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Biomedical subjects

O Ogawa

Publications and source records attributed to O Ogawa.

At least 19 recordsLinked to original sources
PubMed2002

Non-secretor status is associated with female acute uncomplicated pyelonephritis.

OBJECTIVE: To retrospectively analyse the secretor status in women with acute uncomplicated pyelonephritis, as non-secretors of histo-blood group antigens are reportedly at risk of recurrent urinary tract infections (UTIs). PATIENTS AND METHODS: The study included 245 women who had been diagnosed as having acute uncomplicated pyelonephritis in affiliated hospitals over the past 5 years. All women were sent antiseptic swabs, to collect saliva, and a questionnaire to survey their past UTI episodes and menstrual status. Responses with written informed consent were obtained from 106 women (median age 50.5 years, range 17-85). The secretor status was determined using the haemagglutination inhibition assay from the saliva on the swabs. RESULTS: Forty-four (41%) of the women were non-secretors, a significantly higher frequency than in the (control) Japanese population (217 of 960, 22.6%; P< 0.001). The incidence of non-secretors was significantly higher (P < 0.01) in premenopausal (26 of 46, 57%) than in postmenopausal women (18 of 60, 30%). CONCLUSION: These results suggest that non-secretor status is associated with a genetic susceptibility to acute uncomplicated pyelonephritis, especially in premenopausal women.

ABO Blood-Group System↗
PubMed2001

Structural and sequence diversity of the pathogenicity island of uropathogenic Escherichia coli which encodes the USP protein.

A total of 321 uropathogenic Escherichia coli (UPEC) strains and 12 strains of E. coli isolated from stool samples of healthy individuals, which were previously shown to be positive in colony hybridization test using the usp (encoding for the uropathogenic-specific protein) DNA probe, were examined by PCR amplification to determine the size of the usp gene and the pathogenicity island (PI). Three types of size variation were observed for the usp gene and four types for the PI. Sequencing analysis of the PIs from seven representative strains (six UPEC and one from a normal healthy individual) revealed that the usp genes can be classified into two groups, each having different sequences in the 3'-terminal region. The peptides encoded by the three open reading frames (ORFs) downstream of usp had identical 23 amino acid residues in the C-terminal region. The subregion encoding these small ORFs has a mosaic structure constituted of six segments. The positions of these segments vary from strain to strain, and in some strains, two to four segments are deleted. This indicates that rearrangements occur frequently in this region and the mosaic arrangement apparently contributes to the size variation observed in the PCR examination of the usp genes and PIs.

Amino Acid Sequence↗
PubMed2001

ABO-incompatible living-donor kidney transplantation in children.

BACKGROUND: Due to a severe shortage of suitable cadaveric allografts for children awaiting kidney transplants, we have performed a series of ABO-incompatible living kidney transplantations (LKT) at our institution. METHODS: Between July 1989 and March 2000, 16 pediatric patients (3 female, 13 male) underwent ABO-incompatible LKT. The mean age at transplantation was 10.9+/-4.3 years (range 5.1-15.0 years). The donor to recipient ABO blood antigen incompatibility was as follows: A1-->O, 5 patients; B-->O, 6 patients; A1B-->B, 2 patients; and A1B -->B, A1-->B, or B-->A1, 1 patient each. The median pretransplantation anti-A1 titers of eight A-incompatible recipients were 1:128 (IgM, range 1:16 to 1:512) and 1:32 (IgG, range 1:2 to 1:128). Median anti-B titers of seven B-incompatible recipients were 1:32 (IgM, range 1:4 to 1:128) and 1:8 (IgG, range 1:2 to 1:64). All patients received three or four sessions of plasmapheresis (PP) and/or immunoadsorption (IA) to remove the anti-A and/or anti-B antibodies before transplantation. Immunosuppression initially consisted of cyclosporine, methylprednisolone, cyclophosphamide, and antilymphocyte globulin. Splenectomy was performed on all recipients at the time of transplantation. RESULTS: The patients were followed for 6 to 122 months with a mean follow-up of 63 months. All 16 recipients who underwent ABO-incompatible LKT achieved a pretransplant isoagglutinin titer less than 1:8 with 3-4 sessions of PP/IA treatment. Of 16 patients, 10 patients had rebound increase in their IgM and/or IgG anti-A/B titers to greater than 1:64 or predepletion levels within 10 days posttransplantation. In addition, nine patients developed renal dysfunction in association with the rebound increase in their anti-A/B. One patient lost his graft because of uncontrolled delayed hyperacute rejection, whereas eight other recipients recovered completely with pulse steroids and PP/IA therapy. After the third week posttransplant, there was no correlation between the occurrence of AR and their isoagglutinin titers. Moreover, no antibody-mediated rejection was observed, even in recipients with continued high titer anti-A and/or anti-B antibodies. Patient survival is 100% to date. The actuarial 1-year and 5-year graft survival rates are 87% and 85%, respectively. No fatal infectious complications occurred despite the combination of splenectomy and immunosuppressive drugs. CONCLUSIONS: We have demonstrated that with adequate pre- and posttransplant management, successful kidney transplantation across the ABO barrier is possible in the pediatric population. "Accommodation" of the allografts occurred within 2 weeks of transplantation. Subsequently, the long-term graft outcome of ABO-incompatible LKT was comparable to that of ABO-compatible LKT.

ABO Blood-Group System↗
PubMed2001

Prognostic significance of thymidylate synthase activity in bladder carcinoma.

BACKGROUND: 5-fluorouracil (5-FU) is an anticancer agent clinically used against various cancers including bladder carcinoma. 5-FU inhibits thymidylate synthase (TS) and blocks DNA synthesis. TS is the key enzyme in the catalysis of the methylation from deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate. Little is known about the significance of TS in bladder carcinoma. The authors investigated the activity of TS in 82 bladder cancers and prognostic significance of the levels of TS and/or activities of dihydropyrimidine dehydrogenase (DPD), an important enzyme in the degradation of 5-FU. METHODS: The levels of TS and DPD activities in nonfixed, fresh, frozen, bladder carcinoma and normal bladder specimens were determined biochemically by the FdUMP binding assay and the 5-FU degradation assay, respectively. RESULTS: The activity of TS was 10-fold higher in bladder carcinoma compared with normal bladder. TS activity in muscle-invasive bladder carcinoma was threefold higher than that in Ta and T1 cancer. In addition, the activity of TS in T1 bladder carcinoma was threefold higher than that in Ta cancer. The level of TS activity in Grade 3 bladder carcinoma was 4.5-fold and 3.5-fold higher than that in Grade 1 and Grade 2 cancers, respectively. Patients with Ta and T1 bladder carcinoma with low TS activity had a longer postoperative tumor-free period than those with high activity in the 2-year follow-up. Patients with Ta and T1 bladder carcinoma with high or low TS activity were divided into four subgroups: high or low DPD activity subgroups. Patients with low TS activity and high DPD activity had the longest postoperative disease-free period among the 4 subgroups during the 2-year follow-up. CONCLUSIONS: To the authors' knowledge, the current study is the first study that demonstrated that the level of TS activity correlates with both the progression of the stage and the increase of the grade of bladder carcinoma and that elevated TS activity predicts early recurrence in Ta and T1 bladder carcinoma. These results suggested that elevated TS activity might have been associated with a higher chance of progression and recurrence of bladder carcinoma in the patients who participated in this study.

Adult↗
PubMed2001

Significance of serum soluble Fas ligand in patients with bladder carcinoma.

BACKGROUND: The interaction of Fas and Fas ligand (FasL) plays an important role in cytotoxic T-lymphocyte-mediated and natural killer cell-mediated apoptosis against tumor cells. Circulating soluble FasL (sFasL) has been suggested to provide protection from Fas-mediated apoptosis. The current study examined this possibility in patients with bladder carcinoma. METHODS: The levels of sFasL in the serum of 163 patients with bladder carcinoma were determined using an enzyme-linked immunoadsorbent assay. Antiautologous tumor cytotoxic activity was assessed by the 12-hour chromium isotope ((51)Cr) release assay. RESULTS: The mean serum level of sFasL in patients with bladder carcinoma was 2.5-fold higher than that in healthy donors. The level of serum sFasL in patients with muscle-invasive bladder carcinoma was 2.5-fold higher than that in patients with superficial bladder carcinoma. In addition, serum sFasL levels in patients with T1 and Tis bladder carcinoma was 2-fold and 2.7-fold higher, respectively, than levels in patients with Ta bladder carcinoma. The serum level of patients with sFasL in Grade 3 bladder carcinoma were 2.4-fold and 1.7-fold higher than that in patients with Grade 1 and Grade 2 bladder carcinoma, respectively. Patients with Ta bladder carcinoma with a low level of serum sFasL (less than the median value) had a longer postoperative tumor-free interval than patients with a high sFasL level (greater than the median value) in the 5-year follow-up. There was an apparent inverse correlation between the level of serum sFasL and antiautologous tumor cytotoxic activity. CONCLUSIONS: The results of the current study demonstrated that the level of serum sFasL is correlated with both disease progression and increase in the tumor grade, and that an elevated serum sFasL level predicted early recurrence in patients with Ta bladder carcinoma. These findings suggest that elevated serum sFasL levels might be associated with a greater risk of disease progression and recurrence in patients with bladder carcinoma.

Adult↗
PubMed2001

Tumor growth inhibition by arsenic trioxide (As2O3) in the orthotopic metastasis model of androgen-independent prostate cancer.

Arsenic trioxide (As2O3) induces clinical remission of patients with acute promyelocytic leukemia. As a novel anticancer agent for treatment of solid cancers, As2O3 is promising, but no in vivo experimental investigations of its efficacy on solid cancers have been done at clinically obtained concentrations. In addition, the cell death mechanism of As2O3 has yet to be clarified, especially in solid cancers. In this study, human androgen-independent prostate cancer cell lines, PC-3, DU-145, and TSU-PR1 were examined as cellular models for As2O3 treatment, and As2O3-induced cell death and inhibition of cell growth and colony formation were evaluated. The involvement of p38, c-Jun NH2-terminal kinase (JNK), caspase-3, and reactive oxygen species (ROS) were investigated in As2O3-induced cell death. Finally, As2O3 was administered to severe combined immunodeficient mice inoculated orthotopically with PC-3 cells to estimate in vivo efficacy. In all three of the cell lines, at high concentrations, As2O3 induced apoptosis and, at low concentrations, growth inhibition. As2O3 activated p38, JNK, and caspase-3 dose dependently. Treatment with the p38 inhibitor and over-expression of dominant-negative JNK did not guard against As2O3-induced cell death. In contrast with partial protection by the caspase-3 inhibitor, the antioxidant N-acetyl-L-cysteine gave marked protection from As2O3-induced apoptosis and eliminated the activation of p38, JNK, and caspase-3, and the generation of ROS. The orthotopic murine metastasis model showed in vivo tumor growth inhibition in orthotopic and metastatic lesions with no signs of toxicity. This study establishes that As2O3 provides a novel, safe approach for treatment of androgen-independent prostate cancer. Generation of ROS as a therapeutic target for the potentiation of As2O3-induced apoptosis also was shown.

Androgens↗
PubMed2001

BCL10 is not a major target for frequent loss of 1p in testicular germ cell tumors.

The deletion of chromosome 1p is one of the frequent genetic alterations found in testicular germ cell tumors (GCTs), suggesting the presence of a tumor suppressor gene. BCL10, which was identified as a gene altered in mucosa-associated lymphoid tissue lymphoma, has been mapped at 1p22. The gene has been reported to be mutated in a variety of human cancers. In this study, we investigated the allelic deletions on 1p and the mutation of BCL10 in 51 GCTs comprising 30 seminomas and 21 non-seminomatous germ cell tumors. Loss of heterozygosity (LOH) on 1p was tested using three microsatellite markers. The search for BCL10 mutations in each of the three exons was screened by a single-stranded conformation polymorphism (SSCP) analysis and samples with abnormal bandshifts were directly sequenced. LOH at at least one locus tested was found in 42% (21/49) of the tumors (43% of seminomas and 38% of NSGCTs). SSCP and direct sequence analyses revealed that there were single nucleotide polymorphisms at codon 5, 8, 162, and intron 1. However, there were no somatic mutations of BCL10 in the 51 tumors. In support of the previous studies, our results demonstrated that LOH on 1p is frequent in both seminomas and NSGCTs, indicating that there is an important tumor suppressor on 1p in GCT. However, the results indicate that BCL10 is not a candidate target gene of the 1p deletion.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Hypermethylation at 9q32-33 tumour suppressor region is age-related in normal urothelium and an early and frequent alteration in bladder cancer.

Transcriptional silencing by CpG island hypermethylation of gene regulatory regions is one mechanism for inactivation of tumour suppressor genes. Chromosome 9q deletion is frequently found in transitional cell carcinoma (TCC) of the bladder and upper urinary tract and one of the putative tumour suppressor loci has been mapped to 9q32-33. A gene designated as DBCCR1 was identified in the candidate region and its mRNA expression is thought to be suppressed by hypermethylation. To understand the role of hypermethylation in TCC, we evaluated the methylation status of 20 CpG sites of the DBCCR1 5'-CpG island region in a total of 69 tumours from 45 patients, 21 normal urothelial specimens, and six bladder cancer cell lines. Aberrant hypermethylation levels were found in 36 (52%) of 69 tumours without any association with tumour grade or stage. Methylation was weakly detected in the normal urothelium in association with ageing. Although recurrent tumours tended to have higher methylation levels than the initial tumours, the methylation pattern was mostly maintained between multifocal TCCs in individual patients. The results suggest that hypermethylation of the DBCCR1 region is one of the earliest alterations in the development of TCCs and there may be an age-related hypermethylation-based field defect in normal urothelium. Methylator or methylation-resistant phenotype seems to be maintained during multifocal development or recurrence of most TCCs.

Adolescent↗
PubMed2001

Definition of a 1-Mb homozygous deletion at 9q32-q33 in a human bladder-cancer cell line.

We performed detailed molecular analyses of a suspected homozygous deletion on chromosome 9q32-q33 in a bladder-cancer cell line (KYBTDS) derived from a superficial papillary transitional cell carcinoma (TCC). We examined 13 sequence-tagged site (STS) markers mapped along 9q32-q33 by polymerase chain reaction (PCR), and used 13 bacterial artificial chromosome (BAC)/bacteriophage P1-derived artificial chromosome (PAC) genomic clone probes representing these STS markers as probes for dual-color fluorescence in situ hybridization (FISH) analyses to define the deleted region cytogenetically and at the molecular level. Southern blotting confirmed the findings. This combination of techniques revealed that the homozygous deletion in the KYBTDS cell line involved less than 1 megabase of DNA, flanked by markers A003P42 and SGC33380. This interval overlaps part of a common region of deletion observed in a number of primary bladder cancers; moreover, the DNA sequence within the 1-Mb segment corresponds to part of a YAC genomic clone that encompasses a putative tumor suppressor gene, DBCCR1.

Blotting, Southern↗
PubMed2001

Failure of ureteric bud invasion: a new model of renal agenesis in mice.

FUBI (failure of ureteric bud invasion) is a highly inbred strain of mouse with a high spontaneous incidence of uni- or bilateral renal agenesis (60%). Bilateral renal agenesis is lethal within 2 days after birth. The primary defect of FUBI is failure of the ureteric bud to penetrate into the metanephric mesenchyme at around embryonic day 11, resulting in apoptosis of metanephric cells and leading to renal agenesis on the affected side. The metanephros seemed to be normal because co-culturing of the FUBI metanephros with homologous spinal cord induced differentiation of the rudiment, but co-culturing with the homologous ureteric bud frequently did not. Genetic analysis revealed that more than two genes were involved in this malformation and we mapped one of the modifier loci, fubi1, on chromosome 2, at approximately 65 cM from the centromere. In this region, there are two possible candidate genes, Wilms' tumor 1 and formin, that play important roles in kidney development. Some of formin mutants shared a similar phenotype with FUBI; however, there was no difference in the expression of formin in embryonic kidneys between FUBI and control NFS/N mice. Studies of fubi1 congenic mice indicated that interaction of two or more loci is essential for the FUBI phenotype.

Animals↗
PubMed2001

Increased intracellular doxorubicin by anti-FAS monoclonal antibody: a mechanism that enhances the cytotoxicity in renal cell carcinoma cells.

OBJECTIVES: To investigate the effect of anti-Fas monoclonal antibody (mAb) on the intracellular concentration of doxorubicin in renal cell carcinoma (RCC) cells. Little is known about the influence of anti-Fas mAb on the intracellular concentration of chemotherapeutic agents. METHODS: The concentration of intracellular doxorubicin was determined by high-performance liquid chromatography. The mRNA and protein levels of multidrug resistance-associated protein gene were evaluated by reverse transcriptase-polymerase chain reaction and immunocytochemistry, respectively. RESULTS: An increased concentration of doxorubicin inside the cells was found: 2.4-fold in ACHN cells (a human RCC cell line) after treatment with doxorubicin combined with anti-Fas mAb compared with doxorubicin alone. Of the five cases of freshly derived RCC cells treated with doxorubicin and anti-Fas mAb, the intracellular concentration of doxorubicin was increased 2.3 and 2.7-fold in two of them, respectively. Furthermore, both the mRNA and the protein levels of the multidrug resistance-associated protein gene were downregulated after treatment of ACHN cells with anti-Fas mAb. Treatment of ACHN cells with a combination of anti-Fas mAb and doxorubicin resulted in a potentiation of the doxorubicin-mediated cytotoxicity. CONCLUSIONS: The increased intracellular concentration of doxorubicin by anti-Fas mAb might be one of the mechanisms responsible for the enhancement of doxorubicin-mediated cytotoxicity in RCC cells.

ATP-Binding Cassette Transporters↗
PubMed2001

Usefulness of stable HbA(1c) for supportive marker to diagnose diabetes mellitus in Japanese subjects.

To evaluate the adequacy and usefulness of the stable glycated hemoglobin (HbA(1c)) value of 6.5% suggested by the Japan Diabetic Society in 1999 for supportive diagnostic marker of diabetes, we assessed the sensitivity and specificity of an HbA(1c) value of 6.5% in patients who were newly diagnosed by the 75 g oral glucose tolerance test (75g-OGTT). A total of 866 Japanese subjects underwent the 75g-OGTT and HbA(1c) measurement (normal range: 4.3-5.8%). They were divided into three groups [normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetes mellitus (DM)], using the WHO criteria, since no subject with impaired fasting glycemia (IFG) was observed. The cut-off value of HbA(1c) separating DM from NGT or DM from IGT on cumulative distribution curve analysis was 5.9% (sensitivity 0.76 and specificity 0.86) and 5.9% (sensitivity 0.76 and specificity 0.77), respectively. The sensitivity of an HbA(1c) of 6.5% for separation of DM from NGT or IGT by the same analysis was 0.49 and 0.49, respectively. Similarly, the specificity for separation of DM from NGT or IGT was 0.98 and 0.98, respectively. These results mean that 49% of diabetic subjects show an HbA(1c)> or =6.5%, and 51% have an HbA(1c) less than 6.5%, while only 2% of NGT and IGT subjects have an HbA(1c)> or =6.5%, and 98% have a value less than 6.5%. Therefore, the sensitivity of an HbA(1c) value of 6.5% in separating DM from NGT or IGT is low, and thus 6.5% is too high value to use when screening for diabetes. However, the specificity is very high, so an HbA(1c) of 6.5% is a useful supportive marker to diagnose diabetes.

Adult↗
PubMed2001

Expression of Apg-1, a member of the Hsp110 family, in the human testis and sperm.

BACKGROUND: Apg-1 encodes a heat shock protein belonging to the Hsp110 family and is inducible by a 32 degrees C to 39 degrees C heat shock in somatic cells. In mouse testicular germ cells Apg-1 mRNA is constitutively expressed depending on the developmental stage. As human Apg-1 has recently been identified, the expression of Apg-1 in the human testis and sperm was investigated. METHODS: Expression and heat-inducibility of Apg-1 in the human testicular germ cell tumor cell line, NEC8, was analyzed. Using an antimouse Apg-1 antibody, expression of Apg-1 in the human testis and sperm was examined by western blotting after confirmation of the specificity of the antibody. The cells expressing Apg-1 in the testis were further determined by immunohistochemistry. RESULTS: Slight induction of Apg-1 mRNA was detected in NEC8 cells after 32 degrees C to 39 degrees C temperature shift. In the human testis, the antibody specifically recognized Apg-1, which was absent in the testis without germ cells (Sertoli-cell-only syndrome) or arrested at spermatogonia. Spermatocytes and spermatids, but not testicular somatic cells, were positively stained with the anti-Apg-1 antibody. By western blot analysis, Apg-1 was detected in the preparation enriched for sperm from normal volunteers and infertile patients, but not from azoospermia patients. CONCLUSION: Apg-1 is developmentally expressed in human testicular germ cells and sperm, suggesting its role in spermatogenesis and fertilization. Identification of substrates for Apg-1 chaperone activity will help elucidate its function.

Adult↗
PubMed2001

Enhanced sensitivity of bladder cancer cells to tumor necrosis factor related apoptosis inducing ligand mediated apoptosis by cisplatin and carboplatin.

PURPOSE: The development and acquisition of multiple drug resistance in cancer cells are a consequence of cancer chemotherapy and remain a major obstacle in treatment. Therefore, there is an obvious need for alternative approaches, such as immunotherapy and gene therapy. Tumor necrosis factor related apoptosis inducing ligand (TRAIL) is one of the tumor necrosis factor ligand families and it selectively induces apoptosis against cancer cells. Several cytotoxic anticancer drugs also mediate apoptosis and may share the common intracellular pathways leading to apoptosis. We reasoned that combination treatment of cancer cells with TRAIL and drugs may overcome this resistance. We evaluated whether bladder cancer cells are sensitive to TRAIL mediated cytotoxicity and whether TRAIL may synergize with anticancer agents in cytotoxicity and apoptosis 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: Human T24 bladder cancer line was relatively resistant to TRAIL and TRAIL was not cytotoxic against normal bladder cells. Treatment of T24 cells with TRAIL in combination with 5-fluorouracil or mitomycin C did not overcome resistance to these agents. However, treatment of T24 cells with a combination of TRAIL and cisplatin resulted in a synergistic cytotoxic effect. Synergy was also achieved in the cisplatin resistant T24 line (T24/CDDP), 2 other bladder cancer lines and 3 freshly derived bladder cancer cells. The combination of TRAIL and carboplatin resulted in a synergistic cytotoxic effect on T24 cells. However, the combination of TRAIL and trans-diamminedichloroplatinum (II) resulted in an antagonistic cytotoxic effect. The synergy achieved in cytotoxicity with TRAIL and cisplatin was also achieved in apoptosis. Treating T24 cells with cisplatin enhanced the expression of bax but not bcl-2. Incubation of T24 cells with TRAIL increased the intracellular accumulation of cisplatin. CONCLUSIONS: This study demonstrates that combination treatment of bladder cancer cells with TRAIL and cisplatin overcomes their resistance. The sensitization obtained with established cisplatin resistant and freshly isolated bladder cancer cells required low subtoxic concentrations of cisplatin, supporting the in vivo potential application of a combination of TRAIL and cisplatin for treating TRAIL resistant and cisplatin resistant bladder cancer.

Antineoplastic Agents↗
PubMed2001

Distinct microsatellite alterations in upper urinary tract tumors and subsequent bladder tumors.

PURPOSE: Although synchronous and/or metachronous tumor development is common in urothelial cancer, genetic and biological differences in upper urinary tract and bladder tumors are unclear. We compared the genetic alteration pattern in multifocal disease in patients with upper urinary tract and subsequent bladder tumors, and those with recurrent bladder tumor. MATERIALS AND METHODS: Using 21 microsatellite markers on the 8 chromosomal arms 2q, 4p, 4q, 8p, 9p, 9q, 11p and 17p we analyzed 34 tumors from 15 patients with upper urinary tract and subsequent bladder disease, and 70 tumors from 22 with recurrent bladder disease. RESULTS: Judging from the patterns of genetic alterations multifocal tumors were considered to have derived from an identical progenitor cell in 7 of 13 evaluable patients (54%) with upper urinary tract and subsequent bladder tumors, and 16 of 19 (84%) who were evaluable with recurrent bladder tumor. These data confirm the view that seeding or intraepithelial spread is a major mechanism for the multifocal development of urothelial cancer in general. However, a discordant microsatellite alteration pattern in multifocal tumors was observed in 6 of 7 patients (86%) with upper urinary tract and subsequent bladder lesions but in 2 of 16 (13%) with recurrent bladder cancer (p <0.005). CONCLUSIONS: Our results imply that upper urinary tract neoplasms may be genetically more unstable than bladder neoplasms. The implantation of tumor cells from upper urinary tract to bladder may involve additional and diverse genetic alterations. Furthermore, a considerable number of multifocal upper urinary tract and subsequent bladder lesions may arise independently via field cancerization mechanism. Our study indicates that the factors contributing to multifocal development are different in the 2 groups.

DNA, Satellite↗
PubMed2001

Quantitative analysis of gene expressions of vascular endothelial growth factor-related factors and their receptors in renal cell carcinoma.

Vascular endothelial growth factor (VEGF)-related factors are believed to regulate angiogenesis, an essential event in the growth of solid tumors. In this study, we investigated the expression of VEGF-related factor genes (VEGF, VEGF-B, and VEGF-C) and their receptor genes (VEGFR-1 and VEGFR-2) in renal cell carcinoma (RCC). There were significant differences in the expression level of VEGF, VEGFR-1 and VEGFR-2 between RCC and the corresponding normal renal tissue. The expression level of VEGF in the tumor tissue significantly correlated with those of VEGFR-1 and VEGFR-2. Expression levels VEGF-B and VEGF-C genes were not significantly different between RCC and normal renal tissue. A moderate to high protein expression for VEGF, VEGFR-1, and VEGFR-2 was observed in both the tumor cells and the endothelial cells, whereas the protein expression was low for VEGF-B and VEGF-C. The present results suggested that VEGF and its receptors VEGFR-1 and VEGFR-2 cooperates to play a crucial role in the angiogenesis of RCC, while VEGF-B and VEGFR-C may not. Furthermore, since VEGFR-1 and VEGFR-2 proteins were expressed in the tumor cells as well as in the endothelial cells, these receptors may also be responsible for the progression of RCC.

Aged↗
PubMed2001

Antiatherogenic mitochondrial genotype in patients with type 2 diabetes.

OBJECTIVE: To evaluate the significance of a longevity-associated mitochondrial genotype (Mt5178A) derived from a C --> A transversion at nucleotide position 5178 of mitochondrial DNA, which causes a Leu-to-Met substitution within the NADH dehydrogenase subunit 2 gene, in type 2 diabetic subjects. RESEARCH DESIGN AND METHODS: Mt5178 typing was done by polymerase chain reaction-restriction fragment-length polymorphism with the restriction enzyme AluI in 1,148 type 2 diabetic Japanese subjects, and the results were compared with the clinical characteristics. Then, the association of Mt5178 type with early atherosclerotic changes of the bilateral carotid arteries on ultrasonography was assessed in 412 diabetic subjects randomly selected from the original 1,148 type 2 diabetic subjects, while maintaining the same frequency of Mt5178A and Mt5178C. RESULTS: The frequency of Mt5178A in the type 2 diabetic subjects (454 of 1,148; 40%) was not different from that previously found in healthy blood donors (114 of 252; 45%). Clinical characteristics regarding diabetes were not significantly different between the Mt5178A group (n = 454) and the Mt5178C group (n = 694). However, the mean intima-media thickness (IMT) at six sites in the bilateral carotid arteries was significantly smaller in the Mrt5178A group than in the Mt5178C group (0.906 +/- 0.018 vs. 0.995 +/- 0.021 mm, mean +/- SEM, P = 0.022), and the Mt5178 type was significantly correlated with both the mean IMT and the presence of plaque on multiple regression analysis and discriminant analysis. CONCLUSIONS: The Mt5178A genotype may be unrelated to the etiology of type 2 diabetes. However, Mt5178A seems to have an antiatherogenic effect, at least in type 2 diabetic individuals.

Adult↗