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Biomedical subjects

Shingo Yamamoto

Publications and source records attributed to Shingo Yamamoto.

At least 19 recordsLinked to original sources

Escherichia coli isolates associated with uncomplicated and complicated cystitis and asymptomatic bacteriuria possess similar phylogenies, virulence genes, and O-serogroup profiles.

The genetic and serological characteristics of Escherichia coli isolates from patients with uncomplicated cystitis (UC), complicated cystitis (CC), and complicated asymptomatic bacteriuria (CASB) were determined. Phylogenetic group B2 was predominant in all categories. The prevalences of 14 out of 18 virulence factor genes were similar among the three categories, while pap, iha, ompT, and PAI were more frequently seen in isolates associated with UC than CC or CASB.

Bacteriuria↗

Efficient gene transfer by pullulan-spermine occurs through both clathrin- and raft/caveolae-dependent mechanisms.

The feasibility and mechanism of gene delivery by pullulan-spermine, a recently developed cationic polysaccharide, were investigated. Pullulan-spermine-mediated transfection of plasmid DNA resulted in greatly reduced cytotoxicity and a 10-fold increase in the level of gene expression when compared to Lipofectamine 2000, a commercially available cationic lipid. Additionally, after transfection of p53-expressing plasmid DNA by pullulan-spermine but not Lipofectamine 2000, the in vitro proliferation of T24 cells was significantly reduced. Pullulan-spermine-mediated gene expression was inhibited by both chlorpromazine of clathrin-mediated endocytosis inhibitor and methyl-beta-cyclodextrin and filipin of raft/caveolae inhibitors. We conclude that pullulan-spermine is a promising carrier for gene transfection, and that cellular uptake of pullulan-spermine-plasmid DNA complexes is mediated by clathrin- and raft/caveolae-dependent endocytotic pathways.

Asialoglycoprotein Receptor↗

Optimization of sulfonamide derivatives as highly selective EP1 receptor antagonists.

A series of 4-[(2-{isobutyl[(5-methyl-2-furyl)sulfonyl]amino}phenoxy)methyl]benzoic acids and 4-({2-[isobutyl(1,3-thiazol-2-ylsulfonyl)amino]phenoxy}methyl)benzoic acids were synthesized and evaluated for their EP receptor affinities and EP1 receptor antagonist activities. Further structural optimization was carried out to reduce inhibitory activity against hepatic cytochrome P450 isozymes, which could represent a harmful potential drug interaction. Selected compounds were also evaluated for their binding affinities to hTP, hDP, mFP, and hIP, and for their hEP1 receptor antagonist activities. The results of structure-activity relationship studies are also presented.

Benzoates↗

Increased biofilm formation in Escherichia coli isolated from acute prostatitis.

Using crystal violet binding assay, we examined the potential for biofilm formation in 194, 76 and 107 isolates from urine of patients with uncomplicated acute cystitis, pyelonephritis and prostatitis, respectively. The prostatitis isolates showed significantly higher optical density (OD) values compared with cystitis and pyelonephritis isolates (OD(540): 0.82, 0.29 and 0.43, respectively, P<0.0001). Similarly, strains of serotypes O4 and O22, which were commonly isolated from prostatitis, exhibited significantly higher OD values than did other strains. Furthermore, when the 21 prostatitis isolates were examined for expression of curli fimbriae, eight of 12 strains with a high OD value, but only three of nine with a low OD value, expressed curli fimbriae (P=0.0195). These results suggest an association between acute bacterial prostatitis and biofilm formation.

Acute Disease↗

[Hermaphroditism].

Explore the source record for details and available documents.

Adrenal Glands↗

Discovery of heteroaryl sulfonamides as new EP1 receptor selective antagonists.

4-({2-[Isobutyl(phenylsulfonyl)amino]-5-(trifluoromethyl)phenoxy}methyl)benzoic acid (1) is a functional PGE2 antagonist selective for EP1 receptor subtype. Analogs of 1, in which the phenyl-sulfonyl moiety has been replaced with more hydrophilic heteroarylsulfonyl moieties, exhibited more optimized antagonist activity, while some of them showed in vivo antagonist activity. Structure-activity relationship (SAR) studies are also presented.

Alprostadil↗

Design and synthesis of an orally active matrix metalloproteinase inhibitor.

A series of 4-(4-phenoxy)benzoylamino-4-methoxymethyloxymethyl butyric acid hydroxamates, which were derived from l-glutamic acid, were synthesized and evaluated as matrix metalloproteinase inhibitors. Most of the compounds listed in exhibited strong inhibitory activity against MMP-2 and MMP-9, as well as even stronger inhibitory activity against MMP-3, but showed relatively weak inhibition of MMP-1. Structure-activity relationships are discussed.

Administration, Oral↗

Design and synthesis of novel metalloproteinase inhibitors.

A series of N-benzoyl 4-aminobutyric acid hydroxamate analogs were synthesized and evaluated as matrix metalloproteinase inhibitors. Synthetic work was focused on the chemical modification of the 4-aminobutyric acid part using easily available starting materials. As such, chemical modification was carried out using commercially available starting materials such as 4-aminobutyric acid, (+)- and (-)-malic acid, and D- and L-glutamic acid derivatives. Among the compounds tested, N-[4-(benzofuran-2-yl)benzoyl] 4-amino-4S-hydroxymethylbutyric acid hydroxamates derived from L-glutamic acid demonstrated more potent inhibitory activity against MMP-2 and MMP-9 compared with the corresponding 2S-hydroxy analogs or 3S-hydroxy analogs, respectively, which were derived from (-)-malic acid. Structure-activity relationship study is presented.

Benzofurans↗

Discovery of a new chemical lead for a matrix metalloproteinase inhibitor.

A series of N-benzoyl gamma-aminobutyric hydroxamic acids were synthesized and evaluated as matrix metalloproteinase inhibitors. First, we focused on chemical modification of the N-benzoyl residue. Introduction of electron-rich para-substituents was effective to increase the inhibitory activity. Especially, some of the analogs with relatively more planar N-acyl residues, such as 10 and 11, demonstrated more potent activity. Second, chemical modification of the gamma-aminobutyric hydroxamic acid moiety was carried out to optimize the three-dimensional arrangement of the two pharmacophores (hydroxamic acid and N-acyl residues). Among the tested, the gamma-aminobutyric hydroxamic acid moiety was found to be the best spacer for connecting the above-mentioned two pharmacophores. Synthesis and structure-activity relationships are discussed.

Drug Design↗

Biweekly paclitaxel and gemcitabine for patients with advanced urothelial cancer ineligible for cisplatin-based regimen.

BACKGROUND: To avoid cisplatin-related gastrointestinal, renal and other toxicity while maintaining efficacy in the palliative setting or second line chemotherapeutic regimen for cisplatin-resistant urothelial cancer, chemotherapeutic regimens have been investigated that do not include cisplatin. The current study was designed to evaluate efficacy, clinical feasibility and safety of gemcitabine and paclitaxel (GP) regimen in patients with metastatic urothelial cancer who were ineligible for standard cisplatin-based combination chemotherapy. METHODS: Gemcitabine 2500 mg/m(2) and paclitaxel 150 mg/m(2) were administered intravenously every 2 weeks for 23 patients (17 males and 6 females) with advanced urothelial cancer who were ineligible for cisplatin-based chemotherapy; metastatic disease being resistant to cisplatin-based chemotherapy regimen in 14, heavy toxicity in prior cisplatin-based chemotherapy in three, poor ECOG performance in two and impaired renal function in four. Average age was 67 (53-77). Performance status was 0 in 18 patients, 1 in three patients and 2 in two patients. RESULTS: The overall response rate was 30% (95% CI 15.6-50.8%). Of the 23 patients, no patient attained CR and 7 patients had PR. In the cisplatin-resistant group, the response rate was 14.2% (2/14; 95% CI 4.0-39.9%). In the remaining patients ineligible for cisplatin, the response rate was 55.5% (5/9; 95% CI 26.6-81.1%). The median duration of response was 4 months (range 3-8). The median duration of survival for all patients was 12.1 months (95% CI 8.6-15.5). Myelosuppression, predominantly neutropenia, was the most common serious toxicity and toxicity of Grade 3 or greater was observed in six patients (26%). Among non-hematological toxicity, neuralgia was the most commonly observed and occurred in nine patients (39%) although no patient had toxicity of Grade 3 or greater. Three patients had interstitial pneumonitis possibly attributed to gemcitabine. One patient developed severe bilateral disease after two cycles of the regimen, which was partially resolved with corticosteroid therapy. CONCLUSION: GP regimen is effective in some patients with cisplatin-resistant urothelial cancer and promising as second line chemotherapy. GP regimen is more effective and well tolerated as first line chemotherapy in patients ineligible for cisplatin-based chemotherapy. Toxicity is generally mild but care must be taken for patients with risk of interstitial pneumonitis. A further larger scale study is required to confirm the efficacy of the GP regimen.

Aged↗

Successful laparoscopic management of chylous ascites following laparoscopic radical nephrectomy.

A 44-year-old woman developed chylous ascites following laparoscopic transperitoneal left radical nephrectomy with para-aortic lymph node dissection. Because conservative managements failed to stop the lymphatic leakage, laparoscopic lymphostasis was performed. Drinking milk 6 h prior to the operation enabled visualization of chylous ascites. Although a definite fistula was hard to identify, most of the chylous leak disappeared after ligation of the para-aortic tissues at the distal and proximal ends of the previous lymph node dissection. Laparoscopic ligation of the para-aortic bundle of lymph ducts was effective in managing long-standing postoperative chylous ascites.

Adult↗

Epithelial stromal tumor of the seminal vesicle.

Primary tumors of the seminal vesicles are rare neoplasms; there have been only 69 accepted cases. The histologic features are usually adenocarcinoma; however, there are rarely reported epithelial stromal tumors of the seminal vesicles. We report a case of a 70-year-old man with an epithelial stromal tumor of the seminal vesicle who presented without symptoms of bladder outlet obstruction. The patient underwent radical cystoprostatectomy. No signs of tumor recurrence were noted within 14 months of surgery. To our knowledge, 13 cases of epithelial stromal tumors of the seminal vesicle have been previously reported.

Adult↗

Subtyping of uropathogenic Escherichia coli according to the pathogenicity island encoding uropathogenic-specific protein: comparison with phylogenetic groups.

BACKGROUND: Phylogenetic analysis has been used widely to characterize extraintestinal pathogenic Escherichia coli in molecular epidemiological studies. We have recently reported a putative pathogenicity island (PAI), carrying uropathogenic-specific protein (usp) and a unique mosaic structure of small open reading frames following usp, providing four subtypes of PAIusp classified from their sequential patterns. METHODS: A total of 427 E. coli isolates from uncomplicated urinary tract infections (194 cystitis, 76 pyelonephritis, and 107 prostatitis) and 50 fecal isolates were examined for phylogenetic grouping and PAIusp subtyping as well as the prevalence of virulence factors (VF) and O serogroups. RESULTS: Both phylogenetic group B2 and usp-positive strains were equally predominant in cystitis, pyelonephritis and prostatitis (B2, 80.9%, 86.8%, and 86.9%; usp, 79.4%, 93.4%, and 88.8%, respectively). Furthermore, each PAIusp subtype was shown to be closely associated with several VF genes as well as several common O serogroups of uropathogenic E. coli. CONCLUSIONS: In molecular epidemiological studies, PAIusp subtyping will provide additional informative findings of E. coli strains belonging to phylogenetic group B2.

Escherichia coli↗

Testicular seminoma associated with massive necrosis.

A 70-year-old man presented with 2 years history of a painless hard mass in the left scrotum. Both pelvic computed tomography and magnetic resonance image showed enhancement only in the wall of the tumor, indicating a benign disease, rather than a neoplastic lesion. Physical examination 3 weeks after the first presentation showed the remarkable reduction of the left testicular size. Left inguinal orchiectomy was carried out and pathological diagnosis was seminoma with extensive necrotic areas occupying mostly the tumor. Either shrinkage or enlargement of testicular size with a long history demands full investigation for malignancy.

Aged↗

[A case of retroperitoneal dedifferentiated liposarcoma initially diagnosed as malignant fibrous histiocytoma: a case report].

We report a case of retroperitoneal tumor which turned out to be liposarcoma by the histological evaluation of its recurrent tumor, although the initial tumor was diagnosed as malignant fibrous histiocytoma (MFH). A retroperitoneal tumor in a 62-year-old man was removed and pathologically diagnosed as MFH. Five years after the initial surgery, computed tomography (CT) demonstrated a recurrent tumor near the spleen. The tumor was resected together with the spleen, tail of pancreas, and connective tissue due to adhesion and diagnosed as well-differentiated liposarcoma with sclerosing component. Generally dedifferentiated liposarcoma is difficult to distinguish from MFH and the presence of a well-differentiated liposarcoma component in the adjacent adipose tissue leads to the diagnosis of dedifferentiated liposarcoma. The clinical course of the present case indicated that the initial tumor was dedifferentiated liposarcoma and the recurrent tumor developed from the surrounding well-differentiated liposarcoma.

Diagnosis, Differential↗

[BK virus nephropathy in a kidney transplant recipient: a case report and literature review].

BK virus nephropathy (BKVN) has emerged as an important cause of allograft dysfunction and loss in kidney transplant recipients. We present a case in a 30-year-old female who underwent ABO-compatible living kidney transplant from her mother and was maintained with tacrolimus, mycophenolate mofetil and prednisolone. The serum creatinine level was stabilized about 0.9 mg/dl on postoperative day (POD) 35. On POD258, the serum creatinine increased to 1.8 mg/dl and the patient received methylpredonisolone pulse therapy under the diagnosis of acute rejection, which resulted in further increase in creatinine level from 1.8 to 2.6 mg/dl. Urine cytology showed decoy cells, but renal biopsy specimen showed no evidence of viral infection. Despite histopathological findings, positive urine and serum BKV-DNA suggested that allograft dysfunction was caused by BKVN. Therefore, the immunosuppession was reduced and gamma-globuline was given for 2 weeks. After the treatment, urine cytology became negative for decoy cells and serum creatinine level recovered to 2.0 mg/dl. On POD456, serum creatinine level was stabilized about 1.8 mg/dl and decoy cells remained negative.

Adult↗

[Epidemiological survey of sexually transmitted male urethritis in Kyoto Prefecture].

The data of sexually transmitted urethritis in males have been collected at 24 institutes in Kyoto Prefecture since October, 2002. The data collected from January to December in 2004 are summarized herein. A total of 1,275 patients were diagnosed with urethritis during this period. Microbiological examinations isolated Neisseria gonorrhoeae alone in 368 (29%), Chlamydia tracomatis alone in 336 (26%), both in 85 (7%), and others in 453 (36%). Male patients under 20 years old tended to have Chlamydial urethritis, alone or combined with gonococcal infection, and had a predominant infectious source, a non-commercial-sexual-worker female partner, suggesting a profound problem in sexual life of adolescents. The urologist preferred to use quinolones as the first therapeutic modality against male urethritis. However, drug resistance of N. gonorrhoeae, especially against quinolones, has rapidly progressed, which was also observed by a sensitivity examination test. Antibiotics should be used adequately against male urethrits according to the recent guidelines.

Adolescent↗