Biomedical subjects

T Kitamura

Publications and source records attributed to T Kitamura.

At least 73 records · Page 4Linked to original sources

PubMed2001

Photoreductive dehalogenation of halogenated benzene derivatives using ZnS or CdS nanocrystallites as photocatalysts.

ZnS nanocrystallites (nc-ZnS) prepared in N,N-dimethylformamide (DMF) photocatalyze dehalogenation of halogenated benzenes to benzene as the final product from chlorinated benzenes and to difluorobenzenes from fluorinated benzenes in the presence of triethylamine (TEA) as an electron donor under UV light irradiation (lambda > 300 nm). When CdS nanocrystallites (nc-CdS) are used as a photocatalyst (lambda > 400 nm), halogenated benzenes are photoreductively dehalogenated, yielding trichlorobenzene from hexachlorobenzene and tetrafluorobenzene isomers from hexafluorobenzene as the final products. Photoformed electrons on nc-ZnS and nc-CdS have such negative reduction potentials that these electrons reduce polyhalogenated benzenes, leading to the successive dehalogenation. nc-ZnS exhibits higher photocatalytic activitythan nc-CdS due to the more negative potential of the electrons on nc-ZnS than that on nc-CdS. The higher activities of nc-ZnS and nc-CdS compared to their bulk forms are explained as being due to their quantum size effects and the adsorptive interaction between the substrates and the nanosized photocatalysts.

Benzene Derivatives↗

PubMed2001

Proliferation of parenchymal neural progenitors in response to injury in the adult rat spinal cord.

It has long been believed that the fully developed mammalian central nervous system (CNS) lacks significant regenerative capacity. Recent advances have revealed, however, that many regions of the adult CNS contain neural progenitors that have the ability to generate new neurons and glia. Although the periventricular area has been identified as a rich source of these progenitors, their precise location in each region and details of their properties in vivo still remain poorly understood. Here we provide evidence that in the adult rat spinal cord, a significant number of neural progenitors are present, not only in the periventricular area, but also in other regions of the parenchyma. These progenitors could proliferate in vitro as neurosphere-like cell aggregates in the presence of growth factors and also gave rise to neurons and glia under appropriate conditions. We further demonstrate that these parenchymal neural progenitors were capable of proliferating in vivo in response to injury. Immunohistochemical studies suggested that proliferative progenitors emerged throughout the gray and white matter in the lesioned spinal cord. Consistently, an increased number of neurosphere-forming cells could be isolated from injured tissues, and they were able to differentiate into neurons in vitro. The widespread occurrence of neural progenitors in the parenchyma expands the possibility of repairing damaged tissue by activating the latent regenerative potential of the adult spinal cord.

Animals↗

PubMed2001

Noninvasive detection and prediction of bladder cancer by fluorescence in situ hybridization analysis of exfoliated urothelial cells in voided urine.

OBJECTIVES: To investigate the clinical utility of fluorescence in situ hybridization (FISH) of voided urine in the detection of bladder cancer and the prediction of its recurrence. METHODS: FISH with centromere-specific probes for chromosomes 9 and 17 was performed to evaluate the chromosomal alterations of exfoliated urothelial cells in voided urine obtained from 44 patients with bladder cancer and 20 controls. The analysis was also performed in 17 patients with bladder cancer after complete transurethral resection to prospectively determine whether FISH can predict tumor recurrence. RESULTS: The sensitivity to detect bladder cancer by FISH analysis (85%) was significantly higher than that by urine cytologic examination (32%) and by the bladder tumor antigen test (64%) (P <0.0001 and P = 0.026, respectively). The specificity of FISH, cytologic analysis, and the bladder tumor antigen test was 95%, 100%, and 80%, respectively. Among the 17 patients tested after transurethral resection, 7 of 13 FISH-positive patients developed tumor recurrence within the 27-month follow-up period; none of 4 FISH-negative patients developed recurrence during the same period. The recurrence rate in patients with the loss of chromosome 17 was 100%, significantly higher than the 23% for patients without this alteration (P = 0.015). CONCLUSIONS: These findings suggest that FISH analysis of exfoliated urothelial cells in voided urine can efficiently detect bladder cancer and predict its recurrence.

Adult↗

PubMed2001

Cytoarchitectonic subdivisions of the parabrachial nucleus in the Japanese monkey (Macacus fuscatus) with special reference to spinoparabrachial fiber terminals.

The cytoarchitectonic subnuclear organization of the parabrachial nucleus (PB) surrounding the brachium conjunctivum (BC) in the monkey was examined using the Nissl method and the anterograde axonal flow method. PB of the monkey could be divided into the following subnuclei: the dorsal area (DPBM) along the medial surface of the medial three-fourths of BC in the caudal half of medial PB (PBM), the ventral area (VPBM) along the medial surface of the lateral one-fourth of BC in the rostral two-thirds of PB, the ventrolateral part of lateral PB (PBL) lateral to BC throughout PB (EL), the ventral part of the rostral half of PBL ventral to EL (EXL), the medial part of middle PBL along the dorsal surface of BC (VL), the dorsal and lateral marginal part of PBL in the rostral two-thirds of PB (DL), the cell cluster in the dorsomedial part of the rostral half of PBL between VL and DL (CL), the dorsocentral part appearing at the level of root exit of the trochlear nerve between DL and CL and extending to the rostral end of PBL (IL), the area between DL and IL in the rostral one-seventh of PBL (SL), and Kölliker-Fuse nucleus (KF) ventral to EL and BC in the middle one-third of PB and lateral to the lateral pontine tegmentum. After the injection of biotinylated dextran amine into the upper cervical segments, labeled fibers terminated in each subdivision of PB with different densities; most heavily in IL, more heavily in DL and KF, moderately in EL and VPBM, and scarcely in the rest of PB. The present study demonstrated for the first time the subdivisions of PB in the monkey, which were essentially common to those of the rat based on the cytoarchictecture of PB and spinal fiber terminals in it.

Animals↗

PubMed2001

Effects of intracavernous administration of adrenomedullin on erectile function in rats.

We have reported that adrenomedullin (AM)-induced vasodilation is at least in part nitric oxide (NO)-cGMP-dependent in the rat. Although it is well known that NO is much involved in the erectile function, it is controversial as to whether AM influences the erectile function. Thus, we examined the effects of AM on intracavernous pressure (ICP) during penile erection. The left carotid artery of rats was cannulated to monitor of mean arterial pressure (MAP). Bipolar electrodes were positioned on the cavernous nerve. The right cavernous body was cannulated with a needle connected to a pressure transducer to monitor ICP. Electrical stimulation (ES) increased ICP in a voltage-dependent manner. Elevation of ICP continued during ES. The intracavernous injection of 0.5 nmol AM significantly potentiated ES-induced increases in both maximal developed ICP/MAP and area under the curve (ICP trace; AUC). Since AM slightly lowered MAP, ICP was normalized by MAP. i.v. administration of N(omega)-nitro-L-arginine, a NO synthase inhibitor, markedly decreased AM/ES-induced ICP elevation. However, in the presence of E-4021, a cGMP-specific phosphodiesterase inhibitor, AM further increased both ICP/MAP and AUC. These results suggest that a NO-cGMP pathway is involved in the regulation of AM-induced rat cavernous vasorelaxation.

Adrenomedullin↗

PubMed2001

Effects of gastrointestinal stimulant and suppressant pretreatment on the pharmacokinetics of AS-924, a novel ester-type cephem antibiotic.

The effects of pretreatment with the gastrointestinal stimulant domperidone and the suppressant scopolamine butylbromide on the absorption of AS-924, a novel prodrug-type cephem antibiotic, were investigated in six healthy adult male volunteers by a cross-over method. The T(max) of ceftizoxime (CTIZ), the active moiety of AS-924, was slightly prolonged by scopolamine butylbromide (T(max)=1.8 vs. 1.5 h for the group without pretreatment). However, there were no significant differences in pharmacokinetic parameters including T(max), cumulative urinary excretion rates of CTIZ and cumulative urinary excretion rates of pivaloylcarnitine for 12 h after the dosing between the pretreated and control groups. Domperidone did not affect the absorption of AS-924.

Adult↗

PubMed2001

Regulation of Th2 cell differentiation by mel-18, a mammalian polycomb group gene.

Polycomb group (PcG) gene products regulate homeobox gene expression in Drosophila and vertebrates and also cell cycle progression of immature lymphocytes. In a gene-disrupted mouse for polycomb group gene mel-18, mature peripheral T cells exhibited normal anti-TCR-induced proliferation; however, the production of Th2 cytokines (IL-4, IL-5, and IL-13) was significantly reduced, whereas production of IFNgamma was modestly enhanced. Th2 cell differentiation was impaired, and the defect was associated with decreased levels in demethylation of the IL-4 gene. Significantly, reduced GATA3 induction was demonstrated. In vivo antigen-induced IgG1 production and Nippostrongylus brasiliensis-induced eosinophilia were significantly affected, reflecting the deficit in Th2 cell differentiation. Thus, the PcG gene products play a critical role in the control of Th2 cell differentiation and Th2-dependent immune responses.

Animals↗

PubMed2001

The IL-7 receptor controls the accessibility of the TCRgamma locus by Stat5 and histone acetylation.

The IL-7 receptor (IL-7R) plays critical roles in expansion and V(D)J recombination during lymphocyte development. Here we demonstrate that cytokine stimulation rapidly recruits Stat5 and transcriptional coactivators to the Jgamma germline promoter and induces histone acetylation, germline transcription, and accessibility in Ba/F3 cells. We also show that histone acetylation of the TCRgamma locus is significantly reduced in IL-7R-deficient thymocytes and that the introduction of active Stat5 restores the histone acetylation and accessibility of the locus. Furthermore, treatment with histone deacetylase inhibitor recovers the histone acetylation and accessibility in IL-7R-deficient thymocytes. Therefore, these results suggest that Stat5 may recruit the transcriptional coactivators to the Jgamma germline promoter and control the accessibility of the TCRgamma locus by histone acetylation.

Acetylation↗

PubMed2001

Catalytic functionalization of arenes and alkanes via C-H bond activation.

Several novel synthetic reactions of arenes and alkanes discovered and investigated in our laboratory are summarized here. These include olefin arylation, hydroarylation of alkynes, hydroxylation of arenes, carboxylation of arenes and alkanes, and aminomethylation and acetoxylation of alkanes. Most of these reactions are catalyzed by highly electrophilic transition metal cationic species generated in situ in an acid medium, involving electrophilic metalation of C-H bonds of arenes and alkanes which lead to the formation of aryl-metal and alkyl-metal sigma-complexes.

Journal Article↗

PubMed2001

Symptomatic recovery and social functioning in major depression.

OBJECTIVE: To determine whether social functional recovery precedes, runs in parallel with, or lags behind symptomatic recovery from major depressive episodes. METHOD: Psychiatric out-patients or in-patients aged 18 years or over, diagnosed with unipolar major depressive disorder according to DSM-IV, and who had received no antidepressant medication in the preceding 3 months were identified at 23 collaborating centres from all over Japan (n=95). They were rated with the 17-item Hamilton Rating Scale for Depression (HRSD) and the Global Assessment Scale (GAS) monthly, and with the Social Adjustment Scale-Self Report (SAS-SR) 6-monthly. Remission was defined as 7 or less on the HRSD and recovery as 2 or more consecutive months of remission. RESULTS: The GAS ratings showed continuous amelioration from baseline to remission, remission to recovery, and after sustained recovery. The same trends were observed for SAS-SR scores. CONCLUSION: We can expect further amelioration in social adjustment after symptomatic remission and recovery of major depressive episodes.

Major Depressive Disorder↗

PubMed2001

TSLC1 is a tumor-suppressor gene in human non-small-cell lung cancer.

The existence of tumor-suppressor genes was originally demonstrated by functional complementation through whole-cell and microcell fusion. Transfer of chromosome 11 into a human non-small-cell lung cancer (NSCLC) cell line, A549, suppresses tumorigenicity. Loss of heterozygosity (LOH) on the long arm of chromosome 11 has been reported in NSCLC and other cancers. Several independent studies indicate that multiple tumor-suppressor genes are found in this region, including the gene PPP2R1B at 11q23-24 (ref. 7). Linkage studies of NSCLC are precluded because no hereditary forms are known. We previously identified a region of 700 kb on 11q23.2 that completely suppresses tumorigenicity of A549 human NSCLC cells. Most of this tumor-suppressor activity localizes to a 100-kb segment by functional complementation. Here we report that this region contains a single confirmed gene, TSLC1, whose expression is reduced or absent in A549 and several other NSCLC, hepatocellular carcinoma (HCC) and pancreatic cancer (PaC) cell lines. TSLC1 expression or suppression is correlated with promoter methylation state in these cell lines. Restoration of TSLC1 expression to normal or higher levels suppresses tumor formation by A549 cells in nude mice. Only 2 inactivating mutations of TSLC1 were discovered in 161 tumors and tumor cell lines, both among the 20 primary tumors with LOH for 11q23.2. Promoter methylation was observed in 15 of the other 18 primary NSCLC, HCC and PaC tumors with LOH for 11q23.2. Thus, attenuation of TSLC1 expression occurred in 85% of primary tumors with LOH. Hypermethylation of the TSLC1 promoter would seem to represent the 'second hit' in NSCLC with LOH.

Animals↗

PubMed2001

Long-term outcome of endoscopic biopsy and subsequent nephroureterectomy for upper urinary tract tumor.

BACKGROUND: Upper urinary tract tumors can be biopsied using a flexible ureterorenoscope. This study examined retrospectively possible adverse effects of this procedure on patient outcome. METHODS: The study subjects consisted of 16 consecutive patients with renal pelvic tumor (n = 13) and upper ureteral tumor (n = 3). All subjects underwent endoscopic biopsy of their tumor and subsequent total nephroureterectomy between 1989 and 1995. The follow-up period ranged from 4.1 to 9.5 (mean 5.2) years. RESULTS: The overall 5-year survival rate was 87.0%, being 100% in 12 patients with tumors of grade 1 or 2. In contrast, of four patients with grade 3 tumor, three (75%) developed systemic lymphogenous and/or multiple lung metastases within 1 year postoperatively. CONCLUSIONS: The excellent patient outcomes deny any adverse effect of endoscopic biopsy on patients with grade 1 or 2 tumor. However, the endoscopic procedure should be performed prudently when a high grade tumor is suspected.

Aged↗

PubMed2001

Necessity of re-evaluation of estramustine phosphate sodium (EMP) as a treatment option for first-line monotherapy in advanced prostate cancer.

Estramustine phosphate sodium (EMP) was first introduced in the early 1970s for the treatment of prostate cancer, when EMP was supposed to have the dual effect of estrogenic activity and cytotoxicity. For the following decades, it was used mainly in hormone-refractory cases, with a conventional dosage of 4-9 capsules/day, which showed a 30-35% objective response rate. However, a very limited number of cases have been reported that used EMP as a first-line monotherapy in the conventional dosage. One study showed a response rate of 82%, which is at least as effective as conventional estrogen (diethylstilbestrol; DES) monotherapy. Nevertheless, EMP was almost abandoned for the treatment of prostate cancer because of severe adverse side-effects, especially in the cardiovascular system and gastrointestinal tract. Recently, two facts have become evident. First, EMP interferes with cellular microtubule dynamics but does not show alkylating effects. Second, EMP is able to produce a complex with calcium when dairy products are taken concomitantly with EMP, resulting in a decrease in the absorption rate of EMP from the gut. Many clinical trials have been undertaken without warning against concomitant dairy product intake since the introduction of EMP. This fact will jeopardize almost all the clinical trials performed before 1990. It is considered that response rates have been underestimated and better results could have been obtained because side-effects decrease dose-dependently. Low-dose EMP monotherapy (2 capsules/day) has been performed infrequently in previously untreated advanced prostate cancer. The only large trial by the European Organization for Research and Treatment of Cancer in 1984 was biased in selecting patients. Nevertheless, the response rate of EMP is comparable to that of DES. In this study, the adverse side-effects of EMP were less than that of DES. Recently, a study was conducted at the University of Tokyo of 11 patients with advanced prostate cancer on low-dose EMP as first-line monotherapy. The study found that the mean serum prostate-specific antigen level decreased to within the normal range by day 50; mean serum testosterone, leutinizing hormone and follicle-stimulating hormone reduced to undetectable levels by day 20; and mean serum estradiol increased to a very high level within 1 week. These data implicate that low-dose EMP can suppress quickly and adequately the pituitary-gonadal axis, although the antitumor effect has not as yet been elucidated. For these reasons, it is necessary to re-evaluate low-dose EMP monotherapy in previously untreated advanced prostate cancer.

Antineoplastic Agents, Hormonal↗

PubMed2001

Induction of apoptosis by cyclooxygenase-2 inhibitors in prostate cancer cell lines.

Prostaglandins are thought to play an important role in the proliferation of prostate cancer and are highly expressed in prostate cancer tissue. Cyclooxygenase-2 (COX-2), or prostaglandin endoperoxide synthase, is a key enzyme in the conversion of arachidonic acid into prostaglandin. In several cancers, COX-2 contributes to the proliferation and metastasis of cancer cells. To assess the role of COX-2 in prostate cancer, we investigated whether the inhibition of COX-2 affected the proliferation of prostate cancer cells. The human prostate cancer cell lines, LNCaP and PC 3, and a normal prostate stromal cell line (PrSC) were treated with COX-2 inhibitors NS 398 and Etodolac. The proliferation rate of the cell lines was examined using 3(4,5-dimethylethiazoly 1-2-) 2,5-diphonyl tetrazolium bromide (MTT) assays. A DNA fragmentation assay was also used for proof of apoptosis. COX-2 inhibitors could suppress the proliferation of LNCaP and PC 3 cells. In contrast, PrSC was not affected by COX-2 inhibitors. These suppressive effects occurred in a time- and dose-dependent manner. One of mechanisms responsible for cell death was apoptosis. COX-2 seems to play a significant role in the progression of prostate cancer. COX-2 may be a therapeutic target for prostate cancer. Since COX-2 inhibitors suppress proliferation and induce apoptosis in prostate cancer cells, and have no effect in normal prostate stromal cells, COX-2 inhibitors will be useful for the treatment of prostate cancer.

Cyclooxygenase 2↗

PubMed2001

Differences in cell kinetic changes among renal cancer cell lines treated with interferon-alpha.

BACKGROUND: Interferon (IFN)-alpha shows certain clinical effects on the treatment of renal cell carcinoma. The purpose of the present study was to investigate its direct effects and to compare the responses among different human renal cancer cell lines. METHODS: Three cell lines, ACHN, RCC10RGB and OS-RC-2, were incubated with IFN-alpha and evaluated using MTT assay for cell proliferation and two-color flow cytometry for cell-cycle-specific cyclin expressions coupled with DNA ploidy analysis. RESULTS: Interferon-alpha inhibited cell proliferation and caused cell accumulation at S and G2/M phases. However, IFN-alpha induced no significant change in cyclins D1, E, A or B1 expression. Interestingly, cell kinetic changes caused by IFN-alpha were different among cell lines. Cell proliferation was suppressed most in ACHN, then RCC10RGB and least in OS-RC-2. Comparing DNA histograms, ACHN showed distinct increase of G2/M cells associated with elevation of late S cells. RCC10RGB showed a predominant increase of whole S cells accompanied with a slight increase of G2/M. OS-RC-2 showed a modest increase of S cells with a little change of G2/M cells. Chronological observation revealed that S-phase increase and proliferative inhibition appeared on day 1 and day 3, respectively, in ACHN and RCC10RGB, and on day 5 in OS-RC-2. CONCLUSIONS: Interferon-alpha induced substantial cell kinetic interference directly in the tested human renal carcinoma cell lines. The degree of change was different according to the nature of the cell line. It may partly indicate the variety of the efficacy of IFN-alpha treatment against renal cancers.

Carcinoma, Renal Cell↗

PubMed2001

Influence of various hemodialysis membranes on the plasma (1-->3)-beta-D-glucan level.

BACKGROUND: Recently, invasive fungal infections have increased significantly because of the growing number of immunocompromised hosts. The measurement of plasma (1-->3)-beta-D-glucan has been proposed as a useful diagnostic tool for deep mycosis. In this study, we analyzed the alteration of the plasma (1-->3)-beta-D-glucan concentration by using different kinds of hemodialysis (HD) membranes in end-stage renal disease (ESRD) patients and estimated its half-life. METHODS: Twenty-seven patients with ESRD without known fungal infections (with a median age of 66 years old) were enrolled in this study. Cellulose triacetate (CTA) membrane, cellulose (Cu) membrane, and polymethyl methacrylate (PMMA) membrane were used in three consecutive initiations of HD and plasma (1-->3)-beta-D-glucan concentration was measured before and after each HD session. RESULTS: The level did not change between before and after HD when CTA and PMMA membranes were used. In contrast, the plasma (1-->3)-beta-D-glucan level increased greatly after HD using the Cu membrane (from 9.4 to 332 pg/mL in median). Hypothesizing that the plasma (1-->3)-beta-D-glucan level declines exponentially, its median half-life is estimated at 20 hours, which is not affected by hepatic or renal function. CONCLUSIONS: Because the plasma (1-->3)-beta-D-glucan level increases dramatically after HD using the Cu membrane, dialyzers with Cu membrane should be avoided for HD in patients with suspected deep mycosis. The measurement of plasma (1-->3)-beta-D-glucan is also useful for the patients with hepatic or renal failure.

Adult↗

PubMed2001

Leptin augments inflammatory and profibrogenic responses in the murine liver induced by hepatotoxic chemicals.

Lines of evidence suggested a possible link between leptin and hepatic fibrosis; however, whether leptin modulates the fibrogenesis in the liver remains unclear. The purpose of this study, therefore, was to evaluate the effect of leptin on inflammatory and profibrogenic responses in the liver caused by hepatotoxic chemicals. Male C57Bl/6 mice were given carbon tetrachloride (CCl(4)) (0.1 microL/g body weight [BW], intraperitoneally [IP]) and/or recombinant murine leptin (1 microg/g BW, IP) simultaneously, and sacrificed up to 72 hours later. Further, some mice were given thioacetamide (TAA; 200 microg/g BW, IP) and leptin 3 times per week for 4 weeks to evaluate the effect of leptin on chronic fibrogenic responses. A simultaneous injection of leptin enhanced acute CCl(4)-induced necroinflammatory and subsequent fibrotic changes in the hepatic lobules. The steady-state messenger RNA (mRNA) levels of alpha1(I) procollagen and heat shock protein 47 (HSP47) in the liver were potentiated when leptin was injected together with CCl(4). Expression of alpha smooth muscle actin (alpha-SMA) in the liver after CCl(4) treatment was also augmented markedly in combination with leptin. Further, leptin increased transforming growth factor beta1 (TGF-beta1) mRNA in the liver 24 hours after acute CCl(4) about 4-fold higher than CCl(4) alone. Moreover, leptin enhanced hepatic fibrosis and induction of alpha1(I) procollagen mRNA caused by chronic TAA administration. Collectively, these findings indicated that leptin augments both inflammatory and profibrogenic responses in the liver caused by hepatotoxic chemicals. It is postulated that the increase in systemic leptin levels enhances up-regulation of TGF-beta1, leading to activation of stellate cells, thereby augmenting the fibrogenic response in the liver.

Actins↗

PubMed2001

The implication of repeated versus continuous strain on nerve function in a rat forelimb model.

We studied the effect of repeated and continuous nerve strain using a rat forelimb model to investigate whether an innocuous level of strain applied continuously affects nerve function when applied repeatedly. We used the rat medial cord of the brachial plexus and assessed the effects of strain by studying nerve histology (blood-nerve barrier), function (grasping strength), and electrophysiology. Continuous stretching was applied to the rat forelimb for 1 hour at 2 N. After this strain neither histologic analysis, grasping strength, nor electrophysiologic analysis revealed any effect. We then applied repeated strain at both 60 and 120 times per hour; after the latter strain abnormalities in histology, grasping strength, and nerve conduction were identified. There results suggest that a small nerve strain applied repeatedly results in nerve dysfunction. Our data may help explain the cause of nonspecific neural symptoms in the upper extremities of patients with no objective findings.

Animals↗