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Biomedical subjects

K Nishikawa

Publications and source records attributed to K Nishikawa.

At least 145 records · Page 8Linked to original sources
PubMed1999

A clinicopathological study of lung cancer patients with occupational exposure to chrysotile asbestos fibers.

OBJECTIVE: To summarize the features of asbestos-related lung cancer. PATIENTS: Thirty-one lung cancer patients with occupational exposure to chrysotile asbestos fibers. They worked or had worked in one asbestos factory or its subcontracters. RESULT: All patients were male with mean age of 60.6 when diagnosed, and all except one were current or ex-'heavy' smokers. Histological types were fairly evenly divided into adeno-, squamous and small cell carcinoma and 24 (78%) of patients showed 'peripheral type' lung cancers. Regarding clinical stages, 20 patients (65%) were classified as III or IV (advanced stage). Tumor shadow(s) was detected on chest X-ray in 22 patients (71%), and in 5 patients with 'negative' chest X-ray, chest CT was necessary to recognize a primary tumor. Seventeen patients (55%) did not undergo periodical check-ups. CONCLUSION: Occupational asbestos exposure is interpreted as one of the important risks for lung cancer and frequent and accurate observation is necessary.

Adult↗
PubMed1999

[Successful lithium carbonate therapy for a patient with intractable and severe aplastic anemia].

A 16-year-old female patient who had been given a diagnosis of severe aplastic anemia underwent 2 courses of a combined regimen of corticosteroid pulse therapy and androgen therapy. This proved ineffective. Antilymphocyte globulin therapy was also ineffective. The patient was then given lithium carbonate at a dose of 600 mg/day in combination with an androgen derivative. This had a dramatic effect on her peripheral blood smear. Within 3 weeks after the first course of this treatment, she no longer required red blood cell transfusions. Also, once the lithium carbonate dose was increased to 1,200 mg/day, the patient no longer needed exogenous platelet transfusions. Approximately 6 months after the start of combination therapy, a peripheral blood smear showed entirely normal results. However, 2 months after lithium carbonate was discontinued probably as a result of drug-induced liver dysfunction, both leukocytopenia and thrombocytopenia reappeared. Therefore, lithium carbonate was readministered at a dose of 400 mg/day, and later at a dose of 800 mg/day. Again, the patient showed improvements in 3 blood components without any adverse effects. We concluded that lithium therapy was remarkably useful for this patient with intractable and severe aplastic anemia.

Adolescent↗
PubMed1999

[A case of leukemic lymphoma complicated by M-proteinemia: effectiveness of long-term daily administration of oral low-dose etoposide in continuing remission].

A 51-year-old man was admitted with systemic lymph node adenopathy. Hematological examination on admission revealed leukocytosis, and 35% of leukocytes were classified as pathologically abnormal. Moreover, increases in serum IgM (kappa type) and plasma viscosity were recognized. Following biopsy of the lymph node, a diagnosis of non-Hodgkin's lymphoma (diffuse, mixed type) was made. After the implementation of combination chemotherapy, the results of hematological and physical examinations improved. As the nadir receded, serum IgM increased once more, and nine courses of chemotherapy were necessary. In order to promote steady progress toward discharge, etoposide therapy was instituted. Subsequent low-dose etoposide therapy at 50 mg/day rarely resulted in an increase in serum IgM, subjective or objective adverse effects, except for mild lekopenia. After discharge the patient was placed on intermittent etoposide therapy and remained in a state of remission for approximately 11 months. Fortunately, his rehabilitation was successful, and he returned temporarily to his former position. The 2nd remission has continued for approximately seven months. Consequently, long-term low-dose etoposide therapy is speculated to be a significantly useful therapeutic technique for intractable malignant lymphoma.

Administration, Oral↗
PubMed1999

[The effect of propofol as an anticonvulsant].

We observed that propofol was very effective for the refractory general convulsion after surgical operation of cerebral aneurysmal clipping in two patients. The first patient had suffered from asthma. Standard regimens except for thiopental were ineffective for the refractory general convulsion after the operation. So, we administered propofol to the patient, at the dosage of 1 mg.kg-1 intravenously and then, 1 mg.kg-1.hr-1 continuously i.v. Propofol suppressed the general convulsions completely. On the EEG, there were no convulsive spikes. Furthermore, patient's consciousness became clearer during the administration of propofol. The convulsion in the second patient not suffering from asthma, was intractable, too and diazepam, phenytoin, and phenobalbital were not effective. Then, we tried propofol in the same way, and good effect was obtained. Propofol may be an effective medicine for the refractory general convulsion.

Anticonvulsants↗
PubMed1999

A new class of diacidic nonpeptide angiotensin II receptor antagonists: candesartan cilexetil.

Blockade of the action of angiotensin ii (AII) has long been a target for development of novel antihypertensive agents. We recently discovered a novel class of potent non-peptide AII receptor antagonists, benzimidazole-7-carboxylic acids including candesartan. Candesartan is a highly potent and insurmountable antagonist selective in the angiotensin II type-I receptor (AT1). Structure-activity relationship (SAR) studies revealed that the adjacent arrangement of a lipophilic substituent, a tetrazolylbiphenylmethyl moiety and a carboxyl group was the important structural requirement for potent AII antagonistic activity. Especially, the presence of a carboxyl group at the 7-position was found to be essential for insurmountable antagonism. To improve bioavailability of candesartan, chemical modification was examined to yield candesartan cilexetil, a prodrug of candesartan. Candesartan cilexetil is a potent and long-acting blocker that, when given once-daily to patients, provides effective 24 hr blood pressure control.

Angiotensin II↗
PubMed1999

Eradication of Helicobacter pylori using 30 mg or 60 mg lansoprazole combined with amoxicillin and metronidazole: one and two weeks of a new triple therapy.

A new triple therapy using a proton pump inhibitor and two antibiotics shows high efficiency against Helicobacter pylori infection. The aim of this study was to determine the optimal dose and duration of lansoprazole (LA) administration in combination with amoxicillin (AMPC) and metronidazole (MNZ). A total of 91 patients were enrolled in this study. They were divided into four groups: group A, 2 weeks of 30mg LA once daily, 500mg AMPC tid, and 250mg MNZ tid; group B, 2 weeks of 30mg LA bid, 500mg AMPC tid, and 250mg MNZ tid; group C, 1 week of 30mg LA once daily, 500mg AMPC tid, and 250mg MNZ tid; group D, 1 week of 30mg LA bid, 500mg AMPC tid, and 250mg MNZ tid. H. pylori status was determined by the rapid urease test, culture, histology, and 13C-urea breath test before and at least 4 weeks after the end of therapy. The cure rates in a per-protocol analysis and the incidence of adverse events in the evaluated patients were, respectively, 89.5% and 21.1% in group A, 100% and 20.0% in group B, 96.8% and 12.9% in group C, and 92.3% and 26.9% in group D. Most of the adverse events were tolerated. All four regimens in this study showed the same cure rates, and they were effective and well tolerated. One week of triple therapy using once-daily administration of 30mg LA is a good alternative.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1998

Co-expression of yeast amber suppressor tRNATyr and tyrosyl-tRNA synthetase in Escherichia coli: possibility to expand the genetic code.

An efficient system was developed for the co-expression of a yeast tRNATyr/tyrosyl-tRNA synthetase (TyrRS) pair in Escherichia coli. Analysis of suppression patterns using several sets of E. coli and lambda phage mutants indicated that the expressed yeast suppressor tRNATyr was aminoacylated only with tyrosine by its cognate yeast TyrRS and not by E. coli TyrRS or other aminoacyl-tRNA synthetases. This extra tRNA/TyrRS pair is expected to be a key bridgehead for developing an in vivo system for the site-directed incorporation of unnatural amino acids into proteins.

Bacteriophage lambda↗
PubMed1998

Genes from nine genomes are separated into their organisms in the dinucleotide composition space.

A set of 16 kinds of dinucleotide compositions was used to analyze the protein-encoding nucleotide sequences in nine complete genomes: Escherichia coli, Haemophilus influenzae, Helicobacter pylori, Mycoplasma genitalium, Mycoplasma pneumoniae, Synechocystis sp., Methanococcus jannaschii, Archaeoglobus fulgidus, and Saccharomyces cerevisiae. The dinucleotide composition was significantly different between the organisms. The distribution of genes from an organism was clustered around its center in the dinucleotide composition space. The genes from closely related organisms such as Gram-negative bacteria, mycoplasma species and eukaryotes showed some overlap in the space. The genes from nine complete genomes together with those from human were discriminated into respective clusters with 80% accuracy using the dinucleotide composition alone. The composition data estimated from a whole genome was close to that obtained from genes, indicating that the characteristic feature of dinucleotides holds not only for protein coding regions but also noncoding regions. When a dendrogram was constructed from the disposition of the clusters in the dinucleotide space, it resembled the real phylogenetic tree. Thus, the distinct feature observed in the dinucleotide composition may reflect the phylogenetic relationship of organisms.

Amino Acids↗
PubMed1998

Substrate recognition of tRNA (Guanosine-2'-)-methyltransferase from Thermus thermophilus HB27.

Transfer RNA (guanosine-2'-)-methyltransferase (Gm-methylase, EC 2.1. 1.32) from Thermus thermophilus HB27 is one of the tRNA ribose modification enzymes. The broad substrate specificity of Gm-methylase has so far been elucidated using various species of tRNAs from native sources, suggesting that the common structures in tRNAs are recognized by the enzyme. In this study, by using 28 yeast tRNAPhe variants obtained by transcription with T7 RNA polymerase, it was revealed that the nucleotide residues G18 and G19 and the D-stem structure are essentially required for Gm-methylase recognition, and that the key sequence for the substrate is pyrimidine (Py)17G18G19. The other conserved sequences were found not to be essential, but U8, G15, G26, G46, U54, U55, and C56 considerably affected the methylation efficiency. These residues are located within a limited space embedded in the L-shaped three-dimensional structure of tRNA. Therefore, disruption of the three-dimensional structure of the substrate tRNA is necessary for the catalytic center of Gm-methylase to be able to access the target site in the tRNA, suggesting that the interaction of Gm-methylase with tRNA consists of multiple steps. This postulation was confirmed by inhibition experiments using nonsubstrate tRNA variants which functioned as competitive inhibitors against usual substrate tRNAs.

Bacterial Proteins↗
PubMed1998

Association of protein kinase Cmu with type II phosphatidylinositol 4-kinase and type I phosphatidylinositol-4-phosphate 5-kinase.

Protein kinase Cmu (PKCmu), also named protein kinase D, is an unusual member of the PKC family that has a putative transmembrane domain and pleckstrin homology domain. This enzyme has a substrate specificity distinct from other PKC isoforms (Nishikawa, K., Toker, A., Johannes, F. J., Songyang, Z., and Cantley, L. C. (1997) J. Biol. Chem. 272, 952-960), and its mechanism of regulation is not yet clear. Here we show that PKCmu forms a complex in vivo with a phosphatidylinositol 4-kinase and a phosphatidylinositol-4-phosphate 5-kinase. A region of PKCmu between the amino-terminal transmembrane domain and the pleckstrin homology domain is shown to be involved in the association with the lipid kinases. Interestingly, a kinase-dead point mutant of PKCmu failed to associate with either lipid kinase activity, indicating that autophosphorylation may be required to expose the lipid kinase interaction domain. Furthermore, the subcellular distribution of the PKCmu-associated lipid kinases to the particulate fraction depends on the presence of the amino-terminal region of PKCmu including the predicted transmembrane region. These results suggest a novel model in which the non-catalytic region of PKCmu acts as a scaffold for assembly of enzymes involved in phosphoinositide synthesis at specific membrane locations.

1-Phosphatidylinositol 4-Kinase↗
PubMed1998

Effect of neurotropin on the binding of high molecular weight kininogen and Hageman factor to human umbilical vein endothelial cells and the autoactivation of bound Hageman factor.

Bradykinin is generated by activation of the plasma kallikrein-kinin (K-K) cascade and contributes to the symptoms of allergic reactions and the perception of pain. Neurotropin is a biological material obtained from inflamed rabbit skin inoculated with vaccinia virus, which is widely used clinically in Japan as an effective agent for these disorders. Factor XII (FXII) and high molecular weight kininogen (HK), two critical constituents of the plasma K-K cascade, bind to endothelial cells, and bound FXII is autoactivated in the presence of zinc ions. We have investigated the effects of Neurotropin on the interactions of FXII and HK with endothelial cells. Neurotropin inhibited the binding of both proteins to cultured human umbilical vein endothelial cells (HUVEC) and inhibited autoactivation of FXII upon HUVEC in a concentration-dependent manner. These data suggest that the ameliorating effects of Neurotropin in allergic disorders and pain syndromes may be related to this ability to inhibit activation of the K-K cascade and, consequently, the formation of bradykinin.

Binding, Competitive↗
PubMed1998

Cell cycle arrest and antitumor activity of pironetin and its derivatives.

The biological effects of pironetin and its derivatives on cell cycle progression and antitumor activity were studied. At 10-20 ng/ml, both pironetin and its demethyl derivative, NK10958P completely inhibited the cell proliferation of 3Y1 cells, however, epoxypironetin showed only a weak inhibitory activity. The cell cycle analysis revealed that these compounds arrested the cell cycle progression at the M-phase in a dose-dependent manner. These antiproliferative effects of pironetin were also observed in the range 5-25 ng/ml with several tumor cell lines. In CDF1-SLC mice bearing P388 leukemia cells, the intraperitoneal administration of 6.3 mg/kg pironetin over a 5-day period showed a moderate antitumor effect (T/C, 128%). As the chemical structure of pironetin is different from other M-phase inhibitors such as colchicine or vinblastine, pironetin will be the lead compound for a potential new antitumor drug.

Animals↗
PubMed1998

Mutational analysis of the N-ras gene in acute lymphoblastic leukemia: a study of 125 Japanese pediatric cases.

A point mutation of the N-ras gene is one of the known genetic alterations identified in patients with acute lymphoblastic leukemia (ALL), but its clinical importance is still controversial. Using polymerase chain reactions, we examined codons 12, 13 and 61 of this gene in 125 Japanese childhood ALL patients (64 common-ALL, 22 pre-B-ALL, 33 T-ALL, 2 B-ALL, 3 undifferentiated ALL, and 1 unclassified ALL) including 9 relapsed patients. An N-ras point mutation was observed in 14 (11%) patients (9 common-ALL, 3 T-ALL, and 2 undifferentiated ALL; 13 patients at diagnosis and 1 at relapse). The patients with undifferentiated ALL harbored an N-ras mutation at a significantly higher rate. However, no correlation was found between the presence of an N-ras mutation and sex, age, or white blood count. There was no significant difference in the event-free survival rate between 13 fresh patients with an N-ras mutation and 103 patients with a wild-type configuration. The N-ras mutation was present in about 10% of childhood ALL cases but it did not have a prognostic impact. The sequence analyses revealed that the majority of the patients (13/14) had an N-ras mutation of a G to A transition. This finding was consistent with previous reports on N-ras mutations in acute leukemias in which the incidence of a G to A mutation was significantly higher in ALL than in myeloid malignancies.

Child↗
PubMed1998

Response-oriented individualized induction therapy with six drugs followed by four courses of intensive consolidation, 1 year maintenance and intensification therapy: the ALL90 study of the Japan Adult Leukemia Study Group.

Adult patients with acute lymphoblastic leukemia (ALL) were treated according to the ALL90 study, the second prospective study for ALL of the Japan Adult Leukemia Study Group (JALSG). Its characteristics included response-oriented individualized induction therapy with six drugs (doxorubicin, mitoxantrone, vincristine, prednisolone, [corrected] cyclophosphamide and L-asparaginase), and a prospective comparison between allogeneic bone marrow transplantation (allo-BMT) and chemotherapy alone in patients below 45 years of age. The protocol consisted of one or two courses of induction, four courses of consolidation, and three courses of intensification including 12 month maintenance and six times of central nervous system (CNS) prophylaxis. Of 180 evaluable patients (median age, 43), 125 (69%) achieved complete remission (CR). Predicted overall survival (OAS), event-free survival and disease-free survival (DFS) were 15, 10 and 14%, respectively at the median follow-up period of 62 months. No specific toxicities were observed. Leukocytes < 30,000/microliter, normal karyotype, and blasts < 10% in bone marrow at day 15 of induction therapy were significantly favorable prognostic factors for the achievement of CR, DFS and OAS by univariate analysis. Multivariate analysis showed leukocytes < 30,000/microliter and blasts < 10% on day 15 was a significant factor for the achievement of CR, DFS and OAS. Ph-chromosome was found in 28% (36/130) of patients examined and was one of the worst prognostic factors. All Ph positive patients were predicted to die within 600 days. Allo-BMT was not significantly superior to chemotherapy with respect to DFS (P = 0.226). The overall results were inferior to those of the former ALL87 protocol. As reasons, the older median age of 43 years old (vs. 38 years old) and lower dose intensity, especially of l-asparaginase, etc. were suggested. However, patients with good prognostic factors (leukocyte < 30,000/microliter and age < 30 years old) showed better survival than others (P < 0.0001), and the result was similar to that of older children, the high risk group of childhood ALL, suggesting that ALL could be a disease of single entity, showing higher resistance to chemotherapy as patients become older.

Adult↗
PubMed1998

A sensitometric comparison of Kodak Ektavision and Fuji Super HR-S panoramic radiographic films.

OBJECTIVES: The purpose of this study was to compare the combination of Ektavision film and Ektavision intensifying screen with the combination Super HR-S panoramic radiographic film and HR-4 intensifying screen with respect to sensitometric properties and the visualization of anatomic structures. METHODS: The density response and resolution of both panoramic radiographic film/intensifying screen combinations were evaluated through use of the generated characteristic curves and the modulation transfer function. The diagnostic clarity was evaluated by five oral and maxillofacial radiologists who used a rating scale to evaluate the image clarity of selected anatomic structures. RESULTS: The film speed and radiographic contrast, respectively, were 1.3 and 1.2 times higher for Ektavision than for Super HR-S. The image resolution with Ektavision was similar to that with Super HR-S. Ektavision was perceived to provide clearer images of the selected anatomic details than did Super HR-S. CONCLUSION: With respect to the clarity of anatomic structures, Ektavision film, with its higher speed and higher contrast, proved superior to Super HR-S film.

Absorptiometry, Photon↗
PubMed1998

Angiotensin AT1 receptor antagonism and protection against cardiovascular end-organ damage.

This review describes how angiotensin AT1 receptor antagonists (eg, candesartan cilexetil, losartan) effectively protect against end-organ damage including stroke, cardiac hypertrophy, renal dysfunction, glomerulosclerosis, and/or vascular hypertrophy in the models of stroke-prone spontaneously hypertensive rats (SHRSP), SHR, DOCA/salt hypertensive rats, Dahl hypertensive rats and/or 5/6 nephrectomised rats. Particularly in SHRSP and DOCA/salt hypertensive rats, candesartan cilexetil markedly reduced the incidence of stroke and renal injury even at doses which had no effect on blood pressure (BP), suggesting that the tissue protective effects of angiotensin AT1 antagonists are not attributable simply to the normalisation of BP. In the heart, kidney and vascular tissues of SHRSP and the kidney of DOCA/salt hypertensive rats, the mRNA levels for transforming growth factor (TGF)-beta1 and extracellular matrix components (fibronectin, collagen type I, III and IV and laminin) were increased, and the increases of the gene expression were inhibited by treatment with candesartan cilexetil. In addition, there are some reports indicating that angiotensin AT1 receptor antagonists inhibit directly hypertrophy or proliferation of cultured cardiac myocytes and nonmyocytes (fibroblast), cultured mesangial cells and cultured vascular smooth muscle cells, which were stimulated by angiotensin II. These in vitro and in vivo findings suggest that local tissue AT1 receptor stimulation, being accompanied by the increased gene expression of TGF-beta1 and extracellular matrix components may partially contribute to the pathogenesis of cardiovascular end-organ damage.

Angiotensin Receptor Antagonists↗