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T Akiyama

Publications and source records attributed to T Akiyama.

At least 19 recordsLinked to original sources
PubMed1995

Effect of age on postmyocardial infarction ventricular arrhythmias (Holter Registry data from CAST I and CAST II). Cardiovascular Arrhythmia Suppression Trials.

Holter data from the 17,609 postmyocardial infarction patients in the CAST Registry were analyzed to study the effect of age on VPC and VT incidence and frequency. Multivariable analysis demonstrated that age is an important independent predictor of increased ventricular ectopy, with the median rate of VPCs/hour increasing from 0.4 (patients aged < 50 years) to 4.0 (patients aged 75 to 80 years), and the prevalence of VT increasing from 7.3% (patients aged < 50 years) to 15.3% (patients aged 75 to 80 years).

Age Factors↗
PubMed1995

Constitutive overexpression of CDK2 inhibits neuronal differentiation of rat pheochromocytoma PC12 cells.

Changes in the levels of cyclins A, D, and E, p21, and cyclin-dependent kinase 2 (CDK2) were examined in rat pheochromocytoma PC12 cells during neuronal differentiation induced by nerve growth factor (NGF). Expression of cyclin A decreased to an undetectable level after 5 days of exposure to NGF, while expression of CDK2 decreased gradually after day 3. In contrast, the levels of cyclins D1 and E increased gradually through day 10, yet the amount of cyclin E associated with CDK2 decreased concomitant with a decrease in the CDK2 protein level. p21 expression increased gradually after day 7, while the level of CDK2-associated p21 remained unchanged. When human cDNAs encoding cyclins and CDK2 were introduced into PC12 cells, only CDK2 overexpression inhibited NGF-induced differentiation. The cell lines overexpressing CDK2 showed stable and high levels of CDK2 kinase activity during differentiation, whereas parental and vector-transfected cell lines displayed a marked decline in CDK2 kinase activity 1 day after NGF treatment. In cell lines overexpressing cyclins A, D, and E, this reduction of the kinase activity was not apparent until day 3. These results suggest that down-regulation of CDK2 activity is a crucial event for the neuronal differentiation of PC12 cells.

Adrenal Gland Neoplasms↗
PubMed1995

G1 phase arrest induced by Wilms tumor protein WT1 is abrogated by cyclin/CDK complexes.

WT1, the Wilms tumor-suppressor gene, maps to the human chromosomal region 11p13 and encodes a transcriptional repressor, WT1, implicated in controlling normal urogenital development. Microinjection of the WT1 cDNA into quiescent cells or cells in early to mid G1 phase blocked serum-induced cell cycle progression into S phase. The activity of WT1 varied significantly depending on the presence or absence of an alternatively spliced region located upstream of the zinc finger domain. The inhibitory activity of WT1 was abrogated by the overexpression of cyclin E/CDK2 as well as cyclin D1/CDK4. Furthermore, both CDK4- and CDK2-associated kinase activities were downregulated in cells overexpressing WT1, whereas the levels of CDK4, CDK2, and cyclin D1 expression were unchanged. These findings suggest that inhibition of the activity of cyclin/CDK complexes may be involved in mediating the WT1-induced cell cycle block.

3T3 Cells↗
PubMed1995

A case of gallbladder cancer associated with a common bile duct neuroma, and a cystic lesion of the liver with histologic findings similar to those of an inflammatory pseudotumor.

We report a rare case of gallbladder cancer associated with a common bile duct neuroma, and a cystic liver lesion with histologic findings similar to an inflammatory pseudotumor, in a patient who had had no previous abdominal surgery. The patient was a 62-year-old man whose major complaint was fever. Ultrasonography and a computed tomography scan revealed gallstones, an elevated lesion in the gallbladder, and a cystic liver lesion. Endoscopic retrograde cholangiopancreatography demonstrated stenosis of the common bile duct. Cultures of the cystic fluid and gallbladder bile were positive for Staphylococcus aureus. The patient underwent hepatectomy (inferior S4, S5, and S6), cholecystectomy, resection of the common bile duct, and right hemicolectomy. The resected specimens revealed gallbladder cancer with the microscopic appearance of a papillary adenocarcinoma, and a 12 x 4.5 x 3.5 cm cystic liver lesion with a wall 7 mm thick. Histologic studies of the wall of the cystic liver lesion revealed infiltration by histiocytes and plasma cells, and the presence of fibrous connective tissue, which findings are characteristic of inflammatory pseudotumors. A 9 x 6 mm elevated lesion, with the microscopic appearance of a neuroma, was resected from the common bile duct.

Adenocarcinoma, Papillary↗
PubMed1995

Effects of tetraprenylacetone on pancreatic exocrine secretion and acute pancreatitis in two experimental models in rats.

The effects of tetraprenylacetone (TPN), an acyclic polyisoprenoid with antiulcer actions, on pancreatic exocrine secretion, and its preventive and therapeutic effects on acute pancreatitis in two experimental models were studied in rats. Intraduodenal administration of TPN (0, 100, 200, and 400 mg/kg/h) caused dose-dependent increases in pancreatic juice and bicarbonate output without increasing protein output and plasma cholecystokinin (CCK) concentrations. TPN-stimulated pancreatic exocrine secretion was completely abolished by antisecretin serum but it was not by CCK receptor antagonist loxiglumide (50 mg/kg/h). In acute pancreatitis induced by four subcutaneous injections of 20 micrograms/kg cerulein at hourly intervals over, 3 h, TPN (400 mg/kg) given by an oral route either 1 h before the first cerulein injection or immediately after the last injection significantly reduced the increases in serum amylase and lipase activities and pancreatic wet wt. Pretreatment with TPN caused histologic improvements, whereas posttreatment failed to ameliorate histologic alterations. In severe type of acute pancreatitis induced by retrograde intraductal injection of 1.0 mL/kg of 4% sodium taurocholate, TPN exerted no apparent beneficial effects on biochemical and histologic alterations of acute pancreatitis. It is concluded that TPN given by an oral route stimulates pancreatic exocrine secretion through an increase in endogenous secretin release and causes beneficial effects on the experimental model of mild acute pancreatitis in rats.

Acute Disease↗
PubMed1995

Oxygen radical-induced single-strand DNA breaks and repair of the damage in a cell-free system.

Ferric nitrilotriacetate (Fe(3+)-NTA) catalyzes hydrogen peroxide-derived production of hydroxyl radicals, which are known to cause DNA damage. In the present work, Fe(3+)-NTA plus hydrogen peroxide-induced single-strand DNA breaks and repair of the DNA damage were studied in vitro by monitoring DNA damage- and DNA repair-dependent conformational changes of pUC18 plasmid DNA. Single-strand DNA breaks were induced in the pUC18 DNA by Fe(3+)-NTA plus hydrogen peroxide in a dose-dependent fashion. Induction of the DNA damage was inhibited by deferoxamine mesylate (an iron chelator) and by hydroxyl radical scavengers such as dimethyl sulfoxide (DMSO), D-mannitol and ethanol indicating that the DNA damage was caused by hydroxyl radicals which were generated by reaction of Fe(3+)-NTA with hydrogen peroxide. The oxygen radical-induced single-strand DNA breaks were repaired partly (more than 50%) by incubating the damaged DNA at 37 degrees C for 3 h with a partially purified preparation of APEX nuclease (a multifunctional DNA repair enzyme), DNA polymerase beta, four deoxyribonucleoside triphosphates, T4 DNA ligase and ATP. Analyses of the partially purified preparation of APEX nuclease revealed that a 45-kDa protein as well as APEX nuclease in the preparation were involved in the repair of the single-strand DNA breaks. APEX nuclease was suggested to initiate the repair by removing 3' termini blocked by the nucleotide fragments and also by incising the 5' side of AP sites. The 45-kDa protein was suggested to be required for removal of the 5' tags such as 5'-terminal deoxyribose phosphate residues produced by the action of APEX nuclease on AP sites.

Animals↗
PubMed1995

Stability and pharmacokinetic characteristics of oligonucleotides modified at terminal linkages in mice.

To construct the strategy for delivery systems that can control in vivo disposition of antisense oligonucleotides, we studied the stability and basic pharmacokinetic characteristics of oligonucleotides. Decathymidylic acid (T10), a model oligodeoxynucleotide, and its derivatives, 5'-biotin-T10) and 3'-methoxyethylamine 5'-biotin-T10 (3'M5'B-T10), containing phosphoroamidate modification at 3'- and/or 5'-terminal internucleoside linkages, were synthesized. In phosphate-buffered saline (PBS, pH 7.4) containing 10% mouse serum, unmodified T10 was degraded with a half-life of 45 minutes; the degradation half-lives of 5'B-T10 and 3'M5'B-T10 were 11 and 30 h, respectively. In mouse whole blood, 3'M5'B-T10 was relatively stable, and 45% remained intact after 1 h incubation. After intravenous injection of [3H]3'M5'B-T10 into mice at a dose of 1 mg/kg, the radioactivity was rapidly cleared from plasma with a half-life of 2 minutes and accumulated in the kidney, liver, and gallbladder. About 30% of the dose was excreted in the urine within 60 minutes. A much more rapid degradation of [3H]3'M5'B-T10 was observed in vivo than expected from in vitro experiments: more than 90% of the radioactivity in plasma was degradation product at 2 minutes after injection. These results suggested that enzymatic degradation occurred in some compartments in addition to the blood pool. The apparent urinary excretion clearance of [3H]3'M5'B-T10 was close to that of inulin, whereas the apparent hepatic uptake clearance was much greater than that of inulin and comparable to that of dextran sulfate, which is taken up by the liver by scavenger receptors for polyanions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Loss of sensitivity to cholecystokinin stimulation of isolated pancreatic acini from genetically diabetic rats.

Pancreatic exocrine function of a new inbred strain Otsuka Long-Evans Tokushima Fatty (OLETF) rat that develops spontaneous persistent hyperglycemia was evaluated in in vitro isolated pancreatic acini and compared with that in the control Long-Evans Tokushima Otsuka (LETO) rat. Serum glucose and insulin concentrations in the OLETF rats were significantly high (glucose: 270 +/- 12 vs. 208 +/- 10 mg/100 ml, P < 0.01; insulin: 12.4 +/- 1.7 vs. 4.9 +/- 0.6 ng/ml, P) < 0.01), whereas pancreatic wet weight was significantly low (803 +/- 20 vs. 1,138 +/- 17 mg, P < 0.01) compared with those in the LETO rat. Pancreatic acini isolated from the OLETF rat were totally insensitive to cholecystokinin (CCK)-8 stimulation at concentrations of up to 100 nM. However, neither the responsiveness nor the sensitivity to carbamylcholine, bombesin, and secretin of the acini from the OLETF rat was altered or even increased, probably due to the larger amylase content in the OLETF rat acini compared with those of the LETO rat acini (31.5 +/- 2.0 vs. 13.0 +/- 1.1 Somogyi units/micrograms DNA, P < 0.01). The responsiveness to fluoride, a direct activator of guanine nucleotide-binding protein, in the OLETF rat acini was similar to that in the LETO rat, suggesting that the transmembrane signaling and effectors and subsequent intracellular signal transduction molecules in the OLETF rat acini are normal. Moreover, 125I-CCK binding to the acini prepared from the OLETF rat was totally absent. These present results indicate that the OLETF rat has a selective defect in the binding of CCK to its receptors on the acinar cell surface.

Amylases↗
PubMed1995

[Renal transplant calculi in a renal allograft treated with extracorporeal shock wave lithotripsy in a patient with persistent hyperparathyroidism: a case report].

Between 1984 and 1991, six of 105 renal transplant recipients at our institution formed urinary tract calculi after transplantation (5.7%). In these 6 patients, one case of nephrolithiasis in a transplanted kidney was treated with extracorporeal shock wave lithotripsy (ESWL). A 37-year-old woman underwent cadaveric renal transplantation twenty months before, and her renal function remained stable. However calculi in the transplanted kidney and bladder were formed and ESWL was used for the treatment of the renal calculus in the transplanted kidney. She was discharged from the hospital two weeks postoperatively while passing small gravel in the urine after successful fragmentation of the calculus without any major complications. As follow-up KUB film two weeks later demonstrated that all stone fragments had been passed, but she was treated again by ESWL four months later because IVP films four weeks later revealed recurrent calculi in the transplanted kidney. The stones were fragmented successfully and spontaneously passed with voiding. Moreover we performed total parathyroidectomy with autotransplantation for persistent hyperparathyroidism, with subsequent good clinical results.

Adult↗
PubMed1995

[Clinical study on cerebrovascular diseases after renal transplantation].

Between October 1975 and December 1994, 131 renal transplants were performed on our hospital. Eight of these patients had 9 cerebrovascular diseases, which were 2 cerebral hemorrhages, 5 cerebral infarctions, 2 subarachnoid hemorrhages. Five of the 8 patients whose graft functions were bad died. We studied the relationship of the incidence of these complications to some factors as follows; 1) blood pressure, 2) hypercholestemia, 3) duration of hemodialysis, and 4) graft function. The cerebrovascular diseases after renal transplantation were related to the hypertension after renal transplantation and no correlation with the other factors could be found. Therefore, we think that the control of the hypertension after renal transplantation is the most important for the cerebrovascular diseases and the patient's prognosis.

Adult↗
PubMed1995

[A study of chemotherapy for patients with severely advanced gastric cancer--comparison of chemotherapy and route].

We analyzed the clinical response, toxicities, ambulatory and overall survival time among 51 patients with inoperable gastric cancer, to evaluate chemotherapies and drug delivery routes. Twenty-nine patients were treated by Methotrexate/5-FU (FMTX) therapy and 22 by 5-FU/CDDP (FP) therapy. Twenty-five patients were treated by intra-arterial (IA) route and 26 by intra-venous (IV). The response rate of IA therapy was higher than that of IV therapy (p < 0.05), 48% and 19%, respectively. Median survival times of FMTX and FP were 361 and 289 days, respectively, and the 1-year survival rates of FMTX and FP were 44% and 33%, respectively, with no significant differences. Duration of home chemotherapy with FMTX was longer than that with FP, at 130 and 85 days, respectively. There was no difference between duration of home chemotherapy of IA and that of IV. IA chemotherapy showed a higher response rate than IV, but there were no differences in the incidence of side effects and ambulatory and overall survival time.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

[Effect of low dose CDDP/5-fluorouracil therapy on PCNA labeling index and TS inhibition rate of gastric cancer].

The response of gastric cancer to intravenous application of low-dose CDDP plus 5-fluorouracil (FP) was assessed by changes in DNA indices (DIs) and PCNA labeling indices (LIs) by flow cytometry, and by the thymidylate synthetase inhibition rate (TSIR). Pretherapy samples were compared to specimens resected at operation. FP therapy was performed in 10 of 26 specimens and not in the others (C). There was no difference between change in DIs of FP group and that of C group. In FP group, PCNA LI of resected specimen was higher than that of biopsy, although they showed almost the same values in C group. Change in PCNA LIs correlated to TSIR in FP group. These results suggest that FP therapy affects gastric cancer cells in PCNA LIs and TSIR, and that PCNA LIs could be an indicator of the effect of FP therapy as TSIR.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Antiarrhythmic agents in older patients. Current state of knowledge.

The treatment of ventricular arrhythmias in the elderly population is a challenging problem. Elderly patients are more predisposed to arrhythmias, are less responsive to antiarrhythmic agents and are more susceptible to the adverse effects of antiarrhythmic agents. Results from recent trial have altered the general approach to management of ventricular arrhythmias. The results of the Cardiac Arrhythmia Suppression Trials (CAST I and II) exemplified the disappointing results from numerous other studies, revealing the overall lack of efficacy of class I agents in reducing mortality in patients with coronary artery disease and asymptomatic premature ventricular complexes (PVCs). The results of CAST I and II also demonstrated the higher likelihood of older patients developing ventricular arrhythmias and toxicity to antiarrhythmic agents. Combined results of these studies have discouraged empirical antiarrhythmic therapy, especially in older patients with asymptomatic PVCs. In contrast, secondary prevention trials with beta-blockers in post-myocardial infarction patients have shown definitive survival benefit and reduction in ventricular arrhythmias, especially in the older patient population. Smaller trials with amiodarone have also shown survival benefit in post-myocardial infarction patients with or without PVCs. Management of ventricular tachycardia and fibrillation has become less empirical and more systematic with use of electrophysiologically guided and/or Holter monitor-guided therapy. Sotalol and amiodarone are especially effective agents. The efficacy of implantable cardioverter/defibrillators are also being compared with medical therapy systematically in multicentre trials. In general, empirical antiarrhythmic therapy is discouraged especially in the treatment of asymptomatic PVCs and should be reserved for systematic use in life-threatening arrhythmias.

Aged↗
PubMed1994

[Clinical study of TZP-4238 on patients with benign prostatic hypertrophy--with special reference to urodynamics].

Twenty four cases of benign hypertrophy with bladder outlet obstruction were treated with 17 alpha-acetoxy-6-chloro-2-oxa-4,6-pregnadiene-3,20-dione (TZP-4238), and the effects on urodynamic parameters, clinical efficacy, safety, and usefulness were evaluated. Improvement rate of subjective rate of subjective symptoms was 52.9%. Obstructive symptoms improved more prominently than irritation symptoms. A significant improvement in flow rate of nomograms for maximum flow rate (MFR) and average flow rate (AFR) accompanied with the decrease in the prostatic weight were observed. However, no changes were observed on the urethral sphincter electromyography and the urethral pressure profile. A significant decrease of maximum cystometric capacity was observed, although the effective cystometric capacity was not changed. The overall improvement rate for urodynamic parameters was 43.7%. A significant decrease in weight and diameter of the prostate was observed. The prostatic weight decreased in 57.1%, and the average reduction rate was 15.4%. The overall improvement rate concerning clinical efficacy evaluating both subjective symptoms and objective parameters was 58.8%. Adverse reactions were observed in 5 cases. They were judged as not clinically problematic. Taking into account clinical safety and clinical efficacy, the clinical usefulness was 50.0%. TZP-4238 was considered to be an appropriate agent for treating patients with benign prostatic hypertrophy with bladder outlet obstruction.

Aged↗
PubMed1993

Characterization of a new diphenylpyrazolidinone cholecystokinin antagonist in vitro isolated rat pancreatic acini.

The effects of a newly developed diphenylpyrazolidinone cholecystokinin (CCK) antagonist LY219,057 were examined in the isolated rat pancreatic acini and compared with those of devazepide (previously designated L364,718 or MK-329). LY219,057 caused a concentration-dependent inhibition of 100 pM CCK octapeptide (CCK-8)-stimulated amylase release, with a half-maximal inhibition (ID50) at 287.5 +/- 28.4 nM and was 200 times less potent than devazepide (ID50 = 1.4 +/- 0.2 nM). The antagonism was competitive in nature because LY219,057 caused a parallel rightward shift of the dose-response curve for CCK-8-stimulated amylase secretion without altering the maximal increase. LY219,057 significantly inhibited amylase release in response to CCK-8 and cerulein but had no effect on amylase release stimulated by other receptor secretagogs or agent bypassing receptors. LY219,057, whether added at the beginning or 20 min after the CCK-8 stimulation, inhibited amylase release. This compound caused a residual inhibition of the action of CCK-8. Acini preincubated with 1.0 microM LY219,057 for 30 min at 37 degrees C were threefold less sensitive to CCK-8 than the acini preincubated without LY219,057. These results indicate that LY219,057 acts as a potent, competitive, and specific CCK receptor antagonist of the action of CCK on the exocrine pancreas.

Amylases↗
PubMed1993

Pancreatitis and anomalous union of the pancreaticobiliary ductal system in childhood.

From January 1978 to December 1989, 48 patients were diagnosed as having anomalous union of the pancreaticobiliary ductal system (AUPBD) at the Second Department of Surgery, Kanazawa University Hospital and its affiliated hospitals. Among these 48 patients, 13 (28.1%) were children under 13 years of age. Four of these patients had acute pancreatitis. The clinical, radiological, and surgical features of these patients are presented. The chief presenting complaint was epigastric pain in all cases; three patients had recurrent episodes of epigastric pain and had been diagnosed as having autotoxicosis. AUPBD was clearly demonstrated in all patients, three by endoscopic retrograde cholangiopancreatography (ERCP) and one by operative cholangiography. At operation, macroscopic evidence of pancreatitis was recognized in all cases. In one case, roentogenolucent pancreaticolithiases were seen on ERCP. We consider AUPBD as an important cause of pancreatitis in children and advocate ERCP in children who are suspected having biliary tract or pancreatic disease. The diagnosis of AUPBD should be considered when children with abdominal pain and elevated serum or urinary amylase levels are evaluated.

Abnormalities, Multiple↗