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Biomedical subjects

T Hashizume

Publications and source records attributed to T Hashizume.

At least 127 records · Page 7Linked to original sources
PubMed1993

Alteration in expression of Serratia marcescens porins associated with decreased outer membrane permeability.

The porin expression of two clinical isolates of Serratia marcescens, which overproduced cephalosporinase and had decreased outer membrane permeability, were studied in comparison with those of reference strains. Separation of the porin proteins assessed by SDS-PAGE containing urea revealed that both clinical isolates overexpressed a single porin of 44 and 43 kilodalton (kDa), respectively. In contrast, the in-vitro porin deficient mutant, which was derived from the reference strain IFO3736 as latamoxef-resistant, showed decreased outer membrane permeability, but produced low levels of all three peptidoglycan associated porins of 45, 44 and 43 kDa, and overexpressed 39 kDa OmpA protein. These observations suggested that the clinical isolates had a different mechanism of latamoxef resistance compared with the mutant and overexpressed possible narrow transport channels of 44 or 43 kDa. The 45 kDa porin may facilitate a more effective channel than the other two proteins. Heterogeneity of porin profiles between biotypes was also suggested. The two isolates were also resistant to penicillins and cephalosporins tested, but imipenem was the most active agent and inhibited the isolates at 1.56 mg/L.

Anti-Bacterial Agents↗
PubMed1993

In vitro activity of a new carbapenem antibiotic, BO-2727, with potent antipseudomonal activity.

BO-2727, a new 1-beta-methyl-carbapenem, was active at concentrations of 6.25 micrograms/ml or less against gram-positive and gram-negative bacteria, including some imipenem- and/or meropenem-resistant (MICs, > or = 12.5 micrograms/ml) Pseudomonas aeruginosa strains, against which it proved generally fourfold more active than imipenem and meropenem. BO-2727's antipseudomonal activity and its broad spectrum merit further investigation for clinical use by itself, since it was stable in the presence of renal dehydropeptidase I.

Anti-Bacterial Agents↗
PubMed1993

Synthesis and biological activity of 3'-hydroxy-5'-aminobenzoxazinorifamycin derivatives.

As a part of our studies on the syntheses of benzoxazinorifamycin derivatives, 3'-hydroxy-5'-aminobenzoxazinorifamycin derivatives were synthesized, and tested for their antimicrobial activities. The antimicrobial activities of these compounds against gram-positive and gram-negative bacteria were almost identical to those of rifampicin (RFP) and rifabutain (RFB), however, antimicrobial activities against Mycobacterium tuberculosis were superior to RFP, while being similar to RFB. 3'-Hydroxy-5'-(4-alkyl-1-piperazinyl)benzoxazinorifamycin derivatives also had in vitro potent activities against Mycobacterium avium complex (MAC). Their minimal inhibitory concentration values against MAC were 2-256 times greater than RFP and RFB. Their in vivo efficacies against M. tuberculosis and MAC, after oral administration to mice, were superior to RFP and RFB, except for RFB against M. tuberculosis activity in vivo. Although they were absorbed from the gastrointestinal tract, their plasma levels were lower than that of RFP. Among these 5'-(4-alkyl-1-piperazinyl) derivatives, 3'-hydroxy-5'-(4-isobutyl-1-piperazinyl)benzoxazinorifamycin, compound 19 (KRM-1648), was selected as the most promising and its preliminary pharmacokinetic characteristics in mice were investigated. Compound 19 was distributed much more in tissues, especially in spleen and lung, than in plasma and had a long elimination time from tissues.

Animals↗
PubMed1993

Pharmacokinetics of the gastrokinetic agent mosapride citrate after intravenous and oral administrations in rats.

The pharmacokinetics and bioavailability of mosapride citrate ((+/-)-4-amino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2- morpholinyl]methyl]benzamide citrate dihydrate, AS-4370, CAS 112885-42-4) were investigated in rats of both sexes. Plasma levels of mosapride and its des-4-fluorobenzyl metabolite (M-1) were determined after an intravenous dose of 2 mg/kg or an oral dose of 10 mg/kg. There were marked sex-related differences in the mean plasma concentration-time profiles of mosapride after single intravenous and oral administration. After oral administration, the Cmax of the unchanged mosapride in male rats (44 ng/ml) was approximately 1/18 of that in female rats (788 ng/ml). The Cmax of M-1 (277 ng/ml) was 6 times higher than that of mosapride in males, while the Cmax in females (149 ng/ml) was 1/5 of that of mosapride. Male rats exhibited more rapid elimination (t1/2 of 1.9 h) than females (2.8 h). These sex-dependent pharmacokinetics of mosapride in rats would be explained by two reasons: different activity of hepatic drug-metabolizing enzymes to M-1 and partly different distribution volume of mosapride. Oral bioavailability of mosapride was 7% of the dose in males and 47% in females, suggesting extensive first-pass metabolism in males. Once daily 7-day multiple administration did not affect the pharmacokinetics of mosapride both in male and female rats.

Administration, Oral↗
PubMed1993

[Survey for primary tumor site in patients with initial clinical presentation of bone metastasis].

Among the patients who were examined with bone scintigraphy between April 1985 and March 1991, there were 27 patients whose initial clinical manifestation was bone metastasis and who were surveyed for the primary tumor site. The primary tumor site could be identified in 20 patients (74%), consisting of 9 patients with lung cancer, 3 with prostate cancer, 3 with hepatoma, 2 with renal cancer, and one each with thyroid cancer, adrenal cancer, and pleural malignant mesothelioma. In 17 of the 20 patients, the primary site had been detected within two months after presentation. Examinations which were helpful in identifying the primary site included chest radiography, sputum cytology, abdominal sonography, serum prostatic acid phosphatase level and pathologic examination of biopsy specimens. 99mTc-PMT scintigraphy was useful in the diagnosis of the hepatoma when accumulation was observed at the metastatic sites. In 2 patients, lung cancer had been recognized using follow-up chest radiography 3 and 6 months after presentation, respectively. One patient was diagnosed at autopsy as having adrenal cancer. In 7 patients the primary site remains unknown. Histology examination of the biopsy specimen performed in 6 of these patients revealed 4 to be adenocarcinoma and 2 undifferentiated carcinoma. The average survival period of the 17 patients who died was 9.5 months. Four patients are alive, and the outcome in the remaining 6 could not be determined.

Adult↗
PubMed1992

Structure determination of two new amino acid-containing derivatives of adenosine from tRNA of thermophilic bacteria and archaea.

Two new nucleosides have been identified in unfractionated transfer RNA of two thermophilic bacteria, Thermodesulfobacterium commune, and Thermotoga maritima, six hyperthermophilic archaea, including Pyrobaculum islandicum, Pyrococcus furiosus and Thermococcus sp. and two mesophilic archaea, Methanococcus vannielii and Methanolobus tindarius. Structures were determined primarily by mass spectrometry, as 3-hydroxy-N-[[(9-beta-D-ribofuranosyl-9H-purin-6- yl)amino]carbonyl]norvaline, (hn6A), structure 1, and 3-hydroxy-N-[[(9-beta-D-ribofuranosyl-9H-2-methylthiopurin-6- yl)amino]carbonyl]norvaline (ms2hn6A), 2. The amino acid side chain was characterized as 3-hydroxynorvaline (3) by gas chromatography-mass spectrometry of the trimethylsilyl derivative after cleavage from 1 and 2 by alkaline hydrolysis. Evidence for the amino acid-purine carbamoyl linkage was obtained from the collision-induced dissociation mass spectrum of trimethylsilylated 1, and the total structure was confirmed by chemical synthesis of 1.

Adenosine↗
PubMed1992

Mass spectrometry of mRNA cap 4 from trypanosomatids reveals two novel nucleosides.

Synthesis of mRNA in kinetoplastid protozoa involves the process of trans-splicing, in which an identical 39-41-nucleotide (depending on the species) mini-exon is placed at the 5' end of mature mRNAs. The mini-exon sequence is highly conserved among all members of the Kinetoplastida, nucleotides 1-6 being identical in the four genera so far examined. Prior to trans-splicing, the mini-exon donor RNA is capped by the addition of a (5'-5') triphosphate-linked 7-methylguanosine, followed by modification of the first four transcribed nucleotides. Partial structures have been previously deduced for this cap 4 moiety from Trypanosoma brucei and Leptomonas collosoma. We have purified enough cap 4 from T. brucei and Crithidia fasciculata to allow definitive structural analysis by combined liquid chromatography/mass spectrometry and gas chromatography/mass spectrometry. The results, together with the known mini-exon sequence, show that cap 4 in both species has the structure m7G(5')ppp(5')m6(2)AmpAmpCmpm3Ump. The presence of N6,N6,2'-O-trimethyladenosine and 3,2'-O-dimethyluridine, nucleosides previously unknown in nature, were confirmed by rigorous comparison with synthetic standards. The conservation of cap 4 between these divergent genera suggests that this structure may be common to most if not all Kinetoplastida.

Animals↗
PubMed1992

Sphingosine enhances platelet aggregation through an increase in phospholipase C activity by a protein kinase C-independent mechanism.

Sphingosine (a potent inhibitor of protein kinase C) at 5-10 microM, which are concentrations lower than those that inhibit this enzyme activity, enhanced the aggregation of rabbit platelets induced by low concentrations of U46619, platelet-activating factor, thrombin and arachidonic acid, whereas H-7 and staurosporine, other protein kinase C inhibitors, failed to do so. Of the sphingosine analogues which also inhibit protein kinase C, psychosine and lyso-GM3 did not show such an enhancing effect. Sphingosine promoted both Ins(1,4,5)P3 formation and an increase in the cytoplasmic free Ca2+ concentration in response to all the agonists used. Furthermore, the hydrolytic action of exogenously added phospholipase C (from Clostridium perfringens) on platelet membrane phospholipids was dose-dependently enhanced by pretreatment of the platelets with sphingosine. These results imply that sphingosine, at relatively low concentrations, brings about hyperaggregability of the platelets by the agonists employed, probably owing to enhancement of the phospholipase C activity. Such an effect appears to be induced by a mechanism independent of protein kinase C inhibition. We suggest that sphingosine might act as a positive modulator for the stimulus-response coupling in the platelets.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1992

Combination of patch test and IgE for dust mite antigens differentiates 130 patients with atopic dermatitis into four groups.

BACKGROUND: Patients with atopic dermatitis sometimes have positive responses to patch testing (PT) with dust mite antigens, which is believed to correlate with the elevated levels of specific IgE for those antigens. OBJECTIVE: The purpose of this study is to identify the correlation between the PT and serum IgE concerning the mite antigens. METHODS: We studied 130 patients with atopic dermatitis by the PT reaction and the serum level of specific IgE for Dermatophagoides pteronyssinus antigens. RESULTS: Fifty-one of the 130 patients assessed as PT-positive had either high (32 of 130 patients; 24.6%) or low or no (19 of 130 patients; 14.6%) levels of mite-specific IgE; there was a significant difference between the groups with elevated and low IgE. Similarly, a total of 79 PT-negative patients also showed an elevated or low mite-specific IgE (42 of 130 patients [32.3%] or 37 of 130 patients [28.5%], respectively). It was noted that clinical morphologic findings were peculiar to three of the four groups; however, the patients who were PT-negative with a low IgE (37 of 130 patients) showed no particular clinical lesions. CONCLUSION: Comparing the results from our 130 patients, there was no correlation between the serum IgE level and the PT reaction for dust mite antigens. Conversely, the results of PT and mite-specific IgE could be used to divide these patients into four distinct groups, each with its own particular clinical morphology, suggesting the heterogeneity of this disease.

Adolescent↗
PubMed1992

Preferential activation of phospholipase A2 by low concentrations of phosphatidic acid with long-chain fatty acids in rabbit platelets.

The role of phosphatidic acid (PA) in the signal transduction system of platelets was studied using 1-stearoyl 2-arachidonoyl PA (PASA). When PASA was added to rabbit platelets, aggregation occurred. BW755C, a dual inhibitor of cyclooxygenase and lipoxygenase, as well as p-bromophenacyl bromide and mepacrine, inhibitors of phospholipase A2, inhibited the aggregation induced by low concentrations of PASA, but not that induced by high concentrations. PASA also stimulated, in a dose-dependent manner, arachidonic acid liberation, lysophosphatidylcholine and diacylglycerol formation, and mobilization of intracellular Ca2+; all of which were dependent on the presence of Ca2+ in the outer medium. The arachidonic acid liberation was inhibited by p-bromophenacyl bromide or mepacrine, while diacylglycerol formation by low concentrations of PASA was inhibited by BW755C. With platelet membrane fractions or with the platelets made permeable to Ca2+ by pretreatment with ionomycin, PASA caused arachidonic acid liberation in the presence of Ca2+. Furthermore, PASA enhanced the activity of phospholipase A2 partially purified from platelet cytosol acting on 1-palmitoyl-2-[14C]arachidonoyl-glycerophosphoethanolamine. These results provide evidence that PASA preferentially potentiates the activation of phospholipase A2 in cooperation with Ca2+, suggesting that PA acts as a positive feedback regulator to potentiate the activation of phospholipase A2 and contributes to the amplification of platelet activation.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1992

Synthesis and biological activity of 5'-aminobenzoxazinorifamycin derivatives.

Benzoxazinorifamycin reacted with various secondary amines to yield various 5'-substituted aminobenzoxazinorifamycin derivatives. The derivatives exhibited potent activities against gram-positive bacteria and mycobacteria. The antimicrobial activities of these compounds against Mycobacterium tuberculosis and Mycobacterium intracellulare were superior to those of rifampicin. Some of these compounds showed good plasma levels after oral administration in rats.

Animals↗
PubMed1992

Inherited heterozygous protein C deficiency and dysfunctional protein S with recurrent venous thrombotic diseases: a study of three generations of a Japanese family.

We describe a rare occurrence of a family affected with venous thrombosis, exhibiting a protein C (PC) deficiency and dysfunctional protein S (PS). The propositus and his father developed recurrent venous-thrombosis. Their PC deficiency was characterized by low levels of both antigen and activity, and their dysfunctional PS was suggested by low PS activities despite the presence of normal free PS antigen. Over three generations, six family members had a PC deficiency, and three had both a PC deficiency and a dysfunctional PS. The mode of inheritance of PC deficiency appears to be autosomal dominant.

Adolescent↗
PubMed1992

Anomalous multifocal ossification of the os calcis--case report.

A three-month-old female baby was diagnosed by roentgenograms as having bilateral multifocal ossification of the os calcis. Five ossification centers in the bilateral calcaneus were recognized. However, at one year of age the roentgenograms showed only three ossification centers, with cleft separating on both sides the anterior third from the posterior two-thirds of the bone. At two years of age, the three ossification centers had coalesced into a single composite ossification center and the cleft at the calcaneus disappeared.

Calcaneus↗
PubMed1992

Scanning electron microscopic study on dendritic cells and fibroblasts in connective tissue.

Perfusion fixation and intravascular resin injection were used to study in situ the cells of superficial fascia (loose connective tissue) of the rat limb by scanning and transmission electron microscopy. These procedures enabled us to differentiate fibroblasts, representative cells of the connective tissue and so-called "dendritic cells," the other cellular constituent of the tissue, known as possible antigen presenting cells. "Dendritic cells" were amoeboid with some spatular processes by which the cells clung to the collagen fiber bundles. The fine structures characteristics of macrophages; they contained abundant primary and secondary lysosomes and expressed factor XIIIa in their cytoplasm. Fibroblasts, on the other hand, were attenuated, sheet-like cells whose edges were juxtaposed closely to collagen and elastic fibers, and were further anchored by microfibrils. The cells were usually interconnected to each other with gap junctions, thus producing a cellular network in the connective tissue.

Animals↗