Search PubMed⌕ Search

Biomedical subjects

M Koike

Publications and source records attributed to M Koike.

At least 253 records · Page 14Linked to original sources

Common target for 12-O-tetradecanoylphorbol-13-acetate and ras in the transcriptional enhancer of the growth factor-inducible JE gene.

JE gene expression in the mouse osteoblast cell line MC3T3-E1 is activated transiently by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). In ras-transformed MC3T3-E1 cells the JE gene is constitutively expressed at a high level, whereas in their raf-transformed counterparts it is not constitutively expressed or inducible by TPA. Using these cells, we investigated a specific sequence recognized by nuclear factors in the 5'-upstream region of the rat JE gene. By gel-mobility shift assays, we determined that the amount of nuclear factors that bind to the region -130 to -96 bp upstream from the cap site of the rat JE gene (JE-1 probe) increased after TPA treatment of MC3T3-E1 cells. However, in the ras transformants it was elevated constitutively, and in the raf transformants it was not detectable. Both unlabeled JE-1 probe and a probe containing a TPA-responsive element (TGACTCA) competed with the binding of these nuclear factors. Preincubation of the nuclear extracts with fos- or jun-specific antibodies interfered with the binding of the factors to the JE-1 probe. The essential sequence in the JE-1 element for the binding of nuclear factors was found to be TTACTCA. c-fos and c-jun proteins synthesized in vitro could bind to the DNA fragment containing this sequence, but the binding was weaker than to the TPA-responsive element (TGACTCA). These results suggest that the sequence TTACTCA in the JE-1 element is a common target of TPA and ras and that protein complexes containing fos- and jun-related proteins recognize the sequence.

Animals↗

Determination of polycyclic aromatic hydrocarbons in the lung.

Polycyclic aromatic hydrocarbons (PAHs) accumulated in human lung samples from men (n = 236) and women (n = 128) were determined by high-performance liquid chromatography (HPLC) to examine their association with lung cancer. The mean values for benzo[a]pyrene (BaP), benzo[k]fluoranthene (BkF), and benzo[g,h,i]perylene (BghiP) in lungs (ng/g dry lung) of Japanese autopsied patients were 0.54, 0.44, and 0.87, respectively. The modal values were 0.3, 0.3 and 0.5, respectively. Each of the PAH concentrations was highly correlated with the others (r > 0.83). PAH concentrations in the lungs showed age-related increases with low correlation-coefficient values. BaP, BkF and BghiP concentrations in lungs of various subgroups were in the following order: male > female; and lung cancer > all cancers > non-cancer among male not female group. Only BghiP concentration in the lungs of the male smoker group is significantly higher (P < 0.10) than that of the male non-smoker group. Even among non-smoker groups, PAH concentrations in the lungs of male group were significantly higher than those of female group. In the male population, excess exposure to PAHs together with fine carbon particles, such as tobacco smoke or diesel exhaust, correlated with increased prevalence of lung cancer.

Adult↗

Pearson's marrow/pancreas syndrome: a histological and genetic study.

A patient with features of Pearson's syndrome who presented with transfusion-dependent severe macrocytic anaemia, neutropenia, thrombocytopenia, and insulin-dependent diabetes mellitus in the neonatal period is described. His bone marrow was characterized by marked vacuolization of myeloid precursors and ringed sideroblasts. Autopsy examination revealed fibrosis and steatosis of the liver, reduction in the size and number of the islets, fibrosis and acinar atrophy of the pancreas, vacuolation of renal tubules, glomerulosclerosis, and "ragged red" fibres of skeletal muscles. Analysis of mitochondrial DNA (mtDNA) from the autopsied liver and skeletal muscle showed mtDNA heteroplasmy in both tissues, with one population of mtDNA deleted by 7374 bp. The deleted region was bridged by a single nucleotide, C, in normal mtDNA.

Anemia, Sideroblastic↗

Spontaneous IL-2 production in vitro in two patients with pure red cell aplasia.

We investigated spontaneous cytokine production in two patients with pure red cell aplasia (PRCA). The peripheral blood mononuclear cells (PBMNC) from two patients produced IL-2. Cyclosporin A (CyA) suppressed in vitro IL-2 production in one patient, but not in the other. Spontaneous IL-2 production disappeared in one patient 10 months after the start of CyA therapy. The patient for whom CyA therapy was stopped after the disappearance of spontaneous IL-2 production has remained in continuous remission for 1 year. The present case suggests that spontaneous IL-2 production in PBMNC might be an indicator of disease activity.

Cyclosporine↗

The presence of CD5LOW+NK cells in normal controls and patients with pulmonary tuberculosis.

CD5 antigen is present on all normal alpha beta T cells and some B cells. Human NK cells do not usually express CD5 antigen, but we found a subset of CD5LOW+ (low density of CD5) NK cells in some patients with pulmonary tuberculosis. Unlike CD5-NK cells, most CD5LOW+NK cells had HLA-DR. We observed few CD5LOW+NK cells in the normal controls and some in the large granular lymphocyte (LGL) population purified by Percoll density centrifugation. Sorted CD5LOW+NK populations were LGL. The CD5LOW+NK cells had high lytic activity on K562 cells in a 4-h 51chromium release assay. Our results indicate that there is a previously unidentified subset of NK cells.

Adult↗

Inhibition of the multidrug efflux pump in isolated hepatocyte couplets by immunosuppressants FK506 and cyclosporine.

Fluorescence image analysis of isolated rat hepatocyte couplets, which retain a bile canaliculus between them, has shown the presence of transport systems for the bile acid and non-bile acid organic anion in the canalicular membrane. The cells also transported Fura-2 and BCECF, which are fluorescent indicators of intracellular Ca2+ and H+ concentrations, respectively, into the canaliculus. Both Fura-2 and BCECF transports were inhibited by progesterone, verapamil, vinblastine, and daunomycin, indicating that the transports are due to a multidrug efflux pump (P-glycoprotein) in the canalicular membrane. Interestingly, the transport by the multidrug efflux pump was inhibited by immunosuppressants FK506 (tacrolimus) and cyclosporine, their half-maximal inhibitory concentrations in the cell suspension being 10 microM and 0.6 microM, respectively. In contrast, the reported immunosuppressive potency of FK506 is 10- to 100-fold that of cyclosporine. Inhibition by immunosuppressants of the multidrug efflux pump, which is a transporter of cytotoxic and other drugs and present in normal human tissues--such as kidney, liver, the blood-brain barrier, and colon--may, at least partly, explain side effects caused by cyclosporine in these tissues of transplant recipients. FK506 at its clinical concentrations may not inhibit the multidrug efflux pump.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Genetic changes and histopathological grades in human hepatocellular carcinomas.

Loss of heterozygosity (LOH) on chromosomes 1p, 4q, 5q, 8p, 13q, 16q, 17p, and 22q, and mutation of the p53 gene were simultaneously analyzed in 63 hepatocellular carcinomas (HCCs) with distinct histopathological grades, 80% of the tumors being from patients who had been exposed to hepatitis B virus (HBV) or hepatitis C virus (HCV). The frequencies of LOH on 8 chromosomes were 0-25% in 10 well differentiated HCCs, LOH being observed on 4q, 5q and 17p, 21-53% in 26 moderately differentiated HCCs, LOH on 8p and 17p being high, and 29-75% in 27 poorly differentiated HCCs, LOH on 17p, 4q and 8p being the most frequent. p53 gene mutation was detected in moderately and poorly differentiated HCCs at 15% and 52%, respectively, but not at all in well differentiated HCCs. Of the mutations detected, 42% were transition mutation and only 5% were CpG transition, in contrast to the high frequencies of these types of mutations in colon tumors (78% and 54%, respectively). LOH on every chromosome and p53 mutation were more frequent in more advanced tumors, and accumulation of genetic changes increased with increase of the histopathological grade. Frequency of genetic changes in HCCs from HBV-positive patients was comparable to that from HCV-positive patients. The present results suggest that accumulation of genetic changes in multiple tumor suppressor genes, especially LOH on 17p, 4q and 8p, and mutation in p53 gene, are involved in the progression of liver cancer, and LOH on 17p and 4q precedes other genetic changes. Differences in the direction of p53 mutation between HCC and colon carcinoma suggest that liver carcinogens are distinct from colon carcinogens. Furthermore, mechanisms affecting the frequency of LOH in HCCs in HBV-infected patients may be similar to those in HCV-infected patients.

Base Sequence↗

Cell-cycle analysis detecting endogenous nuclear antigens: comparison with BrdU-in vivo labeling and an application to lung tumors.

The versatility of non-radioactive cell-cycle analysis in detecting endogenous nuclear antigens of the proliferating cells was evaluated. Optimal conditions for immunostaining varied in fixation and pretreatment procedures among antigens, bromodeoxyuridine (BrdU), Ki-67 epitope, DNA polymerase alpha and PCNA. A significant correlation between BrdU labeling index (LI) was observed in each positive ratio (PR, positive/total neoplastic cells) for nuclear antigens in tumor-sections which had been labeled in vivo with BrdU. The best correlation was observed in Ki-67 PR (y = 1.26x + 2.5; y = Ki-67 PR; x = BrdU LI; r = 0.97). To determine its prognostic value, Ki-67 analysis was applied to the surgically resected lung tumors. Ki-67 PR were different according to the histologic types of the tumors: 47.8 +/- 3.4% in small cell carcinoma; 29.5 +/- 3.5% in squamous cell carcinoma; 28.3 +/- 4.7% in large cell carcinoma; 15.2 +/- 1.8% in adenocarcinoma and 0.1 +/- 0.1% in mature carcinoid tumor. When the mean value was used to divide each type to a higher or lower proliferative activity (15% Ki-67 PR for adenocarcinoma and 30% for squamous cell carcinoma), the group with the lower Ki-67 PR showed a significantly more favorable prognosis than that of a higher ratio. Ki-67 PR was not correlated with other pathologic factors such as size, lymph node metastasis or pleural involvement. Non-radioactive cell-cycle analysis was feasible and useful for detecting endogenous nuclear antigens even in the lung tumors, particularly when the analysis was coupled with histologic typing.

Antibodies, Monoclonal↗

Increased level/dose ratio of amphotericin-B in premature infants with renal failure.

We introduced continuous intravenous infusion of amphotericin-B (AMPH-B) to extremely low birthweight (ELBW) infants (< 1000 g) with or without renal failure as a single agent for treating definite or probable systemic candidiasis. The species of Candida isolated from blood or tracheal aspirate or urine were C. albicans in seven infants, C glabrata in two, C. tropicalis in one and C. parapsilosis in one. The minimal inhibitory concentrations (MIC) of AMPH-B required against these isolates were less than 0.2 micrograms/mL except for that against one strain of C. albicans (0.78 microgram/mL). Serum AMPH-B levels were 0.31-0.78 (0.51 +/- 0.14) micrograms/mL when doses of 0.2-0.55 (0.32 +/- 0.11) mg/kg per day were being administered. The serum level was higher than the MIC of each isolate in all but one infant who died of disseminated intravascular coagulation and Candida pneumonia. Another infant died of congenital heart disease. The other nine infants survived. The serum level showed no correlation with the daily dose. The ratio of the serum level to the daily dose (L/D ratio) showed a significant correlation to serum creatinine (r = 0.787) and the linear regression curve followed the equation: L/D ratio = 0.223 x serum creatinine + 1.11 (P < 0.01). Few adverse effects due to AMPH-B were noted. Our data may give a simple reference to serum AMPH-B levels during continuous intravenous infusion from the dose and the serum creatinine level.

Acute Kidney Injury↗

Electrochemical prevention of marine biofouling with a carbon-chloroprene sheet.

A carbon-chloroprene sheet (CCS) electrode was used for the electrochemical disinfection of the marine gram-negative bacterium Vibrio alginolyticus. When the electrode was incubated in seawater containing 10 cells per ml for 90 min, the amount of adsorbed cells was 4.5 x 10 cells per cm. When a potential of 1.2 V versus a saturated calomel electrode was applied to the CCS for 20 min, 67% of adsorbed cells were killed. This disinfection was due to the direct electrochemical oxidation of cells and not to a change in pH or to the generation of toxic substances, such as chlorine. In a 1-year field experiment, marine biofouling of a CCS-coated cooling pipe caused by attachment of bacteria and invertebrates was considerably reduced by application of a potential of 1.2 V versus a saturated calomel electrode. Since this method requires low potential electrical energy, use of a CCS coating appears to be a suitable method for the clean prevention of marine biofouling.

Journal Article↗

A Ki-1-positive cell line expressing Epstein-Barr virus antigens, established from a child with Ki-1-positive lymphoma.

We report here the establishment of a CD30 (Ki-1) antigen-positive cell line 'Ki-JK' from a child with anaplastic large cell lymphoma. We characterized this cell line and show that: (i) Ki-JK cells do not grow in soft agar but infrequently produce a tumor or suppressed growth when injected into nude mice; (ii) Ki-JK cells expressed Epstein-Barr virus (EBV) antigens, EBV-associated nuclear antigen-2 and latent membrane protein; (iii) Ki-JK cells are labelled by in situ hybridization using an RNA probe derived from the BamHI W fragment of EBV, and (iv) polymerase chain reaction demonstrates the presence of an EBV BamHI W sequence in DNA of lymphoma and Ki-JK cells. These results suggest an etiological role for EBV in the development of some cases of Ki-1-positive lymphomas.

Adolescent↗

Circulating abnormal cells detected in a patient with immunoblastic lymphadenopathy.

An unusual case of immunoblastic lymphadenopathy (IBL) with circulating CD3-CD4+ cells is reported. A lymph node biopsy specimen showed the characteristic features of IBL. Two-color analyses demonstrated that the circulating abnormal cells were CD3-, CD4+, HLA-DR+, and CD25-. Chromosomal analysis revealed unrelated clones in the lymph node. Though 48% of the peripheral blood lymphocytes were abnormal, no clonal rearrangement of the TcR beta chain gene was detected in the peripheral blood. This case might point out the possibility that some cases of IBL truly had no TcR gene rearrangement and were dysplasias.

CD3 Complex↗

Beta 0-thalassemia trait (IVS-I-1 G-->T) in a Japanese family.

Three subjects in a family with microcytic and hypochromic anemia were studied; red blood cell morphology indicated aniso-poikilocytosis and hypochromasia. Target and tear-drop cells were also noted. In all three cases evaluated, there was an increase in HbA2 levels and a decline in the beta/alpha synthesis ratio. Direct cloning and DNA sequencing identified a point mutation (G-->T) at position 1 of intervening sequence I. The resulting reduction of beta-globin chain synthesis is considered to give rise to beta 0-thalassemia phenotype. This point mutation is to our knowledge, the first case in Japan.

Base Sequence↗

Epstein-Barr virus in pyothorax-associated pleural lymphoma.

Pleural B-cell lymphoma was found in five patients with a history of pyothorax that was the sequelae of tuberculosis 35 to 47 years previously. Epstein-Barr virus (EBV) DNA was detected in all five pleural tumors by polymerase chain reaction and Southern blot hybridization. The lymphoma cells were shown to express the latent membrane protein-1 and the EBV-encoded nuclear antigen-2 by immunocytochemistry and EBV-encoded small RNA by in situ hybridization. Three cases were shown to be EBV subtype A, whereas the remaining two were subtype B, as determined by differences in the EBV-encoded nuclear antigen-2 nucleotide sequence. The patients also had high titers of antibodies against EBV. These findings suggest that EBV is causally associated with the pleural lymphomas that originate at the site of chronic inflammation and fibrosis with a latent period of more than 40 years.

Adult↗

[Parapsoriasis en plaque suspected of progression to mycosis fungoides associated with extranodal malignant B cell lymphoma of the cheek].

A 59-year-old female, clinically diagnosed as having parapsoriasis en plaque for ten years, was referred on June 1991 to the Department of Oral Surgery in the Dental School of showa University with a complaint of painless swelling of the left malar area. The swelling was found to have been caused by a tumor. Since the excised tumor was suspected to be a malignant lymphoma, she was admitted to our hospital. The specimen was subsequently confirmed to be a malignant lymphoma of the diffuse large cell type according to the LSG classification, and was immunologically confirmed to be a B cell lymphoma. In addition, the excised skin was suspected of incipient mycosis fungoides. She was classified as having stage IE disease according to her bone marrow biopsy and other examinations. she was treated with combination of chemotherapy (CHOP) and radiation therapy. This subject was interesting because her tumor probably resulted from a parapsoriasis en plaque skin lesion.

Antineoplastic Combined Chemotherapy Protocols↗

[Testicular relapse, with Ph-positive chromosome after bone marrow transplantation for acute lymphocytic leukemia].

A 25-year-old man with acute lymphocytic leukemia (ALL) had received bone marrow transplantation (BMT). Testicular relapse occurred 6 months after BMT as the first relapse, and couple of weeks later, bone marrow relapse developed. At that time, karyotypic analysis showed Ph-chromosome which was not observed before the first remission and DNA analysis revealed rearrangements of minor BCR, IgL, IgH, TCR and TCR genes. Testicular relapse often develops in ALL of children after BMT. However, some reports, including this report, indicate that testicular relapse following BMT can also occur in adults, so that the incidence of testicular relapse could be reduced either by total body irradiation (TBI) or testicular irradiation before transplantation. Incidence of Ph-positive chromosome following BMT is a key to illuminate the mechanism of the Philadelphia chromosome. Rearrangements of Ig and TCR gene can be considered as an abnormal gene rearrangement occurring at an early stage of B cell proliferation.

Adult↗

Urinary neopterin as a predictive marker of coronary artery abnormalities in Kawasaki syndrome.

We investigated whether urinary neopterin concentrations respond to the pathological conditions (especially coronary artery dilatation) of Kawasaki syndrome. All of 29 children with Kawasaki syndrome had very high urinary neopterin concentrations. Increased urinary neopterin concentrations coincided with fever and with monocytosis in peripheral blood. The urinary neopterin excretion peaking within the first 8 days after onset correlated with the development of coronary artery dilatation. Increased urinary neopterin concentrations indicate that cell-mediated immunity is activated in patients with Kawasaki syndrome. Endogenous interferon-gamma and activation of monocytes/macrophages may play a role in the pathogenesis of Kawasaki syndrome. Not only do neopterin concentrations correlate with symptoms in the acute phase of Kawasaki syndrome, they also act as a predictive marker of coronary artery abnormalities in affected patients.

Biomarkers↗