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Biomedical subjects

R Suzuki

Publications and source records attributed to R Suzuki.

842 records · Page 47Linked to original sources

Effects of adrenergic agents and phosphodiesterase inhibitors on outflow facility and cell shape of bovine trabecular meshwork.

Changes in the outflow facility of perfused calf eyes and in the shape of cells in cultured trabecular meshwork (TM) have been studied, following exposure to adrenergic agents and phosphodiesterase inhibitors (PDE). Dobutamine caused confluent TM cells to change their usual polygonal shape to a characteristic stellate shape. Salbutamol had no effect, but PDE inhibitors, isobutylmethylxanthine (IBMX), theophylline, and caffeine were very effective in producing this shape change. Epinephrine, isoproterenol, dobutamine, and salbutamol did not increase the outflow facility, either at 22 degrees C or 36 degrees C, while theophylline, caffeine, and IBMX did increase it in a dose-dependent manner. On the other hand, the high concentrations of beta-adrenergic agents required to produce even a small change in outflow facility and cell shape argue against the involvement of adrenergic-receptor mediation and may suggest another mechanism; on the other, the enhancement of epinephrine effects by PDE inhibitors and the similar effect produced by cyclic adenosine 3',5'-cyclic phosphate (cAMP) and purines suggest that changes in the cell shape are produced by beta-receptor activation. The beta-adrenergic agents were not effective in changing outflow facility, but the PDE inhibitors were remarkably effective both in changing the shape and in increasing facility.

Administration, Topical↗

Analysis of TCRAV and TCRBV repertoires in healthy individuals by microplate hybridization assay.

We have developed an adaptor ligation PCR-based microplate hybridization assay (MHA) for analysis of T cell receptor alpha chain variable region (TCRAV) and T cell receptor beta chain variable region (TCRBV) repertoires. Forty three TCRAV and thirty eight TCRBV-specific probes were immobilized onto microplate wells in water-soluble carbodiimide. After hybridization of 5'-biotinylated PCR products, quantitative ELISA was carried out and followed by automated colorimetric reading. The conditions for immobilization and hybridization were optimized using representative TCRBV-specific probes. The sensitivity of MHA allows us to detect as low as 40 pg of biotinylated PCR products. The frequencies of individual V segments obtained by MHA were consistent with those obtained by FACS analysis and reverse dot blot assays. Analysis of the entire TCRAV and TCRBV repertoires could be done using a single 96-well plate, and completed in less than 6 h. Simplicity and reproducibility of this method make it suitable for routine laboratory use. The expression of TCRAV and TCRBV segments was next studied in peripheral blood mononuclear cells (PBMC) of 14 healthy donors using the newly developed MHA method. TCRAV8S1, TCRAV23S1, TCRBV2S1, TCRBV3S1, TCRBV4S1, and TCRBV6S5 were highly expressed in PBMC. Further, the TCRAV repertoires among individuals were less variable compared to the TCRBV repertoires. Interestingly, considerable variations in the expression levels of BV3S1, BV4S1, and BV17S1 were observed among individuals. One polymorphic site was found at the coding region of BV4S1, and there were two alleles. These results suggest that variable expression among individuals may be associated with unknown allelic polymorphism in coding and/or regulatory regions of these TCRBV segments, or with disparity in HLA genes.

Flow Cytometry↗

Depth profile of free volume in a mixture and copolymers of poly(N-vinyl-pyrrolidone) and poly(ethylene glycol) studied by positron annihilation spectroscopy.

Effect of hydrogen bonding on the depth profile of the free-volume in a mixture (weight ratio of 65:35) of poly(N-vinyl-pyrrolidone) (PVP) and poly(ethylene glycol) (PEG) and the copolymers of vinyl pyrrolidone with poly(ethylene glycol) diacrylate (PVP-PEGDA) and monomethacrylate (PVP-PEGMMA) was studied using positron annihilation spectroscopy. Doppler broadening energy spectra of annihilation radiation and positron annihilation lifetime were measured as a function of positron incident energy (0-30 keV). Significant variations of the free-volume depth profile in terms of the S parameter, ortho-positronium lifetime, intensity, and lifetime distribution are observed as a result of the hydrogen-bonding replacement of covalent bonds. The polymer mixture with hydrogen bonding through two sides of PEG short chains has a larger free volume and a wider distribution than the comb-structured PVP-PEGMMA and the network structured PVP-PEGDA. A longer ortho-positronium lifetime is observed near the surface than in the bulk. This is interpreted in terms of surface effect, free volume, and hydrogen bonding for drug delivery applications of polymeric materials.

Drug Carriers↗

Studies on cytotoxic constituents in pericarps of Mallotus japonicus, Part I.

Two new phloroglucinol derivatives, named mallotophenone and mallotochromene, were isolated from the pericarps of Mallotus japonicus together with two known compounds, 3-(3,3-dimethylallyl)-5-(3-acetyl-2,4-dihydroxy-5-methyl-6- methoxybenzyl)-phloracetophenone and 2,6-dihydroxy-3-methyl-4-methoxyacetophenone. The new derivatives were confirmed to be 5-methylene-bis-2,6-dihydroxy-3-methyl-4-methoxyacetophenone and 8-acetyl-5,7-dihydroxy-6-(3-acetyl-2,4-dihydroxy-5-methyl-6- methoxybenzyl)2,2-dimethylchromene by their respective chemical and spectral data. Several of the phloroglucinol derivatives isolated from this tree were cytotoxic against the KB system and L-5178Y in cell culture.

Acetylation↗

Serial high resolution CT findings in nonspecific interstitial pneumonia/fibrosis.

PURPOSE: The purpose of this work was to evaluate the radiographic and serial high resolution CT (HRCT) findings in patients with nonspecific interstitial pneumonia/ fibrosis (NSIP). METHOD: We identified 15 patients with biopsy-proven NSIP. Radiography and initial and follow-up CT findings were reviewed. RESULTS: Predominant radiographic findings were bilateral infiltrates distributing in the middle and lower lung zones and decreased lung volumes. At initial CT, predominant patterns were peribronchovascular interstitial thickening (n = 6), parenchymal bands (n = 8), intralobular interstitial thickening (n = 12), and traction bronchiectasis (n = 14). Mixed pattern of ground-glass opacity and consolidation (n = 11) were predominant findings of increased lung opacity. At follow-up CT in 14 cases, the abnormalities had disappeared completely in 3, improved in 9, persisted in 1, and worsened in 1. CONCLUSION: The pulmonary abnormalities observed in NSIP on HRCT can disappear or be diminished in most cases after corticosteroid therapy. Intralobular interstitial thickening and traction bronchiectasis, which have been considered to be indicators of irreversible fibrosis, also show favorable responses.

Adult↗

p27Kip1 is the key mediator of phenylacetate induced cell cycle arrest in human prostate cancer cells.

Treatment with millimolar concentrations of phenylacetate (PA), results in cytostasis, growth inhibition and differentiation in several human cancer cell lines, including prostate cancer. However, the molecular basis of PA-induced biological effects has not been elucidated in detail. In this study we focused on its influence on cell cycle events and investigated alterations in cell cycle regulators in androgen-dependent and independent human prostate cancer cell lines. FACS analysis revealed that suppression of cell growth by PA was due to G1 arrest, with reduced phosphorylation of the retinoblastoma protein (pRb) and CDK2 activity. Expression of p27Kip1 was increased, while p21Cip1, p53, cyclinD1 and cyclin E were not affected by PA. Binding of p27Kip1 to CDK2 increased significantly following treatment with PA. Furthermore, antisense p27Kip1 oligonucleotide attenuated the inhibitory effect of PA. Our results suggested that p27Kip1 might be a critical target in PA-mediated cell growth arrest in prostate cancer cells playing a key role in CDK2 inactivation followed by hypophosphorylation of pRB and subsequent G1 cell cycle arrest.

Antimetabolites, Antineoplastic↗

Inhibition by lombricine from earthworm (Lumbricus terrestris) of the growth of spontaneous mammary tumours in SHN mice.

The effects of lombricine extracted and purified from earthworm (Lumbricus terrestris) skin on the growth of palpable sizes (approximately 5 mm) of spontaneous mammary tumours were studied in SHN mice. In Experiment 1, daily subcutaneous injections of lombricine (0.3 mg/0.05 ml olive oil) inhibited markedly the growth of tumours associated with the retardation of the growth of preneoplastic mammary hyperplastic alveolar nodules. In 1H-NMR spectra, the experimental mice had lower serum levels of lactic acid and glucose than the control. On the other hand, urine of the former group contained higher levels of allantoin, creatine and creatinine than that of the latter. In Experiment 2, lombricine given as diet at the concentration of 120 mg/kg also inhibited the growth of tumours, though to a lesser degree than the injection. The treatment had little effect on 1H-NMR spectra of either serum or urine and normal and preneoplastic mammary gland growth. All results indicate that the inhibition by lombricine of the growth of mammary tumours is at least partly due to the maintenance of homeostasis of the body including the regulation of the excess uptake of glucose as a source of energy and nutrition.

Animals↗

15-Deoxyspergualin, an antiproliferative agent for human and mouse leukemia cells shows inhibitory effects on the synthetic pathway of polyamines.

The mechanism of the antitumor action of 15-deoxyspergualin (DSG) was investigated. DSG inhibited spermidine synthase noncompetitively with putrescine, spermine synthase competitively with spermidine and polyamine oxidase in vitro. Induction of ornithine decarboxylase (ODC) activity observed after subculture of human leukemia cells was blocked by the addition of DSG to the culture medium. In DSG-treated leukemia cells, putrescine, spermidine and spermine levels were markedly depressed. The synthesis of protein was also greatly diminished in these polyamine-depleted leukemic cells, whereas the depressions of DNA and RNA syntheses were minimum. In in vivo experiments, DSG depressed polyamine levels in P388 leukemic ascites cells, and prolonged the survival times of mice bearing the leukemia cells. These results suggest that inhibition of polyamine and protein biosyntheses by DSG is substantially responsible for its antitumor action on the tumor cells.

Acetyltransferases↗

Successful surgical treatment of subaortic stenosis caused by an accessory mitral valve.

A 22-month-old boy with subaortic stenosis was found to have relatively mature mitral valve tissue beneath the aortic valve, associated with a hypertrophic and prominent interventricular septum. This tissue caused obstruction of the left ventricular outflow tract and resulted in a pressure gradient of 70 mmHg between the aorta and the left ventricle. Surgical treatment was successfully performed to excise the tissue and part of the hypertrophic ventricular septum. Results of microscopic examination of the resected specimen are shown and discussed.

Aortic Valve Stenosis↗

Aneurysm of the left subclavian artery associated with Turner's syndrome. Successful surgical treatment.

An unusual case of a 38-year-old woman with Turner's syndrome associated with aneurysmal dilation of the left subclavian artery is presented. Aortography revealed a fusiform aneurysm in the proximal segment of the left subclavian artery, which was as long as 6 cm. The diagnosis of Turner's syndrome was postoperatively confirmed by chromosomal study, which showed 45X0. The aneurysm was successfully removed and reconstruction was done by interposition of a woven Dacron graft, 8 mm in diameter and 6 cm in length, between the thoracic aorta and subclavian artery just proximal to the thoracic outlet. Microscopic findings of the resected tissue of the subclavian artery revealed deposition of acid mucopolysaccharide in the intima and media.

Adult↗

MRI of malignant melanoma of liver.

We report MR images of primary malignant melanoma of the liver. The tumor showed heterogeneously increased signal intensity on both T1- and T2-weighted images. After the administration of gadolinium-DTPA, the lesion presented irregular enhancement. Autopsy revealed a large black mass surrounded by fibrous tissue. The tumor consisted of atypical cells with melanin pigment, and had intratumoral degeneration, necrosis, and hemorrhage.

Aged↗