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Biomedical subjects

Y Ohi

Publications and source records attributed to Y Ohi.

At least 19 recordsLinked to original sources

Expression of thymidine phosphorylase as an indicator of poor prognosis for patients with transitional cell carcinoma of the bladder.

BACKGROUND: Thymidine phosphorylase (TP), which is identical to platelet-derived endothelial cell growth factor (PD-ECGF), stimulates chemotaxis of endothelial cells and is involved in the angiogenesis of human solid tumors. METHODS: The activity and expression of TP were examined in human transitional cell carcinomas (TCCs) of the bladder, and their association with clinicopathologic findings was determined. The activity of the enzyme in 37 TCCs and 12 adjacent nonneoplastic tissues was measured spectrophotometrically. The expression of TP was also examined by immunoblotting. Immunohistochemical analysis was performed on 108 TCCs. RESULTS: TP activity in the carcinomas was higher than that in adjacent normal tissues (P = 0.002). TP activity in Grade 3 tumors or those classified as pT2-4 was higher than in Grade 1 and 2 tumors (P = 0.017) or those classified as pT1 (P = 0.007). The level of expression of TP detected by immunoblotting correlated well with TP activity. Immunohistochemical analyses showed that 62 of 108 cases (57.4%) were TP positive. There was a significant correlation between TP expression and histologic grade, infiltration pattern, local invasion, and lymph node metastasis. TP expression as a prognostic variable was studied using the Cox proportional hazards model. TP overexpression was an independent prognostic factor, as were lymph node metastasis and local invasion. CONCLUSIONS: These findings suggest that TP activity and its level of expression influence the progression of TCC and the prognoses of patients with this disease.

Adult↗

Ultrasound biomicroscopy for examination of the sclerotomy site in eyes with proliferative diabetic retinopathy after vitrectomy.

PURPOSE: We evaluated the capability of ultrasound biomicroscopy (UBM) to predict fibrovascular proliferation at sclerotomy sites in eyes with postoperative vitreous hemorrhage due to proliferative diabetic retinopathy (PDR). METHODS: Ultrasound biomicroscopy was used for examining the sclerotomy sites in 13 eyes of 11 patients with PDR experiencing postoperative vitreous hemorrhage (PDR group). Thirty-nine sclerotomy sites (all entry sites of each eye) were examined before reoperation, and the UBM images were compared with findings obtained during revision of the vitrectomy. Thirteen eyes of 13 patients undergoing vitrectomy for nondiabetic diseases were used as controls and examined after vitrectomy. RESULTS: The UBM images were classified into the following four categories: A, tent; B, spheroid; C, trapezoid; and N, none. The findings were distributed as follows in the PDR group: category A, 18%; B, 5%; C, 56%; and N, 21 %; and as follows in the control group: category A, 28%; B, 5%; C, 5%; and N, 62%. In the PDR group, 11 of 12 sclerotomy sites disclosing fibrovascular proliferation possessed the trapezoidal image. Mean length of trapezoidal base was 2.49+/-0.97 mm and 1.51+/-0.75 mm in the groups with and without fibrovascular proliferation, respectively (P<0.01). The average relative reflectivity of the trapezoidal image against the sclera was 0.501+/-0.169 in the fibrovascular proliferation group and 0.891+/-0.183 in the fibrous ingrowth group (P<0.01). CONCLUSION: Ultrasound biomicroscopy is useful in detecting fibrovascular proliferation at sclerotomy sites because a large and low-reflecting trapezoidal UBM image is highly correlated to its presence.

Adult↗

Sequences in the 5' and 3' R elements of human immunodeficiency virus type 1 critical for efficient reverse transcription.

The genome of human immunodeficiency virus type 1 (HIV-1) contains two direct repeats (R) of 97 nucleotides at each end. These elements are of critical importance during the first-strand transfer of reverse transcription, during which the minus-strand strong-stop DNA (-sssDNA) is transferred from the 5' end to the 3' end of the genomic RNA. This transfer is critical for the synthesis of the full-length minus-strand cDNA. These repeats also contain a variety of other functional domains involved in many aspects of the viral life cycle. In this study, we have introduced a series of mutations into the 5', the 3', or both R sequences designed to avoid these other functional domains. Using a single-round infectivity assay, we determined the ability of these mutants to undergo the various steps of reverse transcription utilizing a semiquantitative PCR analysis. We find that mutations within the first 10 nucleotides of either the 5' or the 3' R sequence resulted in virions that were markedly defective for reverse transcription in infected cells. These mutations potentially introduce mismatches between the full-length -sssDNA and 3' acceptor R. Even mutations that would create relatively small mismatches, as little as 3 bp, resulted in inefficient reverse transcription. In contrast, virions containing identically mutated R elements were not defective for reverse transcription or infectivity. Using an endogenous reverse transcription assay with disrupted virus, we show that virions harboring the 5' or the 3' R mutations were not intrinsically defective for DNA synthesis. Similarly sized mismatches slightly further downstream in either the 5', the 3', or both R sequences were not detrimental to continued reverse transcription in infected cells. These data are consistent with the idea that certain mismatches within 10 nucleotides downstream of the U3-R junction in HIV-1 cause defects in the stability of the cDNA before or during the first-strand transfer of reverse transcription leading to the rapid disappearance of the -sssDNA in infected cells. These data also suggest that the great majority of first-strand transfers in HIV-1 occur after the copying of virtually the entire 5' R.

Animals↗

Overcoming of multidrug resistance by introducing the apoptosis gene, bcl-Xs, into MRP-overexpressing drug resistant cells.

Multidrug resistance associated protein (MRP) is one of drug transport membranes that confer multidrug resistance in cancer cells. Multidrug resistance has been known to be associated with resistance to apoptosis. In this study, using MRP overexpressing multidrug resistant nasopharyngeal cancer cells, we examined the expression of apoptosis related genes including p53, p21WAF1, bax and bcl-Xs between drug sensitive KB and its resistant KB/7D cells. We also examined whether the introduction of apoptosis related gene could increase the sensitivity to anticancer drugs in association with apoptotic cell death. The relative resistances to anticancer drugs in KB/7D cells evaluated by IC50 values were 3.6, 61.3, 10.4 and 10.5 to adriamycin (ADM), etoposide (VP-16), vincristine (VCR) and vindesine (VDS), respectively. The resistance to anticancer drugs in KB/7D cells was associated with the attenuation of internucleosomal DNA ladder formation in apoptosis. Of important, the mRNA expression of bcl-Xs gene in KB/7D cells was decreased in one-fourth as compared to that of KB cells among the apoptosis genes. The mRNA expression of bcl-Xs gene in a bcl-Xs transfected clone (KB/7Dbcl-Xs) was increased about 2-fold compared to that of KB/7Dneo cells, while the mRNA expression of MRP gene was not significantly different in KB/7bcl-Xs and KB/7Dneo cells. The sensitivities to anticancer drugs including ADM, VCR and VDS except VP-16 were increased in KB/7Dbcl-Xs cells, in turn, the relative resistance in KB/7Dbcl-Xs cells was decreased to 1.4, 4.0, and 3.0 in ADM, VCR and VDS, respectively, as compared to those of KB/7Dneo cells. Of interest, the studies on the accumulation of [3H]VCR showed that the decrease of [3H]VCR accumulation in KB/7Dbcl-Xs was not significantly different from that of KB/7Dneo cells. Collectively, these results indicated that the mechanism(s) of drug resistance in KB/7D cells could be explained at least by two factors: a) reduced drug accumulation mediated by MRP; b) resistance to apoptosis due to the decreased expression of the bcl-Xs gene. These results also indicated that the multidrug resistance mediated by MRP might be partially overcome by introducing apoptosis gene into drug resistant cells without modulation of MRP function in drug accumulation.

ATP-Binding Cassette Transporters↗

Expression of vascular endothelial growth factor in patients with testicular germ cell tumors as an indicator of metastatic disease.

BACKGROUND: Angiogenesis is essential for tumor growth and metastasis. Vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP)/platelet-derived endothelial cell growth factor (PD-ECGF) are involved in increased angiogenic activity and disease progression in solid tumors. However, there is no information regarding the association of these angiogenic factors with clinicopathologic findings in testicular germ cell tumors (GCTs). METHODS: The authors examined the expression of VEGF and TP as well as microvessel density in GCTs and their association with clinicopathologic findings. Expression of VEGF and TP and microvessel density were examined immunohistochemically in 80 GCTs, including 33 seminomas (25 tumors with organ-confined disease and 8 with metastasis) and 47 nonseminomatous testicular GCTs (NSGCTs) (20 tumors with organ-confined disease and 27 with metastasis). Expression of VEGF also was examined in four GCTs and one nonneoplastic testis by immunoblotting. RESULTS: VEGF protein was expressed more highly in GCTs compared with nonneoplastic testes. VEGF expression in GCTs was correlated significantly with microvessel count (P < 0.001). Both VEGF expression and microvessel count were correlated with metastasis in seminoma (P = 0.008 and P < 0.001, respectively), but only VEGF expression was identified as statistically significant by multiple regression analysis (P = 0.006). Conversely, four variables (VEGF expression, microvessel count, the presence of venous invasion, and the presence of embryonal carcinoma elements in the primary tumor) were correlated with metastasis in NSGCT (P < 0.001, P < 0.001, P = 0.004, and P = 0.029, respectively). However, multiple regression analysis revealed that only VEGF expression and microvessel count were significant factors for metastasis (P < 0.007 and P < 0.001, respectively). In contrast, high levels of TP were observed in infiltrating cells, but not in the majority of cancer cells. CONCLUSIONS: The findings of the current study suggest that VEGF expression is involved in tumor development, angiogenesis, and metastasis in GCT.

Adolescent↗

In vitro bactericidal activities of beta-lactamases, amikacin, and fluoroquinolones against Pseudomonas aeruginosa biofilm in artificial urine.

OBJECTIVES: To compare bactericidal activities of antimicrobial agents against Pseudomonas aeruginosa biofilms by employing an in vitro model of catheter-associated infection because such infections are refractory to antimicrobial treatment. METHODS: Bactericidal activities of piperacillin (PIPC), ceftazidime (CAZ), panipenem (PAPM), amikacin (AMK), ciprofloxacin (CPFX), and levofloxacin (LVFX) were examined against a P. aeruginosa biofilm generated on a Teflon catheter in artificial urine. The colony-forming activities of biofilm bacteria were determined for 48 hours during the treatment with each drug at concentrations of 1 up to 128 times the minimal bactericidal concentration (MBC), and time-kill curves were constructed by plotting the viable cell counts against time. RESULTS: Although CAZ was more bactericidal to the biofilm bacteria than PIPC, the biofilm bacteria still remained on the catheter during CAZ treatment at a concentration 128 times the MBC for 48 hours. Biofilm bacteria were completely eradicated within 48 hours by treatment with PAPM and AMK at a concentration 64 and 128 times the MBC, respectively. Both CPFX and LVFX eradicated biofilm bacteria completely by 24 hours at a concentration 32 times the MBC. CONCLUSIONS: These results indicate that fluoroquinolones have the most potent bactericidal activity against the P. aeruginosa biofilm generated in urine.

Amikacin↗

Diagnosis and treatment of priapism: experience with 5 cases.

OBJECTIVES: Priapism is a rare disease, but needs early intervention and appropriate management. We present 5 cases, 2 of nonischemic high-flow priapism and 3 of ischemic low-flow priapism. METHODS: Focusing on the differential diagnosis of priapism between the nonischemic high-flow type and the ischemic low-flow type, we reviewed the medical records of 5 patients. RESULTS: Of the examinations carried out, cavernosography, blood gas analysis of cavernosal blood, color Doppler ultrasound, and internal pudendal arteriography were useful in differentiating the type of priapism. Complete detumescence of the penis in 2 cases of high-flow priapism and 3 cases of low-flow priapism was achieved by selective embolization with gelform and by glandular-cavernosal shunting, respectively. No recurrence was observed in any patient, and postoperative erectile function was preserved in 4 patients and is unknown in 1. CONCLUSIONS: These results indicate that angiographic studies provide the most reliable information for the differentiation of the type of priapism. However, color flow Doppler ultrasound and cavernosal blood gas determination can obviate the need for angiographic studies and are noninvasive. Although conservative treatment or even expectant management may be feasible with high-flow priapism, aggressive treatment should be carried out for low-flow priapism immediately after initial treatment fails to achieve detumescence of the penis. Selective embolization of the internal pudendal artery may be the treatment of choice for patients with high-flow priapism.

Adult↗

Bacterial biofilms and catheters in experimental urinary tract infection.

Employing in vitro and in vivo models of catheter-associated infection, biofilm formation of Pseudomonas aeruginosa in artificial urine and bactericidal activity of several classes alone or in combination with a macrolide antibiotic were investigated. In the course of continuous urine flow, bacteria adherent to a Teflon catheter formed microcolonies at 6 h and a biofilm at 24 h. Following 24 h of urine flow, the thickness and the density of the biofilm increased to about 20 microm and 10(8) cfu/mm3, respectively. Of the antibiotics examined, the fluoroquinolones showed the most potent bactericidal activity against the P. aeruginosa biofilms. However, those antibiotics were not always potentiated by the combination with a macrolide antibiotic.

Animals↗

Obesity affects expression of progesterone receptors and node metastasis of mammary carcinomas in postmenopausal women without a family history.

Possible relationships between risk factors, such as obesity and a family history of breast cancer, and prognostic factors of mammary carcinomas were investigated by examining the body mass index of patients and the expression of estrogen (ER) and progesterone receptors (PgR), c-erbB-2 and p53, grade of histology, size of tumors and nodal status of mammary carcinomas. There was no significant difference in the body mass index of premenopausal patients either with or without a family history. For postmenopausal patients, the body mass index was significantly low in patients with a family history compared with patients without a family history. In premenopausal patients with or without a family history and in postmenopausal patients with a family history, there was no significant difference in the body mass index regardless of the mammary carcinoma prognostic factor, such as expression of ER, PgR, c-erbB-2 and p53, grade of histology, size of tumors and nodal status. However, in postmenopausal patients without a family history, body mass index was significantly high for patients with mammary carcinomas that had PgR expression and node metastasis. These results suggest that obesity may affect the PgR status and nodal status of mammary carcinomas in postmenopausal patients without a family history.

Body Mass Index↗

Endorectal ultrasonography for the assessment of rectal wall invasion in intrapelvic tumor: a preliminary report.

BACKGROUND: The purpose of the present study was to determine the usefulness of endorectal ultrasonography (ERUS) in assessing rectal wall involvement in intrapelvic tumors. METHODS: Rectal wall invasion was assessed in 16 patients; 14 with deeply invasive bladder tumors, one with prostatic leiomyosarcoma, and one with prostatic leiomyoma. Computed tomography (CT), magnetic resonance (MR) imaging and ERUS with a flexible-type radial scanner (7.5 MHz) were used and the results were compared with the histopathologic findings in surgical specimens. RESULTS: The normal rectum was shown by ERUS to be a five- or seven-layer structure. Characteristic abnormal ERUS findings included disappearance of the perirectal fat tissue layer with or without disruption of the propria muscle layer. Endorectal ultrasonography accurately assessed rectal wall involvement in all four patients who had two bladder tumors, plus the one patient with prostatic leiomyoma and the one with prostatic leiomyosarcoma. However, ERUS overstaged one of 12 bladder tumors with no rectal wall involvement, which was strongly adhesive to the rectum because of an inflammatory change but had no tumor invasion. There were no cases of understaging by ERUS. In comparison, CT accurately assessed rectal wall involvement in two patients, but overstaged in three and understaged in two. Magnetic resonance imaging, which was performed in 14 patients, accurately assessed rectal wall involvement in two patients, but overstaged in three and understaged in one. CONCLUSION: This preliminary study suggests that ERUS more accurately assesses rectal wall involvement in intrapelvic tumor than CT or MRI.

Adult↗

Multidisciplinary treatment, including laser hyperthermia, for extensive regional metastasis of a penile tumor.

BACKGROUND: There is no reliable treatment for penile tumor with lymph node metastasis. METHODS: We report on a patient with a penile tumor with extensive regional metastasis that was successfully managed with combined laser hyperthermia, radiation and chemotherapy. RESULTS: The patient has survived more than 7 years without evidence of disease. CONCLUSIONS: Multidisciplinary treatment, including laser hyperthermia, may be useful for the treatment of regional metastasis of penile tumor.

Antineoplastic Combined Chemotherapy Protocols↗

Goserelin acetate with or without antiandrogen or estrogen in the treatment of patients with advanced prostate cancer: a multicenter, randomized, controlled trial in Japan. Zoladex Study Group.

OBJECTIVE: The aims of this randomized, controlled study were to investigate the efficacy and safety of long-term monotherapy with the luteinizing hormone-releasing hormone agonist goserelin acetate compared with both short- and long-term combined androgen blockade. METHODS: Patients with advanced prostate cancer (n = 371) were randomized to treatment with goserelin acetate alone or a combination of goserelin acetate plus either long-term or short-term antiandrogen (chlormadinone acetate) or short-term estrogen (diethylstilbestrol diphosphate). RESULTS: There were no significant differences between the treatment groups with respect to objective progression, overall survival or disease-specific survival. Nevertheless, subgroup analysis suggested that patients with minimal disease or a good prognosis might benefit more from combined androgen blockade than other patients. Combined androgen blockade significantly reduced the incidence of disease flare compared with goserelin acetate treatment alone. CONCLUSIONS: Neither short- nor long-term combined androgen blockade had a survival advantage over goserelin acetate alone.

Aged↗

Ca2+ spark as a regulator of ion channel activity.

Ca2+ spark is a local and transient Ca2+ release from sarcoplasmic reticulum (SR) through the ryanodine receptor Ca2+-releasing channel (RyR). In cardiac myocytes, Ca2+ spark is an elementary unit of Ca2+-induced Ca2+ release (CICR) by opening of RyR(s) in junctional SR (jSR), which is triggered by Ca2+-influx through L-type Ca2+ channels to the narrow space between a transverse tubule and jSR. Ca2+ spark has, therefore, been described as the evidence for "the local control of excitation-contraction coupling". In contrast, Ca2+ sparks in smooth muscle have been reported in relation to Ca2+-dependent K+ (K(Ca)) channel activation and muscle relaxation. A spontaneous Ca2+ spark in a superficial area activates 10-100 K(Ca) channels nearby and induces membrane hyperpolarization, which reduces Ca2+ channel activity. In several types of smooth muscle cells, which have relatively high membrane excitability, an action potential (AP) elicits 5-20 Ca2+ hot spots (evoked sparks with long life) in the early stage via CICR in discrete superficial SR elements and activates K(Ca)-channel current highly responsible for AP repolarization and afterhyperpolarization. CICR available for contraction may occur more slowly by the propagation of CICR from superficial SR to deeper ones. The regulatory mechanism of ion channel activity on plasma membrane by superficial SR via Ca2+ spark generation in smooth muscle cells may be analogously common in several types of cells including neurons.

Action Potentials↗

Activation and the interaction of proapoptotic genes in modulating sensitivity to anticancer drugs in gastric cancer cells.

Taxotere (Docetaxel) is a novel microtubulin inhibitor which is currently in phase II/III clinical trial. We found that the sensitivity to taxotere was correlated with apoptotic cell death determined by the internucleosomal DNA ladders in gastric cancer cell lines. The treatment of taxotere activated proapoptotic genes such as bcl-Xs and bax genes. The relationship between the mRNA induction of bcl-Xs and bax genes and the internucleosomal DNA ladders by taxotere was significant, respectively (p<0.05). The introduction of bcl-Xs gene into MKN45 gastric cancer cells increased the sensitivity to VP-16 and taxotere 2-3-fold in the IC50 values, whereas the introduction of bax gene increased the sensitivity to CDDP, VP-16 and taxotere 2-5-fold in the IC50 values, as compared to that of the Neo-transfected MKN45 cells. The mRNA overexpression of bax gene was found in the bcl-Xs-transfected cells. Likewise, the mRNA overexpression of bcl-Xs gene was also found in the bax-transfected cells. These results indicate that the activation of bcl-2 family genes such as bcl-Xs and bax plays a crucial role in modulating apoptotic cell death in the sensitivity to anticancer drugs, and suggest that these proapoptotic genes might interact in the up-regulation for activating downstream signals leading to apoptosis in gastric cancer cells.

Antineoplastic Agents↗

Comparative study of single-dose and three-day therapy for acute uncomplicated cystitis.

To assess the efficacy and safety of a single-dose therapy for acute uncomplicated cystitis (AUC), we compared 4 treatment regimens in 120 women. Patients eligible for the study were randomly assigned to one of four treatment groups: Ciprofloxacin (CPFX) 200 mg in a single oral dose (group A); 200 mg once daily for 3 days (group B); 200 mg twice daily for 3 day (group C); and cefpodoxime-proxcetil (CPDX-PR) 200 mg once daily for 3 days (group D). The efficacy was evaluated 3 days after the single-dose therapy or at the end of a three-day therapy according to the criteria proposed by the Japanese UTI Committee. The overall clinical efficacy in a total of 107 patients was evaluated to be excellent, moderate, and poor in 72 (67.3%), 35 (31.8%), and 1 (0.9%), respectively. The causative organisms were eradicated in 88.0, 85.2, 85.2, and 82.1% of the patients in groups A, B, C, and D, respectively. Recurrence was identified in 3 (2 in group A and one in group D) of 16 patients who were followed at 2 to 3 weeks after the treatment. No adverse reactions related to the antibiotics were recognized in the study. There were no significant differences in the clinical efficacy or recurrence rate among these four treatment regimens. These results indicate that the single-dose therapy of CPFX is the treatment of choice in women with AUC.

Acute Disease↗

[Spontaneous rupture of renal cell carcinoma: a case report].

A 74-year-old man with severe right flank pain and hypochondralgia, was admitted to a hospital where he was found to have an abnormality of the right kidney on computed tomographic (CT) scan. He was referred to our department for further examination and treatment on the next day. Spontaneous rupture of the right renal cell carcinoma was mostly suspected from preoperative clinical findings obtained by ultrasonography. CT scan and angiography. Extravasation was not recognized on angiography. We chose emergent transcatheter arterial embolization prior to radical nephrectomy. The surgical specimen contained a solid and yellowish mass invading into the renal pelvis. Subcapsular rupture was identified. Histopathological diagnosis was renal cell carcinoma consisting of invasive growth of highly atypical epithelial cells with a sarcomatous pattern, and the tumor cells were present in the renal pelvis. He died of lung cancer 26 months after the operation.

Aged↗