Biomedical subjects

K Mori

Publications and source records attributed to K Mori.

At least 343 records · Page 19Linked to original sources

PubMed1999

Co-expression of gamma-glutamylcysteine synthetase sub-units in response to cisplatin and doxorubicin in human cancer cells.

Glutathione (gamma-glutamylcysteinyl glycine, GSH) is believed to be important in the acquisition of resistance to anti-cancer drugs such as cisplatin (CDDP) and doxorubicin (DOX). gamma-Glutamylcysteine synthetase (gamma-GCS) is a key enzyme for maintaining intracellular GSH levels; it is composed of a catalytic heavy (gamma-GCSh) and a regulatory light (gamma-GCSl) sub-unit. In the present study, the expression of gamma-GCS sub-units was examined in human cancer cell lines. The levels of GSH, the expression of gamma-GCSh and gamma-GCSl mRNAs and proteins in human cancer cells were higher in CDDP-resistant cells and DOX-resistant cells than in the drug-sensitive cells. Treatment of CDDP/DOX-resistant human colonic-cancer cells (HCT8DDP) with CDDP and DOX caused simultaneous induction of the expression of gamma-GCSh and gamma-GCSl mRNAs. The transcriptional regulation of gamma-GCS was studied and it was observed that the DNA-binding activity of activator protein 1 (AP-1) is induced by CDDP and DOX using an electrophoretic mobility shift assay. We constructed chimeric genes containing various regions of the gamma-GCSh-promoter gene and the coding region for luciferase. The HCT8DDP cells transiently transfected with a plasmid containing an AP-1 site of the gamma-GCSh-promoter-luciferase construct showed increased luciferase activity when treated with CDDP and DOX. These results suggest that stimulation of the expression of gamma-GCSh by CDDP and DOX is mediated by AP-1, which relates to the resistance of cancer cells to the drug.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1999

Development of telencephalin in the human cerebrum.

Telencephalin (TLN) is a 130kDa, type 1 integral membrane glycoprotein of the immunoglobulin superfamily found in the mammalian central nervous system. TLN shows a molecular structure resembling intercellular adhesion molecules-1 and -3, and binds to the CD11a/CD18 leukocyte integrin. TLN was localized to neuronal dendrites in the telencephalic gray matter: cerebral cortex and basal ganglia. We studied immunohistochemically the expression of TLN in the developing human brain. In the hippocampus, TLN immunoreactivity appeared at 29 gestational weeks (GW), intensified subsequently, and persisted into adulthood. In the temporal cortex, labeling was weak and restricted to the cytoplasm of pyramidal neurons from 35 to 39 GW, but thereafter became diffuse and intense in the cortical layers, especially the molecular layer, by 5 months of postnatal age. The development of TLN was late compared to synaptophysin and microtubule-associated protein 2, suggesting its involvement in the functional maturation of neuronal dendrites and synapses.

Adolescent↗

PubMed1999

Protective effects of bacteriophage on experimental Lactococcus garvieae infection in yellowtail.

The present study describes the in vitro and in vivo survival of Lactococcus garvieae bacteriophages and the potential of the phage for controlling experimental L. garvieae infection in yellowtail. Anti-L. garvieae phages persisted well in various physicochemical (water temperature, salinity, pH) and biological (feed, serum and alimentary tract extracts of yellowtail) conditions, except for low acidity. In the in vivo, the phage PLgY-16 was detected in the spleens of yellowtail until 24 h after intraperitoneal (i.p.) injection, or the phage was recovered from the intestine of yellowtail 3 h after the oral administration of phage-impregnated feed but undetectable 10 h later. Simultaneous administration of live L. garvieae and phage enhanced recovery of the phage from the spleen or intestine. The survival rate was much higher in yellowtail that received i.p. injection of the phage after i.p. challenge with L. garvieae, compared with that of control fish without phage injection. When fish were i.p. injected with phage at different hours after L. garvieae challenge, higher protective effects were demonstrated in fish that received phage treatment at the earlier time. Protection was also obtained in yellowtail receiving phage-impregnated feed, in which fish were challenged by an anal intubation with L. garvieae. Anal-intubated L. garvieae were detected constantly in the spleens of the control fish, while they were detected sporadically and disappeared from the phage-treated fish 48 h later. On the other hand, orally administered phage was detected at high plaque-forming units from the intestines and spleens of the phage-treated fish until 48 h later. These results indicate that intraperitoneally or orally administered anti-L. garvieae phage prevented fish from experimental L. garvieae infection, suggesting potential use of the phage for controlling the disease.

Administration, Oral↗

PubMed1999

Isolation and characterization of CA XIV, a novel membrane-bound carbonic anhydrase from mouse kidney.

Carbonic anhydrase (CA) is involved in various physiological processes such as acid-base balance and transport of carbon dioxide and ions. In this study, we have succeeded in the isolation of a novel CA from the mouse kidney by use of the signal sequence trap method. It is a 337-amino acid polypeptide with a calculated molecular mass of 37.5 kDa, consisting of a putative amino-terminal signal sequence, a CA domain, a transmembrane domain, and a short hydrophilic carboxyl terminus, which we designated CA XIV. The CA domain of CA XIV is highly homologous with those of known CAs, especially extracellular CAs including CA XII, IX, VI, and IV. The expression study of an epitope-tagged protein has suggested that CA XIV is located on the plasma membrane. When expressed in COS-7 cells, CA XIV exhibits CA activity that is predominantly associated with the membrane fraction. By Northern blot analysis, the gene expression of CA XIV is most abundant in the kidney and heart, followed by the skeletal muscle, brain, lung, and liver. In situ hybridization has revealed that, in the kidney, the gene is expressed intensely in the proximal convoluted tubule, which is the major segment for bicarbonate reabsorption and also in the outer border of the inner stripe of the outer medulla. In conclusion, we have cloned a functional cDNA encoding a novel membrane-bound CA. This study will bring new insights into our understanding of carbon dioxide metabolism and acid-base balance.

Amino Acid Sequence↗

PubMed1999

Effects of an interleukin-1beta analogue [Lys-D-Pro-Thr], on incomplete cerebral ischemia-induced inhibition of long-term potentiation in rat hippocampal neurons in vivo.

Although interleukin-1beta (IL-1beta) has recently been implicated in neuronal cell death in vitro and in vivo after global forebrain ischemia, the role of IL-1beta in the functional injuries, i.e. impairment of synaptic transmission, after cerebral ischemia that does not cause neuronal death in the nervous system remains unknown. To address this question, we investigated the effect of short-term incomplete ischemia without apparent neural death on hippocampal long-term potentiation (LTP) in anesthetized rats, and examined the possible role of IL-1beta as an intermediary in this effect. Short-term incomplete cerebral ischemia (10 min) was induced in halothane-anesthetized rats by bilaterally clamping the common carotid arteries. Four days after ischemia, functional injuries in neuronal transmission in the hippocampal formation were observed without significant changes in pathological studies such as neuronal cell death. The LTP elicited in both Shaffer-CA1 synapses and perforant path-dentate gyrus synapses was significantly inhibited by the short-term incomplete ischemia. This inhibition of LTP was blocked by IL-1beta tripeptide antagonist (Lys-D-Pro-Thr), suggesting that the inhibitory effect of mild ischemia on synaptic potentials and LTP may be mediated by the generation of IL-1beta. These findings have important implications for the role of IL-1beta in not only neuronal cell death but also functional injuries without cell loss, perhaps elicited by transient cerebral ischemia.

Anesthesia↗

PubMed1999

A reactivating factor for coenzyme B12-dependent diol dehydratase.

Adenosylcobalamin-dependent diol dehydratase of Klebsiella oxytoca undergoes suicide inactivation by glycerol, a physiological substrate. The coenzyme is modified through irreversible cleavage of its cobalt-carbon bond, resulting in inactivation of the enzyme by tight binding of the modified coenzyme to the active site. Recombinant DdrA and DdrB proteins of K. oxytoca were co-purified to homogeneity from cell-free extracts of Escherichia coli overexpressing the ddrAB genes. They existed as a tight complex, i.e. a putative reactivating factor, with an apparent molecular weight of 150,000. The factor consists of equimolar amounts of the two subunits with Mr of 64,000 (A) and 14,000 (B), encoded by the ddrA and ddrB genes, respectively. Therefore, its subunit structure is most likely A2B2. The factor not only reactivated glycerol-inactivated and O2-inactivated holoenzymes but also activated enzyme-cyanocobalamin complex in the presence of free adenosylcobalamin, ATP, and Mg2+. The reactivating factor mediated ATP-dependent exchange of the enzyme-bound cyanocobalamin for free 5-adeninylpentylcobalamin in the presence of ATP and Mg2+, but the reverse was not the case. Thus, it can be concluded that the inactivated holoenzyme becomes reactivated by exchange of the enzyme-bound, adenine-lacking cobalamins for free adenosylcobalamin, an adenine-containing cobalamin.

Bacterial Proteins↗

PubMed1999

Isolation and expression analysis of a novel human homologue of the Drosophila glial cells missing (gcm) gene.

A novel human homologue (GCMB) of the Drosophila glial cells missing gene (dGCM) was isolated using RACE. GCMB contained a gcm motif sequence and a nuclear targeting sequence similar to that of dGCM and mouse GCMb. Homology searches indicated that GCMB was located within chromosome 6p24.2. Transcripts of GCMB were detected by means of RT-PCR in fetal brain, normal adult kidney, 3/3 medulloblastomas, 1/3 gliomas and 4/8 non-neuroepithelial tumor cell lines. Our data suggest that humans have two homologues of gcm like mice and that human gcm genes form a novel family which may function not only during fetal development but also in the postnatal or pathological stage.

Amino Acid Sequence↗

PubMed1999

Enhanced hepatocyte growth factor expression associated with prolonged rat hepatic allograft survival in recipients pretreated with donor-specific blood.

BACKGROUND: Pretransplantation injection of freshly heparinized donor blood (donor-specific blood transfusion, or DST) significantly prolongs the survival of hepatic allografts from ACI(RT1a) to LEW(RT1l) rats. We investigated hepatocyte growth factor (HGF) expression in rat hepatic allografts of recipients pretreated with or without DST. METHODS: The levels of HGF mRNA and protein in hepatic allografts were determined after transplantation. The localization of HGF+ cells was identified with a rat anti-HGF monoclonal antibody. RESULTS: Plasma HGF concentrations in transplanted rats treated with DST were significantly and persistently increased compared to untreated rats with hepatic allografts. The number of HGF+ cells in hepatic allografts of recipients pretreated with DST on day 14 was significantly greater than that in allografts of untreated recipients on day 7. HGF+ cells were also found in the marginal zone and red pulp of recipient spleens. Northern blot analysis revealed the presence of three HGF+ cell phenotypes: HGF+ED1+, HGF+ED2+, and HGF+ED1-ED2-. Most HGF+ cells were ED1-ED2-. In situ hybridization demonstrated HGF mRNA in the mononuclear cells in the portal and sinusoidal areas as well as the marginal zone and red pulp in both DST-treated and untreated recipient spleens. CONCLUSIONS: Enhanced HGF expression in rat hepatic allografts is associated with immunologic unresponsiveness induced by DST.

Animals↗

PubMed1999

Anatomical and neurochemical peculiarities of the pika retina: basis for lack of circadian rhythm of core temperature.

We have previously reported a complete lack of circadian rhythm in the body temperature of pikas in contrast to other lagomorphs. In this present study, the anatomical and neurochemical findings by immunohistochemical, photo and electron microscopic methods reveal that the photoreceptor system of this animal is poorly developed. This probably explains their stable core body temperature which help them survive in cold temperatures.

Animals↗

PubMed1999

Anti-alpha-fodrin antibodies in Sjögren syndrome and lupus erythematosus.

OBJECTIVES: To investigate the prevalence of anti-alphafodrin antibody in patients with Sjogren syndrome (SS), lupus erythematosus (LE), or both and the association of this antibody with other clinical manifestations. DESIGN: A study of screening and diagnostic tests. Mean follow-up was 152 months (range, 4-572 months). SETTING: A university hospital associated with a research laboratory in Tokyo, Japan. PATIENTS: Nine patients with primary SS, 15 patients with SS secondary to LE, and 44 patients with LE alone. MAIN OUTCOME MEASURES: Frequencies of clinical and laboratory findings, including anti-alpha-fodrin antibody. RESULTS: Anti-alpha-fodrin antibody was more commonly detected in patients with primary (7/9; P<.001) and secondary (9/15; P<.001) SS than in those with LE alone (3/44). When patients with primary and secondary SS were combined and compared with those with LE alone, the sensitivity of anti-alpha-fodrin antibody was 67%, specificity was 93%, and both positive and negative predictive values were 84%. The presence of anti-alpha-fodrin antibody was associated with pernio, hyperglobulinemia, rheumatoid factor positivity, and the presence of anti-SS-B (La) antibody (P<.01) but not with annular erythema, photosensitivity, vasculitis, or renal disorder. CONCLUSIONS: Although anti-alpha-fodrin antibody was detected in patients with SS and in those with LE, it seemed to be more valuable for the diagnosis of SS than was anti-SS-A (Ro) because anti-alpha-fodrin was much less prevalent in patients with LE alone. It may be possible to consider this novel autoantibody as pathophysiologically associated with some extraglandular manifestations characteristically seen in patients with SS.

Adolescent↗

PubMed1999

Expression of the c-kit proto-oncogene in rat hepatic allografts during acute rejection.

The role of the c-kit proto-oncogene in organ allograft rejection is not known. We investigated the level of c-kit expression following allogeneic transplantation of ACI rat liver grafts into LEW recipients. We studied c-kit mRNA and protein expression in groups of transplant recipients receiving hepatic isografts, hepatic allografts, or hepatic allografts after donor-specific blood transfusion (DST). Pretransplantation DST significantly prolonged survival of hepatic allografts. Infiltrates expressing c-kit were observed in allografts to untreated rats but not in groups receiving isografts or allografts following DST. Northern analysis also demonstrated abundant c-kit mRNA transcripts in the untreated allograft group in contrast to the isograft and the DST-treated groups. In addition, significantly more transcripts for interleukin-12 (IL-12), which is synergistic with c-kit, were present in untreated than in DST-treated allograft groups. In contrast, transforming growth factor beta (TGF-beta), which inhibits c-kit synthesis, was expressed abundantly in hepatic allografts to DST-treated rats but not in allografts to untreated animals. Transcripts for IL-10, which inhibits IL-12 production, were significantly more plentiful in hepatic allografts following DST than in those without DST. The results suggest that c-kit proto-oncogene expression in infiltrating cells is associated with rat hepatic allograft rejection.

Animals↗

PubMed1999

Peroxynitrite formation during rat hepatic allograft rejection.

The role of nitric oxide (NO) on tissue injury of hepatic allografts during rejection remains controversial. We investigated inducible nitric oxide synthase (iNOS) expression and formation of peroxynitrite in ACI rat liver grafts implanted in recipients. Animals were divided into four experimental groups: group I, isografts; group II, untreated hepatic allografts; group III, allografts treated with FK506; and group IV, allografts pretreated with donor-specific blood transfusion (DST). Serum nitrite/nitrate, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) concentrations increased significantly in group II rats after transplantation but were significantly lower in groups I, III, and IV. The numbers of macrophages that reacted with an antimacrophage iNOS monoclonal antibody as well as iNOS messenger RNA (mRNA) levels in liver specimens were also much lower in groups I, III, and IV as compared with group II. Immunostaining and Western blot analysis showed prominent tissue nitrotyrosine expression in untreated hepatic allografts, but not in allografts treated with FK506 or donor-specific blood. These results suggest that one of the mechanisms by which production of NO results in injury in rat hepatic allografts may be because of its reaction with superoxide to form peroxynitrite.

Animals↗

PubMed1999

Effects of SIVmac infection on peripheral blood CD4+CD8+ T lymphocytes in cynomolgus macaques.

We have previously reported that CD4+CD8+ double-positive (DP) T cells with a resting memory phenotype exist in a substantial proportion of peripheral blood lymphocytes of adult cynomolgus macaques. In this study, we examined the effects of simian immunodeficiency virus of macaque (SIVmac) infection on DP T cells. In vitro, SIVmac239 nef-open (239) and its nef-deletion mutant replicated well in both CD4+CD8- and DP T cells. However, when the macaques were infected with 239, DP, but not CD4+CD8-, T cells were transiently increased in parallel with cell activation and viral replication, followed by depletion within 1 month postinfection. Interestingly, the nef gene was required for depletion but not for the increase and activation of DP T cells. These data suggest that the pathogenic SIV infection may downmodulate production and/or blood circulation of DP T cells by a Nef function-related mechanism(s) different from that for the depletion of CD4+CD8- T cells.

Animals↗

PubMed1999

Selective visual and auditory attention toward utterances-a PET study.

The purpose of this study was to reveal functional areas of the brain modulating processing of selective auditory or visual attention toward utterances. Regional cerebral blood flow was measured in six normal volunteers using positron emission tomography during two selective attention tasks and a control condition. The auditory task activated the auditory, inferior parietal, prefrontal, and anterior cingulate cortices. The visual task activated the visual association, inferior parietal, and prefrontal cortices. Both conditions activated the same area in the superior temporal sulcus. During the visual task, deactivation was observed in the auditory cortex. These results indicate that there exists a modality-dependent selective attention mechanism which activates or deactivates cortical areas in different ways.

Adolescent↗

PubMed1999

Halothane decreases calcium sensitivity of rat aortic smooth muscle.

PURPOSE: To examine the effect of halothane on the cytosolic Ca2+ concentration ([Ca2+]i)-tension relationship of rat aortic smooth muscle. METHODS: Rat aortic rings without endothelia were loaded with the fluorescent Ca2+ indicator, Fura PE3-AM, and then mounted in organ baths. The changes in isometric tension and [Ca2+]i were measured simultaneously. In one series ionomycin (10 nM-3 microM) was added to normal Krebs' solution cumulatively in the absence and presence of halothane (1.5%, 3%). In the other series, CaCl2 (0.3-3 mM) was added to Ca2+-free Krebs' solution including high KCl (50 mM), phenylephrine (100 nM) or prostaglandin F2alpha (PGF2alpha, 1-3 microM) in the absence and presence of halothane (1.5%, 3%). The linear part of [Ca2+]i-tension relationship was analyzed by a linear regression. RESULTS: Halothane, 1.5%, had no effect on the normal [Ca2+]i-tension relationship obtained with the calcium ionophore, ionomycin (10 nM-3 microM), but halothane 3% decreased the slope of the relationship (0.239 +/- 0.037 for control and 0.110 +/- 0.010 for halothane 3%, P < 0.05). Halothane, 1.5% and 3%, did not change the [Ca2+]i-tension relationship obtained with CaCl2 (0.3-3 mM) in the presence of high KCl (50 mM) or phenylephrine (100 nM). In contrast, halothane, 3%, inhibited the intercept of [Ca2+]i-tension relationship obtained with CaCl2 (0.3-3 mM) in the presence of prostaglandin F2alpha (PGF2alpha, 1-3 microM) (45.708 +/- 4.233 for control and 26.997 +/- 2.522 for halothane 3%, P < 0.01). CONCLUSION: Halothane decreases the Ca2+ sensitivity and that in the presence of PGF2.

Anesthetics, Inhalation↗

PubMed1999

Total esophagectomy versus proximal esophagectomy for esophageal cancer at the cervicothoracic junction.

To investigate the adequate extent of esophagectomy and lymphadenectomy for an esophageal cancer localized at the cervicothoracic junction, the mortality and morbidity rates, survival rates, and patterns of recurrence were retrospectively analyzed in two groups-14 patients who underwent total esophagectomy with or without laryngectomy and 15 patients who underwent proximal esophagectomy with or without laryngectomy-at Kurume University Hospital from 1981 to 1996. Proximal esophagectomy with or without laryngectomy resulted in a lower hospital mortality rate and better overall survival for patients who underwent curative esophagectomy compared with total esophagectomy with or without laryngectomy. Multivariate analysis indicated that the extent of esophagectomy (total esophagectomy versus proximal esophagectomy) was not a prognostic factor. The incidence of recurrence was not different between the two groups. Lymph node metastasis or recurrence from such esophageal cancers was localized to the neck and upper mediastinum. For an esophageal cancer localized at the cervicothoracic junction, therefore, proximal esophagectomy with or without laryngectomy and with cervical and upper mediastinal lymphadenectomy could be better indicated for preselected patients.

Aged↗

PubMed1999

Brain metabolites in the hippocampus-amygdala region and cerebellum in autism: an 1H-MR spectroscopy study.

Histological abnormalities of the brain in autism have been investigated extensively. We studied metabolites in the hippocampus-amygdala (HA) region and cerebellum. We examined the right HA region and left cerebellar hemisphere of 27 autistic patients 2-18 years old, 21 boys and 6 girls and 10 normal children 6-14 years old, 4 boys and 6 girls, using the STEAM sequence. This sequence was used to minimise the influence of relaxation times. The N-acetyl aspartate (NAA) concentration was significantly lower (P = 0.042) in autistic patients than in normal children (9.37 and 10.95 mM, respectively). There was no significant difference in other metabolites. The correlation coefficient (r value) of NAA between the HA region and cerebellum was 0.616. The decreased NAA concentration may be due to neuronal hypofunction or immature neurons. The NAA concentration in the HA region and cerebellum may be related, because of neuronal circuits or networks.

Adolescent↗

PubMed1999

A phase II study of irinotecan and infusional cisplatin with recombinant human granulocyte colony-stimulating factor support for advanced non-small-cell lung cancer.

PURPOSE: We administered chemotherapy consisting of a combination of 5-day continuous infusion of cisplatin (20 mg/m2 per day) plus irinotecan (160 mg/m2 per day, as a bolus, on day 1) with recombinant human granulocyte colony-stimulating factor (rG-CSF) support to previously untreated advanced non-small-cell lung cancer (NSCLC) patients, and evaluated the effectiveness and safety of this therapy. PATIENTS: Enrolled in the study were 41 NSCLC patients. RESULTS: Of the 41 patients, 24 achieved a partial response. The response rate was 58.5% (95% confidence interval, 42.2% to 74.8%), with a median response duration of 32.1 weeks. The median survival time was 44.8 weeks and the 1-year survival rate was 44%. A total of 100 courses of therapy were given. The major toxic effects were grade 3 or 4 diarrhea (23%), granulocytopenia (20%), thrombocytopenia (15%) and anemia (15%). There were no treatment-related deaths. CONCLUSIONS: Combination chemotherapy with irinotecan plus infusional cisplatin with rG-CSF support was well tolerated and effective in patients with advanced NSCLC.

Adult↗