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Biomedical subjects

T Takano

Publications and source records attributed to T Takano.

At least 343 records · Page 19Linked to original sources
PubMed1995

[Chemotherapy of uterine endometrial cancer].

In recent years, the incidence of endometrial cancer has tended to increase gradually in Japan. Most cases (early cancer of stage I and II) are treated by hysterectomy alone, and the prognosis has been relatively good. From analysis of the poor prognostic factors in endometrial cancer, we understood that additional therapy is necessary for patients who have the following factors: degree of differentiation: G3; invasion to > 1/2 myometrium; metastases to pelvic or para-aortic lymph node, isthumus-cervix extension; surgical stage III and more. However, for patients with advanced inoperable and recurrent cancer, a radiotherapy, is not so sensitive to endometrial cancer has been used. A first line establish a chemotherapy has not been established either. Various attempts have been made to establish a chemotherapy for endometrial cancer. As a result, adriamycin (ADR) and cisplatin (CDDP) have proved effective as single agents. For patients with early cancer who have the poor prognostic factors mentional above, irradiation and polychemotherapy regimens (CAP and AP) are effective. Since the progression of endometrial cancer is dependent on sex steroid hormones, antitumor effects of Medroxyprogesterone acetate (MPA) are expected to be effective for patients with estrogen receptor (ER) positive and progesterone receptor (PR) positive cancer, or with well-differentiated adenocarcinoma (G1 type) histologically. Although several forms of therapy are capable of inducing objective remission as adjuvant treatment, all treatment for advanced and recurrent disease remains palliative, and responses and survival for patients treated with irradiation and chemotherapy remain short. Furthermore, we should examine new methods such as new drug application of key drugs like ADR and Pt pharmaceutical preparation, improvement of Dose intensity of the key drugs and Biochemical modulation, CPT-11, Taxol and assembly of key drugs, along with the Circadian approach in the light of Biochronology.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

[Contamination of flexible fiberoptic bronchoscopes with Mycobacterium chelonae linked to an automated endoscope disinfection machine--on the relationship between the presence of the organism in the intestinal tract and contamination of disinfection machine, and a case of gallbladder and bile duct infection with M. chelonae].

In 1993, thirteen strains (8.7%) of M. chelonae were isolated from bronchoalveolar lavage fluid (BALF) obtained by bronchoscopy of 150 patients in Tachikawa-sogo (T) hospital, where the same automated disinfection machine was commonly used for cleaning, sterilization and disinfection of fiberbronchoscope and fibercolonoscope except 3 bronchoscopes disinfected by gas sterilization. Since January 1994, manual cleaning and sterilization has been applied for bronchoscope, and thereafter no strain of M. chelonae was isolated from BALF of 55 patients in the T hospital. While only one strain (3%) of M. chelonae was isolated from BALF of 33 patients in Ota (O) hospital, but many strains of M. chelonae were isolated from intestinal fluid obtained by fibercolonoscopy of the patients. Manual method of cleaning and disinfection was performed for both bronchoscopes and colonoscopes in the O hospital from the beginning. Based on these results, it was suggested that M. chelonae are commonly present in the colon (intestine) of normal persons. Thus colonoendscope may be often contaminated with the organism and subsequently the automated disinfecting machine may also be contaminated with the organism which is resist and against usual disinfection procedure, and resulted in bronchoscope contamination. If the presence of M. chelonae in intestinal tract is not rare, bile duct may be naturally infected with the organism. A case of cholecystitis and cholangitis caused by M. chelonae, which has not been reported previously, was found in the T hospital.

Aged↗
PubMed1995

[Early relapse after peripheral blood stem cell transplantation in acute myelogenous leukemia with t(8;21)].

We report a 3-year-old boy with acute myelogenous leukemia, who relapsed very early after peripheral blood stem cell transplantation (PBSCT). He was admitted with a tumor in maxillar sinus and hemorrhagic diathesis and was diagnosed as having acute myelogenous leukemia with t(8;21). He achieved complete remission with etoposide, cytosine arabinoside and mitoxantrone. After 8 courses of consolidation therapy and marrow ablative chemotherapy, he received PBSCT. G-CSF was given from day 0 because of severe infection. WBC and platelete counts rapidly increased, however, from day 20 platelet count spontaneously decreased. Concomitantly bone marrow examination revealed the presence of blastic cells. RT-PCR showed that the presence of AML 1/MTG 8 chimera mRNA in the cryopreserved PBSC samples. In vitro analysis also revealed that leukemic cells had G-CSF receptors and increased 3H-thymidine uptake in the presence of G-CSF. These findings strongly suggest that the reinfusion of leukemic cells in PBSC and the administration of G-CSF after PBSCT might be relevant to early relapse in this patient.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Effects of cadmium on glutathione metabolism in Hep G2 cells.

Effects of cadmium on hepatic glutathione (GSH) metabolism were characterized in a human-derived hepatoma cell line, Hep G2 cells. Intracellular GSH concentrations were significantly increased after incubation with cadmium at 5 and 10 microM for 24 and 48 hr. The rate of resynthesis of GSH after depleting cellular GSH by 0.5 mM of diethylmaleate was higher in cadmium (5 microM)-pretreated cells than that in untreated controls. GSH efflux from cadmium-pretreated cells was two-fold higher than that in untreated controls. On the other hand, incubation with cadmium at 5 and 10 microM for 60 min did not decrease GSH efflux. These findings suggest that increased intracellular GSH concentrations are attributed to enhanced synthesis of GSH under cadmium exposure, although the possibility of decreased intracellular consumption of GSH should further to be studied.

Animals↗
PubMed1995

[Isolation of nontuberculous mycobacteria during colonoscopy].

We conducted a survey on nontuberculous mycobacteria (NTM) isolated in association with colonscopy at two hospitals. NTM was isolated from the fluid-phase of colonic contents in 17.6% of the specimens obtained at hospital A and in 46.3% at hospital B. The rate of isolation from the preexamination suction fluid was 9.5% and 43.3% at hospital A and B, respectively. Tap water samples from both hospitals were examined and proved to be free from contamination with NTM. The mycobacterial species isolated at hospital A were M. chelonae subsp. abscessus, M. chelonae subsp. chelonae, M. fortuitum, and M. gordonae. M. chelonae subsp. abscessus was the only mycobacterial species isolated at hospital B. M. avium complex was not isolated at either hospital. By an additional procedure to cleans and decontaminate the endoscopes by suction with Maskin ethanol solution, the incidence of isolation of NTM from the fluid-phase of colonic contents was significantly reduced. None of the patients from whom NTM was isolated exhibited positive signs of colonic NTM infection by the endoscopic examination and non had any underlying diseases which might induce immune suppression. We suspect that most of the NTM isolates have originated from the contaminated endoscope. In conclusion, when a colonscopic examination is carried out in suspicion of NTM disease in intestine, it is essential to reassess the possibility of mycobacterial contamination of the colonscopes and implement appropriate steps for cleansing and sterilization of them.

Colitis↗
PubMed1995

Human chronic gastric ulcer and connexin.

In this study we investigated the relationship between chronic gastric ulcers and the appearance of connexin 32 or connexin 43. Samples were taken endoscopically and the appearance of connexin 32 or connexin 43 was assessed by Western blotting using anticonnexin 32 or anticonnexin 43 antibodies. Normal gastric mucosa contained both connexin 32 and connexin 43. In contrast, gastric mucosa surrounding a chronic gastric ulcer lesion contained a smaller amount of connexin 32 and connexin 43. We also investigated the relationship between the appearance of connexins and ulcer healing. Antiulcer treatment for chronic gastric ulcer was administered. When ulcer healing was observed, connexins 32 and 43, which decreased at the active ulcer stage, had returned almost to levels observed in normal gastric mucosa. These data clearly indicate that disappearance of both connexin 32 and connexin 43 is closely related to the stage of chronic gastric ulcer lesions.

Anti-Ulcer Agents↗
PubMed1994

Angiotensin II binding activity in cultured porcine arterial endothelial cells.

Angiotensin II (A II) binding activity was detected in the particulate fraction (100,000 g, 60 min precipitate) of cultured porcine aortic endothelial cells. Scatchard analysis of the binding activity indicated a single class of binding sites with a dissociation constant (Kd) of 1.1 nM and a total binding capacity (Bmax) of 125 fmol/mg protein. The binding of [125I]A II was inhibited by excess unlabelled A II, A II analogues ([Sar1, Ile8]A II and [Sar1, Ala8]A II), A I (angiotensin I) and A III (angiotensin III), but not by bradykinin. Type specific A II receptor antagonists, losartan (type 1 angiotensin II receptor) and PD123319 (type 2 angiotensin II receptor), did not inhibit the binding. These results suggest that the A II specific binding protein(s) or receptor(s) is present in arterial endothelial cells, and that it is different from typical type 1 and type 2 angiotensin II receptors.

Angiotensin II↗
PubMed1994

Role of cytoplasmic tail phosphorylation sites of platelet-activating factor receptor in agonist-induced desensitization.

The platelet-activating factor (PAF) receptor couples with multiple signaling pathways such as activation of phospholipase C, phospholipase A2, and mitogen-activated protein kinase and the inhibition of adenylate cyclase. The PAF-induced signals are attenuated by repetitive or long standing applications of the agonist (homologous desensitization). To investigate mechanisms underlying the agonist-induced desensitization, we constructed mutant forms of the cloned guinea pig PAF receptor and stably expressed them in Chinese hamster ovary cells. The cells expressing the wild type receptor transiently activated phospholipase C in response to PAF. Intracellular inositol 1,4,5-trisphosphate level and intracellular Ca2+ concentration reached the maximal levels within 20 s and returned to the basal levels in several minutes, even in the continuous presence of the ligand. In contrast, a truncated PAF receptor lacking the carboxyl-terminal cytoplasmic tail induced sustained elevations of inositol 1,4,5-trisphosphate and intracellular Ca2+ concentrations. Similar findings were noted in another mutant, in which the Ser/Thr residues in the carboxyl-terminal tail were substituted with Ala. Both mutant PAF receptors more potently activated the other signals (mitogen-activated protein kinase kinase, arachidonate release, and inhibition of adenylate cyclase) than did the wild type receptor. Thus, while the carboxyl-terminal cytoplasmic tail of the PAF receptor is not required for the forward activation of multiple signals, it does have a critical role for signal attenuation induced by the agonist through phosphate accepters. We also noted that the synthetic peptide of the PAF receptor carboxyl-terminal tail was strongly phosphorylated by the recombinant beta-adrenergic receptor kinase 1, suggesting that it or its relatives might be involved in PAF receptor phosphorylation and homologous desensitization.

Amino Acid Sequence↗
PubMed1994

Molecular basis of a null mutation in soybean lipoxygenase 2: substitution of glutamine for an iron-ligand histidine.

We have investigated the nucleotide sequence and expression of lox2, a mutant form of the gene encoding lipoxygenase 2, an enzyme responsible for unpleasant flavors in soybean [Glycine max (L) Merr.] seeds. Although lox2 transcripts accumulate normally, there are no detectable transcripts for lipoxygenase 1 or 3 in mutant lines that display similar phenotypes characterized by the lack of corresponding lipoxygenase activity and protein in mature seeds. The enzymatically inactive lox2 gene product is readily detectable in mid-maturation-stage seeds but is apparently unstable, since it is absent from mature seed. The protein sequence deduced from the cDNA and genomic DNA sequences of lox2 differs from that of the wild-type gene, Lox2, in the substitution of glutamine for His-532. It is known that His-504 in soybean lipoxygenase 1, which corresponds to His-532 in lipoxygenase 2, is one of the iron-binding ligands essential for lipoxygenase activity. Here we present evidence that the missense mutation substituting Gln for His-532 results in the loss of lipoxygenase 2 from mature soybean seeds.

Alleles↗
PubMed1994

Column-switching high-performance liquid chromatographic analysis of BO-2727, a new carbapenem antibiotic, in human plasma and urine by direct injection.

A column-switching high-performance liquid chromatographic method has been developed for the simple and sensitive analysis of BO-2727 (I) in human plasma and urine. Plasma samples were diluted with an equal volume of a stabilizer, and the mixture was directly injected onto the HPLC system. The analyte was enriched in a pre-treatment column, while endogenous components were eluted to waste. The analyte was then backflushed onto an analytical column and quantified with ultraviolet detection. Urinary concentrations were determined in a similar way except that the enriched analyte was eluted in the foreflush mode to a cation-exchange column used for chromatographic separation. The standard curves for the drug were linear in the range of 0.05-50 micrograms/ml in plasma and 0.5-100 micrograms/ml in urine. The limits of quantification for plasma and urine were found to be 0.5 micrograms/ml and 0.5 micrograms/ml, respectively. This method was used to support Phase I clinical pharmacokinetic studies.

Anti-Infective Agents↗
PubMed1994

A monoclonal antibody against oxidized lipoprotein recognizes foam cells in atherosclerotic lesions. Complex formation of oxidized phosphatidylcholines and polypeptides.

In this study we have used homogenates of human atheromatous plaque as immunogen to establish a murine monoclonal antibody which recognizes oxidized low density lipoprotein (LDL). This monoclonal antibody, FOH1a/DLH3, reacted with oxidized LDL, but enzyme-linked immunosorbent assay showed that it had no reaction with native, acetylated, or malonaldehyde-treated LDL. The antibody cross-reacted with oxidized high density lipoprotein, suggesting that specific sequences of the apolipoprotein B are not essential for antigen recognition by the antibody. Immunohistochemical analysis of thin paraffin sections from human coronary arteries showed that foam cells derived from macrophages in atherosclerotic lesions were heavily stained by this antibody. Several other structures in the lesions, including swollen collagen fibers, cellular debris in necrotic cores, and endothelial cells, were moderately stained. The epitope of this antibody was characterized by a model antigen-generating system using ferrous ion-induced peroxidation of lipids. When the total lipid fraction extracted from LDL was treated with the ferrous ion-induced peroxidation system, the reaction mixture was recognized by the antibody. Antigenic product(s) was produced only when phosphatidylcholine (PC) was treated with the ferrous ion-induced peroxidation, other lipids failed to react to the antibody. To investigate the possible formation of a complex of antigenic product with a polypeptide, a synthetic peptide and a rabbit antiserum against the peptide were used. Reaction mixture of ferrous ion-induced peroxidation of PC in the presence of the peptide was added to a microtiter well precoated with the monoclonal antibody FOH1a/DLH3. After washing, the peptide remaining in the well was detected with rabbit antiserum against the peptide, whereas no reactivity was observed when peptide alone was added to the well. Binding of the antigenic complex to the precoated monoclonal antibody was competed by oxidized PC produced in the absence of any polypeptide. We conclude that oxidized phospholipid product(s) is the epitope of the monoclonal antibody and that the oxidized phospholipid forms complexes with polypeptides. The antigenic materials are detected in foam cells in atherosclerotic lesions.

Amino Acid Sequence↗
PubMed1994

Functional coupling of SSTR4, a major hippocampal somatostatin receptor, to adenylate cyclase inhibition, arachidonate release and activation of the mitogen-activated protein kinase cascade.

Somatostatin has a modulatory role in regulating the membrane conductance in hippocampal neurons. To examine the signal transducing molecules involved in this process, we isolated the cDNA encoding the dominant rat hippocampal somatostatin receptor, SSTR4. Distribution of SSTR4 in the adult central nervous system was restricted to the hippocampus, cerebral cortex, striatum, hypothalamus, and thalamus, as determined by Northern blot analysis and in situ hybridization. In SSTR4-expressing Chinese hamster ovary cells, SSTR4 was functionally coupled not only to inhibition of adenylate cyclase, but also to activation of both arachidonate release and mitogen-activated protein (MAP) kinase cascade, with similar ED50 values. All of these pathways, including both MAP kinase kinase and MAP kinase activation, were completely blocked by pretreatment with pertussis toxin. On the other hand, neither inositol 1,4,5-trisphosphate synthesis nor intracellular Ca2+ mobilization was induced upon SSTR4 stimulation. These data indicate that the hippocampal functions of somatostatin might be mediated through diverse but selective second messenger systems activated via SSTR4 and reveal an unsuspected coupling of a neuronal SSTR subtype to a mitogenic signaling pathway. SSTR4, in addition, provides a useful system to study the Ca(2+)-independent, Gi-dependent (pertussis toxin-sensitive) pathway of MAP kinase activation.

Adenylate Cyclase Toxin↗
PubMed1994

cDNA sequences encoding human fructose 1,6-bisphosphatase from monocytes, liver and kidney: application of monocytes to molecular analysis of human fructose 1,6-bisphosphatase deficiency.

Fructose 1,6-bisphosphatase deficiency is an autosomal recessive inherited disorder of gluconeogenesis. We could isolate cDNAs encoding human fructose 1,6-bisphosphatase from normal monocytes, liver and kidney, but not from normal lymphocytes. The cDNAs contained an open reading frame coding for 338 amino acids, and their nucleotide sequences in monocytes and liver were identical. G644C645 nucleotides in this sequence were the same as those of cDNA from HL-60 cells, although our result differed from a previous report (M. El-Maghrabi et al. (1993) J. Biol. Chem. 268, 9466-9472) on an alteration to C644G645 nucleotides in human liver cDNA resulting in a change of Gly-214 to Ala-214 in the enzyme. The Gly-214 (GGC) residue was therefore conserved in the enzymes hitherto isolated from humans and other animals. Analysis of monocytes in seven patients with fructose 1,6-bisphosphatase deficiency showed a DNA fragment with apparent normal size in two sisters but no detectable DNA fragment in the other five patients. Monocytes were thus useful as an alternative source for mRNA from human liver for the molecular analysis of fructose 1,6-bisphosphatase deficiency.

Alanine↗
PubMed1994

Transfected platelet-activating factor receptor activates mitogen-activated protein (MAP) kinase and MAP kinase kinase in Chinese hamster ovary cells.

The platelet-activating factor (PAF) was seen to potently activate mitogen-activated protein (MAP) kinase and MAP kinase kinase through the cloned guinea pig PAF receptor stably expressed in Chinese hamster ovary (CHO) cells. Both 42- and 44-kDa MAP kinases were activated and tyrosine-phosphorylated in response to PAF. The PAF receptor also triggered the production of inositol phosphates and the release of arachidonic acid and inhibited cyclic AMP accumulation. Differential inhibitory effects of pertussis toxin (PTX) on these signals suggested that the PAF receptor couples to both PTX-sensitive and -insensitive G proteins in CHO cells. MAP kinase and MAP kinase activations were partially regulated by PTX-sensitive G proteins. The PAF receptor did not trigger any detectable increase in the GTP form of Ras under the conditions in which the human insulin receptor expressed in the same parent CHO cells potently increased the level. Since these agonists induced comparable MAP kinase activations through cognate receptors, Ras seems to play different roles in MAP kinase activation by the two different classes of receptors. The activation of MAP kinase by the cloned PAF receptor may explain part of the mechanisms underlying PAF-induced differentiation and proliferation in non-inflammatory cells.

Animals↗
PubMed1994

Pathogenesis of cerebellar deformity in experimental Chiari type I malformation caused by mumps virus.

We sought to elucidate the pathogenesis of Chiari type I malformation using an experimental model of hydrocephalus produced by inoculating hamsters with mumps virus. Dilatation of the lateral ventricules was detected in all brains inoculated at 2, 10, and 25 days of age. The cerebellum in hamsters inoculated at 2 and 10 days of age showed elongation and flattening of the vermis and protrusion or notching of the uvula. All layers, i.e., the molecular, Purkinje cell, and granular layers, and the white matter were preserved, but had become narrow. Purkinje cells remained normal. Hamsters inoculated at 25 days of age did not develop the cerebellar deformity. Mumps virus antigen was detected in all ependymal cells and in some epithelial cells of the choroid plexus in all hamsters that had been inoculated at 2, 10, or 25 days of age. Results suggest that Chiari type I malformation is caused by two main factors occurring simultaneously, i.e., increasing intracranial pressure and rapid histogenesis of the cerebellar cortex.

Animals↗
PubMed1994

Apolipoprotein E5 and E7 in apparently healthy Japanese males: frequencies and relation to plasma lipid levels.

In order to determine the frequencies of apolipoproteins (apo) E5 and E7 and their relation to plasma lipid levels, apo E phenotypes were determined in 608 healthy Japanese male adults by two-dimensional gel electrophoresis. Apo E5 and E7 were observed in 2.8% of the subjects, in addition to the three common apo E isoforms, E2, E3, and E4. Apo E5 was divided into two subtypes based on the migration rate on SDS/PAGE, E5f is the type with faster migration and E5s slower migration. The gene frequencies were: the epsilon 3 allele, 0.841; the epsilon 4 allele, 0.095; the epsilon 2 allele, 0.049; the epsilon 7 allele, 0.009; the epsilon 5 allele encoding apo E5f (the epsilon 5f allele), 0.004; and the epsilon 5 allele encoding apo E5s (the epsilon 5s allele), 0.001. The five individuals with apo E5f and the eleven with apo E7 were heterozygotes and normocholesterolemic. Also plasma apo B and apo E levels were not increased in any subjects with apo E5f or apo E7. The data suggests that apo E5f and E7 are not rare in the Japanese population but that neither apo E5f nor E7 are associated with hypercholesterolemia in most of the heterozygotes.

Adult↗