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T Hashizume

Publications and source records attributed to T Hashizume.

At least 73 records · Page 4Linked to original sources
PubMed1997

Effects of growth hormone (GH)-releasing hormone and its analogs on GH secretion from cultured adenohypophysial cells in cattle.

The effects of the human growth hormone (GH)-releasing hormone (hGRF(1-44)-NH2: hGRF-44), bovine GRF (bGRF(1-44)-NH2: bGRF-44), and their analogs (hGRF(1-29)-NH2, [D-Ala2]- hGRF(1-29)-NH2, bGRF(1-29)-NH2,[D-Ala2,Ala15]-bGRF(1-29)-NH2) as well as rat GRF(rGRF) on bovine GH release from anterior pituitary (AP) cells were studied in vitro in steers. The AP cells were incubated for 2 hr with the GRFs after preincubation for 3.5 d. Both of the hGRF-44 and hGRF(1-29)-NH2 (hGRF-29) significantly stimulated GH release from cultured cells at doses from 10(-14) to 10(-8)M (P < 0.01). The analog [D-Ala2]-hGRF-29 significantly induced GH release in media at doses from 10(-18) to 10(-8) M (P < 0.01). The bGRF-44, bGRF(1-29)-NH2 (bGRF-29), and [D-Ala2, Ala15]-bGRF-29 significantly induced GH release in media at doses as low as 10(-18), 10(-17), and 10(-16)M, respectively (P < 0.01). At doses from 10(-11) to 10(-8)M, there were no significant differences in GH-releasing potency between the hGRFs and bGRFs. The rGRF significantly stimulated GH release at doses ranging from 10(-14) to 10(-8) M (P < 0.01). The linear regression tests showed that the hGRFs, bGRFs, and rGRF, at doses from 10(-14) to 10(-8)M, induced GH release in a dose-related manner (P < 0.01). These results suggest that the hGRF, bGRF, and their analogs, as well as rGRF, are potent secretagogues of GH release from adenohypophysial cells in vitro in cattle.

Animals↗
PubMed1997

Sphingosine enhances arachidonic acid liberation in response to U46619 through an increase in phospholipase A2 activity in rabbit platelets.

Treatment of rabbit platelets for 1 min with 10-15 microM sphingosine enhanced arachidonic acid liberation after stimulation with U46619, although sphingosine or U46619 alone elicited little liberation of the lipid. Thrombin-induced arachidonic acid liberation was not influenced by sphingosine up to 10 microM, and was suppressed at concentrations higher than 20 microM. Sphingosine also promoted lysophosphatidylcholine formation in response to U46619, indicating that sphingosine caused an increase in hydrolytic action of phospholipase A2 (PLA2). The enhancing effect of sphingosine on arachidonic acid liberation decreased with increases in pretreatment time, accompanied by the conversion of sphingosine to sphingosine-1-phosphate. Of various sphingosine derivatives examined, sphingosine-1-phosphate, N,N-dimethylsphingosine, and N-acetylsphingosine (C2-ceramide) showed little enhancing effect on arachidonic acid liberation. Sphingosine increased cytosolic PLA2 activity in response to U46619 with enhancement of mitogen-activated protein kinase activity. These results indicate that sphingosine potentiates the transduction process of stimulus-PLA2 activation, resulting in enhancement of arachidonic acid liberation.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1997

Therapeutic efficacy of BO-3482, a novel dithiocarbamate carbapenem, in mice infected with methicillin-resistant Staphylococcus aureus.

The in vivo activity of BO-3482, which has a dithiocarbamate chain at the C-2 position of 1beta-methyl-carbapenem, was compared with those of vancomycin and imipenem in murine models of septicemia and thigh infection with methicillin-resistant Staphylococcus aureus (MRSA). Because BO-3482 was more susceptible than imipenem to renal dehydropeptidase I in a kinetic study of hydrolysis by this renal enzyme, the therapeutic efficacy of BO-3482 was determined during coadministration with cilastatin. In the septicemia models, which involved two homogeneous MRSA strains and one heterogeneous MRSA strain, the 50% effective doses were, respectively, 4.80, 6.06, and 0.46 mg/kg of body weight for BO-3482; 5.56, 2.15, and 1.79 mg/kg for vancomycin; and >200, >200, and 15.9 mg/kg for imipenem. BO-3482 was also as effective as vancomycin in an MRSA septicemia model with mice with cyclophosphamide-induced immunosuppression. In the thigh infection model with a homogeneous MRSA strain, the bacterial counts in tissues treated with BO-3482-cilastatin were significantly reduced in a dose-dependent manner compared with the counts in those treated with vancomycin and imipenem-cilastatin (P < 0.001). These results indicate that BO-3482-cilastatin is as effective as vancomycin in murine systemic infections and is more bactericidal than vancomycin in local-tissue infections. The potent in vivo activity of BO-3482-cilastatin against such MRSA infections can be ascribed to the good in vitro anti-MRSA activity and improved pharmacokinetics in mice when BO-3482 is combined with cilastatin and to the bactericidal nature of the carbapenem.

Animals↗
PubMed1997

In vitro evaluation of BO-3482, a novel dithiocarbamate carbapenem with activity against methicillin-resistant staphylococci.

BO-3482, a dithiocarbamate carbapenem, inhibited clinical isolates of methicillin-resistant staphylococci (MRS) at 6.25 microg/ml (MIC at which 90% of isolates tested are inhibited [MIC90]), while the MIC90 of imipenem was > 100 microg/ml. BO-3482 was generally less active than imipenem against methicillin-susceptible Staphylococcus aureus, streptococci, enterococci, and gram-negative bacteria, although BO-3482 showed better activity (MIC90) than imipenem against Enterococcus faecium, Haemophilus influenzae, Proteus mirabilis, and Clostridium difficile. The affinities (50% inhibitory concentrations) of BO-3482 for penicillin-binding protein (PBP) PBP 2' of MRS and PBP 5 of E. faecium (both PBPs have low affinities for ordinary beta-lactam antibiotics) were 3.8 and 20 microg/ml, respectively, reflecting the greater activity of BO-3482 against MRS than against E. faecium.

Anti-Bacterial Agents↗
PubMed1997

Effects of growth hormone-releasing hormone (GRF) analogs, bovine and rat GRF on growth hormone secretion in cattle in vivo.

Effects of bovine and human growth hormone-releasing hormone (GRF) analogs (bGRF(1-29)-NH2: bGRF-29, [D-Ala2, Ala15]-bGRF-29, [D-Ala2]-hGRF(1-29)-NH2: [D-Ala2]-hGRF-29), bovine GRF (bGRF(1-44)-NH2: bGRF-44), as well as rat GRF (rGRF) on GH release were studied in female calves. Intravenous (i.v.) bolus injections of 0.25 microg/kg BW of bGRF-29, [D-Ala2, Ala15]-bGRF-29, and [D-Ala2]-hGRF-29 stimulated GH release. Plasma GH levels began to rise 10 min after the injection of each peptide, and significant increases in GH concentrations were obtained at 60, 180 and 150 min after the injection of bGRF-29, [D-Ala2, Ala15]-bGRF-29 and [D-Ala2]-hGRF-29, respectively. The concentrations of GH 80 min after the injection of [D-Ala2, Ala15]-bGRF-29 were significantly higher than those after the injection of [D-Ala2]-hGRF-29 (except at 80 and 90 min) or bGRF-29. The i.v. bolus injections of 0.25 microg/kg BW of bGRF-44 and rGRF stimulated GH release, and the GH-releasing potency of rGRF was approximately equal to that of bGRF-44. The plasma GH responses to the repeated i.v. injection of bGRF-29 or [D-Ala2, Ala15]-bGRF-29 at 2-h intervals were examined. bGRF-29 acutely increased plasma GH levels after each injection, and the high GH levels decreased to the basal values within 2 h. In contrast, high GH levels induced by [D-Ala2, Ala15]-bGRF-29 were gradually decreased but not lowered to basal values throughout the experiment. These results show that [D-Ala2, Ala15]-bGRF-29 has longer-lasting and greater GH-releasing activity than the other GRF analogs in female calves, and the GH-releasing potency of rat GRF is approximately equal to that of bovine GRF in cattle in vivo.

Animals↗
PubMed1997

In vitro and in vivo evaluation of BO-2727 against imipenem- and/or meropenem-resistant Pseudomonas aeruginosa.

The in vitro and in vivo activity of BO-2727, a carbapenem antibiotic, against resistant clinical isolates of Pseudomonas aeruginosa was studied. The geometric mean MICs against three groups of clinical isolates resistant to imipenem, meropenem and both carbapenems were 4.28, 4.08 and 5.44 micrograms/ml, respectively. BO-2727 also inhibited multiply antibiotic resistant isolates and laboratory mutants including a nalB-type mutant, which showed resistance to antibiotics such as imipenem, meropenem, ceftazidime, and/or ciprofloxacin, at less than 1.56 micrograms/ml. Overall, BO-2727 was 4-fold more active than biapenem, meropenem, panipenem and imipenem with an MIC90 of less than 6.25 micrograms/ml. The presence of basic amino acids in minimal medium less affected the antipseudomonal activity to a minimal extent, suggesting that BO-2727 has diverse penetration routes through the outer membrane other than OprD channel, which facilitates the diffusion of basic amino acids and carbapenems. The in vitro activity of BO-2727 reflected well in its therapeutic efficacy in experimental systemic infection in mice. These results suggest a possibility for the development of antipseudomonal carbapenems having activity against imipenem- and/or meropenem-resistant P. aeruginosa as well as a broad spectrum encompassing Gram-positive and -negative bacteria.

Animals↗
PubMed1997

Affinities of BO-2727 for bacterial penicillin-binding proteins and morphological change of gram-negative rods.

Affinities of BO-2727, a new carbapenem, for penicillin-binding proteins (PBPs) of Escherichia coli. Pseudomonas aeruginosa and Staphylococcus aureus were studied. BO-2727 showed preferential affinity for PBP-2 of E. coli. and induced swollen and ovoid cells, when the organism was exposed to the MIC. In contrast, BO-2727 bound to both PBPs-2 and -3 of P. aeruginosa to a similar extent, and induced short filament cells with bulge. As compared with imipenem and meropenem, there was an observed difference in the affinity, especially for PBP-3, in both organisms; BO-2727 displayed intermediate affinity for PBP-3 between meropenem and imipenem. Studies on the affinity for PBPs of methicillin-susceptible S. aureus showed that the IC50 values for PBP-1 was roughly correlated with the MIC values of carbapenems tested, but those for the PBPs-2 and -3 appeared to be greater than the MIC values. In further studies on the affinity for PBP-2' of methicillin-resistant S. aureus. BO-2727 displayed better binding kinetics than imipenem, which reflected the better activity of BO-2727 than that of imipenem.

Bacterial Proteins↗
PubMed1997

[Lesion-related factors associated with restenosis after percutaneous transluminal coronary angioplasty in the absence of patient-related factors].

Restenosis after percutaneous transluminal coronary angioplasty (PTCA) is one of the biggest problems in the treatment of coronary artery disease. Although many studies have been performed on lesion-related factors, they are influenced by patient-related factors such as smoking, hyperlipidemia, and the presence of acute coronary syndrome. In this study, lesion-related factors were assessed in the absence of other factors by univariate and multivariate analysis. One hundred and nine lesions were reviewed in 37 consecutive patients with both restenotic lesion(s) and non-restenotic one(s) confirmed by coronary arteriography performed 4.4 +/- 2.2 months after PTCA. Angiographic findings before and immediately after angioplasty were compared between restenotic and non-restenotic lesions. The overall lesion-restenosis rate was 42%. Univariate analysis revealed that calcified lesions (p < 0.05), multiple irregularities (p < 0.01) before angioplasty, residual percentage stenosis (p < 0.05), and angiographical intraluminal haziness (p < 0.05) were related to restenosis. Intimal dissection after PTCA was not associated with restenosis. Multivariate analysis with multiple logistic regression revealed that multiple irregularities (t = 2.8) was the most predictive of restenosis before PTCA and residual percent stenosis (t = 2.6) after the procedure. Coronary lesions with calcification or multiple irregularities indicate high risk of restenosis after PTCA. Optimal dilatation of the lesions without intraluminal haziness regardless of intimal dissection is important to prevent restenosis.

Aged↗
PubMed1997

[Primary pulmonary lymphoma diagnosed from monoclonality of lymphocytes in a transbronchial biopsy specimen].

A 57-year-old man was found on a routine chest X-ray examination to have three infiltrative shadows: two in the right lung field and one in the left. Examination of a transbronchial biopsy specimen revealed infiltration of many small lymphocytes under the bronchial mucosa. In situ hybridization showed that they were monoclonal, and primary pulmonary lymphoma was diagnosed. The patient also had liver cirrhosis, diabetes mellitus, and hypertension. He was treated with a combination of pirarubein, cyclo-phosphamide, vindesine, prednisolone, and etoposide, but the tumors did not shrink. Therefore, as of the time of this writing he was being given only etoposide.

Biopsy↗
PubMed1997

[Pleural B cell lymphoma presenting as paraplegia].

A 54-year-old man felt pain on the right side of his chest. Two months later, paraplegia developed. A chest CT scan revealed a pleural effusion and a mass lesion along the right parietal pleura. The lesion extended directly into the adjacent part of the spinal canal and compressed the spinal cord. Cytologic examination of the pleural effusion revealed atypical lymphoid cells, and examination of a transcutaneous biopsy specimen showed monotonous atypical B lymphocytes. The diagnosis was pleural malignant lymphoma. Chemotherapy induced a partial remission, but 14 months after the first examination he died of central nervous system involvement. Pleural lymphoma can directly compress the spinal cord and cause paraplegia. Early diagnosis and therapy greatly affect the outcome in patients with spinal cord compression.

Humans↗
PubMed1997

Tumor angiogenesis in pulmonary adenocarcinomas: relationship with basic fibroblast growth factor, its receptor, and survival.

Tumor angiogenesis was examined in tissue specimens from 120 patients with a pulmonary adenocarcinoma. The microvascular density (MVD) was determined by the factor 8-related antigen (F8RA), and the basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor 1 (FGFR1) protein expressions were immunologically studied with the MVD. Patients with over 30 counts of the MVD showed significantly poorer prognosis than those with less than 30 counts. bFGF and FGFR1 expressions correlated with tumor angiogenesis and prognosis. Univariate analysis showed that the MVD, bFGF, and FGFR1 had a significant effect on prognosis, and multivariate analysis of three prognostic factors revealed the MVD correlated with survival. Our findings suggest that bFGF and FGFR1 expressions play an important role in tumor angiogenesis and that the bFGF and FGFR1 expressions promote angiogenesis and metastasis in pulmonary adenocarcinoma, and that the MVD is a useful prognostic marker for assessing the outcome of a pulmonary adenocarcinoma.

Adenocarcinoma↗
PubMed1996

Quantitative measurement of dihydrouridine in RNA using isotope dilution liquid chromatography-mass spectrometry (LC/MS).

A method has been developed for the microscale determination of 5,6-dihydrouridine, the most common post-transcriptional modification in bacterial and eukaryotic tRNA. The method is based on stable isotope dilution liquid chromatography-mass spectrometry (LC/MS) using [1,3-15N2]dihydrouridine and [1,3-15N2]uridine as internal standards. RNA samples were enzymatically digested to nucleosides before addition of the internal standards and subsequently analyzed by LC/MS with selected ion monitoring of protonated molecular ions of the labeled and unlabeled nucleosides. Sample quantities of approximately 1 pmol tRNA and 5 pmol 23S rRNA were analyzed for mole% dihydrouridine. Dihydrouridine content of Escherichia coli tRNASer(VGA) and tRNAThr(GGU) as controls were measured as 2.03 and 2.84 residues/tRNA molecule, representing accuracies of 98 and 95%. Overall precision values for the analyses of E. coli tRNASer(VGA) and E. coli tRNAThr(GGU), unfractionated tRNA from E. coli and 23S rRNA from E. coli were within the range 0.43-2.4%. The mole% dihydrouridine in unfractionated tRNA and 23S rRNA from E. coli were determined as 1.79 and 0.0396%, corresponding to 1.4 and 1.1 residues/RNA molecule respectively.

Chromatography, High Pressure Liquid↗
PubMed1996

Conformational flexibility in RNA: the role of dihydrouridine.

In order to further understand the structural role of the modified nucleoside dihydrouridine in RNA the solution conformations of Dp and ApDpA were analyzed by one- and two-dimensional proton NRM spectroscopy and compared with those of the related uridine-containing compounds. The analyses indicate that dihydrouridine significantly destabilizes the C3'-endo sugar conformation associated with base stacked, ordered, A-type helical RNA. Equilibrium constants (Keq = [C2'-endo]/[C3'-endo]) for C2'-endo-C3'-endo interconversion at 25 degrees C for Dp, the 5'-terminal A of ApDpA and D in ApDpA are 2.08, 1.35 and 10.8 respectively. Stabilization of the C2'-endo form was shown to be enhanced at low temperature, indicating that C2'-endo is the thermodynamically favored conformation for dihydrouridine. DeltaH values show that for Dp the C2'-endo sugar conformation is stabilized by 1.5 kcal/mol compared with Up. This effect is amplified for D in the oligonucleotide ApDpA and propagated to the 5'-neighboring A, with stabilization of the C2'-endo form by 5.3 kcal/mol for D and 3.6 kcal/mol for the 5'-terminal A. Post-transcriptional formation of dihydrouridine therefore represents a biological strategy opposite in effect to ribose methylation, 2-thiolation or pseudouridylation, all of which enhance regional stability through stabilization of the C3'-endo conformer. Dihydrouridine effectively promotes the C2'-endo sugar conformation, allowing for greater conformational flexibility and dynamic motion in regions of RNA where tertiary interactions and loop formation must be simultaneously accommodated.

Drug Stability↗
PubMed1996

Structural characterization of U*-1915 in domain IV from Escherichia coli 23S ribosomal RNA as 3-methylpseudouridine.

Mass spectrometry-based methods have been used to study post-transcriptional modification in the 1900-1974 nt segment of domain IV in 23S rRNA of Escherichia coli, a region which interacts with domain V in forming the three- dimensional structure of the peptidyl transferase center within the ribosome. A nucleoside constituent of M r 258 (U*)which occurs at position 1915, within the highly modified oligonucleotide sequence 1911-psiAACU*Apsi-1917, was characterized as 3-methylpseudouridine (m3psi). The assignment was confirmed by chemical synthesis of m3psi and comparison with the natural nucleoside by liquid chromatography-mass spectrometry. 3-Methylpseudouridine is previously unknown in nature and is the only known derivative of the common modified nucleoside pseudouridine thus far found in bacterial rRNA.

Base Sequence↗
PubMed1996

Insulin-like growth factor-II as a prognostic factor in pulmonary adenocarcinoma.

We stained resected specimens from 117 patients with pulmonary adenocarcinoma for insulin-like growth factor-II (IGF-II) by the avidin-biotin-peroxidase (ABC) method and evaluated the usefulness of IGF-II as a prognostic factor. The patients were classified into the IGF-II (+) groups showing staining of 1% or more cancer cells (60 patients) and the IGF-II (-) groups showing staining of <1% (57 patients). The 5-year survival rate was 22% in the IGF-II (+) group and 54% in the IGF-II (-) group (P<0.01). Our results suggest the usefulness of IGF-II stainability as a prognostic factor of pulmonary adenocarcinoma.

Adenocarcinoma↗
PubMed1996

The basic fibroblast growth factor and its receptor in pulmonary adenocarcinomas: an investigation of their expression as prognostic markers.

The expression of basic fibroblast growth factor (bFGF) and its receptor, the high-affinity type I basic fibroblast growth factor receptor (FGFR-1): were immunohistologically studied in tissues specimens from 167 patients with a pulmonary adenocarcinoma. Of the 167 specimens, 82 (49%) expressed bFGF and 104 (62%) expressed FGFR-1, bFGF and FGFR-1 were simultaneously expressed in 72 (43%). It was also found that many patients who showed intensely positive staining for bFGF were also positive for FGFR-1, and that the expression of bFGF or FGFR-1 or both was associated with p-stage, T and N factors. The overall prognosis was significantly poorer in the bFGF-positive or FGFR-1-positive patients than in negative patients (P < 0.01). The prognosis was also significantly poorer in all patients positive for both bFGF and FGFR-1 than in those negative for both (P < 0.01); this was also true for stage I patients (P < 0.05). Multivariate analysis showed that bFGF had a significant affect on prognosis, whereas FGFR-1 did not. As FGFR-1 is significantly linked with the bFGF expression, it may be that FGFR-1 interferes with the bFGF effect on survival. These findings suggest that bFGF and FGFR-1 play important roles in tumour progression, and that bFGF expression may be a useful prognostic marker for pulmonary adenocarcinomas.

Adenocarcinoma↗
PubMed1996

Expression of PDGF, IGF-II, bFGF and TGF-beta 1 in pulmonary adenocarcinoma.

Effects of the expression of the platelet-derived growth factor (PDGF), insulin-like growth factor-II (IGF-II), basic fibroblast growth factor (bFGF) and transforming growth factor (TGF)-beta 1 were studied individually and in combinations with the clinicopathologic features and prognosis of pulmonary adenocarcinoma using paraffin embedded tissue specimens. Tumor sections from 90 patients with pulmonary adenocarcinoma were stained immunohistochemically for PDGF, IGF-II, bFGF and TGF-beta 1 by the ABC method. The survival rate was worse in patients in whom each of the four growth factors was expressed than in those where growth factors were not expressed. The reduced expression of the four growth factors correlated with less tumor aggressiveness and better prognosis of pulmonary adenocarcinoma.

Adenocarcinoma↗