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T Andoh

Publications and source records attributed to T Andoh.

At least 127 records · Page 7Linked to original sources
PubMed1995

Molecular cloning of the plc1+ gene of Schizosaccharomyces pombe, which encodes a putative phosphoinositide-specific phospholipase C.

Exploiting the polymerase chain reaction, we have isolated a gene that encodes a putative phosphoinositide-specific phospholipase C (PLC) of the fission yeast Schizosaccharomyces pombe. Inspection of the nucleotide sequence of the gene revealed an open reading frame that can encode a polypeptide of 899 amino acid residues with a calculated molecular mass of 102 kDa. This putative polypeptide contains both the X and Y regions that are conserved among three classes of mammalian PLC, and also contains a presumptive Ca(2+)-binding site (an E-F hand motif). The structure of the putative protein is most similar to that of the delta class of PLC isozymes. To investigate the role of this gene, designated plc1+, gene disruption was carried out by interrupting the coding region with the ura4+ marker. Growth of plc1 cells was temperature-sensitive in rich medium, and cells could not grow in synthetic medium. Expression of the PLC1 gene of Saccharomyces cerevisiae suppressed the growth defect phenotype of plc1- cells, a strong suggestion that the plc1+ gene encodes PLC.

Amino Acid Sequence↗
PubMed1995

ICRF-193, an inhibitor of topoisomerase II, demonstrates that DNA replication in sperm nuclei reconstituted in Xenopus egg extracts does not require chromatin decondensation.

A bis(2,6-dioxopiperazine) derivative, ICRF-193, is a specific inhibitor of topoisomerase II without cleavable complex-stabilizing activity. In Xenopus egg extract containing ICRF-193, demembranated sperm head chromatins were inhibited from decondensation. However, nuclear envelope-lamina assembled on the inhibited chromatins. The nuclear envelope-lamina continued to expand even after loss of contact with the chromatin surface. On the other hand, semiconservative DNA replication was initiated as soon as the lamina was assembled onto the surface of condensed chromatin, though the initiation was retarded and its extent was reduced, compared with that in noninhibited chromatins. Thus, it is concluded that topoisomerase II activity is not required for the formation of active DNA replication clusters and the extension of nuclear envelope-lamina on the chromatin, while the nuclear envelope-mediated decondensation of sperm chromatins is dependent on topoisomerase II activity.

Animals↗
PubMed1995

Aphidicolin-sensitive DNA polymerase is incorporated into the chromatin during nuclear envelope assembly in Xenopus egg extract.

The mechanism for incorporation of aphidicolin-sensitive DNA polymerase into reconstituting sperm nuclei was studied in a Xenopus egg extract cell-free system. Aphidicolin-sensitive DNA polymerase activity was sedimented along with the light membrane fraction of Xenopus egg extract on a discontinuous sucrose gradient. Treatment of the egg extract with Triton X-100 caused DNA polymerase activity to migrate to a lighter density position at which free proteins were distributed. DNA polymerase activity was incorporated into the reconstituting sperm nuclei from the egg extract, but no nuclear incorporation was observed in nuclei incubated in egg extracts which had been treated with Triton X-100 or sonicated. The incorporation was also prohibited by several different treatments of the egg extract resulting in incomplete assembly of the nuclear membrane on the sperm nuclei. On the other hand, there was no inhibition of nuclear incorporation into the sperm nuclei reconstituting in the extracts which had been depleted of WGA-binding pore complex proteins or which contained a specific inhibitor of topoisomerase II (ICRF-193). In these two cases, the nuclear double-layered membrane assembled normally, although in the former case the sperm nuclei lacked lamina and did not initiate DNA replication, and in the latter case the sperm nuclei did not decondense but initiated DNA replication. Thus, it is concluded that DNA polymerase activity is incorporated into the reconstituting nuclei via the membraneous/particulate fraction of the egg extract simultaneously with nuclear double-layered membrane assembly. The lamina assembly and the transport system via the nuclear envelope pore complex are suggested not to participate in DNA polymerase nuclear incorporation.

Animals↗
PubMed1995

Linderniosides A and B, oleanane saponins from Lindernia pyxidaria.

Two new oleanane-type triterpene saponins, named linderniosides A and B, were isolated from the whole plants of Lindernia pyxidaria, together with a known triterpene glycoide, medicagenic acid 3-O-glucuronide. The structures of these compounds were determined on the basis of spectral and chemical evidence.

Antifungal Agents↗
PubMed1995

Cyclosporine A induced arteriolopathy in a rat model of chronic cyclosporine nephropathy.

Chronic cyclosporine (CsA) nephrotoxicity is a major complication of heart, bone marrow, and renal transplantation, and is characterized in humans by striped interstitial fibrosis, tubular dilatation and atrophy, and hyalinization of hilar arterioles. This last feature is highly specific for cyclosporine injury and has been difficult to reproduce in normotensive animal models. Salt-depletion has been shown to sensitize rodents to the effects of CsA and accelerate the disease process. We conducted sequential studies in chronically salt depleted, pair fed rats treated with CsA (15 mg/kg, s.c.) or an equivalent dose of olive oil vehicle, and found a histologic lesion associated with CsA that consisted of striped cortical interstitial fibrosis, tubular dilatation and atrophy, and hyalinization of many afferent arterioles. The arteriolopathy was first detected at day 10 with progressive hyalinization of arterioles continuing until termination of the study at day 35. The arteriolopathy consisted initially of eosinophilic granular transformation of smooth muscle cells comprising afferent hilar glomerular arterioles, and progressed to foci of smooth muscle cell vacuolization and accumulation of discrete hyaline deposits in vessel walls. Electron microscopy demonstrated marked accumulation of typical renin granules throughout the smooth muscle cell cytoplasm, corresponding to the eosinophilic granular transformation revealed histologically. Immunocytochemistry confirmed the up-regulated production of renin in these vessels. This study documents a rodent model for CsA arteriolopathy and CsA-associated interstitial fibrosis that strikingly reproduces the most characteristic nephropathic effects of cyclosporine found in human patients treated with this agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Cellular proliferation and macrophage influx precede interstitial fibrosis in cyclosporine nephrotoxicity.

Chronic cyclosporine (CsA) nephrotoxicity is a major complication of solid organ transplantation, and is characterized histologically by striped tubulointerstitial fibrosis, tubular atrophy, and hyalinization of the afferent arteriole, a highly specific finding in cyclosporine injury. The salt-depleted rat model of chronic cyclosporine nephropathy mimics these lesions in humans. We conducted sequential studies of this model in groups of pair fed rats (N = 6) treated with CsA (15 mg/kg, s.q.) or an equivalent dose of olive oil. Proliferation of tubular and interstitial cells was documented early in the medulla by day 5 (3.2 +/- 2.1 vs. 0.81 +/- 0.4 cells/HPF in CsA vs. control, P < 0.02), and was maximal in areas of interstitial fibrosis by day 35 (7.9 +/- 3.7 vs. 0.52 +/- 0.2 cells/HPF in CsA vs. control, P < 0.005). The interstitial fibrosis was associated with a significant macrophage influx by day 35 (13.9 +/- 3.5 vs. 1.5 +/- 0.32 cells/HPF, CsA vs. control, P < 0.005), which correlated with increased cortical tubular staining for the macrophage adhesion protein, osteopontin. Elevated serum creatinine correlated with interstitial fibrosis at day 35 (0.85 +/- 0.11 vs. 0.40 +/- 0.03 mg/dl Cr, CsA vs. control, P < 0.005) by linear regression (r = 0.9, P < 0.05). Medullary proliferation and interstitial fibrosis correlated with decreased tubular concentrating ability, and higher urinary volume. Cortical interstitial fibrosis was maximal at day 35 and was associated with an increase in type I and type IV collagen deposition, while tubular injury was associated with increased vimentin expression. Tubular interstitial cells also expressed increased vimentin early in the medulla (day 10) and later in the cortex. Both groups remained normotensive despite significantly elevated juxtaglomerular (JG) apparatus renin expression in CsA treated animals, implicating the intrarenal-renal renin-angiotensin system in this disease. We conclude that cyclosporine nephrotoxicity is associated with early tubular and interstitial cell proliferation, and a significant macrophage influx that precedes the development of cortical interstitial fibrosis and afferent arteriolar hyalinosis. These early cellular changes correlate with functional abnormalities including decreased creatinine clearance (CCr) and decreased medullary concentrating ability, which stabilized despite progressive fibrosis. These cellular events may be important in the pathogenesis of chronic CsA nephrotoxicity.

Animals↗
PubMed1995

Cytosolic free calcium elevation in vascular smooth muscle cells induced by cerebrospinal fluid from patients with subarachnoid hemorrhage--biochemical nature of the calcium-mobilizing factor.

The present study was undertaken to characterize the biochemical nature of the factor in cerebrospinal fluid (CSF) from patients with subarachnoid hemorrhage (SAH) that induces a transient elevation of cytosolic free calcium in cultured vascular smooth muscle cells. Cell-free CSF collected from patients on days 7-10 after SAH was treated in three different ways: heating, ultrafiltration, and salting out with ammonium sulfate. The effects of the resultant solutions on the level of cytosolic free calcium in cultured vascular smooth muscle cells were then examined. Heated CSF and ultrafiltrated solution containing substances with molecular weights of less than 10,000 caused no significant elevation of cytosolic free calcium. Proteins precipitated by 50-75% saturated ammonium sulfate caused an increase in the level of cytosolic free calcium and also produced a rapid accumulation of inositol 1,4,5-trisphosphate in vascular smooth muscle cells. The results indicate that the factor responsible for the increase in cytosolic free calcium in cultured vascular smooth muscle cells is a protein with a molecular weight of more than 10,000, and the factor stimulates receptor-mediated phosphoinositide breakdown.

Calcium↗
PubMed1995

[A case of recurrent constrictive pericarditis complicated with atrial septal defect].

A case of recurrent constrictive pericarditis complicated with atrial septal defect (ASD) was operated successfully at our institute. ASD was missed at the time of the first operation. The combination of ASD and constrictive pericarditis is rare and this case is the fifth reported one in Japan. Difficulty in diagnosis of ASD and operative procedure for recurrent constrictive pericarditis are described and discussed.

Heart Septal Defects, Atrial↗
PubMed1995

[A case of non-small-cell primary lung cancer invading distal aortic arch and left subclavian artery].

A 71-year-old male patient was referred to our institute for abnormal mediastinal shadow. It was proved to be squamous cell carcinoma arising in left S1 + 2 and involving distal aortic arch and left subclavian artery (T4N2M0 Stage IIIB). The cancer responded well to the preoperative induction therapy and it was resected completely with associated resection of distal aortic arch and left subclavian artery. Both arteries were replaced with Dacron grafts. With induction therapy and extended operation, this patient of non small cell T4 primary lung cancer is expected to acquire long term survival.

Aged↗
PubMed1994

Antitumor bisdioxopiperazines inhibit yeast DNA topoisomerase II by trapping the enzyme in the form of a closed protein clamp.

The mechanism of inhibition of eukaryotic DNA topoisomerase II [DNA topoisomerase (ATP-hydrolyzing), EC 5.99.1.3] by a member of the bisdioxopiperazine family of anticancer drugs, ICRF-193, was investigated by using purified yeast DNA topoisomerase II. In the absence of ATP, ICRF-193 has little effect on the binding of the enzyme to various forms of DNA. In the presence of ATP, the drug converts the enzyme to a form incapable of binding circular DNA. Incubation of a preformed circular DNA-enzyme complex with ICRF-193 and ATP converts the complex to a form stable in molar concentrations of salt. These results can be interpreted in terms of the ATP-modulated protein-clamp model of type II DNA topoisomerases [Roca, J. & Wang, J. C. (1992) Cell 71, 833-840]; ICRF-193 can bind to the closed-clamp form of the enzyme and prevents its conversion to the open-clamp form. This interpretation is further supported by the finding that whereas both ATP and the drug are needed to form the salt-stable circular DNA-enzyme complex, ATP is not needed for maintaining this complex; furthermore, a signature of the closed-clamp form of the enzyme, Staphylococcus aureus strain V8 endoproteinase cleavage site at Glu-680, is observed if the enzyme is incubated with both ATP and ICRF-193. Inhibition of interconversion between the open- and closed-clamp forms of type II DNA topoisomerases offers a new mechanism in the selection and design of therapeutics targeting this class of enzymes.

Adenosine Triphosphate↗
PubMed1994

Inhibition of DNA topoisomerase II by ICRF-193 induces polyploidization by uncoupling chromosome dynamics from other cell cycle events.

ICRF-193, a novel noncleavable, complex-stabilizing type topoisomerase (topo) II inhibitor, has been shown to target topo II in mammalian cells (Ishida, R., T. Miki, T. Narita, R. Yui, S. Sato, K. R. Utsumi, K. Tanabe, and T. Andoh. 1991. Cancer Res. 51:4909-4916). With the aim of elucidating the roles of topo II in mammalian cells, we examined the effects of ICRF-193 on the transition through the S phase, when the genome is replicated, and through the M phase, when the replicated genome is condensed and segregated. Replication of the genome did not appear to be affected by the drug because the scheduled synthesis of DNA and activation of cdc2 kinase followed by increase in mitotic index occurred normally, while VP-16, a cleavable, complex-stabilizing type topo II inhibitor, inhibited all these processes. In the M phase, however, late stages of chromosome condensation and segregation were clearly blocked by ICRF-193. Inhibition at the stage of compaction of 300-nm diameter chromatin fibers to 600-nm diameter chromatids was demonstrated using the drug during premature chromosome condensation (PCC) induced in tsBN2 baby hamster kidney cells in early S and G2 phases. In spite of interference with M phase chromosome dynamics, other mitotic events such as activation of cdc2 kinase, spindle apparatus reorganization and disassembly and reassembly of nuclear envelopes occurred, and the cells traversed an unusual M phase termed "absence of chromosome segregation" (ACS)-M phase. Cells then continued through further cell cycle rounds, becoming polyploid and losing viability. This effect of ICRF-193 on the cell cycle was shown to parallel that of inactivation of topo II on the cell cycle of the ts top2 mutant yeast. The results strongly suggest that the essential roles of topo II are confined to the M phase, when the enzyme decatenates intertwined replicated chromosomes. In other phases of the cycle, including the S phase, topo II may thus play a complementary role with topo I in controlling the torsional strain accumulated in various genetic processes.

Animals↗
PubMed1994

Effects of strong pulsed magnetic fields on the cardiac activity of an open chest dog.

The heart of an open chest dog was stimulated by strong magnetic fields which were damped sinusoidal pulses with the one-cycle period of 1.47 ms. Stimulation effects were detected by electrocardiograph (ECG) and arterial blood pressure as a function of the strength of the field, the triggering point in the cardiac cycle, and the position of a stimulating coil. The threshold for arrhythmias was a minimum for the stimuli triggered at the apex of the T wave and on the P wave in the ECG. Premature ventricular and premature atrial contractions occurred according to whether the coil was placed over the ventricles or the atria. Ventricular defibrillation can not be attained by the magnetic stimulus with the flux density of 9.2 T which was the maximum field used.

Animals↗
PubMed1994

Nephrotoxicity of immunosuppressive drugs.

Drugs used to modify the immune response in solid organ transplantation or autoimmune disease may cause dose-related nephrotoxicity. Cyclosporine, FK506, cyclosporine G, and rapamycin have all been studied experimentally and to a more limited extent in patients. This paper summarizes this literature using data from clinically relevant animal models.

Acute Kidney Injury↗
PubMed1994

[Serum and tissue levels of cefodizime in the pediatric patients].

We administrated cefodizime (40 mg/kg) to 13 patients with simple herniorrhaphy in the pediatric field and determined its concentrations in tissues and serums. The mean serum and tissue levels of cefodizime after administration were 43.1 +/- 13.3 micrograms/ml, and 23.1 +/- 6.4 micrograms/g, respectively, at 3 hours. Cefodizime concentrations of the tissue and serum were maintained at relatively high levels for many hours. The ratio of cefodizime concentrations in tissue to serum became high at 3 hours after administration, and this suggests that tissue concentrations decreased more slowly than serum levels, and cefodizime concentrations in tissue were maintained at fairly high levels over a long period. No side effects caused by cefodizime were observed. From pharmacokinetic and clinical observations, cefodizime appears to be a safe and effective injectable antibiotic for the treatment of infections in children.

Bacterial Infections↗
PubMed1994

[Giant serpentine aneurysm followed up for more than 10 years: report of a case and review of the literature].

We report a case of a giant serpentine aneurysm (GSA) located at the left internal carotid artery (ICA) and middle cerebral artery (MCA) treated by ligation of the left ICA with superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis. The aneurysm form changed variously during the follow-up period. A 35-year-old man was admitted with severe headache and convulsion. CT scan demonstrated subarachnoid hemorrhage. Left carotid angiogram demonstrated a giant serpentine aneurysm. Ligation of the ICA with STA-MCA anastomosis was performed because of the difficulty involved in clipping. Right carotid angiogram obtained 5 years later revealed disappearance of the tortuous vascular channel and a new aneurysmal shadow at the left carotid bifurcation. The size of the aneurysmal shadow increased gradually over 10 years. MRI and MR angiography which clearly demonstrated the presence of the aneurysm and the vascular channel simultaneously were considered useful methods for diagnosis of GSA. The authors reviewed previous reports of 19 cases and investigated the mechanism of GSA.

Adult↗