Biomedical subjects

O Yoshida

Publications and source records attributed to O Yoshida.

At least 73 records · Page 4Linked to original sources

PubMed1998

Identification of S, F1C and three PapG fimbrial adhesins in uropathogenic Escherichia coli by polymerase chain reaction.

S and F1C fimbrial adhesins often expressed by uropathogenic Escherichia coli are genetically homologous. A multiply primed polymerase chain reaction (PCR) was developed for discriminating the S (sfa) and F1C (foc) fimbrial operons. A total of 270 uropathogenic E coli strains and 80 fecal isolates were examined. PCR specifically detected the sfa and foc alleles in 105 (93%) of 113 sfa/foc+ strains by DNA hybridization. Furthermore, 87% of sfa+ uropathogenic E. coli simultaneously possessed the genes encoding the class III P fimbrial adhesin (prsG(J96)), alpha-hemolysin and cytotoxic necrotizing factor 1. Statistical analysis showed the class II P fimbrial adhesin (papG(IA2)) and F1C fimbria to be associated with high relative virulence in pyelonephritis and cystitis, respectively. The multiply primed PCR developed should be useful for assessing the contribution of the S and F1C fimbriae in the pathogenesis of urinary tract infections.

Adhesins, Escherichia coli↗

PubMed1998

[Therapeutic effect of cefluprenam on polymicrobial urinary tract infection associated with Enterococcus faecalis, using the infectious urolithiasis model in rats].

We examined the therapeutic effect of cefluprenam (CFLP) on the polymicrobial urinary tract infection associated with infectious stones as compared to that of ceftazidime (CAZ), using the experimental polymicrobial urinary tract infection caused by Proteus mirabilis (P. mirabilis), Pseudomonas aeruginosa (P. aeruginosa) and Enterococcus faecalis (E. faecalis). In order to form bladder stones in rats, a sterile zinc ring was implanted as a foreign body, followed by inoculating P. mirabilis E05106 transurethrelly. Thereafter, P. aeruginosa E030033 and E. faecalis 966 were inoculated according to the same way. CFLP or CAZ was administered intravenously twice a day for 5 days. The therapeutic effect was evaluated by the eradication of these bacteria from the urine, the kidney and stones, inhibition of growth of stones, and also a value of BUN. The urinary excretion rates of CFLP and CAZ was also determined (20 mg/kg). In result, CFLP significantly more effective in the eradication of P. mirabilitis, P. aeruginosa and E. faecalis from the urine, the kidney and stones than the control than the control (p < 0.05). Furthermore, CFLP significantly more effective in the eradication of P. aeruginosa from the urine and also E. facalis from the urine and stones (p < 0.05). Meanwhile, CAZ significantly more effective in the eradication of P. mirabilis from the urine, the kidney and stones and also P. aeraginosa from the kidney and stones than the control. However, CAZ did not show eradicative effect on E. faecalis. The urinary excretion rates of CFLP and CAZ at rats were 59.3% and 59.4%, respectively, within 8 hrs after administration, showing a similar excretion pattern. CFLP exhibited the prominent therapeutic effect on polymicrobial urinary tract infection associated with infectious stones caused by P. mirabilis, P. aeruginosa and E. faecalls. On the basis of these results, it has been strongly suggested that CFLP is highly beneficial in the management of intractable polymicrobial urinary tract infectious in clinic.

Animals↗

PubMed1998

Analysis of effects of stimulation in vitro of ovalbumin primed lymph node cells on adoptive transfer of experimental immune mediated blepharoconjunctivitis in Lewis rats.

AIM: To analyse the role of stimulation in vitro of lymphocytes on the augmentation of experimental immune mediated blepharoconjunctivitis (EC, formerly EAC) in Lewis rats induced by adoptive transfer. METHODS: Two weeks after immunisation with ovalbumin (OVA), rat draining lymph nodes were collected and 50 x 10(6) cells were injected into naive syngeneic recipients either directly or after culture in vitro with OVA, concanavalin A (Con A), or purified protein derivative (PPD) for 3 days. Four days after injection the rats were topically challenged with OVA. 24 hours later, they were sacrificed and eyes and spleens were harvested for histology and proliferation assay. In some experiments, naive recipient rats were irradiated with 7 Gy gamma ray before transfer. The expression of adhesion molecules and cytokine profile of OVA primed lymph node cells were also investigated. RESULTS: Both infiltrated cell number and splenocyte proliferation in the recipients of stimulated cells were higher than those of unstimulated cells. In vitro stimulation with OVA or Con A induced a severe cellular infiltration, while stimulation with PPD did not. Irradiation markedly diminished cellular infiltration. Stimulation in vitro upregulated the CD4/CD8 ratio by four times and augmented expression of CD25, I-A, ICAM-1 molecules on OVA primed lymph node cells by about five times. IFN-gamma was detected in OVA primed cells by stimulation in vitro, while IL-4 mRNA was extinguished by stimulation in vitro. CONCLUSIONS: Augmentation of EC by stimulation in vitro of transferred lymphocytes might depend on the upregulation of expression of cell surface molecules and cytokine shift as well as augmented antigen specificity.

Adoptive Transfer↗

PubMed1998

Occludin is concentrated at tight junctions of mouse/rat but not human/guinea pig Sertoli cells in testes.

Occludin is the only integral membrane protein identified to date as a component of tight junctions (TJs). Here, we examined the distribution and expression of occludin in murine testis bearing well-developed TJ. In the adult mouse testis, occludin was concentrated at TJ strands, which are located at the most basal regions of lateral membranes of Sertoli cells. In immunoblotting, occludin showed a characteristic multiple banding pattern, suggesting that occludin is highly phosphorylated in the testis. In 1-wk-old mouse testis, occludin was distributed diffusely at the lateral membranes of Sertoli cells, and even at this stage, highly phosphorylated occludin was detected. With development, occludin gradually became concentrated at the most basal regions of Sertoli cells. The same results were obtained in rat, but unexpectedly occludin was not detected in human or guinea pig Sertoli cells by immunofluorescence microscopy as well as by immunoblotting. Inasmuch as TJs are also well developed in Sertoli cells of these species, we concluded that, at least in the testes of these species, there are some Sertoli cell-specific isoforms of occludin or other TJ-associated integral membrane proteins that differ from occludin.

Animals↗

PubMed1998

Decreased expression of cold-inducible RNA-binding protein (CIRP) in male germ cells at elevated temperature.

Physiological scrotal hypothermia is necessary for normal spermatogenesis and fertility in mammals. Cirp is a recently identified cold-inducible RNA-binding protein that is inducible at 32 degrees C in mouse somatic cells in vitro. Cirp is constitutively expressed in the testis of mouse and structurally highly similar to RBM1, a candidate for the human azoospermia factor. To elucidate the role played by Cirp in spermatogenesis, we investigated its expression levels during spermatogenesis and after heat stress. In the mouse testis, cirp mRNA was detected in the germ cells, and the level varied depending on the stage of differentiation. Also, a high level of Cirp protein was detected immunohistochemically in the nucleus of primary spermatocytes. Expression of Cirp was decreased in the GC-2spd(ts) mouse germ cell line when culture temperature was raised from 32 degrees C to 37 degrees C. When mouse testis was exposed to heat stress by experimental cryptorchidism or immersion of the lower abdomen in warm (42 degrees C) water, the expression of Cirp was decreased in the testis within 6 hours after either treatment. In human testis with varicocele analyzed immunohistochemically, germ cells expressed less Cirp protein than those in the testis without varicocele. These results demonstrated that CIRP expression is down-regulated at elevated temperature in male germ cells of mice and humans. Analysis of Cirp expression in the testes will help elucidate the molecular mechanisms leading to male infertility.

Adult↗

PubMed1998

Learning curve and conversion to open surgery in cases of laparoscopic adrenalectomy and nephrectomy.

PURPOSE: We examine how the level of experience acquired by the laparoscopist affects the outcome of laparoscopic adrenalectomy and nephrectomy, and what is necessary to avoid complications in these surgeries. MATERIALS AND METHODS: We retrospectively evaluated the experience levels of 8 urological laparoscopists between 1991 and 1995. In addition, other cases that were converted to open surgery were collected from the institutes with which the 8 laparoscopists were affiliated. RESULTS: The rates of conversion to open surgery were 6.4% in 204 cases of adrenalectomy and 14.3% in 63 of nephrectomy. Conversion rates were related to blood loss volume but not operative time. The major causes of conversion were bleeding in 45% of cases and adhesion in 34%. There were no mortalities. Mean operative time decreased significantly, reaching that of open surgery as the number of procedures increased up to 20 adrenalectomies and 10 nephrectomies. The volume of blood lost remained low from the early experience. Blood transfusion rates were 4.4% for adrenalectomy and 11.1% for nephrectomy. CONCLUSIONS: Operative time of these procedures decreased significantly with surgeon experience and reached that of open surgery. Cases in which adhesion is anticipated should be restricted to avoid conversion. These laparoscopic procedures are acceptable as a standard operative techniques for adrenal and renal diseases.

Adrenal Gland Diseases↗

PubMed1998

Seminal tract obstruction caused by childhood inguinal herniorrhaphy: results of microsurgical reanastomosis.

PURPOSE: Childhood inguinal herniorrhaphy is a frequent causes of seminal tract obstruction. We investigate the characteristics of this obstruction, surgical techniques for reanastomosis and outcomes in patients with bilateral or unilateral obstruction caused by inguinal herniorrhaphy in childhood. MATERIALS AND METHODS: We treated 22 men an average of 30.5 years old in whom average duration of obstruction was 27.1 years. Obstruction was bilateral in 9 patients and unilateral in 13, and 14 had azoospermia preoperatively. Microsurgical 2 layer vasovasostomy and/or specific tubule epididymovasostomy was performed. RESULTS: Inguinal and crossed vasovasostomy was done in 18 and 4 patients, respectively. The distal end of the vas was found at the internal inguinal ring or in the pelvic cavity in 57.1% of the vasa and more than 3 cm. of the vas had been resected in 37%. Sperm was noted in vasal fluid in 45.2% of the vasa during the operation and the patency rate of inguinal vasovasostomy was 88.9%. Ipsilateral epididymovasostomy performed after patent inguinal vasovasostomy in 5 patients with secondary epididymal obstruction resulted in normal sperm density and 3 pregnancies. In 7 men more than 2 procedures were done. There was sperm in the ejaculate in 12 of the 14 patients who had had azoospermia preoperatively and apparently increased sperm density postoperatively in 4 of the 8 who had not had azoospermia preoperatively. Pregnancy was achieved by 7 of the 21 married men (33.3%). CONCLUSIONS: Microsurgical reanastomosis of the seminal tract resulted in high patency and pregnancy rates in cases of seminal tract obstruction caused by childhood inguinal herniorrhaphy. Patients should elect seminal tract reanastomosis or assisted reproductive technology using epididymal or testicular sperm after receiving sufficient information on each treatment modality.

Adult↗

PubMed1998

[Clinical application of intraoperative ultrasonography for bilateral multilocular cystic renal cell carcinoma: a case report].

A 45-year-old man was referred to our department for further examination of the renal complicated cyst which was found incidentally by ultrasonography. Another complicated cyst in the left kidney was detected by subsequent dynamic CT and ultrasonography, which suggested bilateral cystic renal cell carcinoma. Bilateral partial nephrectomy was performed. Intraoperative ultrasonography was useful for diagnosis of multilocular cystic renal cell carcinoma (MCRCC). It disclosed multiple septa of the right renal complicated cyst which were not revealed by any preoperative examinations. It was also a useful adjunct to partial nephrectomy. It helped to identify the extent of deep intra-parenchymal lesions. The final diagnosis was bilateral synchronous multilocular cystic renal cell carcinoma. This is the second case of bilateral synchronous multilocular cystic renal cell carcinoma reported in Japan. We reviewed the clinical characteristics of 59 cases of MCRCC in the Japanese literature including the present case.

Carcinoma, Renal Cell↗

PubMed1998

Therapeutic effects of dopamine D1/D2 receptor agonists on detrusor hyperreflexia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned parkinsonian cynomolgus monkeys.

The effects of dopamine receptor agonists on urinary bladder function were evaluated in normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned parkinsonian cynomolgus monkeys to investigate the therapeutic efficacy in the treatment of urinary symptoms in Parkinson's disease. Under ketamine anesthesia, cystometrograms exhibited significant reduction in the volume threshold for the micturition reflex in MPTP-lesioned parkinsonian monkeys when compared with those of normal monkeys. The selective dopamine D2 receptor agonist bromocriptine significantly reduced the bladder volume threshold for the micturition reflex by 25 to 30% in both normal and MPTP-lesioned animals. The nonselective D1/D2 receptor agonist pergolide significantly reduced the bladder volume threshold by 22% in normal monkeys, but increased the volume threshold by 50% in MPTP-lesioned parkinsonian monkeys. Another D1/D2 agonist (5R,8R,10R)-6-methyl-8-(1,2,4-triazol-1-ylmethyl) ergoline maleate (BAM-1110) also increased the bladder volume threshold (by 80%) in parkinsonian monkeys without significant effects on the micturition reflex in normal monkeys. The reduction in the volume threshold by bromocriptine in both normal and MPTP-treated groups and by pergolide in normal monkeys was suppressed by pretreatment with the selective D2 antagonist sulpiride, whereas the increment in the volume threshold by pergolide and BAM-1110 in parkinsonian monkeys was antagonized by pretreatment with the selective D1 antagonist SCH 23390, but not by sulpiride. These findings suggest that concurrent activation of D1/D2 receptors, rather than selective stimulation of D2 receptors, might be beneficial for treating urinary symptoms caused by detrusor hyperreflexia in Parkinson's disease.

Animals↗

PubMed1998

Sensitization of human bladder cancer cells to Fas-mediated cytotoxicity by cis-diamminedichloroplatinum (II).

PURPOSE: The resistance of bladder cancer to anticancer chemotherapeutic drugs is a major problem. Several immunotherapeutic approaches have been developed to treat drug-resistant tumor cells. The Fas antigen (Fas)-Fas ligand pathway is involved in cytotoxic T lymphocyte and natural killer cell-mediated cytotoxicity. Like the Fas ligand, anti-Fas monoclonal antibody (mAb) induces apoptosis in tumor cells expressing Fas. Several anticancer drugs also mediate apoptosis and may share with Fas common intracellular pathways leading to cell killing. We reasoned that treatment of drug-resistant cancer cells with a combination of anti-Fas mAb and drugs might overcome their resistance. This study has investigated whether anticancer drugs synergize with anti-Fas mAb in cytotoxicity against bladder cancer cells. MATERIALS AND METHODS: Cytotoxicity was determined by a 1-day microculture tetrazolium dye assay. Synergy was assessed by isobolographic analysis. RESULTS: Treatment of the T24 human bladder cancer cell line with anti-Fas mAb in combination with 5-fluorouracil, mitomycin C or methotrexate did not overcome resistance to these agents. However, treatment of T24 tumor cells with a combination of anti-Fas mAb and cisdiamminedichloroplatinum (II) (CDDP) resulted in a synergistic cytotoxic effect. In addition, the CDDP-resistant T24 line (T24/CDDP) was sensitive to treatment with a combination of anti-Fas mAb and CDDP. Synergy by combination of anti-Fas mAb and CDDP was also achieved in three other bladder cancer lines and four freshly derived human bladder cancer cells. The combination of anti-Fas mAb and carboplatin also resulted in a synergistic cytotoxic effect on T24 cells; however, the combination of anti-Fas mAb and trans-diamminedichloroplatinum (II) resulted in an additive cytotoxic effect. Treatment with CDDP enhanced the expression of Fas on T24 cells. The synergy achieved in cytotoxicity with anti-Fas mAb and CDDP was also achieved in apoptosis. Incubation of T24 cells with anti-Fas mAb increased the intracellular accumulation of CDDP. Treatment of freshly isolated bladder cancer cells with CDDP enhanced their susceptibility to lysis by autologous lymphocytes. CONCLUSIONS: This study demonstrates that combination treatment of bladder cancer cells with anti-Fas mAb and CDDP overcomes their resistance. Synergy was achieved with established CDDP-resistant bladder cancer cells and freshly isolated bladder cancer cells. In addition, the sensitization required low concentrations of CDDP, thus supporting the potential in vivo application of combination of CDDP and immunotherapy in the treatment of CDDP- and/or immunotherapy-resistant bladder cancer.

Antibiotics, Antineoplastic↗

PubMed1998

Prognostic significance of soluble Fas in the serum of patients with bladder cancer.

PURPOSE: The interaction of Fas antigen (Fas) and Fas ligand plays an important role in cytotoxic T lymphocyte- and natural killer cell-mediated cytotoxicity against cancer cells. Circulating soluble Fas (sFas) antagonizes cell-surface Fas function and may interfere with immune surveillance against autologous tumors. This possibility was examined in patients with bladder cancer. MATERIALS AND METHODS: The levels of sFas in the serum of 173 patients with bladder cancer were determined by using an enzyme-linked immunosorbent assay. Cytotoxicity of anti-Fas monoclonal antibody was examined by a 1-day microculture tetrazolium dye assay. Anti-autologous tumor cytotoxic activity was determined by the 12-hour 51Cr release assay. RESULTS: The mean serum level of sFas in patients with bladder cancer was threefold higher than the mean in normal donors. The patients were divided into 2 groups based on the level of sFas in the serum. Bladder cancer patients with low level of serum sFas (less than the mean value) had a higher disease-specific survival rate, when compared with those with high level of serum sFas (greater than the mean value) in the 5-year followup. There were no statistical differences in patients' age and sex, as well as histological stage and grade of bladder cancer between the patients with high and low levels of serum sFas. Furthermore, patients with Ta bladder cancer with a low level of serum sFas had a longer postoperative tumor-free interval than those with high level in the 5-year followup. Cytotoxic activity of peripheral blood lymphocytes against autologous tumor cells was examined in 25 patients. There was an inverse correlation between the level of serum sFas and anti-autologous tumor cytotoxicity. CONCLUSIONS: The findings suggest that elevated levels of sFas in the serum might be associated with poor prognosis in patients with bladder cancer.

Adult↗

PubMed1998

Interleukin-1 alpha and interleukin-1 beta production in peripheral whole blood from patients with urological cancer.

The activities of interleukin-1 alpha (IL-1 alpha) and interleukin-1 beta) were investigated in peripheral whole blood from 30 patients with bladder cancer, 12 patients with renal cell carcinoma, 18 patients with prostatic cancer and 16 healthy subjects. Heparinized blood was cultured in the absence and presence of various concentrations of bacterial lipopolysaccharide (LPS). The culture supernatants were obtained and activities of IL-1 alpha and IL-1 beta were determined by enzyme-linked immunosorbent assay (ELISA). In the absence of LPS stimulation, neither IL-1 alpha nor IL-1 beta was spontaneously produced in blood cultures from patients with bladder cancer, renal cell carcinoma or prostatic cancer compared with control subjects. After stimulation with various concentrations of LPS, blood cultures from patients with bladder cancer, renal cell carcinoma, prostatic cancer, those from control subjects produced IL-1 alpha and IL-1 beta in a dose-dependent manner, and IL-1 beta was predominant in all supernatants. The activities of IL-1 alpha and IL-1 beta showed no significant differences between the patients with bladder cancer, renal cell carcinoma or prostatic cancer and control subjects. This study suggested that the patients with bladder cancer renal cell carcinoma and prostatic cancer did not spontaneously produce IL-1 alpha or IL-1 beta, but that the ability to produce IL-1 alpha and IL-1 beta in response to LPS stimulation was not significantly impaired.

Adult↗

PubMed1998

Characterization of the immunopathogenic responses to ovalbumin peptide 323-339 in experimental immune-mediated blepharoconjunctivitis in Lewis rats.

PURPOSE: We recently reported the essential role of cellular immunity on the induction of experimental immune-mediated blepharoconjunctivitis (EC, formerly EAC) by using ovalbumin (OVA) as a model antigen in Lewis rats. The purpose of this study was to investigate the possible induction of EC by immunization with an OVA peptide (OVA 323-339). METHODS: Lewis rats were immunized with various doses of OVA or OVA 323-339 in complete Freund's adjuvant. Three weeks later they were challenged with OVA or OVA 323-339 by eye drops; 24 h after challenge, eyes including lids, lymph nodes and blood were harvested after clinical evaluation. An OVA 323-339-specific cell line (S816) was established by periodical stimulation with this peptide. Pathogenicity of S816 was tested by adoptive transfer of S816 into syngeneic recipient rats after challenge with OVA or OVA 323-339. RESULTS: All rats immunized with OVA 323-339 developed EC after challenge with OVA or OVA 323-339. Rats immunized with OVA 323-339 at doses as low as 0.01 microg had severe clinical scores. OVA-primed rats also developed EC after challenge with OVA 323-339. OVA-primed lymph node cells responded to OVA but not to OVA 323-339. OVA 323-339-primed lymph node cells responded to OVA 323-339 but not to OVA and produced IFN-gamma by stimulation with either OVA or OVA 323-339 (three- to fourfold more than with OVA-primed lymph node cells). Recipient rats of S816 developed severe EC after challenge with either OVA or OVA 323-339. CONCLUSION: OVA 323-339 was identified as a potent pathogenic peptide in EC.

Adoptive Transfer↗

PubMed1998

[Expression of major histocompatibility complex antigens and adhesion molecules on renal cell carcinoma cells, and effect of interferon-alpha and/or cimetidine on the expression].

Recently the combined therapy with interferon-alpha (IFN-alpha) and cimetidine has been reported to be effective against advanced renal cell carcinoma (RCC). IFN-alpha and cimetidine have an antitumor effect partly due to enhancement of cytotoxic activity of lymphocytes against cancer cells. We examined the expression of major histocompatibility complex (MHC) antigens and adhesion molecules on 4 fresh RCC cells and 5 RCC cultured cell lines, which have an important role in recognition and killing of cytotoxic lymphocytes against cancer cells. The effect of treatment with IFN-alpha and/or cimetidine on the expression of MHC antigens and adhesion molecules on RCC cells was also investigated. MHC class I and leukocyte function-associated antigen-3 (LFA-3) were expressed on all RCC cells, but not MHC class II. Intercellular adhesion molecule-1 (ICAM-1) and B7 were expressed on 6 and 5 of 8 RCC cells, respectively. IFN-alpha significantly augmented the expression of MHC class I in 6 of 9 RCC cells, ICAM-1 in 1 and LFA-3 in 2 of 8 RCC cells. However, IFN-alpha did not affect the expression of MHC class II and B7. On the other hand, cimetidine enhanced the expression of LFA-3 in 2 of 8 RCC cells, but not MHC antigens, ICAM-1 or B7. The combination of IFN-alpha and cimetidine did not show a synergistic enhancing effect on the expression of MHC antigens, ICAM-1, LFA-3 or B7. These results suggest that IFN-alpha augments the sensitivity of RCC cells to lysis by cytotoxic lymphocytes partly due to the enhancement of expression of MHC class I, ICAM-1 and LFA-3 on RCC cells, and that cimetidine also augments the susceptibility of RCC cells to lymphocytes by the enhanced expression of LFA-3 on RCC cells.

Adjuvants, Immunologic↗

PubMed1998

[Three cases of the nephrogenic adenoma of the bladder].

Nephrogenic adenoma is a rare, benign tumor of the urinary tract. The origin of this tumor is supposed to be a metaplastic transformation of urothelium in response to stimulation such as recurrent urinary tract infections or surgical trauma. We experienced three cases of nephrogenic adenoma originating in the bladder. The first patient was a 29-year-old man with right vesicoureteral reflux (VUR). When Teflon injection for VUR was performed, a papillary tumor was found on the right wall of the bladder. Transurethral resection of the bladder tumor (TUR-Bt) was performed. The second patient was a 72-year-old woman who was suffering from chronic cystitis. Although she was treated with antibiotics for one year, the symptoms were not improved. Cystoscopy showed multiple papillary tumors at the retrotrigonum of the bladder and TUR-Bt was performed. The third patient was a 75-year-old man who had a history of the left pelvic and bilateral ureteral tumors. Left radical nephroureterectomy and right radical ureterectomy with an ileal graft replacement was performed. Three years later, cystoscopy demonstrated a papillary tumor at the retrotrigonum, which was resected transurethrally. Our cases are the 20th to 22nd cases of the nephrogenic adenoma of the bladder reported in the Japanese literature.

Adenoma↗

PubMed1998

[Synchronous multifocal development of invasive transitional cell carcinoma of the urinary tract in a patient with renal failure receiving long-term hemodialysis: a case report].

We report a case of transitional cell carcinoma in a patient with chronic renal failure receiving hemodialysis for 22 years. A 55-year-old man was admitted to our hospital. Under diagnosis of invasive bladder cancer and left renal pelvic tumor, removal of the whole urinary tract, e.g., bilateral nephroureterectomy and total cystourethrectomy was performed. Transitional cell carcinoma was found in bilateral renal pelvis, left ureter, bladder and prostate in the resected specimen. Thirteen months after the operation, multiple lung metastases and pathologic bone fracture of the 4th lumber vertebra were found. Chemotherapy (3 courses of modified CISCA, consisting of cisplatin, adriamycin and cyclophosphamide) was performed, but the died of systemic metastases of cancer and bleeding due to perforation of multiple gastric ulcers.

Carcinoma, Transitional Cell↗

PubMed1997

Involvement of NK1+ CD4- CD8- alphabeta T cells and endogenous IL-4 in non-MHC-restricted rejection of embryonal carcinoma in genetically resistant mice.

Non-MHC-restricted rejection mechanisms against the murine MHC-negative F9 embryonal carcinoma cells were analyzed. Strains of C57BL/6 (B6) background were resistant to the tumors irrespective of H-2 haplotypes, while others, including BALB/c background, were susceptible. This resistance was suggested to be mediated primarily by the host thymus-dependent alphabeta T cells, since both athymic B6 nude and normal B6 mice depleted with alphabeta T cells showed susceptible phenotype. The difference of the nature of alphabeta T cells infiltrating in H-2-identical B6- and BALB.B-derived tumors was then comparatively analyzed. It was revealed that unique T cells with NK1+ CD4- CD8- (double negative (DN)) alphabeta TCR+ phenotype were accumulated significantly in B6, but few in BALB.B mice. The population freshly isolated from the F9 tumor tissues preferentially expressed potent IL-4 mRNA, and was suggested to be mostly responsible for the endogenous IL-4 production. Indeed, the injection of either anti-NK1.1 or anti-IL-4-neutralizing Ab into the normal B6 rendered them significantly susceptible to the tumor cells. These results strongly suggested that NK1+ DN alphabeta T cells were responsible primarily for the rejection mechanisms against F9 tumors. Histologically, F9 tumors in B6 mice were characterized by abundant macrophage infiltration and massive tumor necrosis, neither of which was observed in those in BALB.B nor B6 mice preinjected with anti-IL-4 Ab, indicating that both histologic features in the resistant strain were dependent on the endogenous IL-4. Present results provide one of the first instances in which a recently emerging minor T cell subpopulation, thymus-dependent NK1+ DN alphabeta T cells, plays an essential role in anti-tumor responses in vivo.

Animals↗

PubMed1997

Detection of telomerase activity in exfoliated cells in urine from patients with bladder cancer.

BACKGROUND: Telomeres are specific structures located at the ends of chromosomes that help maintain chromosome stability. In most tissues, telomeres become shorter as cells divide, a phenomenon thought to be associated with limitations on normal cell proliferation. Almost all types of cancer cells, including bladder cancer cells, express the enzyme telomerase, which can maintain or extend telomere length. PURPOSE: We examined telomerase activity in tumor specimens from a cohort of patients with bladder cancer and determined whether telomerase could be detected in exfoliated cancer cells present in urine from these patients. METHODS: Spontaneously voided urine specimens and bladder-washing fluids (obtained by propelling normal saline into the bladder through a catheter and then withdrawing the liquid contents) were taken from 45 patients before they underwent surgery. Telomerase activity was examined by means of the TRAP (telomeric repeat amplification protocol) assay on extracts of tumor samples from 42 patients and extracts of exfoliated cells in urine and bladder-washing fluid from 42 and 43 patients, respectively. Standard cytologic examination (Pap staining) of urine specimens was also used to detect exfoliated cancer cells. RESULTS: Telomerase activity was found in 41 (98%; 95% confidence interval [CI] = 87%-100%) of the 42 tumor samples examined. In contrast, it was not detected in normal bladder tissue from two autopsied individuals who were free of bladder cancer and five of six individuals who had bladder cancer. Telomerase was detected in exfoliated cells in 23 (55%; 95% CI = 39%-70%) of the 42 spontaneously voided urine specimens and in 36 (84%; 95% CI = 69%-93%) of the 43 bladder-washing fluids examined. Considering voided urine specimens and bladder-washing fluids together, telomerase was detected in exfoliated cells from 40 (89%; 95% CI = 76%-96%) of the 45 patients. Telomerase activity was not detected in bladder-washing fluids from 12 cancer-free individuals. Cancer cells were detected by means of standard cytologic examination in the urine of 19 (42%; 95% CI = 28%-58%) of the 45 patients. Urine cytologic examination detected cancer cells in one (8%; 95% CI = 0%-38%) of 12 patients with grade 1 tumors and in 13 (46%; 95% CI = 28%-66%) of 28 patients with grade 2 tumors. In contrast, telomerase activity was detected in exfoliated cells (in voided urine or bladder-washing fluids) from nine (75%; 95% CI = 43%-95%) of 12 patients with grade 1 tumors and from 27 (96%; 95% CI = 82%-100%) of 28 patients with grade 2 tumors. CONCLUSION AND IMPLICATION: Telomerase activity can be detected in exfoliated cells in urine from patients with bladder cancer, and measurement of this activity appears to be more sensitive in detecting the presence of cancer than standard urine cytologic examination. These findings suggest that measuring telomerase activity in exfoliated cells would be useful in the diagnosis and follow-up of patients with bladder cancer, a possibility that warrants further study.

Aged↗