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Biomedical subjects

Shingo Yamamoto

Publications and source records attributed to Shingo Yamamoto.

At least 37 records · Page 2Linked to original sources

[Orthotopic bladder substitution].

Orthotopic bladder substitution is the most desired form of urinary diversion because the patient can restore normal voiding after cystectomy. However, urethral recurrence must be seriously considered and the patients with a risk of urethral recurrence are not indicated. Each method of bladder substitution has merits and demerits. We compared the Mainz method and the Studer method of orthotopic bladder substitution we performed on 8 and 11 patients, respectively since 1992. The Studer orthotopic ileal bladder substitution has given better results with better voiding pattern and less complication rates. We consider the Studer ileal bladder substitution as a good technique to restore normal voiding after cystectomy.

Aged↗

[Intra-arterial chemotherapy for invasive bladder cancer (T2-3N0M0)].

We assessed the effectiveness of intra-arterial MVAC chemotherapy or a combination of intra-arterial chemotherapy and external beam radiotherapy based on diagnostic images and histological (transurethral) examination in 15 cases with T2-3NOM0 between January 2003 and September 2005. When the clinical response was assessed one month after the treatments, a complete response (CR) was achieved in 20% (1/5) and 50% (5/10) by intra-arterial MVAC chemotherapy and a combination of intra-arterial chemotherapy and external beam radiotherapy, respectively. Total radical cystectomy was required on one patient during the follow-up period of 4-26 months. Although our result showed that the combination of external beam radiation therapy and intraarterial cisplatin effectively contributed to the preservation of the bladder with localized invasive bladder cancer, radical cystectomy is required when CR is not achieved after this treatment.

Aged↗

Novel matrix metalloproteinase inhibitors: generation of lead compounds by the in silico fragment-based approach.

Generation of structurally new matrix metalloproteinase inhibitors was successfully carried out using an in silico technique. In order to identify the small fragment interacting with residues in the S1' pocket of MMP-1 through hydrogen bonds, we performed in silico screening using the LUDI program. As a result, acetyl-L-alanyl-(N-methyl)amide (Ac-L-Ala-NHMe) was selected to link with another fragment, hydroxamic acid that interacted with catalytic zinc. By this approach, the L-glutamic acid derivative 2b was discovered to be a new type of matrix metalloproteinase inhibitor. Further transformation to reduce its peptidic nature and improve activity yielded nonpeptidic lead compounds as inhibitors of MMP-1, -2, -3, and -9.

Magnetic Resonance Spectroscopy↗

Monthly paclitaxel and carboplatin with oral estramustine phosphate in patients with hormone-refractory prostate cancer.

BACKGROUND: We aimed to determine the safety and efficacy of monthly paclitaxel and carboplatin with oral estramustine phosphate in patients with hormone-refractory prostate cancer (HRPC). METHODS: Patients with prostate cancer that was progressing despite androgen ablation therapy were treated with i.v. paclitaxel, 175 mg/m2, over 3 h, followed by carboplatin (area under the curve, 5) on day 1, with oral estramustine phosphate, 280 mg twice daily, for a 28-day treatment cycle. Estramustine phosphate was precluded in those patients who had experienced adverse effects during prior chemotherapies. Patients were evaluated for response every cycle, and the treatment was continued until the cancer progressed. RESULTS: Twenty-one patients with progressive hormone-refractory disease were treated for a median of 4 cycles (range, 1 to 11 cycles). Estramustine phosphate was precluded in seven patients. Post-therapy decreases in serum prostate-specific antigen levels of 50% and 75%, respectively, were seen in 43% and 19% of the patients (95% confidence intervals, 22% to 64% and 2% to 36%). Of the nine patients with measurable disease, 1 (11%) had a complete response and 2 (22%) had a partial response. The overall median time to progression was 4 months, and the median survival time for all patients was 11 months. Major grade 3 or 4 adverse effects were anemia (29%), neutropenia (48%), and thrombocytopenia (24%). Mild peripheral neuropathy and myalgia/arthralgia were observed in 11 (52%) and 9 (43%) patients, respectively. CONCLUSION: Monthly paclitaxel and carboplatin with oral estramustine phosphate has significant antitumor activity and is well tolerated in patients with progressive HRPC.

Administration, Oral↗

Induction of smooth muscle cell-like phenotype in marrow-derived cells among regenerating urinary bladder smooth muscle cells.

Tissue regeneration on acellular matrix grafts has great potential for therapeutic organ reconstruction. However, hollow organs such as the bladder require smooth muscle cell regeneration, the mechanisms of which are not well defined. We investigated the mechanisms by which bone marrow cells participate in smooth muscle formation during urinary bladder regeneration, using in vivo and in vitro model systems. In vivo bone marrow cells expressing green fluorescent protein were transplanted into lethally irradiated rats. Eight weeks following transplantation, bladder domes of the rats were replaced with bladder acellular matrix grafts. Two weeks after operation transplanted marrow cells repopulated the graft, as evidenced by detection of fluorescent staining. By 12 weeks they reconstituted the smooth muscle layer, with native smooth muscle cells (SMC) infiltrating the graft. In vitro, the differential effects of distinct growth factor environments created by either bladder urothelial cells or bladder SMC on phenotypic changes of marrow cells were examined. First, supernatants of cultured bladder cells were used as conditioned media for marrow cells. Second, these conditions were reconstituted with exogenous growth factors. In each case, a growth factor milieu characteristic of SMC induced an SMC-like phenotype in marrow cells, whereas that of urothelial cells failed. These findings suggest that marrow cells differentiate into smooth muscle on acellular matrix grafts in response to the environment created by SMC.

Animals↗

Association of a genetic polymorphism of the E-cadherin gene with prostate cancer in a Japanese population.

The E-cadherin gene has been identified as having a physiological role in cellular attachment, and is hypothesized to participate in carcinogenesis. A polymorphism (an A to C substitution) in the 5'-untranslated region has a direct effect on E-cadherin gene transcriptional regulation. We explored the association between E-cadherin gene polymorphism and the risk of prostate cancer in a Japanese population. The subjects consisted of 236 patients with prostate cancer, 209 benign prostatic hyperplasia (BPH) patients and 139 male controls. A marginally significant difference was found between prostate cancer patients and male controls (P = 0.053). No significant difference was observed between prostate cancer and BPH patients. When patients with prostate cancer were divided into two groups, stage A+B and stage C+D, a significant difference was observed between progressive cancer patients (stage C+D) and male controls (odds ratio = 1.93, P = 0.016). It is possible that the presence of one A allele resulted in an increased risk of cancer progression.

Aged↗

Renal scarring is associated with nonsecretion of blood type antigen in children with primary vesicoureteral reflux.

PURPOSE: Nonsecretor status of blood type antigen has been associated with higher risk of urinary tract infection (UTI) in women. However its implication in the modern management for pediatric UTI remains unclear. We evaluate the impact of secretor status on clinical course in children with primary vesicoureteral reflux (VUR). MATERIALS AND METHODS: From 1998 to 2002, 382 cases of primary VUR presented to our institute and were treated either surgically or nonoperatively in accordance with the American Urological Association guideline. Of these potential candidates 128 patients and their guardians volunteered to be entered into the study. Antiseptic swabs to collect saliva were sent to them. The secretor status was determined using the hemagglutination inhibition assay from the eluted saliva on the swabs and medical records of responders were evaluated retrospectively. RESULTS: Secretor status was not associated with gender, VUR grade, presentation, history of breakthrough UTI, laterality of VUR and conservative vs surgical treatment. However, nonsecretor status weakly correlated with decreased split renal function and significantly correlated with the presence of focal renal scarring (40.9% vs 21.7% for children with and without scarring, respectively) as determined by technetium dimercapto-succinic acid renal scan. CONCLUSIONS: These results demonstrate that secretor status represents unrecognized host disposition that affects the clinical course of primary VUR. Further study is needed to determine the significance of secretor status for clinical management and pathophysiology of VUR.

Blood Group Antigens↗

[Primary transitional carcinoma of the remaining ureter after nephrectomy for pyonephrosis: a case report].

A case of primary carcinoma of the remaining ureter is reported. A 70-year-old man presented with asymptomatic gross hematuria. Three years ago, he had received right nephrectomy for pyonephrosis. Although drip infusion pyelography (DIP) and cystoscopy showed no abnormal findings, computed tomography (CT) and retrograde ureterography demonstrated the irregular thickening of the right remaining ureteral wall. He underwent right ureterectomy with bladder cuff resection. Pathological examination revealed transitional cell carcinoma of the remaining ureter. He has been free of disease for 3 years.

Aged↗

[Retroperitoneal ganglioneuroma presenting as a soft tissue mass surrounding the aorta: report of a case].

A 37-year-old man was hospitalized for a soft tissue mass around the aorta which had been incidently found by abdominal CT. Radiological finding and laboratory data were nonspecific for retoroperitoneal fibrosis, lymphnode metastasis of testicular carcinoma and lymphoma. Ultrasonography guided biopsy of the mass revealed ganglioneuroma of the retoroperitoneum. No growth of the mass was observed at 14 months follow up.

Adult↗

[A case of accelerated acute rejection in kidney transplantation rescued by plasma exchange].

A 30-year-old female received living donor kidney transplantation from her mother. The surgical procedure was uneventfully performed and urine output was observed a few minutes after reperfusion. However, 24 hours after the surgery, the urine volume rapidly decreased with worsened renal blood flow as determined by Doppler ultrasonography, diagnosed as accelerated acute rejection (AAR). Plasma exchange (PE) combined with therapies including administration of steroids and OKT3 dramatically improved the renal status, resulting in maintenance of good renal function (serum Cr; 1.5 mg/dl) even after 18 months PE was considered as a powerful tool for AAR, and the literature was reviewed.

Acute Disease↗

[The influence over the long-term prognosis of BCG therapy and the surgical treatment in superficial bladder cancer treatment].

From the view point that total cystectomy is important in treatment of carcinoma in situ (CIS) of the bladder, we reviewed the cases showing resistance to bacillus Calmette-Guerin (BCG) among 42 CIS treated with intravesical BCG. Twenty-six cases were cured by BCG treatment. Twelve total cystectomies were done in 16 cases of BCG-resistant CIS of the bladder. Four died with urethral invasion or upper urinary tract recurrence. There was invasion into the prostate in 3 cases. The development of CIS to the upper urinary tract and the prostatic urethra is not rare and this has an influence on the prognosis. In bladder CIS treatment, the inspection to see extravesical progression is necessary. It is important not to delay the radical cystectomy.

Adjuvants, Immunologic↗

[Oncocytoma associated with acquired cystic disease of kidney (ACDK): a case report].

A case of renal oncocytoma associated with acquired cystic disease of kidney (ACDK) in a 56-year-old man is reported. He had received hemodialysis for 15 years because of chronic renal failure. Computed tomography (CT) was performed because of distention in the upper abdomen, revealing a right renal tumor. He underwent laparoscopic right nephrectomy, and was diagnosed with renal oncocytoma. There have been reported 8 cases of renal oncocytoma in hemodialysis patients, and our case was the third one associated with ACDK in the literature.

Adenoma, Oxyphilic↗

[Prostate cancer with penile metastasis: a case report].

A 77-year-old man presented with complaints of dysuria, nocturia and painless nodule on his penis. Laboratory examination revealed elevated serum prostate-specific antigen (PSA) and CA19-9. Pathological examinations on prostate and penile biopsy specimens revealed prostate adenocarcinoma with penile metastasis. The patient was diagnosed as having prostate cancer stage D2 (T4N1M1) with bone, lymph node and penile metastases. There was no response to initial hormonal therapy with the surgical castration and diethylstilbestrol. However, decrease of the tumor size, as well as PSA and CA19-9 values were achieved after the combined chemotherapy with Estramustine, Paclitaxel and Carboplatin.

Adenocarcinoma↗

[Spontaneous rupture of renal angiomyolipoma: a case report].

A 55-year-old woman presented with sudden right lower abdominal pain. Computed tomography demonstrated retroperitoneal hematoma associated with minus-density area, diagnosed as spontaneous rupture of angiomyolipoma. Super-selective transarterial embolization was performed, but anemia and right abdominal pain became worse in spite of conservative therapy including transfusion, indicating re-rupture of the renal tumor. Although partial nephrectomy was planned, right nephrectomy was finally performed because of massive intraoperative bleeding. Accurate diagnosis and prompt treatment are required when life-threatening rupture of renal tumor is suspected.

Abdomen, Acute↗

Type I collagen can function as a reservoir of basic fibroblast growth factor.

Storage and release of endogenous growth factors by the extracellular matrix (ECM) are important biological events that control tissue homeostasis and regeneration. The interaction between basic fibroblast growth factor (bFGF) and heparan sulfate proteoglycans has been extensively studied and used as a prototype model of such a system, while the lower affinity of fibrillar type I collagen for bFGF has generally been considered biologically insignificant. However, our present investigation revealed that bFGF spontaneously interacts with type I collagen solution and sponges under in vitro and in vivo physiological conditions, and is protected from the proteolytic environment by the collagen. bFGF incorporated in a collagen sponge sheet was sustainedly released in the mouse subcutis according to the biodegradation of the sponge matrix, and exhibited local angiogenic activity in a dose-dependent manner. Intramuscular injection of collagen microsponges incorporating bFGF induced a significant increase in the blood flow in the murine ischemic hindlimb, which could never have been attained by bolus injection of bFGF. These results suggest the significance and therapeutic utility of type I collagen as a reservoir of bFGF.

Animals↗

Lansoprazole-tacrolimus interaction in Japanese transplant recipient with CYP2C19 polymorphism.

OBJECTIVE: To report a patient with a high tacrolimus blood concentration after lansoprazole administration and assess the potential interaction between tacrolimus and lansoprazole. CASE SUMMARY: A 34-year-old Japanese man underwent a living-donor kidney transplantation having received tacrolimus, mycophenolate mofetil, and prednisolone for immunosuppression. Lansoprazole was administered from postoperative day 4 as prophylaxis of ulcers. The trough concentration of tacrolimus increased markedly after the introduction of lansoprazole, while results of liver function tests were within normal limits. Lansoprazole was stopped on day 15 and was replaced with famotidine on day 17. The trough concentration of tacrolimus returned to the therapeutic range after administration of lansoprazole ceased. Genetic analysis revealed a heterozygous mutation at exon 5 of the CYP2C19 gene (CYP2C19*1/*2) in this patient. DISCUSSION: Lansoprazole is metabolized by 2 enzymes, CYP2C19 and CYP3A4. Since tacrolimus is also metabolized by CYP3A4, the blood concentration of tacrolimus in this patient who had a CYP2C19 gene mutation may have been elevated by decreased hepatic elimination of lansoprazole. An objective causality assessment revealed that this interaction was probable. CONCLUSIONS: Trough concentrations of tacrolimus should be monitored closely for optimizing the dosage regimen in patients receiving concomitant lansoprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Collagenous matrices as release carriers of exogenous growth factors.

We have investigated the use of natural and synthetic collagenous matrices as carriers of exogenous growth factors. A bladder acellular matrix (BAM) was processed from rat bladder and compared with sponge matrix of porcine type 1 collagen. The lyophilized matrices were rehydrated by the aqueous solutions of basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), platelet derived growth factor-BB (PDGF-BB), vascular endothelial growth factor (VEGF), insulin like growth factor-1 (IGF-1) and heparin binding epidermal growth factor-like growth factor (HB-EGF), to obtain the matrix incorporating each growth factor. The rehydration method enabled the growth factor protein to distribute into the matrix homogeneously. In vivo release test in the mouse subcutis revealed that, the property of BAM for growth factor release was similar to that of collagen sponge. Among the growth factors examined, bFGF release was the most sustained, followed by HGF and PDGF-BB. bFGF released from the two matrices showed similar in vivo angiogenic activity at the mouse subcutis in a dose-dependent manner. These findings demonstrate that the collagenous matrices function as release carriers of growth factors. This feature is promising to create a scaffold, which has a nature to control the tissue regeneration actively.

Animals↗

Verotoxin induces rapid elimination of human renal tumor xenografts in SCID mice.

PURPOSE: Verotoxins (VTs) are subunit toxins produced by enteropathogenic Escherichia coli. The VT receptor glycolipid Gb3, which mediates the cytotoxicity of VTs, has been reported to be elevated on the surface of several tumor cell lines. In this study the effect of VT1 as an antineoplastic agent was assessed using various human urological cancer cell lines. MATERIALS AND METHODS: The expression of Gb3 on human cancer cell lines originating from renal cell carcinoma (ACHN, A-704, CAKI-1 and CAKI- 2), prostate cancer (LNCaP and PC3) and testicular tumor (2102Ep) were examined by FACScan (Becton Dickinson, Sunnyvale, California). These cell lines were cultured with various concentrations of VT1 and subjected to microculture tetrazolium dye assay for determination of cell viability. Furthermore, ACHN cells were inoculated into the backs of SCID mice and intratumor injection of VT1 was performed. Pathological samples were examined by hematoxylin and eosin staining as well as by TUNEL assay. RESULTS: The growth of ACHN, CAKI-1, A-704, 2102Ep and LNCaP but not CAKI-2 and PC3 was significantly inhibited by co-incubation with VT1, as determined by microculture tetrazolium dye assays, consistent with FACScan results for Gb3 expression. When mice bearing ACHN tumors were injected with VT1, rapid reduction in the size of subcutaneous tumors was observed with complete regression within 5 to 7 days. Pathological examination by the TUNEL method indicated that the cytotoxicity of VT1 was mediated by apoptosis. CONCLUSIONS: These results suggest that VTs could be candidates for antineoplastic agents against Gb3 expressing tumors for clinical use.

Animals↗