Search PubMed⌕ Search

Biomedical subjects

T Tamura

Publications and source records attributed to T Tamura.

At least 415 records · Page 23Linked to original sources
PubMed1997

Metabolism of azetirelin, a new thyrotropin-releasing hormone (TRH) analogue, by intestinal microorganisms.

PURPOSE: We evaluated the effect of luminal bacterial metabolism on intestinal absorption of azetirelin in rats. In vitro characteristics of bacterial metabolism of azetirelin were also investigated with the goal of overcoming the low stability of the peptidic drug against luminal microorganisms. METHODS: Plasma azetirelin levels after oral administration to antibiotic-pretreated rats was examined. In vitro incubation experiments with bacterial suspensions were also performed to clarify the location of azetirelin breakdown activity as well as the effects of oxygen, pH, and various protease inhibitors on drug metabolism. RESULTS: Plasma azetirelin levels were sustained after oral administration to antibiotic-treated rats. Incubation with rat luminal contents demonstrated that azetirelin was metabolized by anacrobic bacteria, which are predominant in the distal intestine. Fecal suspensions from rats, dogs, and humans showed comparable metabolic activity. Azetirelin breakdown in the bacterial suspension was pH-dependent and was inhibited in the presence of bacitracin or puromycin. CONCLUSIONS: Bacterial metabolism influences the degree of absorption of azetirelin in the distal intestine. Control of the luminal pH environment may be a practical method for improving the stability of azetirelin against intestinal microorganisms.

Animals↗
PubMed1997

Phase I study of sequentially administered topoisomerase I inhibitor (irinotecan) and topoisomerase II inhibitor (etoposide) for metastatic non-small-cell lung cancer.

We conducted a phase I study of irinotecan (CPT-11) and etoposide (VP-16) given sequentially to untreated patients with metastatic non-small-cell lung cancer. Arm A: CPT-11 was given over 90 min on days 1-3 and VP-16 was given over 60 min on days 4-6. Arm B: VP-16 was given on days 1-3 and CPT-11 on days 4-6. G-CSF was given to all patients daily on days 7-17. Twenty-seven patients were entered randomly at the two arms. The major dose-limiting toxicities in arms A and B were granulocytopenia and diarrhoea. Transient elevations of transaminases and bilirubin were observed in both arms. The degree of the toxicities did not differ between the two arms. The maximum tolerated doses (MTDs) were 60 mg m-2 CPT-11 and 60 mg m-2 VP-16 in both arms. Of the 13 patients who received more than two cycles, two out of five achieved partial response (PR) at the first level of arm A and one out of four achieved PR at the second level of arm B. We conclude that these schedules of sequential CPT-11 and VP-16 administration were inappropriate because of severe toxicities.

Adult↗
PubMed1997

Preferential codon usage and two types of repetitive motifs in the fibroin gene of the Chinese oak silkworm, Antheraea pernyi.

In this paper we describe the peculiar structures and preferential codon usage found in wild silkworm fibroin genes. We determined a 1350 bp nucleotide sequence from the Chinese oak silkworm, Antheraea pernyi. The deduced amino acid sequence was partitioned into thirteen polyalanine-containing repetitive motifs, which was one of the characteristics of Antheraea fibroins. Eleven of these arrays can be classified into two types of motifs depending on difference in amino acid sequences following polyalanine. Repetitive motifs structurally similar to those of A. pernyi were detected in a homologue of the Japanese oak silkworm, Antheraea yamamai. The most remarkable feature of this study was preferential codon usage, especially seen in alanine synonymous codons within both homologues of Antheraea: isocodon GCA most frequently occurred in alanine isocodons. In contrast, GCU isocodon was the most abundant in Bombyx mori fibroin heavy chain that lacks polyalanine arrays. This result strongly suggests different modes of selective constraint between the two types of fibroin gene. The similar finding that GCA isocodon was most frequent in two dragline silk sequences of the spider, Nephila clavipes, is consistent with our results because of the repetitive polyalanine-containing arrays seen in spider dragline silk.

Amino Acid Sequence↗
PubMed1997

Sodium azide induces relaxation of the canine gastric body by activating a guanylate cyclase-dependent pathway.

In order to study the inhibitory mechanism by which sodium azide eliminates smooth muscle contraction in vivo and in vitro, gastrointestinal motility was monitored via chronically implanted force transducers in the stomach and duodenum of conscious dogs. Circular smooth muscle strips with myenteric plexus from the canine gastric body were used for in vitro measurement of isometric tension. In conscious dogs, sodium azide (50 micrograms kg-1, i.v.) abolished both the spontaneously occurring phase III contractions and postprandial motility. Exogenous motilin (100 ng kg-1)- and bethanechol (50 micrograms kg-1)-induced contractions were also abolished by sodium azide. In vitro, sodium azide and electrical field stimulation (EFS) caused a concentration- or frequency-dependent nonadrenergic noncholinergic relaxation in the gastric body strips. The relaxation induced by EFS, but not sodium azide, was abolished by tetrodotoxin. NG-nitro-L-arginine and oxyhaemoglobin failed to attenuate the relaxant effect of sodium azide, but strongly inhibited EFS-induced relaxation. Methylene blue inhibited both sodium azide- and EFS-induced relaxation. cGMP concentrations in muscle strips were markedly increased by sodium azide. These findings indicate that sodium azide induces relaxation in the canine gastric body through a direct action on smooth muscle, by activating a guanylate cyclase-dependent pathway; endogenous NO synthesis does not participate in this inhibitory mechanism.

Adrenergic alpha-Antagonists↗
PubMed1997

Demonstration of an E-box and its CNS-related binding factors for transcriptional regulation of the mouse type 1 inositol 1,4,5-trisphosphate receptor gene.

The type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) is expressed abundantly in the CNS, such as in cerebellar Purkinje cells and the hippocampus. We established a tissue-specific cell-free transcription system and studied regulatory properties of the 5' upstream region of the IP3R1 gene by use of this system. Deletion analyses of the promoter revealed several cis elements that function significantly in brain nuclear extracts. Among those elements, sequences from -398 to -295 showed the most predominant cerebellum-specific positive function. Footprint analyses demonstrated a factor-binding region from -334 to -318, termed box-I, that contained an E-box consensus sequence. Electrophoretic mobility shift assay revealed CNS-related basic helix-loop-helix proteins for the box-I. Mutational studies using the function assay and competitive electrophoretic mobility shift assays demonstrated a good correlation between the box-I-binding factors and the activated transcription. Box-I-binding factors were present abundantly in adult mouse CNS, whereas their existence was restricted in embryonic and nonneural tissues. Transient chloramphenicol acetyltransferase assay for the IP3R1 promoter revealed the requirement of box-I in Neuro2a neuroblastoma cells. In the postnatal CNS, multiple basic helix-loop-helix factors are expressed abundantly, some of which are suggested to activate IP3R1 gene expression in the mammalian CNS.

Animals↗
PubMed1997

Localisation of MHC class II, lymphocytes and immunoglobulins in the oviduct of laying and moulting hens.

1. Our aim was to determine the presence and numbers of immunocompetent cells in the oviduct of laying and moulting hens. Immunocompetent cells were localised by immunocytochemistry throughout the entire length of the oviduct. 2. In laying birds, MHC class II+ cells were observed in the subepithelial and middle part of the stroma of all oviducal segments and the mucosal epithelium of the infundibulum and vagina. CD3+ cells were also localised in subepithelial and middle part of stroma as well as in mucosal epithelium of each oviducal segment. Bu-lb+ and IgG+ cells were also observed in the epithelium and subepithelial and middle part of the stroma of all oviducal segments, though stroma of the magnum, isthmus and uterus contained few Bu-lb+ cells. IgA+ cells were observed only in the mucosal epithelium of the magnum in small numbers. 3. In moulting hens, there were few numbers of immunocompetent cells in the mucosal epithelium of each oviducal segment, although CD3+ cells were observed in the infundibulum and vagina. In the subepithelial stroma, the populations of MHC class II+ cells in the infundibulum, magnum and uterus, CD3+ cells in the infundibulum and vagina, as well as IgG+ cells in each oviducal segment except for isthmus were smaller than in laying hens. In contrast, the number of immunocompetent cells in the middle part of stroma of moulting hens were equal to or greater than in laying hens. 4. These results suggest that the oviducal immune function is active in the surface tissues of the mucosa in laying hens, whereas it is reduced in moulting hens.

Animals↗
PubMed1997

Prognostic factors and prognostic staging system for small cell lung cancer.

This study was performed to assess the prognostic factors and the predictors of long-term (3-year) survival in patients with small cell carcinoma of the lung, accrued in one randomized trial, and to define patient subgroups showing significantly different survivals using recursive partitioning and amalgamation analysis. A total of 300 patients with small cell carcinoma of the lung were entered into a randomized study comparing cyclophosphamide, adriamycin and vincristine (CAV), cisplatin and etoposide (PE) and alternating treatments of CAV and PE. Of these, 286 patients were analysed for the present study of prognostic factors. Multivariate analysis showed that poor performance status (2-3) (P = 0.0001), extensive disease (P = 0.0015) and abnormally elevated serum lactate dehydrogenase (P = 0.0001) and alkaline phosphatase (P = 0.0013) were independently adverse pretreatment prognostic factors. Of limited disease patients, performance status (P = 0.029) and white blood cell count (P = 0.044) had a significant influence on the probability of 3-year disease-free survival. Using recursive partitioning and amalgamation analysis, three classes of similar prognosis were identified: the most favorable class was defined by knowledge of lactate dehydrogenase (normal), performance status (0-1) and serum sodium levels (normal) with median survival time of 16.0 months, and the class with the poorest prognosis was defined by knowledge of lactate dehydrogenase (elevated) and performance status (2-3) (median survival time 6.6 months). The intermediate class had a median survival time of 9.4 months. In conclusion, this subclassification system will be used for the design, implementation and interpretation of clinical studies as well as decision-making in individual patients.

Adult↗
PubMed1997

Chemical structure of lipid A from Helicobacter pylori strain 206-1 lipopolysaccharide.

The chemical structure of a novel lipid A, which was obtained as a major component from lipopolysaccharide of Helicobacter pylori strain 206-1, was determined to be a glucosamine beta(1-6) disaccharide 1-(2-aminoethyl)phosphate acylated by (R)-3-hydroxyoctadecanoic acid and (R)-3-(octadecanoyloxy)octadecanoic acid at the 2- and 2'-position, respectively. The absence of a phosphoryl group at the 4'-position and fatty acyl groups at the 3- and 3'-position, and the stoichiometric presence of 2-aminoethyl phosphate at the 1-position are unique features, distinguishing it from the lipid A of enterobacteria.

Carbohydrate Sequence↗
PubMed1997

Analysis of the stability of mutant lysozymes at position 15 using X-ray crystallography.

His 15 of hen lysozyme is located at the protein surface and is partly buried by the neighboring residues. The side chain of His 15 forms hydrogen bonds with surrounding residues and these hydrogen bonds are somewhat buried. A series of mutant lysozymes at the position 15 (Gly, Ala, Val, and Phe) was prepared, and their stabilities were analyzed by GdnHCl denaturation and X-ray crystallography. The mutants were less stable than the wild type at pH 5.5 and 35 degrees C. In H15G and H15A, X-ray crystallography revealed two fixed water molecules at the mutated region, which formed similar hydrogen bonds to those in the wild type. On the other hand, it was suggested that the hydrogen bonds were disrupted and that several unfavorable van der Waals' contacts occurred in H15V and H15F. Therefore, we concluded that His 15 stabilized the lysozyme structure by forming hydrogen bonds and the best packing with the neighboring residues. Moreover, we found that the method of protein stabilization by increasing the hydrophobicity of an amino acid residue was not always effectively applicable, especially when the residue had formed a hydrogen bond.

Animals↗
PubMed1997

Involvement of apoptosis and lysosomal hydrolase activity in the oviducal regression during induced molting in chickens: a cytochemical study for end labeling of fragmented DNA and acid phosphatase.

Induced molting improves egg producing functions in hens. We investigated the mechanism of oviducal regression during induced molting. Involvement of apoptosis and autolysis in the oviducal regression process was analyzed by terminal deoxynucleotidyl transferase (T'dt)-mediated biotinylated deoxyuridine triphosphates (dUTP) nick end-labeling TUNEL) and an enzyme histochemistry for acid phosphatase. Nuclei positive for TUNEL were negligible and acid phosphatase staining was weak in the oviduct of laying hens. The frequency of TUNEL-positive nuclei was significantly increased in tubular gland cells of magnum, isthmus, and shell gland 2 d after cessation of egg laying and significantly decreased thereafter. The intensity of acid phosphatase staining was gradually increased during oviducal regression and extremely high on Day 7 after cessation of egg laying. These results suggest that during oviducal regression in induced molting hens, apoptosis is induced in the earlier stage of oviducal regression and autolysis occurs thereafter eventually, the glandular cells disappear.

Acid Phosphatase↗
PubMed1997

Changes in the population of proliferating cells in chicken anterior pituitary during induced molting: an immunocytochemical analysis for proliferating cell nuclear antigen.

The goal of this study was to determine whether cell proliferation is increased in the anterior pituitary during an induced molting period in chickens. The anterior pituitaries were collected from: 1) laying hens before initiation of an induced molt (control hens), 2) molting hens 2 to 16 d after cessation of lay, and 3) second cycle laying hens 1 d after returning to lay. Pituitary cephalic and caudal lobes were processed for immunocytochemistry of proliferating cell nuclear antigen (PCNA), and positive cells were counted by an image analyzer using light microscopy. In cephalic and caudal lobes, a small number of positive cells were observed in controls and molting hens 2 d after cessation of lay. The frequency of PCNA-positive cells started to increase from 7 d after cessation of lay (3 d after refeeding), and a significantly higher frequency of positive cells was observed in both lobes of molting hens 13 d after cessation of lay when compared to control hens, molting hens 2 d after cessation of egg lay, and second cycle laying hens. The frequency of PCNA-positive cells in second cycle laying hens decreased to a similar level to that of control hens. These results suggest that anterior pituitary tissue may be remodeled partially by a proliferation of cells during induced molting in hens.

Animals↗
PubMed1997

Cell proliferation in the process of oviducal tissue remodeling during induced molting in hens.

Tissue remodeling and calcium binding protein-D28K (CaBP-D28K) dynamics were examined in the oviduct relative to induced molting. The oviducal tissues of premolting, 7, 10, 13, and 16 d after cessation of laying, and postmolting hens were examined. Frequency of proliferating cells and immunoreactive CaBP-D28K molecules were identified by immunocytochemistry for proliferating cell nuclear antigen (PCNA) and Western blot for CaBP-D28K. The relative frequency of PCNA-positive cells in the mucosal epithelium of the magnum, isthmus, and shell gland was low in premolting and 7 d after the cessation of egg laying. In the magnum and isthmus it was markedly increased in 10 and 13 d after cessation, followed by a slight decrease at 16 d after cessation. The frequency in the shell gland was kept high 10, 13, and 16 d after cessation. The frequency of PCNA-positive cells in each segment was decreased when the birds resumed laying. In the stroma of magnum and isthmus where the tubular glands were located, the frequency of PCNA-positive cells was significantly increased 10 d after the cessation of egg laying relative to premolting and 7 d after cessation. In postmolting hens and in hens 16 d after cessation, the frequency was decreased to a same level to that of premolting hen. In the shell gland, the frequency of PCNA-positive cells was high at 10, 13, and 16 d, and diminished in postmolting hen. Single immunoprecipitate band for CaBP-D28K was observed in the shell gland of premolting, postmolting, and younger hens, whereas the density of bands was greater in postmolting hens and younger hens than in premolting hens. We suggest that the oviducal tissues are remodeled by replacing the old glandular cells with new ones that are derived from the mucosal epithelium and uninvoluted glandular cells. Such rejuvenation of shell gland tissue may lead the improvement of CaBP-D28K induction.

Analysis of Variance↗
PubMed1997

Haloarcula argentinensis sp. nov. and Haloarcula mukohataei sp. nov., two new extremely halophilic archaea collected in Argentina.

Strains arg-1T (T = type strain) and arg-2T, two new strains of extremely halophilic archaea, were isolated from the soils of the Argentine salt flats. The taxonomic features of arg-1T were similar to, but distinct from, those of the type strain of Haloarcula vallismortis and other Haloarcula species. On the 16S rRNA phylogenetic tree, strain arg-1T formed a cluster together with Haloarcula species. Strain arg-2T differed in its glycolipid composition but still was more closely related to the genus Haloarcula than to other established genera. We propose that strain arg-1T be classified as a member of a new species, Haloarcula argentinensis, and that strain arg-2T be classified as a member of Haloarcula mukohataei sp. nov., although arg-2T may belong to a new genus or a subgenus of the genus Haloarcula. The type strain of H. argentinensis is strain arg-1 (= JCM 9737), and the type strain of H. mukohataei is strain arg-2 (= JCM 9738).

Argentina↗
PubMed1997

A new genus of the order Actinomycetales, Spirilliplanes gen. nov., with description of Spirilliplanes yamanashiensis sp. nov.

Actinomycete strain YU127-1T (T = type strain), which produces zoospores, was isolated from a soil sample. The aerial mycelium of this organism at maturity forms short chains of spores. The hyphae form coils, and sporangia are not observed. Strain YU127-1T contains glutamic acid, glucosamine, glycine, alanine, and meso-diaminopimelic acid in its cell wall (wall chemotype II), 3-O-methylmannose, mannose, xylose, and glucose as whole-cell sugars, meanaquinone 10(H4), and glycolyl cell wall polysaccharides and has a guanine-plus-cytosine content of 69.0 mol%. Mycolic acids are absent. Phosphatidylinositol and phosphatidylethanolamine are diagnostic phospholipids. The chemotaxonomic data, except for the lack of arabinose in the whole-cell sugars, indicate that this strain belongs to the family Micromonosporaceae. The morphological and physiological characteristics and chemotaxonomic and phylogenetic data for this strain differ from those of the previously described actinomycetes. We therefore propose a new genus, spirilliplanes, for this organism; the type species of the genus is Spirilliplanes yamanashiensis sp. nov., and the type strain of S. yamanashiensis is strain YU127-1 (= IFO 15828).

Actinomyces↗
PubMed1997

A verrucous lesion on skin grafted after necrotizing fasciitis in a diabetic patient successfully treated with combined topical 5-FU and tacalcitol.

Many complications of diabetes mellitus involve the feet. These include infections, neuropathy, vasculopathy, and poor wound healing. Neuropathy causes chronic pressure or friction on an area of sensory loss and occasionally causes verrucous skin lesions. We describe a diabetic patient, complicated by necrotizing fasciitis, who developed a verrucous skin lesion on a skin graft site. The verrucous skin lesion was treated successfully with combined topical 5-fluorouracil and vitamin D3 application.

Administration, Topical↗
PubMed1997

Molecular characterization of the mde operon involved in L-methionine catabolism of Pseudomonas putida.

A 15-kb region of Pseudomonas putida chromosomal DNA containing the mde operon and an upstream regulatory gene (mdeR) has been cloned and sequenced. The mde operon contains two structural genes involved in L-methionine degradative metabolism: the already-identified mdeA, which encodes L-methionine gamma-lyase (H. Inoue, K. Inagaki, M. Sugimoto, N. Esaki, K. Soda, and H. Tanaka. J. Biochem. (Tokyo) 117:1120-1125, 1995), and mdeB, which encodes a homologous protein to the homodimeric-type E1 component of pyruvate dehydrogenase complex. A rho-independent terminator was present just downstream of mdeB, and open reading frames corresponding to other components of alpha-keto acid dehydrogenase complex were not found. When MdeB was overproduced in Escherichia coli, the cell extract showed the E1 activity with high specificity for alpha-ketobutyrate rather than pyruvate. These results suggest that MdeB plays an important role in the metabolism of alpha-ketobutyrate produced by MdeA from L-methionine. Accordingly, mdeB encodes a novel E1 component, alpha-ketobutyrate dehydrogenase E1 component, of an unknown alpha-keto acid dehydrogenase complex in P. putida. In addition, we found that the mdeR gene was located on the opposite strand and began at 127 bp from the translational start site of mdeA. The mdeR gene product has been identified as a member of the leucine-responsive regulatory protein (Lrp) family and revealed to act as an essential positive regulator allowing the expression of the mdeAB operon.

Amino Acid Sequence↗
PubMed1997

Phase II study of irinotecan and etoposide in patients with metastatic non-small-cell lung cancer.

PURPOSE: To determine the effects of irinotecan (CPT-11) given in combination with etoposide (VP-16) in metastatic non-small-cell lung cancer (NSCLC), to evaluate response and survival rates, and to determine the qualitative and quantitative toxicities of the combination chemotherapy. PATIENTS AND METHODS: Sixty-one metastatic NSCLC patients received concurrent administration of CPT-11 and VP-16 for 3 days with recombinant human granulocyte colony-stimulating factor (rhG-CSF) support. RESULTS: Fifty-nine patients were assessable for response and all 61 patients were assessable for toxicity and survival. Fifty-six patients were treated with two or more courses of chemotherapy. Thirteen patients achieved a partial response (PR), 36 showed no change (NC), and 10 showed progressive disease (PD). The overall response rate was 21.3% (95% confidence interval, 12.9% to 33.1%). The median duration of PRs was 141 days (range, 62 to 299). Of the hematologic toxicities, 14 (23%) and 24 (39%) patients experienced grade 3 or 4 leukopenia and neutropenia, respectively. The toxicities were feasible. Treatment-related death occurred in one patient who suffered hypovolemic shock induced by hematemesis. The median survival time was 10.0 months and the 1-year survival rate was 36.1%. CONCLUSION: Combination chemotherapy with concurrent administration of CPT-11 and VP-16 with rhG-CSF support was only modestly effective against metastatic NSCLC, with feasible toxicities of moderate diarrhea and pulmonary toxicity. The results were equivalent to those expected with either cisplatin-based chemotherapy or with CPT-11 alone.

Adenocarcinoma↗