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Biomedical subjects

T Hashizume

Publications and source records attributed to T Hashizume.

At least 37 records · Page 2Linked to original sources

[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

[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

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

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

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

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

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

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

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

Sphingosine enhances phosphatidylinositol 4-kinase activity in rabbit platelets.

The modulating effect of sphingosine on the metabolism of inositol phospholipids was investigated using rabbit platelets. When [3H]arachidonic acid- or [3H]inositol-labeled platelets were incubated at 37 degrees C with sphingosine, the radioactivity of the phosphatidylinositol (PI) fraction obtained on TLC decreased time-dependently up to 5 min, and phosphatidylinositol monophosphate (PIP) and phosphatidylinositol bisphosphate (PIP2) increased concomitantly, though neither arachidonic acid nor 1,2-diacylglycerol was formed. The effect of sphingosine was dose-dependent, the maximum effect being observed at 20 microM. Treatment with a sphingosine derivative, sphingosine-1-phosphate (Sph-1-P) or N-hexanoyl-sphingosine (C6-ceramide), did not result in an increase in PIP. The increased radioactivity of PIP with sphingosine was attributable to an increase in phosphatidylinositol 4-phosphate, but not phosphatidylinositol 3-phosphate. Furthermore, wortmannin, an inhibitor of PI 3-kinase, did not affect the modulating effect of sphingosine at 100 nM, at which the enzyme is known to be completely inhibited. The activity of PI 4-kinase in the platelet lysate was increased by sphingosine but not by Sph-1-P. These results suggest that sphingosine enhances the activity of PI 4-kinase and thereby contributes to the regulation of inositol phospholipid metabolism.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

Immunohistochemical detection of basic fibroblast growth factor as a prognostic indicator in pulmonary adenocarcinoma.

The expression of basic fibroblast growth factor (bFGF) was studied immunohistochemically in tissue specimens from 157 patients with pulmonary adenocarcinoma. Tumor cells that expressed bFGF were found in 89 patients (74%). The expression of bFGF was correlated with T and M in the TNM classification, disease stage and curability. The 5-year survival rate was 24% in bFGF-positive patients but 66% in bFGF-negative patients, the difference being significant (P<0.01). The 5-year survival rate of patients with stage I disease was 73% in those who were bFGF-positive but 88% in those who were bFGF-negative, the difference being significant (P<0.05). Multivariate analysis showed that the expression of bFGF was significantly related to prognosis. These findings suggest that bFGF plays an important role in tumor progression and that its expression may be a useful prognostic indicator for pulmonary adenocarcinoma.

Adenocarcinoma

Studies on internal structure of tablets. VI. stress dispersion in tablets by excipients.

The aim of this study was to reduce the stress concentration of a medicine by dispersing the stress in tablets at tableting by addition of excipients. The mechanism of the stress dispersion was elucidated. Phenacetin (PHE) was used as a model of crystalline medicine with a high brittleness, and the degree of stress dispersion was evaluated by the change in the exposed surface area of PHE. To learn the mechanical strength of tablets, the crushing strength and friability were measured, their internal structure was analyzed by the porosity and pore size distribution, and stress relaxation experiments were performed. The results were as follows. Calcium silicate (Florite RE, FLR) showed a high stress dispersion effect, adding a high formability and mechanical strength to tablets. It was thought that the high stress dispersion resulted from the rapid stress relaxation caused by the plastic deformation and brittleness fracture of pores in FLR under a low compression pressure. Thus the stress caused locally on PHE particles may disperse.

Drug Compounding

The effects of xylazine on plasma concentrations of growth hormone, insulin-like growth factor-I, glucose and insulin in calves.

The purpose of the present study was to examine the responses of plasma growth hormone (GH) and insulin-like growth factor-I (IGF-I) levels to intravenous injection of xylazine in female dairy calves. Xylazine (0.05, 0.15 and 0.30 mg/kg body wt., i.v.) injections induced a significant dose-dependent increase in plasma GH level within 30 min. After plasma GH levels reached peaks, GH concentrations began to decrease immediately and they returned to control levels 1 h after xylazine injection. Plasma IGF-I concentration tended to be suppressed by xylazine treatment. Xylazine induced a significant dose-dependent increase in plasma glucose for 3.5 to 5.5 h after the treatments. Xylazine also induced a significant decrease in plasma insulin level within 30 min after treatments. The present data suggested that xylazine stimulates GH release in cattle.

Analgesics

Effects of atipamezole, an alpha 2-adrenergic antagonist, and somatostatin on xylazine-induced growth hormone release in calves.

In order to clarify the mechanism of xylazine-induced GH release, we investigated the effects of atipamezole, a selective alpha 2-adrenergic antagonist, and somatostatin (SRIF) on xylazine-stimulated GH release in calves. Xylazine injection (0.30 mg/kg BW, iv) induced a rapid increase in the GH concentration. When atipamezole was used in combination with xylazine, it blunted the increase in the plasma GH concentration induced by the xylazine injection. The GH levels at 15-50 min after the simultaneous injection of xylazine and atipamezole were significantly (P < 0.05) lower than the corresponding values in the animals given xylazine alone. The area under the GH response curve for 120 min after the simultaneous injection of xylazine and atipamezole was significantly (P < 0.05) smaller than that for the xylazine alone. A series of five intravenous injections of 1 mg of SRIF at 10-min intervals also blunted xylazine-stimulated GH release. Atipamezole partially suppressed xylazine-induced hyperglycemia, but SRIF completely suppressed the hyperglycemia for the first 60 min after the xylazine injection and the suppression by SRIF was stronger than that by atipamezole. On the other hand, both atipamezole and SRIF failed to blunt xylazine-induced hypoinsulinemia. The present results suggest that xylazine stimulates GH release via the alpha 2-adrenergic pathway in cattle, but the mechanism of xylazine-induced hyperglycemia remains to be determined.

Adrenergic alpha-Antagonists

[Eosinophilic pneumonia presenting as a mass shadow].

A 35-year-old man underwent routine chest roentgenography and a mass shadow was seen in the left lung field. Examination of a transbronchial lung biopsy specimen revealed that many eosinophils had infiltrated under the bronchial mucosa and into the alveolar septum. The total serum IgE concentration was high, and skin tests with Aspergillus antigen and serum precipitating antibodies against Aspergillus were positive. The mass lesion disappeared without any therapy, and a cystic lesion remained. Mediators released from eosinophils were thought to have damaged the lung tissue. We should have administrated corticosteroids as soon as possible.

Adult

Bilirubin is oxidized in rats treated with endotoxin and acts as a physiological antioxidant synergistically with ascorbic acid in vivo.

We examined the possibility that bilirubin physiologically acts as an antioxidant by using scurvy-prone ODS-od/od rats treated with endotoxin (lipopolysaccharide: LPS). Recently, bilirubin oxidative metabolites were isolated from human urine and named biotripyrrin-a and biotripyrrin-b. The LPS injection markedly increased bilirubin oxidative metabolites in urine of rats fed an ascorbic acid-free diet. This increase was supressed by feeding an adequate amount of ascorbic acid, a physiological antioxidant. the concentrations of biotripyrrin-a and -b in urine collected 6.5-10 h after the LPS injection were lower in rats fed an ascorbic acid-supplemented diet than in rats fed an ascorbic acid-free diet. Moreover, feeding with ascorbic acid suppressed the elevation of hepatic mRNA level of heme oxygenase-1, the rate-limiting enzyme of bilirubin biosynthesis, in rats injected with LPS. These findings suggest that bilirubin is oxidized in rats treated with LPS and acts as a physiological antioxidant synergistically with ascorbic acid in vivo.

Animals