human bladder cancer in part through the regulation of MMPs production.

Cell Division↗

Image cytometry for quantitative analysis of DNA in the testes of infertile men with varicocele: comparison with flow cytometry.

PURPOSE: The first aim of this study is to evaluate the usefulness of image cytometry comparing flow cytometry to analyze the spermatogenesis using testicular biopsy specimens obtained from infertile male. The second is to investigate the spermatogenesis of infertile men with varicocele by image cytometry. MATERIALS AND METHODS: A total of 76 biopsy specimens of testicular tissue were obtained from 38 infertile men with varicocele and 6 specimens of normal testicular tissue controls were obtained from 6 volunteers at vasectomy. They were evaluated by image cytometry and pathohistological examination. Out of 76 specimens, 21 biopsy tissues were also analyzed by flow cytometry, and the results by both image cytometry and flow cytometry were compared. Two specimens from Sertoli cell only testes were also examined by image and flow cytometry. RESULTS: In comparative study, image cytometry revealed a decrease in the proportion of haploid and diploid cells (18.8 +/- 6.6% and 32.4 +/- 7.4%), and an increase in that of tetraploid cells (21.8 +/- 5.6%) vs. the flow cytometry findings (haploid, 25.9 +/- 9.2%; diploid, 36.8 +/- 6.5% and tetraploid, 15.1 +/- 5.9%). Image cytometric analysis of the testes of varicocele patients showed 15.9 +/- 5.6% haploid, 31.7 +/- 7.9% diploid and 16.2 +/- 8.9% tetraploid cells in the left testis of infertile men, while their right testis showed 16.6 +/- 5.4% haploid, 30.0 +/- 7.6% diploid and 17.2 +/- 6.4% tetraploid cells. The testes of normal men showed 37.6 +/- 8.3% haploid, 19.4 +/- 4.8% diploid and 17.4 +/- 5.8% tetraploid cells. The left and the right testes of the patients with varicocele showed a lower proportion of haploid cells and a higher proportion of diploid cells vs. the testes from normal men. The proportions of the haploid and diploid cells are correlated with sperm concentration. CONCLUSION: Image cytometry could exclude interstitial cells, Sertoli cells, and sperm on the static image, so produced an accurate assessment of spermatogenesis. The alteration in the germ cell population in the testes of infertile men with varicocele suggested that the impairment mostly affected the cells in the meiotic stage.

Adult↗

Neuroendocrine cells in the prostatic carcinomas after neoadjuvant hormonal therapy.

Prostate cancer is a malignant tumor that is likely to increase in incidence in Japan. The most troublesome facet of this tumor is its conversion from a hormone-sensitive status to an insensitive one. Neuroendocrine differentiation may help explain this phenomenon. We studied the prevalence of neuroendocrine cells in prostate carcinoma after androgen ablation therapy. Radical prostatectomy specimens from 28 patients who had undergone neoadjuvant endocrine therapy with luteinizing hormone-releasing hormone analogue were retrospectively studied. Immunohistochemical staining was used to assess the localization of neuroendocrine cells. Neuroendocrine differentiation index, defined as the sum of the immunoreactivity scores of the specimens against anti-chromogranin A and anti-neuron specific enolase antibodies, was developed. Overall, 46.4% and 53.6% of the prostate carcinomas contained chromogranin A and neuron-specific enolase positive cells, respectively. Localization of these neuroendocrine cells in tumors was patchy. Two specific types of neuroendocrine cells were identified: a closed type and an open type based on the location of the neuroendocrine cells. The neuroendocrine differentiation index correlated with tumor grade, but not with tumor stage. The prevalence of neuroendocrine cells in higher grade prostatic carcinoma may help to explain the insensitivity of these cancers to hormonal therapy.

Adenocarcinoma↗

Organ-site dependence for the production of urokinase-type plasminogen activator and metastasis by human renal cell carcinoma cells.

We examined the role of urokinase-type plasminogen activator (u-PA) in the metastasis of the human renal cell carcinoma (HRCC) implanted in athymic nude mice. Cells from a HRCC KG-2 line were implanted in orthotopic (kidney) and ectopic (subcutaneous) organs. The KG-2 cells implanted in the kidney produced local tumors and lung metastases, whereas those implanted subcutaneously produced only local tumors. The production of u-PA was determined by immunohistochemistry and an enzyme-linked immunosorbent assay (ELISA). High levels of u-PA were produced by the metastatic kidney tumors and lung metastases, whereas the subcutaneous tumors produced low levels. KG-2 cells co-cultured with mouse kidney or lung fibroblasts produced higher levels of u-PA than KG-2 cells co-cultured with mouse skin fibroblasts. Furthermore, KG-2 cells cultured with the conditioned medium from mouse kidney or lung fibroblasts produced higher levels of u-PA than KG-2 cells cultured with the conditioned medium from mouse skin fibroblasts. The results indicate that the expression of u-PA by KG-2 cells is one of the important factors that determine their metastatic potential and that the production of u-PA is influenced by the organ microenvironment, including soluble factors produced by surrounding fibroblasts.

Animals↗

[Molecular urology: the present situation and prospects of gene therapy].

We discuss the current status and views of human gene therapy for urological cancer. The genetic causes of many hereditary diseases have been identified as a result of the remarkable advancement of genetic engineering, and the molecular mechanisms of these diseases have also been clarified. The concept is that it is possible to treat diseases at the genetic level by replacing abnormal genes or restoring lost genes when the causative abnormal genes involved have been identified at the deoxyribonucleic acid level. In this Symposium "Current status and views of human gene therapy", we invited contributions clinical physicians and researchers in the first line of gene therapy in the United States. In addition, young Japanese urologists researching basic gene therapy were invited to participate. Japanese urologists who often treat malignant tumors should aggressively pursue a treatment method in the new field of gene therapy for cancer in Japan. We are expecting the Symposium to yield significant findings.

Genetic Engineering↗

[Clinical application for gene therapy in prostate cancer].

Hormone treatment, radiotherapy and anti-cancer chemotherapy are often used to treat prostate cancer. However, there is no effective method of treating hormone-independent prostate cancer. In this study, we attempted to establish a new treatment method for hormone-independent prostate cancer. We developed a new recombinant adenovirus vector containing a suicide gene and controlled by a tissue specific promoter, and examined the usefulness of gene therapy for hormone-independence and PSA expression in prostate cancer. We have also examined the usefulness of gene therapy involving an adenovirus and various tumor suppressor genes for human prostate cancer cells, which are under trial in the United States.

Adenoviridae↗

Elevation of serum levels of matrix metalloproteinase-2 and -3 as new predictors of recurrence in patients with urothelial carcinoma.

BACKGROUND: The relationship between serum levels of matrix metalloproteinase-2 (MMP-2) and MMP-3 and recurrence in patients with urothelial carcinoma after complete resection was studied to determine whether the enzymes could be a new predictor of recurrence. METHODS: Serum levels of MMP-2 and MMP-3 in 146 healthy controls, 52 patients with superficial (noninvasive) and 35 patients with advanced (invasive or metastatic) bladder carcinoma, and 30 patients with advanced upper urothelial carcinoma (renal pelvis and ureter) were measured by a one-step sandwich enzyme assay. RESULTS: Among the 53 patients with advanced urothelial carcinoma who underwent complete resection, the 1- and 3-year disease free survival rates of patients with elevated serum levels of either or both of the enzymes were 51% and 19%, respectively, whereas those of patients with normal serum levels of these enzymes were much higher, 86% and 79%, respectively (P < 0.005). In pT2N0M0 and pT3N0M0 patients who underwent complete resection, the recurrence rate in those with preoperative elevated serum levels of either or both of the enzymes was significantly higher than that in patients with normal levels (75% vs. 8%; P < 0.001). The 1- and 3-year disease free survival rates of pT2N0M0 and pT3N0M0 patients with elevated serum levels of either or both of the enzymes were 55% and 21%, respectively, which was significantly lower than that of patients with normal levels (92%; P < 0.001). CONCLUSIONS: The results of this study indicate that the elevation of serum levels of either MMP-2 or MMP-3 or both could be new predictors of recurrence in patients with advanced urothelial carcinoma after complete resection.

Adult↗

Messenger ribonucleic acids for fibroblast growth factors and their receptor in bladder and renal cell carcinoma cell lines.

FGF-like growth factors have been detected in the urine of patients with bladder or renal cell carcinoma. FGF-1-like and FGF-2-like proteins have been detected in the urine of patients with bladder carcinoma. However, the expression of FGFs and their receptor in bladder and renal cell carcinoma cells remains limited. We measured the mRNA levels of FGFs and their receptor in these carcinoma cell lines by means of RT-PCR. We detected FGF-8 mRNA expression in murine cell lines of bladder and renal cell carcinomas but not in those of the normal bladder and kidney. Furthermore, FGF-8 mRNA expression was detected in all human bladder and renal cell carcinoma cell lines tested. We also frequently detected FGF-1, FGF-2 and FGF-5 mRNA expression in human bladder and renal cell carcinoma cell lines. These results indicate that FGF-8 is also candidate for marker of these types of carcinoma as well as FGF-1 and FGF-2.

Animals↗

Introduction of basic fibroblast growth factor gene into mouse renal cell carcinoma cell line enhances its metastatic potential.

To clarify the role of basic fibroblast growth factor (FGF-2) in the malignant progression of renal cell carcinoma, we transfected the FGF-2 gene, which lacks the typical signal sequence, into RenCa, a mouse renal cell carcinoma cell line that does not express FGF-2 mRNA. In an in vitro tumor cell invasion assay, the FGF-2-transfected cell lines (RenCa/F) exhibited 3- to 4-fold higher invasive potential than either the parental RenCa (RenCa/P) or the vector-only transfected cell line (RenCa/C). Zymography showed a marked increase in matrix metalloproteinase 2 (MMP-2) production in the culture supernatants of RenCa/F. Furthermore, when injected i.v. or into the renal subcapsule in syngeneic mice, RenCa/F formed more than 10 times as many metastatic nodules in the lung as did RenCa/P and RenCa/C. Metastases to the liver and mesenteric lymph nodes were observed only after the injection of RenCa/F into the renal subcapsule. In contrast, there was no significant difference in either cell proliferation in vitro or tumor growth in vivo among RenCa sublines. These results suggest that if it is overexpressed, endogenous native FGF-2 plays an important role in the invasion and metastasis of renal cell carcinoma, probably through the production of MMP-2.

Animals↗

The significance of E-cadherin in transitional-cell carcinoma of the human urinary bladder.

E-cadherin is a Ca(2+)-dependent intracellular adhesion molecule in the epithelial tissue. The urothelium also expresses E-cadherin molecules. We determined E-cadherin expression in bladder carcinoma immunohistochemically and investigated its relationship with pathological and clinical data. The percentage of cases showing pattern B, less than 50% of which cancer cells expressed the same intensity of E-cadherin as did the normal epithelium, was higher in cases of high-grade or high-stage tumors as compared with those of low grade or low stage. Heterogeneous staining was observed in the same specimens, which suggested changes in the cell phenotype. Immunoblotting demonstrated no evidence of gross alteration of E-cadherin molecules. The decrease in E-cadherin expression was associated with the invasiveness of bladder carcinoma, as has been reported in other carcinomas.

Cadherins↗

Assessment of germ-cell kinetics in the testes of patients with varicocele using image analysis of immunostained proliferating cell nuclear antigen.

OBJECTIVE: To examine the germ-cell kinetics of varicocele testis using proliferating cell nuclear antigen (PCNA) immunostaining and image cytometry to evaluate the staining intensity, and to compare the proliferative index (PI) of varicocele and normal testes. PATIENTS AND METHODS: Fifty-six testicular biopsy specimens were taken from 28 patients with varicocele during high ligation. The specimens were fixed and embedded in paraffin, and sections immunostained using an anti-PCNA antibody. The PI was measured using an image analyser and expressed as the percentage of the total nuclear area stained positively with PCNA monoclonal antibody, assessed from > 20 seminiferous tubules. Sections stained with haematoxylin and eosin were used to determine Johnsen's score using conventional microscopy. Normal control testicular biopsies were obtained from subjects undergoing vasectomy. RESULTS: In patients with varicocele, both testes had a significantly lower PI than normal testes; the mean (SD) PI of the right and left testes was 11.3% (4.1) and 11.3% (4.8), respectively, and the PI of normal testes was 21.7% (3.1). There was no significant correlation between PI and sperm concentration or Johnsen's score. CONCLUSION: PI is useful for assessing germ-cell kinetics; in patients with varicocele both testes showed a deterioration in DNA synthesis, suggesting that reduced DNA synthesis is one of the causes of spermatogenic dysfunction in the varicocele testes.

Adult↗