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Biomedical subjects

Kazuhiro Suzuki

Publications and source records attributed to Kazuhiro Suzuki.

At least 91 records · Page 5Linked to original sources
PubMed2002

Requirement for the lymphocyte semaphorin, CD100, in the induction of antigen-specific T cells and the maturation of dendritic cells.

CD100 belongs to the semaphorin family, several members of which are known to act as repulsive axonal guidance factors during neuronal development. We have previously demonstrated that CD100 plays a crucial role in humoral immunity. In this study, we show that CD100 is also important for cellular immunity through the maturation of dendritic cells (DCs). CD100(-/-) mice fail to develop experimental autoimmune encephalomyelitis induced by myelin oligodendrocyte glycoprotein peptide, because myelin oligodendrocyte glycoprotein-specific T cells are not generated in the absence of CD100. In vitro studies with T cells from OVA-specific TCR-transgenic mice demonstrate that Ag-specific T cells lacking CD100 fail to differentiate into cells producing either IL-4 or IFN-gamma in the presence of APCs and OVA peptide. In addition, DCs from CD100(-/-) mice display poor allostimulatory capabilities and defects in costimulatory molecule expression and IL-12 production. The addition of exogenous soluble rCD100 restores normal functions in CD100(-/-) DCs and further enhances functions of normal DCs. Furthermore, treatment of Ag-pulsed DCs with both soluble CD100 and anti-CD40 before immunization significantly enhances their immunogenicity. This treatment elicits improved T cell priming in vivo, enhancing both primary and memory T cell responses. Collectively, these results demonstrate that CD100, which enhances the maturation of DCs, is essential in the activation and differentiation of Ag-specific T cells.

Animals↗
PubMed2002

A novel immunosuppressive drug, FTY720, prevents the cancer progression induced by cyclosporine.

Cyclosporine A (CsA), the most frequently used immunosuppressive drug, has been reported to induce cancer by a cell-autonomous mechanism. Herein, we report that FTY720, a novel immunosuppressant, prevents CsA-induced alterations in both morphology and cell motility at a low concentration (0.1 microM) and induces the CsA-treated cancer cells to undergo apoptosis at a higher concentration (more than 5 microM). The inhibitory activity of FTY720 is unrelated to the decrease of TGF-beta. We believe that a combination treatment with FTY720 and CsA not only results in a synergistic effect on allografts, but also, reduces the incidence of cancer in transplant patients.

Apoptosis↗
PubMed2002

Genistein, a soy isoflavone, induces glutathione peroxidase in the human prostate cancer cell lines LNCaP and PC-3.

Genistein is a major component of soybean isoflavone and has multiple functions resulting in antitumor effects. Prostate cancer is 1 of the targets for the preventive role of genistein. We examined the effect of genistein on human prostate cancer (LNCaP and PC-3) cells. Proliferation of both cell lines was inhibited by genistein treatment in a dose-dependent manner. To obtain the gene expression profile of genistein in LNCaP cells, we performed cDNA microarray analysis. The expression of many genes, including apoptosis inhibitor (survivin), DNA topoisomerase II, cell division cycle 6 (CDC6) and mitogen-activated protein kinase 6 (MAPK 6), was downregulated. Expression levels were increased more than 2-fold in only 4 genes. The glutathione peroxidase (GPx)-1 gene expression level was the most upregulated. Quantitative real-time polymerase chain reaction revealed significant elevation of transcript levels of GPx-1 in both LNCaP and PC-3 cells. Upregulation of gene expression levels accompanied elevation of GPx enzyme activities. In contrast, no significant changes were observed in the gene expression levels and enzyme activities of the other antioxidant enzymes, superoxide dismutase and catalase. GPx activation might be one of the important characteristics of the effects of genistein on prostate cancer cells.

Antineoplastic Agents↗
PubMed2002

Hypertonicity-induced transmitter release at Drosophila neuromuscular junctions is partly mediated by integrins and cAMP/protein kinase A.

The frequency of quantal transmitter release increases upon application of hypertonic solutions. This effect bypasses the Ca(2+) triggering step, but requires the presence of key molecules involved in vesicle fusion, and hence could be a useful tool for dissecting the molecular process of vesicle fusion. We have examined the hypertonicity response at neuromuscular junctions of Drosophila embryos in Ca(2+)-free saline. Relative to wild-type, the response induced by puff application of hypertonic solution was enhanced in a mutant, dunce, in which the cAMP level is elevated, or in wild-type embryos treated with forskolin, an activator of adenylyl cyclase, while protein kinase A (PKA) inhibitors decreased it. The response was also smaller in a mutant, DC0, which lacks the major subunit of PKA. Thus the cAMP/PKA cascade is involved in the hypertonicity response. Peptides containing the sequence Arg-Gly-Asp (RGD), which inhibit binding of integrins to natural ligands, reduced the response, whereas a peptide containing the non-binding sequence Arg-Gly-Glu (RGE) did not. A reduced response persisted in a mutant, myospheroid, which expresses no integrins, and the response in DC0 was unaffected by RGD peptides. These data indicate that there are at lease two components in the hypertonicity response: one that is integrin mediated and involves the cAMP/PKA cascade, and another that is not integrin mediated and does not involve the cAMP/PKA cascade.

Adenylyl Cyclases↗
PubMed2002

Autopsy findings of patients with urological neoplasms.

BACKGROUND: A study was carried out to gain extensive understanding of the disease status in patients who had suffered and died of urological neoplasms. METHODS: The subjects were 524 patients who had died at the Department of Urology of Gunma Cancer Center. The autopsy rate for each urological, neoplasm, the extent of the disease, and incidental diseases were analyzed. RESULTS: Autopsies were performed in 27.1% (142/524) of the patients. Frequent metastatic sites were the lymph nodes, bone, and lung in prostate neoplasms; the lymph nodes, liver, and lung in bladder neoplasms; and the lymph nodes, lung, and bone in kidney neoplasms. In the 116 patients with these three major urological neoplasms, the autopsy findings of all patients were compatible with progression of the disease, except for 5 cases (acute myocardial infarction in 2 and liver failure in 3). Multiple primary cancers were seen in 21.6% (25/116), and other cancers that caused death, apart from those at urological sites, were confirmed in 7 patients (pancreas in 2, and esophagus, lung, gallbladder, liver, and uterus in 1 patient each). CONCLUSION: Autopsies revealed the macroscopic and microscopic extent of the disease and the presence of incidental disease beyond the diagnosis made in the patient's lifetime.

Adolescent↗
PubMed2002

Estrogen treatment of prostate cancer increases triglycerides in lipoproteins as demonstrated by HPLC and immunoseparation techniques.

BACKGROUND: Estrogen administration is known to increase serum triglyceride concentrations. This study measured changes in lipoproteins of patients with prostate cancer treated with estrogen to determine whether the increased triglyceride concentrations are associated with atherogenic lipoprotein patterns. METHODS: Fifteen patients (52-87 years) with histologically diagnosed prostate cancer received diethylstilbestrol diphosphate (250 mg/day). Serum samples were collected before and after 1 and 2 weeks of treatment. Cholesterol and triglyceride profiles of major lipoproteins were determined by HPLC, remnant-like particle cholesterol and triglyceride concentrations by an immunoseparation technique, and apolipoproteins by immunologic methods. RESULTS: Estrogen treatment induced a 63.3% increase in total triglyceride concentrations, which occurred in all major lipoprotein classes with significant increases in HDL-triglycerides (130.4%), LDL-triglycerides (60.7%) and VLDL-triglycerides (56.2%). HDL-cholesterol increased significantly by 26.8%, while LDL-cholesterol decreased (15.6%). Remnant-like particle triglyceride concentrations also increased significantly by 77%, whereas remnant-like particle cholesterol concentrations remained unchanged. Apolipoproteins A-I and A-II increased; apolipoprotein E and Lp(a) decreased. CONCLUSIONS: The techniques used here conveniently demonstrated that short-term estrogen treatment in prostate cancer patients resulted in triglyceride enrichment of all major lipoprotein classes but did not induce changes in the lipoprotein profiles generally recognized as increasing risk for cardiovascular disease, except for the elevation of plasma triglyceride and remnant-like particle triglyceride.

Aged↗
PubMed2002

In vivo gene transfer of hepatocyte growth factor to skeletal muscle prevents changes in rat kidneys after 5/6 nephrectomy.

Hepatocyte growth factor (HGF) has been reported to be a renal regeneration factor. We previously reported that HGF acts as a renotropic factor, inducing cell recovery from ischemic injury or drug toxicity. Gene transfer by electroporation, which uses plasmid DNA as the vector, has several advantages over the conventional gene transfer method using viral vectors, inducing the ability to perform repeated transfers without apparent immunologic responses to the DNA vector. We recently demonstrated that electroporation of the HGF gene into skeletal muscle was an effective treatment for liver injury in an animal model. We presently investigated prevention of development of chronic renal disease by repetitive HGF gene transfer in rats with 5/6 nephrectomy. Hepatocyte growth factor gene transfer-treated rats showed better growth in body weight than untreated rats. Histologic changes such as glomerulosclerosis and interstitial fibrosis were significantly ameliorated by HGF gene transfer compared with untreated rats. Hepatocyte growth factor gene transfer by electroporation into skeletal muscle is feasible and effective against morphologic injury in subtotally nephrectomized rats.

Animals↗
PubMed2002

Tumor-associated tissue eosinophilia of penile cancer.

BACKGROUND: Tumor-associated tissue eosinophilia (TATE) occurs in many kinds of cancer. This study analyzed whether TATE improves the survival of penile cancer patients. METHODS: In 17 patients with penile cancer, survival was compared between the TATE-positive group and the TATE-negative group. Tissue eosinophils were observed by transmission electron microscopy. RESULTS: In all cases, 5-year survival was 72.9% in the TATE-positive group (n = 8) and 38.9% in the TATE-negative group (n = 9; P = 0.131). In stage III and IV, it was 60% in the TATE-positive group (n = 5) and 0% in the TATE-negative group (n = 5; P = 0.058). Transmission electron microscopy images revealed the vigorous infiltration of tissue eosinophils. CONCLUSIONS: It is suggested that TATE improves the survival of patients with advanced penile cancer. However, a greater number of subjects is needed to prove statistical significance.

Eosinophilia↗
PubMed2002

Prolonged liver dysfunction caused by hemosiderosis in a renal transplant recipient.

BACKGROUND: Liver dysfunction is a frequent complication that arises in the period following kidney transplantations, often resulting in death. We reported a case proving hemosiderosis as a cause of prolonged liver dysfunction after cadaveric kidney transplantation. METHODS: A 47-year-old man, who had been undergoing hemodialysis, was referred to our hospital on 2 November 1999. On the same day, cadaveric kidney transplantation was performed, and serum creatinine level reached a normal level within 2 weeks after surgery. However, serum transaminase gradually increased in the postoperative period. Serum ALT rose up to 116 IU/L on day 20 after the operation and 215 IU/L on day 30. Microscopic examination by needle biopsy revealed hemosiderosis of the liver. Recombinant human erythropoietin was administered and phlebotomy was performed. Liver function improved as a result. CONCLUSION: Early histological diagnosis can be a useful marker in predicting the course of chronic liver disease.

Cadaver↗
PubMed2002

Usefulness of PSA screening in outpatients with bladder cancer: preliminary results.

BACKGROUND: We performed prostate-specific antigen (PSA) screening and evaluated its usefulness in outpatients with bladder cancer who may have an elevated risk for prostate cancer. METHODS: Sixty-one new or followed-up outpatients with bladder cancer were examined between September 1999 and December 2000 in the Department of Urology, Gunma University Hospital, Japan. PSA was measured after informed consent was obtained, and patients in whom the PSA level was 4.1 ng/mL or higher were selected for thorough examination. In the examination, one examiner performed DRE (digital rectal examination) and, based on DRE and TRUS (transrectal ultrasonography) findings, determined whether prostate biopsy was indicated. RESULTS: The average age of the 61 cases was 69.1 +/- 8.6 years, and the average PSA level was 3.5 +/- 5.8 ng/mL. The PSA level was 4.1 ng/mL or higher in 11 (18.0%) patients, nine of whom underwent six-sextant biopsy under TRUS guidance. Of these nine cases, four (6.6%) were diagnosed as having prostate cancer. The Gleason score was 7 in three cases and 9 in one case. The clinical stage was T2N0M0 in three cases and T3N0M0 in one case. CONCLUSIONS: On PSA screening in patients with bladder cancer and patients with a history of transurethral resection of the bladder tumor (TUR-BT), prostate cancer was found in 6.6%. This rate is higher than in the general population. These cancers were classified into intermediate to high-risk groups, and the prognosis of prostate cancers could be more important than those of the bladder cancers in two cases (50%). We conclude that PSA screening for inpatients with bladder cancer may be useful.

Aged↗
PubMed2002

Usefulness of prostate-specific antigen velocity in screening for prostate cancer.

BACKGROUND: The cut-off value of prostate-specific antigen velocity (PSAV) was investigated in relation to the initial prostate-specific antigen (PSA) value in subjects with initial values of 1.0-4.0 ng/mL, and the usefulness and limitations of PSAV as a screening test for prostate cancer were examined. METHODS: In this study, 4883 men who underwent mass screening for prostate cancer two or more times between 1987 and 1998 and had initial PSA levels of 1.0-4.0 ng/mL were investigated. The subjects ranged in age from 42 to 96 years (mean: 68.0 +/- 6.6 years). The cut-off value of PSAV was set at 0.1-1.5 ng/mL per year, and the sensitivity, specificity, efficiency and positive predictive value (PPV) of PSAV for detecting prostate cancer were determined according to the initial PSA value. A similar examination of the average PSAV was carried out in 2888 subjects with three or more visits for mass screening for prostate cancer. RESULTS: The diagnostic efficiency of PSAV was optimal with cut-off values of 0.3 and 0.75 ng/mL per year in those subjects with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively, but the PPV was low at 1.8% in subjects with initial PSA levels of 1.0-1.9 ng/mL. When the cutoff value of PSAV was set at 1.2 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 ng/mL, the PPV increased to 7.3% and the sensitivity was 40%. The diagnostic efficiency of the average PSAV was optimal at the cut-off values of 0.2 and 0.4 ng/mL per year in subjects with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively, but the PPV was low at 2.2% in the subjects with initial PSA values of 1.0-1.9 ng/mL. When the cut-off value of PSAV was set at 0.75 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 ng/mL, the PPV was 9.8% and the sensitivity was 46%. CONCLUSION: It is possible to improve the diagnostic accuracy of prostate cancer screening using the cut-off value of PSAV and average PSAV in subjects with initial PSA levels of 1.0-4.0 ng/mL. The cut-off values of PSAV should be set at 1.2 and 0.75 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively. The cut-off values of the average PSAV should be set at 0.75 and 0.4 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively.

Adult↗
PubMed2002

Erosion of a penile prosthesis due to an indwelling urethral catheter as a late complication.

A case of erosion of a penile prosthesis caused by indwelling of a catheter in the urethra is reported. A 73-year-old man had maintained sexual intercourse with penile prostheses (Jonas prosthesis, 19 cm) for 11 years without any complications until he developed cerebral infarction. One month after starting an indwelling urethral catheter in a neurosurgery clinic, the left-side penile prosthesis eroded from the area of the fossa navicularis, and was immediately removed. This type of complication is not unusual in patients with a neurogenic bladder. However, it is not well recognized in patients who suddenly develop a neurogenic bladder following a long-term uneventful period after the implantation of penile prostheses. Therefore, urologists should inform patients who receive this type of treatment that erosion of the prosthesis may develop when they need an indwelling urethral catheter as a late complication.

Aged↗
PubMed2002

Enhanced Escherichia coli invasion of human brain microvascular endothelial cells is associated with alternations in cytoskeleton induced by nicotine.

Although epidemiological studies have shown that exposure to tobacco smoking significantly increases the risk of bacterial meningitis, heretofore the pathogenic effects of smoking on this disease have been poorly understood. In order to dissect this issue, we have investigated the effects of nicotine, the major component of tobacco, on E. coli invasion of human brain microvascular endothelial cells (HBMEC). Our studies showed that E. coli invasion of HBMEC was significantly enhanced by nicotine in a dose-dependent manner. The nicotine-mediated enhancement was associated with actin cytoskeleton rearrangement and morphological changes in the eukaryotic host cell that are essential for bacterial entry. The recombinant IbeA protein and alpha-bungarotoxin (a nicotinic acetylcholine receptor antagonist) were able to efficiently block the nicotine-mediated cellular effects, suggesting the involvement of the IbeA and nicotinic receptors. Blocking of phosphatidylinositol 3-kinase (PI3K) by LY294002 abolished the entry of E. coli in HBMECs treated with nicotine in a dose-dependent manner. Inhibition of PI3K was associated with decreased phosphorylation of Akt and actin cytoskeletal rearrangement. In contrast to PI3K, blockage of Rho kinase (ROCK) by Y27632 upregulated both nicotine- and E. coli-mediated cellular responses. Thus, this study provides experimental evidence for the first time that the major component of tobacco, nicotine, enhances meningitic E. coli invasion of HBMEC through modulation of cytoskeleton.

Actin Cytoskeleton↗
PubMed2002

Salvage external beam radiotherapy for local recurrence without systemic progression or prostate specific antigen recurrence of prostate cancer after initial hormonal therapy: is it possible to identify patients likely to have good treatment outcomes?

BACKGROUND: We attempted to identify factors that predict the outcomes of salvage external beam radiotherapy (sEBRT) in patients who showed local recurrence without systemic progression or isolated prostate specific antigen (PSA) recurrence after initial hormonal therapy. METHODS: The subjects were 33 patients who were diagnosed as having local recurrence without systemic progression (30 cases) or isolated PSA recurrence (three cases). Of these patients, those with continuously decreasing PSA levels, which were 1.0 ng/ml or less 1-1.5 years after sEBRT, were regarded as good responders (GR) whereas the remaining patients were regarded as poor responders (nGR). Survival rates in these patients and factors that distinguish GR from nGR were evaluated retrospectively. RESULTS: The cancer-specific 10-year survival rate was 82.4% in the 33 patients, 100% in the 21 GR patients and 55% in the 12 nGR patients (P < 0.0001). Stepwise variable selection to discriminate between GR and nGR revealed that the time from sEBRT initiation to the nadir PSA was the most significant factor (P = 0.000097). Before sEBRT, GR can be predicted in patients with pre-sEBRT PSA <30.0 ng/ml and PSA doubling time (PSADT) >7.0 months, with a sensitivity of 95.2% (20/21), a specificity of 100% and an accuracy of 97.0%. CONCLUSION: Good responses to sEBRT can be expected in patients with local recurrence without systemic progression or isolated PSA recurrence after initial hormonal therapy when the patients show both pre-sEBRT PSA <30.0 ng/ml and PSADT >7.0 months.

Aged↗
PubMed2002

[Chromophobe cell renal carcinoma: a case report].

We report a case of chromophobe cell carcinoma in a 41-year-old woman who was admitted to our hospital because of right upper abdominal pain. We performed right radical nephrectomy under the diagnosis of renal cell carcinoma. The cut surface appearance of the tumor was homogeneous, grey beige and solid. This tumor was diagnosed as chromophobe cell renal carcinoma after microscopic and immunohistochemical studies. We report our case with reference to the relevant literature.

Adult↗