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Biomedical subjects

T Asano

Publications and source records attributed to T Asano.

At least 361 records · Page 20Linked to original sources
PubMed1996

Effect of mitochondrial and/or cytosolic glycerol 3-phosphate dehydrogenase overexpression on glucose-stimulated insulin secretion from MIN6 and HIT cells.

The glycerol phosphate shuttle consists of FAD-linked mitochondrial glycerol 3-phosphate dehydrogenase (mGPDH) and its cytosolic NAD-linked isoform (cGPDH). Impaired mGPDH activity has recently been suggested to be one of the primary causes of insulin secretory defects in beta-cells. We found that mGPDH and cGPDH activities in MIN6 cells are comparable to those of isolated islets and higher than those in HIT cells by eightfold and threefold, respectively. Therefore, we selected the MIN6 cell line as a beta-cell model with normally regulated insulin secretion and normal shuttle enzyme activities and the HIT cell line as a beta-cell model with impaired insulin secretion and lower activities of these enzymes. The role of these dehydrogenases in glucose-stimulated insulin secretion was addressed by examining the effects of overexpression of mGPDH and/or cGPDH via recombinant adenoviruses in these cells. Infection with recombinant adenovirus with a cDNA encoding the Escherichia coli beta-galactosidase gene resulted in expression of its gene in 90% of MIN6 and HIT cells. Infection with a recombinant adenovirus with mGPDH cDNA (Adex1CAmGPDH) caused 2.1-fold and 5.7-fold increases in dehydrogenase activity as compared with those of control MIN6 and HIT cells, respectively. Infection with a recombinant adenovirus with cGPDH cDNA (Adex1CAcGPDH) caused a more than 50-fold increase in activity in both cell lines. Glycerol phosphate shuttle flux, as estimated by [2-3H]glycerol conversion to [3H]H2O, was increased to 120-130% by infection with Adex1CAmGPDH, but not with Adex1CAcGPDH infection, in both MIN6 and HIT cells. No further increase in flux through the glycerol phosphate shuttle was detected when the cells were infected with Adex1CAmGPDH together with Adex1CAcGPDH. Furthermore, neither [U-14C]glucose oxidation nor the insulin secretory response to glucose was affected in either cell line. Thus, mGPDH abundance in MIN6 and HIT cells is not directly related to their insulin secretory capacity in response to glucose, and reduced expression of mGPDH is not the primary cause of abnormal insulin secretory responses in HIT cells. The present data indicate that the emerging hypothesis pointing to mGPDH deficiency as a possible cause of NIDDM needs to be carefully evaluated.

Adenoviridae↗
PubMed1996

Infantile acute monocytic leukemia with tumor formation in the skin expressing adhesion molecules as seen by electronmicroscopy.

We report a case of infantile acute monocytic leukemia associated with solid tumors in the skin. Light microscopy showed that the tumor cells were mainly spindle-shaped and arranged in tandem. Immunohistochemical staining showed that fibronectin was detected in the extracellular matrix (and partially on the surface of tumor cells), integrin alpha 5 beta 1 on the cell surface, and vinculin and actin were detected in the cytoplasm of the tumor cells. Electron microscopy showed that the tumor cells had perpendicular transmembranous fibrils and closely situated collections of cytoplasmic microfilaments beneath the cell membrane suggesting fibronexus-like structures. We conclude that the expression of fibronectin, integrin alpha 5 beta 1, vinculin, cytoplasmic actin and fibronexus-like structure in leukemic cells indicate these cells possess an adhesive function. The mechanism of formation of the extramedullary solid tumors in this patients involved these adhesion molecules of the tumor cells.

Bone Marrow↗
PubMed1996

Effects of a hydroxyl radical scavenger on delayed ischemic neurological deficits following aneurysmal subarachnoid hemorrhage: results of a multicenter, placebo-controlled double-blind trial.

A water-soluble, novel synthetic compound, AVS ((+/-)-N, N'-propylenedinicotinamide; nicaraven) has no demonstrable vasoactive properties but scavenges hydroxyl radicals in aqueous environmental conditions at neutral pH. Based on the results of preceding experimental and clinical studies showing marked ameliorative effects of AVS on cerebral vasospasm and ischemic brain damage, a multicenter, placebo-controlled double-blind clinical trial was undertaken to verify its beneficial effects on delayed ischemic neurological deficits (DINDs) due to vasospasm and on the overall outcome of patients with subarachnoid hemorrhage (SAH). A total of 162 patients with SAH who had Glasgow Coma Scale scores between 7 and 15 on admission were enrolled in the trial. Drug administration (4 g AVS or 4 g glucose as placebo; infused intravenously for 6-8 hours once a day) was begun within 5 days post-SAH and continued for 10 to 14 days. Intent-to-treat analysis of these patients revealed that the overall incidence of DINDs, which was defined as an exacerbation of impaired consciousness and/or focal neurological deficits, was significantly reduced, by 34.5% (placebo 54.2%, AVS 35.5%; p < 0.05, Mann-Whitney U-test). The Glasgow Outcome Scale (GOS) score at 1 month was significantly improved by AVS (p < 0.05, U-test). At 3 months, the difference in the GOS scores between the groups became marginal on U-tests (p < 0.10), but the percentage of good outcome tended to increase, with a relative increase of 20.3% (AVS 76.3%, placebo 63.4%; p < 0.10, chi-square test), and the cumulative incidence of death was significantly reduced (p < 0.05, log-rank test). No significant adverse reaction attributable to treatment was observed. the usefulness of AVS in therapy for SAH is strongly indicated by the fact that the agent significantly ameliorated DINDs, leading to a marked improvement in the GOS scores at 1 month, as well as a reduction in the cumulative incidence of death by 3 months.

Adult↗
PubMed1996

[Historical investigation on herbal and medical literatures of processing and effect of Rehmanniae Radix].

The radix of Rehmannia glutinosa has been applied to medicinal use since ancient times, and has been called Kiou in the Han dynasty and has been classified by prepared methods, with each preparation given a different name. There were Syoujiou, Kanjiou and Zyukujiou etc. The first was introduced in the Sinnou-honzoukyou and the first and second had been used to prepare some prescriptions contained in the Kinki-youryaku and so on. The third began to appear on the medical and herbal literatures from the Tang period to the early Song. The Rehmanniae Radix has been used as the main material of Hokyoyouketu prescriptions, and by the use of Zyukujiou, their efficacy was regarded to be particularly stronger than the others. The preparation of Hatimigan recorded in the Kinki-youryaku had been used in Kanjiou but was later replaced with Zyukujiou. We should rethink about the quality and process of Chinese herbs on the pharmacy of Kampo medicine.

China↗
PubMed1996

[Cerebral atrophy and ventricular enlargement in physiological ageing--a morphometrical study in 28 autopsy brain of normal old people].

It is generally agreed that the adult human brain shows atrophy with advance of ageing. Although this phenomenon has been confirmed, mainly by measurement on CT images, there were only a few studies on brains over the age of 70 years. We measured the cranial cavity volume brain volume and ventricular volume in 28 normal autopsy brains of from 63 to 96 years of age (mean 81.4 years). We found that the ratio between the brain volume and the cranial cavity volume (B/C ratio), and the ratio between the ventricular volume and the brain volume (V/B ratio), had no significant correlation to age (B/C ratio: r = 0.22, p = 0.28, V/B ratio; r = 0.13, p = 0.50). Although our results are compatible with the previous studies on very old people, they are different from those on middle aged and presenile people. We considered that the cerebral atrophy become far less marked after 70 years of age.

Aged↗
PubMed1996

Effect of herbimycin A on renal cancer cell growth.

We investigated the effect of herbimycin A on the monolayer growth of 4 human renal cell carcinoma (RCC) cell lines and a normal renal tubular cell line (RTC 13) using MTT [3-(4,5-dimethylthiszol-2,5-diphenyl tetrazolium bromide)] assay. Herbimycin A induced remarkable growth inhibition in each RCC cell line tested, without any morphological changes of the cells. At the concentration of 500 ng/ml, herbimycin A caused more than a 30% growth inhibition in all RCC cells (p < 0.005 vs RTC 13), while less than 7% growth inhibition was observed in RTC 13 at the same herbimycin A concentration. The cell cycle was estimated by analysing DNA (deoxyribonucleic acid) content using a FACS. A DNA histogram of RCC cells treated at herbimycin A showed a block in the cell cycle at the S and G2M phases. However, little effect by herbimycin A on RTC 13 cells was observed. Our results suggest that protein tyrosine kinases inhibitors, like herbimycin A, may offer a new treatment option for RCC patients.

Antibiotics, Antineoplastic↗
PubMed1996

Lysosomal glycolipid storage in the renal tubular epithelium in mastomys (Praomys coucha).

The renal proximal tubular epithelium of MCC strain of mastomys (Praomys coucha) exhibited a number of cytoplasmic vacuoles after conventional paraffin-embedding procedures. These vacuoles were strongly PAS-positive in cryostat sections. Ultra-structurally, they were double membrane-bound structures filled with myelin figures and acid phosphatase-positive electron-dense matrix. Immunofluorescent microscopy revealed that these structures contained GM2 ganglioside. Other tissues or organs were histologically normal. Mating experiments indicated that the ganglioside storage in MCC mastomys is inherited as an autosomal recessive trait.

Animals↗
PubMed1996

[Histopathological prognostic factors in 146 patients with renal cell carcinoma: comparison between incidental and non-incidental cases].

To characterize the prognostic factors among pathological structural pattern, cell type, infiltration, and incidental or non-incidental renal cell carcinoma (RCC), we reviewed the records of 146 patients with RCC who underwent nephrectomy at our institute. The patients were 26 to 86 years old (mean age 58). The men-to-women ratio was 3.2:1. The tumor originated in the right kidney in 83 patients and in the left in 63. The solid pattern was associated with poorer survival than other patterns (p < 0.01). Spindle or pleomorphic cell type had poorer survival than common type (p < 0.01). The number of incidentally discovered RCC has increased since 1986, and survival is better than in non-incidental RCC, because of smaller tumor size, low stage tumor (stages 1, 2; 83.6%), and fewer papillary or solid type. In addition, there were no spindle or pleomorphic cell type, grade 3 or INF gamma-positive case. Survival is good even when the tumor is large.

Adult↗
PubMed1996

Transfection of a human topoisomerase II alpha gene into etoposide-resistant human breast tumor cells sensitizes the cells to etoposide.

The etoposide-resistant human breast cancer cell line MDA-VP was derived from MDA-parent cells by sequential selection in increasing concentrations of etoposide. MDA-VP cells express a lower amount of topoisomerase II alpha mRNA than the MDA-parent does, have mutations in topoisomerase II alpha (topo II) cDNA, and show cross-resistance to doxorubicin and amsacrine. We investigated whether transfer of a normal human topoisomerase II alpha (H-topo II) gene into MDA-VP cells could overcome their resistance to etoposide. H-topo II in a mammalian expression vector containing a glucocorticoid-inducible mouse mammary tumor virus (MMTV) promoter (pMAMneo) was transfected into MDA-VP cells (MDA-VP-hTOP2MAM). These H-topo II-transfected cells showed increased H-topo II mRNA expression and protein levels compared with MDA-VP parental cells or with MDA-VP cells transfected with the control pMAM vector (MDA-VP-MAM). Following cell exposure to dexamethasone, DNA-protein cleavable complex formation and cytotoxicity induced by etoposide, doxorubicin, and amsacrine were increased in the MDA-VP-hTOP2MAM cells compared with MDA-VP-MAM cells. However, these changes were short-lived, and by 24 h, cytotoxicity, cleavable DNA-protein complex formation, and H-topo II protein levels returned to baseline values. These results indicate that sensitivity of MDA-VP cells correlated with changes in cellular H-topo II. The gene transfer of a normal H-topo II gene can sensitize MDA-VP cells to the actions of multiple antineoplastic agents that target topo II.

Amsacrine↗
PubMed1996

[Growth inhibition of human pancreatic cancer by farnesyl transferase inhibitor].

Ras is one of the key components in the signal transduction for cell growth. For acquisition of biological activity, Ras protein is required to bind to the inside of the plasma membrane after post-translational farnesylation. Manumycin, a competitive farnesyl transferase inhibitor, inhibits the growth of human pancreatic cancer cells (SUIT-2, MIAPaCa-2, AsPC-1, BxPC-3) in a dose dependent manner. The inhibitory concentration (IC50) of cell lines with a mutant K-ras gene (SUIT-2, MIAPaCa-2, AsPC-1) was lower than that of BxPC-3 with a wild-type. A high concentration of manumycin induced apoptosis, which is related to the inhibition of cell growth. Inhibition of Ras activity might be a new anti-cancer therapy in pancreatic cancer in which Ras plays a role.

Alkyl and Aryl Transferases↗
PubMed1996

Beta-cell loss and glucose induced signalling defects in diabetes mellitus caused by mitochondrial tRNALeu(UUR) gene mutation.

Japanese diabetic patients with diabetic mothers were screened, using peripheral leukocytes, for an A to G transition at nucleotide pair 3243, a tRNALeu(UUR) mutation of the mitochondrial gene. This mutation was identified in four pedigrees from among 300 unrelated patients. Diabetes mellitus cosegregated with the mutation, except in one young subject, and was maternally inherited. Long-term follow-up revealed that the underlying disorder, in affected individuals, is a progressive impairment of insulin secretion. In accordance with this finding, the mutation was found to be highly prevalent in a diabetes mellitus subset termed slowly progressive IDDM; the mutation was identified in 3 out of 27 subjects enrolled in the prospective study of islet cell antibody (ICA)-positive, initially non-insulin-dependent diabetic Japanese patients, who are at high risk of progressing to insulin dependence over several years. The histologic characteristics of slowly progressive insulin-dependent diabetes mellitus include substantial loss, though incomplete, of pancreatic beta-cells. Mitochondrial gene defects in beta-cells could therefore cause glucose-induced signalling defects as well as beta-cell loss. This would explain the wide range of diabetic phenotypes, from NIDDM to IDDM, in patients with this mitochondrial gene mutation.

Adult↗
PubMed1996

[Nicorandil, as ATP-sensitive K+ channel opener, potentiated morphine analgesia].

Recent reports demonstrated that K+ channels could contribute to signal transmission in the brain and spinal cord, and opioids' action may be related to K+ channels' functions. We investigated the antinociceptive effect of epidurally injected ATP-sensitive K+ channel opener, nicorandil, using tail flick test in rats. Epidural nicorandil (100 micrograms.rat-1) increased % maximum possible effect (%MPE) of epidural morphine (1, 10 micrograms.rat-1) from -3% to 40% (P < 0.05) and 46% to 65%, respectively. Epidural glibenclamide (10 micrograms.rat-1), ATP-sensitive K+ channel blocker, antagonized this effect. Epidural nicorandil alone (10 approximately 100 micrograms.rat-1) showed no antinociceptive effects. Systemic nicorandil (100 micrograms.rat-1, i.m.) did not increase the epidural morphine analgesia. These data suggest that the K+ channel opener could point the way to a new approach to pain treatment.

Adenosine Triphosphate↗
PubMed1996

[Organ Preservation].

Organ procurement is the first step of organ preservation. We have developed "in situ machine wash out technique with CMH solution" for the purpose of rapid cooling and complete elimination of blood. The utility of this technique was confirmed by both experimentally and clinically. Two major techniques have been used for organ preservation. One is a simple cold storage. Using this method, it is easy to transport organs for transplantation. In addition, availability of UW solution is another advantage of this method. The other is a continuous hypothermic perfusion. Despite of complexity and difficulty of organ transportation, this technique has some advantages, such as viability assay and pretreatment of organs before transplantation. In our experimental studies, viability assays of canine liver and pancreas were achieved using a organ perfusion machine. We also succeeded to prolong the survival of canine pancreatic allograft by pretreatment of anti-Ia antibody during perfusion. While, cryopreservation is most suitable for cell preservation like pancreatic islets. Recently, gene technology was applied for organ preservation studies. In the future, this might become a potent tool for studies in this field.

Cryopreservation↗