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Biomedical subjects

S Kamidono

Publications and source records attributed to S Kamidono.

At least 109 records · Page 6Linked to original sources

Clinical outcome of microsurgery for obstructive azoospermia.

BACKGROUND: Recent technical advances in microscopy have greatly improved the reconstruction of the seminal tract in cases of obstructive azoospermia. METHODS: We evaluated the clinical outcome of 28 patients with obstructive azoospermia who underwent microsurgical reconstruction (i.e. vasovasostomy or unilateral epididymovasostomy). Diagnoses included postvasectomy (n = 9), childhood inguinal herniorrhaphy (n = 10) and cases of unknown cause (n = 9). Six of the unknown cases proved to be inoperable. We analyzed the outcome of the surgical reconstructions of operable cases according to the causes of obstruction, duration of obstruction, quality of the fluid obtained from the distal seminal tract (concentration, morphology and motility of sperm) and the histologic findings of the testis. RESULTS: The surgical outcome was analyzed with regard to the incidence of patency and pregnancy. The incidence of patency achieved in nine vasectomy cases was 89%, while the incidence of pregnancy was 44%. In contrast, the incidence of patency in the nine operable cases with herniorrhaphy was 44%, while the pregnancy rate was 0%. Of four cases of unknown cause who underwent epididymovasostomy, the incidence of patency was 100% and the incidence of pregnancy was 75%. The outcomes were worse in post-vasectomy cases with long-term obstruction of more than 10 years; however, this was not statistically significant. The outcome was significantly worse in cases with low sperm concentrations. There was no significant relationship between histologic findings and surgical outcome. CONCLUSIONS: The surgical outcome of vasovasostomy of postherniorrhaphy cases was significantly worse than that of post-vasectomy cases. With regard to epididymovasostomy, a unilateral repair was clinically evaluated.

Adult↗

Pharmacokinetics of natural human IFN-alpha in hemodialysis patients.

A pharmacokinetic study of natural human interferon-alpha (IFN-alpha) was conducted in hemodialysis patients. Natural human IFN-alpha was intramuscularly (i.m.) administered to 8 hemodialysis patients at a single dose of 5 million IU and to 7 patients undergoing hemodialysis at the same dose once daily for 5 successive days. The serum antiviral activity was determined by a cytopathic effect bioassay. In the single dose study, the serum antiviral activity reached a maximum (Cmax) of 56.4 +/- 33.3 IU/ml at 8.3 +/- 2.7 h after dosing, and the area under the serum concentration-time curve (AUC0-24h) was 957.2 +/- 601.8 IU h/ml. The Cmax and AUC0-24h values at day 5 following the repeated dosing were both 2.6-fold higher than those of day 1, and the serum antiviral activity reached a steady state within 3 days after initiation of repeated administration. The serum antiviral activity in hemodialysis patients showed a tendency to increase compared with that in the subjects with normal renal function, but the magnitude of the differences was not great. In one nonhemodialysis patient with poor renal function (creatinine clearance < 30 ml/min), no increases in serum antiviral activity owing to repeated dosing were observed. The main adverse events seen were fever (4 of 13, 30.8%), leukopenia (3 of 13, 23.1%), and fatigue (2 of 13, 15.4%). These results suggest that dosage modifications of natural human IFN-alpha are unnecessary for patients with low renal function, even those undergoing hemodialysis.

Aged↗

Assisted reproduction for infertile patients with 9 + 0 immotile spermatozoa associated with autosomal dominant polycystic kidney disease.

We investigated the clinical feature of patients with totally immotile spermatozoa due to 9 + 0 ultrastructural flagellar defects and polycystic kidney disease. We also tried to establish the feasibility of applying modern assisted reproduction technology (ART) in these patients. During 6-year interval a total of 1956 Japanese men were referred to the male infertility clinic. Of them, 16 were diagnosed to have immotile spermatozoa and four of them exhibited axonemal 9 + 0 defects in the sperm flagella. These four also had autosomal dominant polycystic kidney disease (ADPKD). Intrauterine insemination (IUI) and conventional in-vitro fertilization and embryo transfer failed to achieve fertilization. Intracytoplasmic sperm injection (ICSI) with 100% immotile spermatozoa was performed in all four cases. Two-pronuclear fertilization was obtained in 27 of the 70 (38.6%) of the successfully injected oocytes, but no pregnancy resulted. In one case, a few motile spermatozoa were present at the second cycle of ICSI, a pregnancy was successfully achieved using these spermatozoa. While immotile spermatozoa from patients with the axonemal 9 + 0 defect achieved fertilization by ICSI, the embryos failed to develop. Our results indicate that the central microtubules may play a role in fetal development. Since the 4 patients with 9 + 0 defects also had ADPKD, the genetic linkage between these two conditions should be studied by molecular biological methods so as to aid our ability to counsel such patients.

Cytoplasm↗

Klinefelter's syndrome in the male infertility clinic.

The clinical features of patients with Klinefelter's syndrome attending a male infertility clinic have been investigated in order to consider their assisted reproduction treatment options. Over 12 years, a total of 148 patients with sterility due to azoospermia had Klinefelter's syndrome. Eight patients were shown by fluorescence in-situ hybridization (FISH) on metaphase spreads to be mosaic (46,XY/47,XXY), and 140 patients showed only 47,XXY. Small testes were observed in 95% of patients and gynaecomastia was seen in 12.4%. Half of the patients showed hypergonadotrophic hypogonadism, while others showed normogonadism (usually hypergonadotrophic). Spermatozoa were observed in semen from one patient with mosaicism and one without. Three-colour FISH revealed hyperploidy in 2.7% and 2.3% of these spermatozoa respectively. Multiple-site testicular biopsies in five recent patients were performed and yielded a specimen with round and elongated spermatids in one patient with 47,XXY karyotype. This sample was cryopreserved for future intracytoplasmic sperm injection. At follow-up, 46% of couples had chosen artificial insemination with donor sperm, and none had chosen adoption. Two patients developed testicular tumours, one a mature teratoma and the other a Leydig cell tumour. Two patients required androgen replacement therapy.

Adult↗

Clinical outcome of high-dose chemotherapy combined with peripheral blood stem cell transplantation for male germ cell tumors.

Peripheral blood stem cell transplantation (PBSCT) is widely performed currently instead of bone marrow transplantation (BMT) because bone marrow reconstruction is better and the procedure is less invasive. We applied 26 courses of high-dose chemotherapy (1250 mg/m2 of carboplatin, 1500 mg/m2 of etoposide and 7.5 g/m2 of ifosfamide) to 14 male patients with germ cell tumors. Eleven patients underwent high-dose chemotherapy as induction after two to three courses of conventional BEP therapy. The remaining three patients had recurrent disease after conventional chemotherapies. Peripheral blood stem cells were harvested during previous chemotherapy and sufficient CD34+ cells were harvested for transplantation. Although all patients had grade 4 hematotoxicity, the white blood cell count recovered to more than 1000/microl within 8-11 days after PBSCT. No treatment-related death was found. Nine of 14 patients (64.3%) remain disease free at 18 months of median follow up time (range 12-60). We conclude that high-dose chemotherapy is a safe and effective means of treating advanced or refractory germ cell tumors in male patients.

Adult↗

The significance of the difference in bacterial adherence between bladder and ileum using rat ileal augmented bladder.

OBJECTIVES: Intestinal segments are frequently used in the reconstruction of the urinary tract. Chronic bacteriuria is frequently observed in these patients, but the reason is not clearly understood. Therefore, we studied the difference in bacterial adherence between bladder and ileum using the rat ileal augmented bladder model to investigate the cause of chronic bacteriuria. MATERIALS AND METHODS: Augmentation of the bladder using ileum and a sham operation were performed under sodium pentobarbital in 102 and 10 Sprague-Dawley rats, respectively. At three months after the operation, urinary pH and plasma concentration of sodium, chloride and potassium were measured and urinary culture was done. Urovirulence factors of Escherichia coli aspirated from augmented bladder were detected by polymerase chain reaction (PCR). Five to six rats with negative urinary cultures after the augmentation were used for each experimental cystitis. E. coli with type I pili aspirated from augmented rats and three clinically isolated strains of E. coli, C5 (type I pili, aerobactin), C92 (type I pili, aerobactin, P fimbriae), and C189 (type I pili, aerobactin, P fimbriae, CNF), were transurethrally inoculated into the augmented bladder of rats. Fourteen days after inoculation, rats were sacrificed and colony-forming units (CFU) per mg. of tissue of bladder and ileum were measured. RESULTS: After operation, urinary pH and the serum level of chloride in all augmented groups were higher than those of the controls. Bacterial colonization was observed in 56 of 89 rats. Most of them were E. coli having only type I pili as a virulence factor. In contrast, the sham operated group revealed no bacterial colonization. In experimental cystitis, E. coli with only type I pili aspirated from augmented rats and E. coli C5 were clearly adhered to ileum rather than to bladder, but E. coli C92 and C189 showed no significant difference with respect to adherence to the two tissues. In experimental cystitis II, E. coli C5 with D-mannose were washed out in 3 of 5 rats by 14 days, while E. coli C5 without D-mannose were not washed out in all rats by 14 days. CONCLUSIONS: These results suggested that the difference in bacterial adherence due to urovirulence factors, especially type I pili, is one of the main causes of asymptomatic bacteriuria after urinary reconstruction.

Animals↗

Calcium ionophore, ionomycin inhibits growth of human bladder cancer cells both in vitro and in vivo with alteration of Bcl-2 and Bax expression levels.

PURPOSE: The objective of this study was to characterize the antiproliferative effects of the calcium ionophore, ionomycin on the human bladder cancer cell line HT1376 both in vitro and in vivo. MATERIALS AND METHODS: The in vitro growth rate of HT1376 after treatment with ionomycin was measured by using the MTT assay. The apoptotic features in HT1376 after ionomycin treatment were evaluated by flow cytometric analysis and DNA degradation assay. Bcl-2 and Bax expression levels in HT1376 after ionomycin treatment were examined by Northern and Western blot analyses. The effects of intratumoral injection of ionomycin on the growth of subcutaneous HT1376 tumors established in athymic nude mice were then tested. The efficacy of combined treatment with ionomycin and cisplatin against HT1376 growth was also examined. RESULTS: The in vitro growth rate of HT1376 was suppressed by ionomycin in a dose- and time-dependent manner, and characteristic apoptotic DNA degradation was observed in HT1376. Ionomycin treatment caused a marked decrease in the ratios of Bcl-2 to Bax mRNA and protein in HT1376 cells. Intratumoral injection of ionomycin into subcutaneous HT1376 tumors reduced the tumorigenicity in nude mice. Furthermore, these in vivo growth-inhibitory effects of ionomycin were significantly enhanced by pretreatment with cisplatin. CONCLUSIONS: These findings suggest that ionomycin-based therapy could be used as a novel therapeutic strategy for advanced bladder cancer through the effective induction of apoptosis by decreasing the ratio of Bcl-2 to Bax.

Animals↗

Cytotoxicity of adenoviral-mediated cytosine deaminase plus 5-fluorocytosine gene therapy is superior to thymidine kinase plus acyclovir in a human renal cell carcinoma model.

PURPOSE: An estimated 11,600 Americans will die of renal cell carcinoma in 1998. The lack of effective chemotherapy or radiotherapy requires the investigation of novel treatment modalities. We compared two forms of toxic gene therapy, cytosine deaminase (CD) plus 5-fluorocytosine (5-FC) and thymidine kinase (TK) plus acyclovir (ACV), in pre-clinical models of human renal cell carcinoma. MATERIALS AND METHODS: Replication-deficient recombinant adenoviral vectors containing the Rous sarcoma virus promoter driving CD (Ad-RSV-CD) or TK (Ad-RSV-TK) gene expression were constructed and tested for in vitro cell-killing assays at various viral multiplicity of infection (MOI) and in vivo for growth inhibition of a human renal cell carcinoma, SK-RC-29 models. Subcutaneous tumors of SK-RC-29 were examined by electron microscopy for presence of intercellular gap junctions. Levels of expression of the gap junctional associated connexin 43 protein in SK-RC-29, 31, 38, 42, 52 human RCC cell lines were examined by western immunoblotting. RESULTS: In vitro cell-killing assay comparing Ad-RSV-CD/5F-C and Ad-RSV-TK/ACV at a wide range of MOI (2.5 to 20) revealed superior cell-kill by Ad-RSV-CD/5-FC over Ad-RSV-TK/ACV. Consistent with these results, we observed that Ad-RSV-CD/5-FC but not Ad-RSV-TK/ACV demonstrated a significant in vivo tumor growth inhibition. These results are corroborated by the lack of gap junctions in SK-RC-29 subcutaneous tumors by the electron microscopy and the absence of connexin-43 in all five human RCC cell lines by western immunoblotting. CONCLUSION: We have demonstrated in this study that Ad-RSV-CD/5-FC is superior to Ad-RSV-TK/ACV for the treatment of human RCC in cell culture and animal models. The results are supported by the lack of gap junctional communication between RCC cells assessed by connexin-43 expression.

Acyclovir↗

Elevation of urokinase-type plasminogen activator and its receptor densities as new predictors of disease progression and prognosis in men with prostate cancer.

We examined whether two newly defined parameters, the density of urokinase-type plasminogen activator (uPAD) and the density of its receptor (uPARD), which were determined by dividing the serum levels of uPA and uPAR by the prostate volume, respectively, could be used as predictors of the progression and prognosis of prostate cancer (PC). Serum levels of uPA and uPAR in 40 healthy controls, 70 patients with benign prostatic hypertrophy (BPH) and 80 patients with PC were measured by a sandwich enzyme immunoassay, and prostate volume was measured by ultrasonography. The mean levels of uPAD and uPARD in patients with PC were significantly higher than those in healthy controls and patients with BPH. Furthermore, the uPAD and uPARD levels in PC patients with metastasis were significantly elevated compared with those in patients without metastasis. Among patients who underwent radical prostatectomy, the levels of uPAD and uPARD in patients with pathologically organ-confined disease were significantly lower than in those with advanced disease. The overall survival rate of PC cancer patients with elevated levels of either uPAD or uPARD, or of both, was significantly lower than that of patients with normal levels of uPAD and uPARD. In addition, Cox's multivariate analysis revealed that the elevation of uPAD or uPARD level, or of both, was strongly associated with overall survival in PC patients. These findings suggest that the elevation of uPAD or uPARD, or of both, could be used as new predictors of progression and prognosis in patients with PC.

Adult↗

[Development and characterization of a monoclonal antibody which recognizes a new prostate-organ specific antigen].

PURPOSE: Development and characterization of monoclonal antibodies which recognizes a new prostate-organ specific antigen. METHOD: For development of monoclonal antibodies, hybrid cells were prepared by fusion of spleen cells of BALB/c mice immunized with the homogenates of surgically resected prostatic tissue and P 3 x Ag 8 U 1 (P 3 U 1) murine myeloma cells. Supernatants of hybrid clones were primarily screened using an ELISA on human prostatic cancer cell line PC-3 and human bladder cancer cell line T-24. In the secondary screening, they were tested on normal tissues by immunohistochemical staining. To characterize the antigens, biochemical analyses were performed using seminal plasma as an antigen by western blotting and gel filtration, and the reactivity of antibodies were compared with that of antibodies against prostatic acid phosphatase (PAP), prostate-specific antigen (PSA) and gamma-seminoprotein (gamma-Sm). RESULTS: A monoclonal antibody termed KP-9 was obtained and it only reacted with PC-3 and prostate tissues, but did not react with other cell lines and normal tissues. Immunohistochemical staining of prostate tissue revealed that KP-9 stained grandular epithelium and grandular exudate of normal and malignant prostatic tissues, and especially, strongly stained the apical site of grandular epithelium. Western blotting and gel filtration of seminal plasma suggested that the molecular weight of the KP-9 antigen was more than 300,000 and was different from PAP, PSA and gamma-Sm. CONCLUSION: We have developed a monoclonal antibody, KP-9 which specifically reacts with prostatic cancer as well as benign prostatic tissues. The antigen recognized by KP-9 appeared to be a new prostate-organ specific antigen and may be a useful marker for prostatic cancer such as PAP, PSA and gamma-Sm.

Animals↗

Assisted reproduction technology for patients with congenital bilateral absence of vas deferens.

PURPOSE: We investigate the frequency of cystic fibrosis transmembrane conductance regulator gene mutations in Japanese patients with congenital bilateral absence of the vas deferens, and assess treatment outcomes of assisted reproduction interventions. MATERIALS AND METHODS: In 10 Japanese patients with bilateral congenital absence of the vas deferens genetic analysis was performed for known frequent mutations of the cystic fibrosis transmembrane conductance regulator gene using polymerase chain reaction amplification followed by dot-blot hybridization with the allele-specific oligonucleotide probes and direct sequencing. Intracytoplasmic sperm injection using spermatozoa retrieved from the testes was performed in 7 of the couples. RESULTS: No known mutations of the gene were detected in the patients. However, analysis of the polythymidine tract polymorphism in intron 8 revealed 30% allele frequency of 5T. Pregnancy was achieved in 7 cycles of intracytoplasmic sperm injection using spermatozoa retrieved from the testes. CONCLUSION: The 5T variant in intron 8 polythymidine tract was identified with high allelic frequency in Japanese patients with congenital bilateral absence of the vas deferens, suggesting that the disease in Japan is also partially caused by this particular mutation of the cystic fibrosis transmembrane conductance regulator gene. Modern assisted reproduction technology offers an important option for patients with congenital bilateral absence of the vas deferens.

Adult↗

[A case of true carcinosarcoma in bladder diverticulum].

We report a case of carcinosarcoma arising from a bladder diverticulum. A 71-year-old male was referred to our hospital for macroscopic hematuria. Two diverticula were identified in the left wall of the urinary bladder, one of which showed a broad-based tumor. The bladder tumor was resected using a transuretheral approach and the tumor was histologically diagnosed as leiomyosarcoma. The patient underwent partial resection of the bladder including the two diverticula and the tumor. Pathological examination revealed that the resected specimen was composed of three elements, transitional cell carcinoma (G3), squamous cell carcinoma, and leiomyosarcoma. Thus, the patient was diagnosed with carcinosarcoma. He died 5 months after surgery to remove the panperitonitis carcinomatosa. This case is the 38th reported case of bladder carcinosarcoma in Japan.

Aged↗

[Expression of CD44 variant isoform in urine samples of urothelial cancer patient].

CD44v8-10 variant isoform is frequently expressed in many kinds of cancers. We have already reported that 77% of bladder cancer specimens expressed CD44v8-10 and using CD44v8-10/CD44v10 competitive reverse transcription-polymerase chain reaction (CC-RT-PCR), we detected exfoliated urothelial cancer cells in urine samples of urothelial cancer patients (Int J Cancer 79: 560, 1998, J Urol 160: 2004). In this paper, we review the expressing of CD44 variant isoform in various kinds of cancers, and the principle of CC-RT-PCR which can be a novel screening method for urothelial cancer.

Carcinoma, Transitional Cell↗

Relative expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in mouse renal cell carcinoma cells regulates their metastatic potential.

To clarify the significance of the balance between matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) in the progression of renal cell carcinoma, we transfected both the MMP-2 and TIMP-2 genes simultaneously into RenCa, a mouse renal cell carcinoma cell line that does not express detectable levels of either MMP-2 or TIMP-2 mRNAs, and established several clones with various MMP-2:TIMP-2 expression ratios. On the basis of the quantitative evaluation of the MMP-2: TIMP-2 mRNA expression ratio by Northern blot analysis, we selected a clone overexpressing MMP-2 alone (RenCa/M), a clone overexpressing TIMP-2 alone (RenCa/T), and two kinds of clones overexpressing both, i.e., one with a high (RenCa/MTh) and one with a low (RenCa/MTl) MMP-2: TIMP-2 ratio, to compare the tumor cell phenotypes. In an in vitro tumor cell invasion assay, the MMP-2:TIMP-2 ratios of the RenCa sublines were directly correlated with their invasive potential. The invasive abilities of the parental RenCa cells induced by conditioned media from RenCa sublines were also correlated with the MMP-2:TIMP-2 ratios of the sublines. The cell adhesion assay showed the inverse correlation between the MMP-2 expression levels in the sublines and their cell adhesion to several extracellular matrix components. Furthermore, when injected i.v. or into the renal subcapsule in syngeneic mice, RenCa sublines formed metastatic nodules in the lungs, and the number of nodules was correlated with the MMP-2:TIMP-2 ratio of each clone. In contrast, despite the growth-inhibitory effects of TIMP-2 overexpression, MMP-2 overexpression had no effect on either proliferation in vitro of RenCa sublines or on their growth as tumors in vivo. These results suggest that the MMP-2:TIMP-2 expression ratio is a critical factor in the invasion and metastasis of renal cell carcinoma.

Animals↗

Glutamate-induced currents in acutely dissociated guinea pig locus coeruleus neurons.

To investigate the properties of L-glutamate (Glu) receptors in single locus coeruleus (LC) neurons at mature stage, we recorded the Glu-induced currents in the LC neurons acutely dissociated from adult guinea pigs, using the whole-cell patch-clamp technique. The concentration-current relationships show that Glu-induced currents in LC neurons might be predominantly mediated by non-NMDA receptors rather than NMDA receptors. The current-voltage relationship of NMDA or non-NMDA receptor-mediated currents indicated that both subtypes of the Glu-receptors operate non-selective cation channels, and that the NMDA receptor-operated channels but not the non-NMDA receptor-operated channels are permeable to Ca2+. These results suggest that in LC neurons, the normal excitatory neurotransmission may be mediated through non-NMDA receptors, and that NMDA receptors may be involved in intracellular signal transduction by their Ca2+ permeability.

Animals↗

[Laparoscopic resection of retroperitoneal tumors: report of two cases].

Here we report two rare cases of retroperitoneal tumors which were found incidentally and resected laparoscopically. Case 1; A 43-year-old woman presented with general fatigue and revealed liver dysfunction. Although the initial diagnosis with computed tomography (CT) was left non-functioning adrenal tumor, it was proven as a retroperitoneal tumor adjacent to the left adrenal gland by laparoscopic examination. The tumor was resected laparoscopically and diagnosed histopathologically as a solitary retroperitoneal neurofibroma. Case 2; A 68-year-old man was being followed for a renal stone and a perirenal tumor was found by CT. It was resected laparoscopically and diagnosed as a mature retroperitoneal teratoma by histopathological examination. We conclude that laparoscopic resection is useful for the retroperitoneal tumors as well as for adrenal tumors.

Adult↗