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Biomedical subjects

Kenjiro Kohri

Publications and source records attributed to Kenjiro Kohri.

At least 37 records · Page 2Linked to original sources

Complete response of a recurrent advanced urachal carcinoma treated by S-1/cisplatin combination chemotherapy.

We report a case of recurrent advanced urachal carcinoma with right internal iliac node and left lung metastases in a 34-year-old man. After receiving partial cystectomy including en bloc resection of the urachus and with bilateral pelvic lymph node dissection, he was treated with five courses of S-1 and cisplatin combination chemotherapy. He remains free from the disease after a 30-month follow-up period. S-1/cisplatin combination chemotherapy is suggested to be a potent tool for controlling advanced urachal carcinoma.

Adenocarcinoma↗

Development of multiple calculi in the duplex system ureterocele.

A 61-year-old man presented complaining of pollakisuria and nocturia. A plain radiograph of his kidney, ureter and bladder and intravenous urography revealed numerous calculi in the upper kidney of his left renal pelvis and ureterocele. A transurethral incision of ureterocele (TUI-ureterocele) and extracorporeal shock wave lithotripsy were performed. On TUI-ureterocele, the many calculi were found to be almost the same size and spherical in form. The postoperative clinical course was uneventful.

Humans↗

The role of Ni(2+)-sensitive T-type Ca(2+) channels in the regulation of spontaneous excitation in detrusor smooth muscles of the guinea-pig bladder.

OBJECTIVE: To explore the role of Ni(2+)-sensitive T-type Ca(2+) channels in the generation of spontaneous excitation of detrusor smooth muscles. MATERIALS AND METHODS: In isolated detrusor smooth muscle bundles of the guinea-pig bladder, changes in the membrane potential and muscle tension were measured using intracellular microelectrodes and isometric tension recording. Changes in the intracellular Ca(2+) concentration were recorded from bundles loaded with the fluorescent dye fura-PE3. RESULTS: Detrusor smooth muscles had two types of spontaneous electrical activity, i.e. individual and bursting action potentials. Ni(2+) (30 microM), a blocker for T-type Ca(2+) channels, reduced the frequency of individual action potentials without changing their amplitude. Higher concentrations of Ni(2+) (100-300 microM) converted individual action potentials into the bursts, as did apamin (0.1 microM), a blocker of small-conductance Ca(2+)-activated K(+) channels (SK). They also increased the amplitudes of spontaneous Ca(2+) transients and corresponding contractions whilst reducing their frequencies. In preparations which generated bursting action potentials, nifedipine (1 microm) converted action potentials into spontaneous transient depolarizations (STDs), and subsequent applications of Ni(2+) (100 microm) abolished STDs. Gadolinium (100 microM) and SKF96365 (10 microM), blockers for nonselective cation channels, and niflumic acid (100 microm), a blocker for Ca(2+)-activated Cl- channels, had no effect on either the amplitude or frequency of spontaneous action potentials. CONCLUSIONS: The T-type Ca(2+) channel may have dual roles in generating spontaneous excitation in detrusor smooth muscles. First, activity of these channels may account for the preceding depolarizations that lead to action potentials. Second, Ca(2+) influx through T-type Ca(2+) channels may couple functionally to SK channels, contributing to the stability of the resting membrane potential in detrusor smooth muscle. Thus, pharmacological manipulation of T-type Ca(2+) channels in detrusor smooth muscles could be of potential value for treating the overactive bladder.

Action Potentials↗

Pitfalls with MRI evaluation of prostate cancer detection: comparison of findings with histopathological assessment of retropubic radical prostatectomy specimens.

INTRODUCTION: To assess differences between MRI findings and histopathologically defined prostate cancer localization, we compared clinical results with mapping of radical prostatectomy specimens, and conducted a retrospective MRI cancer localization re-assessment by a urologist-technician after surgery. METHODS: We performed MRI for a total of 37 suspected prostate cancer patients. Subsequently, all underwent retropubic radical prostatectomy after prostate biopsy for confirmation of the diagnosis. All the specimens were studied histopathologically with serial sectioning using a whole organ approach. RESULTS: Of the 37 patients, 26 had positive MRI findings. All the surgical specimens contained cancerous lesions, and 23 had multiple foci. Twenty-four of the MRI-positive cases (92.3%) demonstrated coincidence of both MRI and histopathologically defined lesions. In the single focus cases, 78.6% (11/14) demonstrated exact coincidence, but in the multifocal cases there were no cases with exact coincidence of MRI and histopathological findings (0/23). CONCLUSION: MRI evaluation cannot be considered an effective diagnostic tool in itself for detection of prostate cancers because sensitivity is far from satisfactory, especially in multi-focal cases.

Aged↗

Lack of prophylactic effect of incadronate on skeletal lesions associated with implants of prostate cancer.

OBJECTIVES: To evaluate prophylactic effects of bisphosphonate (BP) on skeletal lesions induced by prostate cancer (CaP). METHODS: Incadronate, a third-generation BP, was administered weekly for 4 weeks, with or without 4-week pre-administration, to rats whose calvaria had been inoculated with syngeneic CaP tissue. RESULTS: The transplanted CaP grew up and caused bone resorption with osteoblastic changes regardless of incadronate treatment. Although decrease in bone resorption accompanied by reduced number of osteoclasts was shown by incadronate administration, pre-administration had no additional inhibitory effect on bone destruction and Ki-67 labeling indices of CaP cells were not altered. CONCLUSIONS: These results indicate that application of BP alone is not sufficient to prevent skeletal lesions due to CaP in patients with high risk of bone metastases although it is useful in inhibition of cancer-induced bone resorption with osteoblastic changes.

Animals↗

Interaction between spontaneous and neurally mediated regulation of smooth muscle tone in the rabbit corpus cavernosum.

Interaction between spontaneous and neurally mediated regulation of tone in the corpus cavernosum smooth muscle (CCSM) of the rabbit was investigated. Changes in isometric muscle tension, intracellular Ca2+ concentration ([Ca2+]i) and membrane potential were recorded. CCSM developed spontaneous contractions, transient increases in [Ca2+]i (Ca2+ transients) and depolarizations. This spontaneous activity was abolished by blocking L-type Ca2+ channels (nicardipine, 1 mum), sarcoplasmic reticulum Ca2+ pump activity (cyclopiazonic acid, 10 microm), Ca2(+)-activated Cl- channels (niflumic acid, 10 mum) or cyclooxygenase-2 (COX-2; NS-398, 1 microm). Transmural nerve stimulation initiated either alpha-adrenergic contractions or nitrergic relaxations of CCSM depending on the level of muscle tone. NS-398 suppressed nerve-evoked contractions by about 70% but caused only a 40% reduction in the corresponding Ca2+ transient. Blocking nitric oxide synthase with N(omega)-nitro-l-arginine (LNA, 100 microm) reinforced nerve-evoked Ca2+ transients by about 150%, whilst increasing the corresponding Ca2+ transients by only 20%. In CCSM preparations that had been pre-contracted with either noradrenaline (0.3 microm) or prostaglandin F(2alpha) (0.1 microm), nerve stimulation inhibited about 70% of the contraction and caused only a 20% decrease in [Ca2+]i. Fluorescent immunohistochemistry with COX-2 antibodies and the reverse transcriptase-polymerase chain reaction (RT-PCR) method showed that the enzyme and its mRNA were highly expressed in the CCSM. These results suggest that spontaneously produced prostaglandins (PGs) not only contribute to the generation of spontaneous contractions but also facilitate nerve-evoked contractions. Conversely, spontaneously released nitric oxide (NO) suppresses excitation. Thus, interaction between spontaneous and neurally mediated regulation of CCSM tone may be fundamental to maintaining the muscle contractility. In addition, both PGs and NO appear to alter CCSM tone with only small changes in [Ca2+]i.

Action Potentials↗

In vivo gene transfer by electroporation allows expression of a fluorescent transgene in hamster testis and epididymal sperm and has no adverse effects upon testicular integrity or sperm quality.

The study of gene function in testis and sperm has been greatly assisted by transgenic mouse models. Recently, an alternative way of expressing transgenes in mouse testis has been developed that uses electroporation to introduce transgenes into the male germ cells. This approach has been successfully used to transiently express reporter genes driven by constitutive and testis-specific promoters. It has been proposed as an alternative method for studying gene function in testis and sperm, and as a novel way to create transgenic animals. However, the low levels and transient nature of transgene expression that can be achieved using this technique have raised concerns about its practical usefulness. It has also not been demonstrated in mammals other than mice. In this study, we show for the first time that in vivo gene transfer using electroporation can be used to express a fluorescent transgene in the testis of a mammal other than mice, the Syrian golden hamster. Significantly, for the first time we demonstrate expression of a transgene in epididymal sperm using this approach. We show that expression of the transgene can be detected in sperm for as long as 60 days following gene transfer. Finally, we provide the first systematic demonstration that this technique does not lead to any significant long-term adverse effects on testicular integrity and sperm quality. This technique therefore offers a novel way to study gene function during fertilization in hamsters and may also have potential as a way of creating transgenic versions of this important model species.

Animals↗

Anticancer effect of hyperthermia on prostate cancer mediated by magnetite cationic liposomes and immune-response induction in transplanted syngeneic rats.

BACKGROUND: The hyperthermic effect of magnetic particles was examined in rat prostate cancer in vivo. Magnetic cationic liposomes (MCLs) have a positive surface charge and generate heat in an alternating magnetic field (AMF) due to hysteresis losses. METHODS: Rat prostate cancer cells (PLS 10; androgen independent) were injected subcutaneously into the flank of F344 rats. MCLs were injected into rat prostate cancer nodules that had grown to 5-6 mm in diameter, and were then exposed to an AMF. Tumor growth rates were measured. To examine whether hyperthermia caused immune induction for PLS 10, cytotoxicity assays and immunohistochemical staining for CD3, CD4, CD8, and Heat Shock Protein (HSP) 70 were performed. RESULT: The tumor temperature increased to 45 degrees C whereas the body temperature remained at around 38 degrees C. Tumor regression was observed in the hyperthermic group. CD3, CD4, and CD8 immunocytes were present in the tumor tissues of the rats exposed to hyperthermia, but they were not detected in any of the tumor tissue of untreated rats. HSP70 also appeared in the viable area at its boundary with the necrotic area. The cytotoxic activity of tumor-transplanted rats for PLS 10 cells increased in hyperthermic-treatment rats. CONCLUSION: These results suggest that hyperthermia using MCLs is an effective therapy for prostate cancer, since this treatment appears to kill the prostate cancer cells not only directly by heating but also by inducing an immune response. This therapy may cure not only the primary lesion but also metastatic lesions.

Animals↗

Predicting response to methotrexate, vinblastine, doxorubicin, and cisplatin neoadjuvant chemotherapy for bladder cancers through genome-wide gene expression profiling.

PURPOSE: Neoadjuvant chemotherapy for invasive bladder cancer, involving a regimen of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC), can improve the resectability of larger neoplasms for some patients and offer a better prognosis. However, some suffer severe adverse drug reactions without any effect, and no method yet exists for predicting the response of an individual patient to chemotherapy. Our purpose in this study is to establish a method for predicting response to the M-VAC therapy. EXPERIMENTAL DESIGN: We analyzed gene expression profiles of biopsy materials from 27 invasive bladder cancers using a cDNA microarray consisting of 27,648 genes, after populations of cancer cells had been purified by laser microbeam microdissection. RESULTS: We identified dozens of genes that were expressed differently between nine "responder" and nine "nonresponder" tumors; from that list we selected the 14 "predictive" genes that showed the most significant differences and devised a numerical prediction scoring system that clearly separated the responder group from the nonresponder group. This system accurately predicted the drug responses of 8 of 9 test cases that were reserved from the original 27 cases. Because real-time reverse transcription-PCR data were highly concordant with the cDNA microarray data for those 14 genes, we developed a quantitative reverse transcription-PCR-based prediction system that could be feasible for routine clinical use. CONCLUSIONS: Our results suggest that the sensitivity of an invasive bladder cancer to the M-VAC neoadjuvant chemotherapy can be predicted by expression patterns in this set of genes, a step toward achievement of "personalized therapy" for treatment of this disease.

Aged↗

Examination of the anti-oxidative effect in renal tubular cells and apoptosis by oxidative stress.

The incidence of urolithiasis has increased in the industrialized nations. However, both the pathogenesis and methods for its prevention remain to be clarified. We demonstrate that the antioxidative effect of green tea decreases the formation of calcium oxalate stones, OPN (osteopontin) expression, and apoptosis, and increases SOD (superoxide dismutase) activity in rat kidney tissues. The inhibitory effect of green tea on calcium oxalate urolithiasis is most likely due to its antioxidative effects. Therefore, we examined oxidative stress in vivo applied to Madin-Darby canine kidney (MDCK) cells, to which catechin, an antioxidant, was added. To evaluate the effects of oxidative stress on MDCK cells, we use a hypoxic condition because hypoxia is known to lead to oxidative stress. Confluent cultures of MDCK cells were exposed to (-)epigallocatechin 3 gallate (EGCG) (0, 0.1, 0.5, 5.0 mg/ml) for 2, 4, 8 or 16 h to determine changes in protein secretion and apoptosis. OPN protein expression was observed in MDCK cells of all 16 groups. The levels of expression of OPN protein were the same among all groups. In all groups, SOD protein expression was observed. In the groups exposed to EGCG 0.5, 5.0 mg/ml, SOD staining was more enhanced than in the EGCG 0 and 0.1 mg/ml groups. No deposits were detected in any of the 16 groups. RT-PCR was performed to detect sequences from OPN (979 bp) and SOD (447 bp). Quantitative analyses showed that SOD activity decreased gradually in all groups. Only in the EGCG 0 mg/ml 16 h group were TUNEL-positive cells observed. In the other groups, TUNEL-positive cells were not detected. EGCG used as an antioxidant protects renal tubular cell from cellular injury caused by oxidative stress through SOD protein expression.

Animals↗

Effect of testicular biopsy in childhood on spermatogenesis, fertility, and paternity in adulthood--a mouse model study.

OBJECTIVES: To study the effect of testicular biopsy in childhood on spermatogenesis, fertility, and paternity in subsequent adulthood using an animal model. Considerable controversy exists as to whether testicular biopsy should be performed in children. METHODS: Four-week-old male ICR mice were subjected to unilateral testicular biopsy (group 1), bilateral biopsy (group 2), or a sham operation (group 3). At 8 weeks of age, the testicular weight, seminiferous tubular diameter, and manifestation of apoptosis were examined. The motility of sperm obtained from the epididymides of the same testes was also examined. Fertility and paternity was assessed in each mouse by housing it with 2 age-matched females for 2 weeks. RESULTS: No significant differences were found in the testicular weight, mean seminiferous tubular diameter, or number of apoptotic germ cells between the biopsied and unbiopsied side in group 1 or between groups 2 and 3. No significant differences were noted in the average sperm motility rate between the biopsied (30.5% +/- 14.5%) and unbiopsied side (35.8% +/- 19.2%) in group 1, or between groups 2 (37.6% +/- 18.0%) and 3 (39.3% +/- 10.0%). All females who coupled with the male mice in all groups became pregnant. The average number of offspring from the 2 female mice was not significantly different among the three groups (group 1, 13.1 +/- 2.3; group 2, 12.3 +/- 2.0; and group 3, 11.3 +/- 3.0). CONCLUSIONS: The spermatogenesis, fertility, and paternity of mature mice were unaffected by testicular biopsy in childhood.

Age Factors↗

Preventive effects of green tea on renal stone formation and the role of oxidative stress in nephrolithiasis.

PURPOSE: Urinary stones are similar to arteriosclerosis in epidemiology, mechanism, calcification composition and age at frequent occurrence. The calcification that occurs in arteriosclerosis is inhibited by antioxidants. Green tea leaves contain approximately 13% catechins, which have been shown to have antioxidant effects. We investigated the inhibitory, antioxidative effects of green tea on calcium urinary stone formation. MATERIALS AND METHODS: A total of 120 Wistar rats were divided into 4 groups, namely group 1-control rats receiving saline, group 2-stone group rats administered ethylene glycol (EG) and vitamin D3, group 3-drink group rats administered EG, vitamin D3 and green tea given as drinking water, and group 4-powder group rats administered EG, vitamin D3 and 2.5% powdered green tea leaves mixed in a powder diet. Pooled 24-hour urine samples and blood samples were collected and the 2 kidneys were excised 7, 14 and 21 days after administration, respectively. One kidney was used for immunohistological examination of osteopontin, superoxide dismutase (SOD), p65, p53 and bcl-2 expression, in situ hybridization of osteopontin and detection of apoptosis, while the other was used for quantitative analysis of SOD activity. RESULTS: Green tea treatment decreased urinary oxalate excretion and calcium oxalate deposit formation. Green tea treatment increased SOD activity compared with the stone group. The degree of apoptosis in the stone group was significantly increased compared with the drink and powder groups. CONCLUSIONS: The inhibitory effect of green tea on calcium oxalate urolithiasis is most likely due to antioxidative effects.

Animals↗

A polymorphism of the osteopontin gene is related to urinary calcium stones.

PURPOSE: We investigated polymorphisms of the osteopontin (OPN) gene to explore whether they could be used as a gene marker for determining the risk of urinary calcium stones. MATERIALS AND METHODS: A total of 76 patients with urinary calcium stones and 124 controls were studied. Two single nucleotide polymorphisms with nonsynonymous amino acid located at positions 9,402 (Arg/His) and 9,171 (Asn/Ser) in the OPN gene were genotyped using the TaqMan 5' nuclease assay in a PRISM 7700 sequence detection system. Results were analyzed with Fisher's exact test. RESULTS: Results revealed a significant different polymorphism at OPN gene position 9,402 between patients with urinary calcium stones and control subjects. The frequency of the A/G genotype at position 9,402 in patients with urinary calcium stones was significantly higher than that in control subjects (p <0.01). The frequency of the A allele at position 9,402 was significantly higher in the patient than in the control group (4.6% vs 0.4%, p <0.01). There was no statistical difference in this polymorphism at OPN gene position 9,402 between genotype distribution and clinical characteristics associated with urinary calcium stones. There was no difference in the polymorphism at OPN gene position 9,171 between the patient and control groups. CONCLUSIONS: Polymorphism at position 9,402 of the OPN gene is highly associated with urinary calcium stones and it is a candidate genetic marker for evaluating the genetic risk of urinary calcium stone disease, whereas polymorphism at position 9,171 of the OPN gene is not associated with urinary calcium stone disease.

Adult↗

Effect of epidermal growth factor on spermatogenesis in the cryptorchid rat.

PURPOSE: Epidermal growth factor (EGF) is secreted mainly from the submandibular glands. Submandibular gland ablation causes a marked decrease in male fertility, which suggests that EGF influences spermatogenesis. We investigated the effect of EGF in combination with orchiopexy on cryptorchid rat testes in which tubular deterioration had become partially irreversible. MATERIALS AND METHODS: Unilaterally cryptorchid rats were obtained by daily administration of 7.5 mg flutamide (Nihonkayaku, Tokyo, Japan), an androgen receptor antagonist, to pregnant rats. At age 10 weeks the unilaterally cryptorchid rats underwent orchiopexy with or without EGF administered into the cryptorchid testis. EGF solution (10 microg/ml) was delivered into the seminiferous tubules by retrograde perfusion through the rete testis. At 14 days testicular recovery was assessed based on the maturity of spermatogenesis using a modified Johnsen score and from the number of apoptotic germ cells per seminiferous tubule. RESULTS: Mean Johnsen score +/- SEM was significantly higher in the orchiopexy with EGF than in the orchiopexy without EGF group (7.85 +/- 0.12 vs 7.12 +/- 0.13, p <0.001). The number of apoptotic germ cells tended to be smaller in the orchiopexy with EGF group than in the orchiopexy without EGF group (0.16 +/- 0.05 vs 0.28 +/- 0.08). CONCLUSIONS: Although orchiopexy for cryptorchidism partly improved spermatogenesis, recovery was limited. EGF administered in combination with orchiopexy was more effective for spermatogenesis than orchiopexy alone. This may be applicable in patients with cryptorchidism.

Analysis of Variance↗

Novel technique for correcting penile curvature with severe hypospadias; ventral lengthening with tunica vaginalis flap patching.

The adequate correction of penile curvature is essential for successful hypospadias surgery. We describe a novel technique to correct severe penile curvature with a tunica vaginalis flap on the penile ventrum. We applied a tunica vaginalis flap to lengthen the ventral aspect of the tunica albuginea in two boys with significant curvature and proximal hypospadias. Tunica vaginalis flap patching to the ventral aspect of the penis is safe and technically feasible. If penile curvature is severe or the penis is small in hypospadiac patients, lengthening the ventral aspect using a tunica vaginalis flap is likely to expand instead of dorsal plication or ventral graft.

Child, Preschool↗

Congenital prepubic sinus: a variant of dorsal urethral duplication (Stephens type 3).

Abstract A 3-year-old boy was admitted for yellowish discharge from a tiny opening in the midline prepubic area on the dorsal base of the penis. No other symptom related to the genitourinary tract was noted. Sinuousgraphy showed a non-communicating sinus tract with the urinary tract. At surgical exploration, through a diamond-shaped incision, a 4.5 cm-long sinus was found that ended blindly as a fibrous cord at the anterior surface of the pubic symphisis. Histologically, it was lined by stratified squamous epithelium and surrounded by bundles of smooth muscle and collagen. According to Stephens' classification, the sinus appears to be a variant of dorsal urethral duplication of Stephens type 3.

Child, Preschool↗