A useful predictor in machine perfusion preservation for kidney transplantation from non-heart-beating donors.
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Cadaver↗
Biomedical subjects
T Nagao
Publications and source records attributed to T Nagao.
Prediction of kidney nonfunction after transplantation with machine perfusion preservation.
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Adult↗
Diffusion anisotropy of Ag and In on Si(1 1 1) surface studied by UHV-SEM
Anisotropic features of Ag and In electromigration on clean and Au-precovered Si(1 1 1) surfaces were studied by in situ scanning electron microscopy in ultrahigh vacuum. It was noted that the migration direction of Ag was determined by both applied direct-current direction and step orientation on the substrate surface; on an Si(1 1 1) surface with steps inclined with respect to the current direction, the electromigration direction shows an apparent deviation from the accurate current direction. On clean and Au-precovered Si(1 1 1) surfaces with various coverages of Au (within submonolayer range), the migration behaviors of Ag and In drastically changed with Au coverages and showed different diffusion anisotropy (either thermal diffusion and electromigration) depending on the adsorbate surface structures. Particularly, on a beta-square root of 3 x square root of 3-Au surface of one monolayer Au coverage, In migrated with the highest mobility across the step bands, whereas In showed only a slow movement on the 7 x 7 clean surface due to a migration barrier at step edges. This result implied that the beta-square root of 3 x square root of 3-Au surface phase served as an intermediate layer for In adatoms migration. On the contrary, Ag showed negligible migration on the beta-square root of 3 x square root of 3-Au surface, while the 7 x 7 surface was the substrate for appreciable migration of Ag atoms. The results are discussed in terms of step-edge barriers in migration and on-terrace migration.
Journal Article↗
Outcome following a population screening programme for oral cancer and precancer in Japan.
The purpose of this study was to evaluate the validity and outcome of an oral mucosal screening programme conducted in Japan. All adults over the age of 40 years resident in Tokoname city were invited by letter to attend a free general health screen and oral examinations annually. Twenty- to 39-year-old females were also encouraged to participate. During the years 1996-98, a total of 19056 subjects (5885 male, 13171 female: mean age 60.7+/-11.3 years) were examined by three types of screeners: postgraduate dental residents (n=17), hospital dentists (n=5) and general dental practitioners (n=15). In the cohorts examined screening dentists recorded oral mucosal lesions in 783 (4.1%) subjects. Of those detected with mucosal lesions, 200 (25.5%) were referred and 137 (68. 5%) attended for follow up examination in hospital departments by specialists with full diagnostic back up facilities. Thirty-nine subjects were confirmed as having oral cancer or precancer (two squamous cell carcinomas, 37 leukoplakias) and 40 with lichen planus. Five false positives (3.6%) were found. Among the cases referred under other diagnostic labels no cancers were detected. Among those who attended for confirmation of oral cancer or precancer by a specialist, sensitivity, specificity and positive predictive value were 0.92, 0.64 and 0.78, respectively. In males with oral cancer/leukoplakia, the prevalence of smoking, drinking and combined habits was higher than those with lichen planus or among negative subjects. The sensitivity and specificity determined from this research suggests that the performance of the Japanese dentists employed in screening was satisfactory. An attendance of 68% for re-examination by specialists compares well with other reported studies measuring patient compliance.
Adult↗
Serum antioxidant micronutrients and the risk of oral leukoplakia among Japanese.
A population-based case-control study was designed for the investigation of any association between serum micronutrient levels and oral leukoplakia. Out of a total of 9536 subjects over the age of 40 years who participated in the oral mucosal screening programme in Tokoname city, 48 cases detected with oral leukoplakia (38 male:10 female) were recruited. For each case, four controls matched by age and sex were selected from the same cohort. We examined the fasting serum levels of retinol, alpha-tocopherol, zeaxanthin and lutein, cryptoxanthin, lycopene and carotenoids (alpha-carotene and beta-carotene) by high-performance liquid chromatography. Among males with leukoplakia mean serum lycopene and beta-carotene levels (0.175+/-0.202, 0.357+/-0.295 micromol/l) were significantly lower than those of controls (0.257+/-0.252, 0.555+/-0.408 micromol/l) (P<0.05, P<0.005). Logistic regression analysis with leukoplakia as the dependent variable showed that high serum levels of beta-carotene were related to low risk of oral leukoplakia (odds ratio 0.160, 95% C.I.: 0.029-0.866, P<0.05). There were no significant differences in any of the serum nutrients estimated in female subjects. Our results suggest for the first time that high serum levels of beta-carotene may provide protection against oral precancer for the Japanese male.
Adult↗
Amino acid residues contributing to stabilization of Fusarium heterosporum lipase.
Fusarium heterosporum lipase is composed of an N-terminal large peptide of 275 amino acids and a C-terminal peptide of 26 amino acids. The thermostability of the lipase was remarkably decreased by cleavage of the C-terminal peptide. Hence, we attempted to specify the amino acids in the C-terminal peptide that are responsible for the stabilization of the lipase. Replacement of Asp293 with Ala, Asn, and Lys caused a significant decrease in thermostability, but its mutation to Glu did not decrease the stability significantly. These findings showed that the lipase with the C-terminal peptide was stabilized by an ionic bond between the negative charge of Asp293 and positive charge of an amino acid of the N-terminal large peptide. The thermostability of the lipase gradually decreased with increasing deletion size from the C-terminus, and a 13-amino acid deletion decreased the stability to the level of the lipase not having the C-terminal peptide. These results suggested that the 13-amino acid region from the C-terminus participated in the lipase stability. In addition, the lipase production correlated well with the lipase stability, showing that the C-terminal peptide also influenced the lipase productivity.
Journal Article↗
Anti-AIDS agents 38. Anti-HIV activity of 3-O-acyl ursolic acid derivatives.
Based on our previous finding that 3-O-acyl-betulinic and -oleanolic acids, especially the 3-O-(3',3'-dimethyl)-succinyl derivatives (2 and 4), demonstrated potent anti-HIV activity [EC(50) < 0.00035 and 0.00086 microM; therapeutic index (TI) > 20 000 and 22 326, respectively], several 3-O-acyl-ursolic acids were prepared and evaluated for anti-HIV activity. Ursolic acid (6) was equipotent (EC(50) 4.4 microM) with oleanolic acid (EC(50) 3.7 microM), although it was slightly toxic (IC(50) 14.3 microM, TI 3.3). 3-O-Diglycoryl-ursolic acid (10) demonstrated relatively potent anti-HIV activity with an EC(50) of 0. 31 microM and a TI of 155.5. In contrast, 3-O-(3', 3'-dimethylsuccinyl)-ursolic acid (8), which is analogous to the extremely potent anti-HIV betulinic acid and oleanolic acid derivatives 2 and 4, displayed only weak anti-HIV activity (EC(50) 2.1 microM, TI 23.6).
Anti-HIV Agents↗
Calcium antagonist isradipine reduces metabolic alterations in acute cerebral ischemia in spontaneously hypertensive rats.
The present study was designed to examine the effect of a calcium antagonist isradipine (PN200-110: PN) on local cerebral blood flow and brain tissue metabolism after 1-hour supratentorial ischemia induced by bilateral carotid artery ligation (BCL) in spontaneously hypertensive rats (SHR). PN, dissolved in ethanol plus polyethylene glycol 400, diluted with saline to make the final concentration of 0.25mg/ml and 2.5mg/ml, was administered subcutaneously either 30 min prior to BCL or just after the induction of incomplete cerebral ischemia (n = 7 in each group). Vehicle injection was served as a control group (n = 7). Cerebral blood flow in the parietal cortex (CBF) and the cerebellar cortex (CeBF) was measured by hydrogen clearance technique, and the supra- and infratentorial metabolites of the brain frozen in situ were determined by the enzymatic method. Blood pressure was lowered, but CBF was increased by PN administration in pre-BCL treatment study. After 1 hour of BCL, CBF decreased to around 10% or less of the resting value, being insignificant among the groups. Brain adenosine triphosphate was better preserved in PN-administered groups. The increase in lactate level tended to reduce dose dependently by PN treatment. PN also reduced the metabolic alterations in brain tissue with significance, even when administered just after the induction of forebrain ischemia. It is considered that pre- as well as post-BCL administration of PN is beneficial to attenuate the metabolic alterations in incomplete forebrain ischemia in SHR.
Acute Disease↗
A comparison of prednisolone and methylprednisolone for renal transplantation.
A large difference in immunosuppressive potency between methylprednisolone and prednisolone has been suggested in vitro. However, the selection of the best glucocorticoid for renal transplantation has been seldom considered so far. Thus, the present study was undertaken to compare therapeutic efficacy between prednisolone and methylprednisolone in renal transplantation. We studied 42 renal transplant recipients who were operated on between 1990 and 1994. The patients were divided into two treatment groups: a methylprednisolone/ cyclosporine group (n = 19) and a prednisolone/cyclosporine group (n = 23). Clinical outcome and drug side effects were compared retrospectively between the treatment groups 24-84 months after transplantation. The overall graft survival time in patients treated with methylprednisolone/cyclosporine was superior to that in patients treated with prednisolone/cyclosporine (p < 0.05). Among the recipients from cadaver donors, 5/16 (31.3%) treated with prednisolone required nephrectomy, whereas none of the 10 patients treated with methylprednisolone received nephrectomy (p < 0.01). An examination of the recipients from living related donors revealed that serum creatinine levels 24-36 months after operation were significantly lower in the methylprednisolone group (p < 0.05). Cyclosporine trough levels and glucocorticoid side effects were similar between the treatment groups. The results raised the possibility that methylprednisolone is superior to prednisolone when combined with cyclosporine for maintenance immunosuppressive therapy in renal transplantation.
Adult↗
Reduced stability of retinoblastoma protein by gankyrin, an oncogenic ankyrin-repeat protein overexpressed in hepatomas.
Hepatocellular carcinoma (HCC) is one of the most common cancers in Asia and Africa, where hepatitis virus infection and exposure to specific liver carcinogens are prevalent. Although inactivation of some tumor suppressor genes such as p53 and p16INK4Ahas been identified, no known oncogene is commonly activated in hepatocellular carcinomas. Here we have isolated genes overexpressed in hepatocellular carcinomas by cDNA subtractive hybridization, and identified an oncoprotein consisting of six ankyrin repeats (gankyrin). The expression of gankyrin was increased in all 34 hepatocellular carcinomas studied. Gankyrin induced anchorage-independent growth and tumorigenicity in NIH/3T3 cells. Gankyrin bound to the product of the retinoblastoma gene (RB1), increasing its phosphorylation and releasing the activity of the transcription factor E2F-1. Gankyrin accelerated the degradation of RB1 in vitro and in vivo, and was identical to or interacted with a subunit of the 26S proteasome. These results demonstrate the importance of ubiquitin-proteasome pathway in the regulation of cell growth and oncogenic transformation, and indicate that gankyrin overexpression contributes to hepatocarcinogenesis by destabilizing RB1.
3T3 Cells↗
Primary large-cell neuroendocrine carcinoma of the parotid gland: immunohistochemical and molecular analysis of two cases.
Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a newly proposed clinicopathologic entity; a few cases of LCNEC have been reported in other sites, such as the uterine cervix and the thymus. In the salivary glands, LCNEC is extremely rare and is not recognized as a specific entity in the World Health Organization classification. We retrospectively reviewed from our files 1675 cases of surgically resected primary parotid gland tumors and found 2 cases of LCNEC that fulfilled the criteria of pulmonary LCNEC. These cases occurred in 72- and 73-year-old men who had short histories of enlarging parotid gland tumors. The tumors were composed of large cells that exhibited organoid, solid, trabecular, and rosette-like growth patterns with a high mitotic rate and a conspicuous tendency for necrosis. The tumor cells were polygonal and characterized by a moderate nuclear:cytoplasmic ratio, coarse chromatin, and conspicuous nucleoli. Immunohistochemical examination revealed that the tumor cells were positive for six general neuroendocrine markers, cytokeratin, p53, bcl-2, epidermal growth factor receptor, and cyclin D1. Markedly reduced expressions of p21Waf1 and p27Kip1 were also noticed. The Ki-67 labeling index was more than 50% in both cases. One case showed loss of heterozygosity at TP53 accompanied by a p53 gene point mutation. Loss of heterozygosity at chromosome 9p21 was detected in both cases; one was accompanied by a p16 gene silent point mutation. Both patients died of the disease, with recurrence 5 months and 4 years after surgery, respectively. These findings indicate that LCNEC is a rare but distinct salivary gland tumor with highly aggressive biologic behavior. Multiple alterations of cell cycle regulators and tumor suppressor genes may play an important role in presenting the biologic characteristics of this rare parotid gland tumor.
Aged↗
Hyperbaric oxygen (HBO) therapy for acute traumatic cervical spinal cord injury.
STUDY DESIGN: A retrospective study of spinal cord injury (SCI) treated with and without hyperbaric oxygen (HBO) therapy. OBJECTIVES: To report on the use of HBO in spinal cord injury. SETTING: Neurosurgical Unit, Tokyo, Japan. METHODS: Thirty-four cases of hyperextension spinal cord injury without bone damage and previous history of surgical intervention were divided into two groups, with (HBO) or without (non-HBO) therapy. The neurological findings at admission and their outcomes were evaluated by means of Neurological Cervical Spine Scale (NCSS)1 and the average improvement rates in individual groups were compared. RESULTS: The improvement rate ranged from 100% to 27.3% with the mean value of 75. 2% in the HBO group, while these values were 100%, 25.0% and 65.1% respectively in the non HBO group. CONCLUSION: In the HBO group, the improvement rate indicated effectiveness in acute traumatic cervical spinal cord injury.
Adult↗
Dietary diacylglycerol suppresses accumulation of body fat compared to triacylglycerol in men in a double-blind controlled trial.
We examined the effects of the long-term ingestion of dietary diacylglycerols (DG) in a double-blind controlled study of human lipid metabolism. Healthy men (n = 38; aged from 27 to 49 y, body mass index (BMI) ranging from 21.8 to 27.4 kg/m(2)) completed the study. To accustom the subjects to the test diets prior to the experiment, they were supplied with test diets of triacylglycerol (TG) oil for 4 wk (control period). The test oils (10 g/d) were included in bread, mayonnaise or shortbread and served for the breakfast. The target for total lipid intake was 50 g/d (15 g for breakfast, 15 g for lunch and 20 g for dinner) throughout the study. The subjects were then divided into two groups so that mean BMI and the hepatic fat content, determined by computed tomography, for each group were not different. One group (DG group) consumed test meals containing DG-rich oil (10 g/d) while the other group (TG group) consumed the same meal as during the control period. Ten grams of the DG-rich oil contained 5.5 g 1,3-DG, 2.5 g 1,2-DG and 2 g TG. The actual lipid intake during the study was 43 g/d. Body weight, BMI and waist circumference decreased in both groups at the end of the test period of 16 wk. However, the magnitudes of decreases in these variables were significantly greater in the DG group than in the TG group. Decreases of total fat, visceral fat area and subcutaneous fat area of the abdominal traverse images of computed tomography in the DG group were also significantly greater than those in the TG group. Hepatic fat content decreased significantly in the DG group while no change was observed in the TG group. Serum lipid concentrations (TG, total cholesterol, free fatty acid) and related metabolites (glucose, insulin, total ketone body) did not change significantly in either group. Thus, in contrast to TG, DG apparently suppressed accumulation of fat and possibly reduces the risk of diseases associated with visceral fat obesity.
Abdomen↗
Influence of corn oil and diet on reproduction and the kidney in female Sprague-Dawley rats.
The purpose of this study was to investigate the influence of corn oil administration on gestation, parturition, and lactation in rats, in conjunction with diets differing in composition of nutrients. Rats were divided into two groups, each fed different commercial pellets for rodents, CA-1 or CE-2, different from each other mainly in the source of protein. Female Sprague-Dawley rats in both diet groups were administered 0 (untreated control), 2, or 10 ml corn oil/kg body weight by gavage during the premating period (2 weeks), the mating period, the gestation period, and the lactation period (until day 3 of lactation). Food consumption of both the 10 ml/kg corn oil groups was significantly reduced throughout the study. Body weight gain in the 10 ml/kg corn oil group fed the CA-1 diet was significantly reduced on days 0 through 4 of lactation. Neither mating nor fertility indices were affected, and no clinical signs were observed during the gestation period in any groups. Several dams in the 10 ml/kg corn oil group fed the CA-1 diet, however, showed abnormal conditions after parturition, and three dams became moribund. Pup viability was also reduced in this group. Histopathologic examination of the kidneys of dams in the 10 ml/kg corn oil group fed the CA-1 diet revealed severe lesions in the proximal tubular epithelium, i.e., necrosis and fatty degeneration. Females in any group fed the CE-2 diet showed neither abnormal condition after parturition nor any severe lesions in the kidney. These data show that the combination of corn oil and diet with a particular constitution may cause adverse effects on the renal tubules in pregnant and/or lactating rats, suggesting that corn oil gavage as a vehicle can be a confounding factor in the reproductive toxicity studies, depending on the diet.
Animals↗
Oral cancer screening as an integral part of general health screening in Tokoname City, Japan.
OBJECTIVES: To measure the attendance and compliance rates in oral mucosal screening (OMS) offered as part of a general health screen (GHS) undertaken as an organised programme in Japan. METHODS: In 1996, all adults over the age of 40 years resident in Tokoname City were invited by letter to attend a free GHS annually, conducted by the municipal cooperation and the medical and dental societies of Tokoname City. In the later years only those who attended in 1996 were reinvited. Females aged less than 39 years were also allowed to attend if they wished to participate in the GHS. The GHS consisted of completion of a self administered questionnaire to identify past and current illnesses and any medications used by the screened population coupled with a routine physical check, chest x ray, ECG, and blood and urine examination. The GHS was programmed annually during the years 1996 to 1998. All those attending the GHS were invited to participate in an OMS conducted under the same roof by a visiting dentist (n=37). A referral pathway was established for screen positives requiring follow up. RESULTS: A total of 19 305 subjects (5955 males, 13350 females; mean age 59.2 years; 7033 in 1996, 6289 in 1997, and 5983 in 1998) attended the GHS. Of those who attended the GHS, 19 056 (98.7%) attended the OMS (1.3% refused). This rate was fairly constant over the three years. Excluding repeat examinations, new cases recruited for OMS over the three years were 8723. Of those participating in OMS, 4269 (60.7%) attended all three years. In the cohorts examined, screening dentists recorded oral mucosal lesions in 5.4% in 1996, in 4.0% in 1997, and in 2.6% in 1998. Overall, this amounted to a positive detection rate of 4.1%, or 4.9% excluding repeat examinations. A higher prevalence of oral pre-cancer was recorded among male smokers. CONCLUSIONS: The overall results suggest that although compliance with attending a free GHS was low (26.2%) among Japanese subjects over 40 years of age, of those who complied 74-76% reattended annually. Hence a satisfactory participation rate can be obtained in Japan for OMS when this is coupled to a GHS conducted at the same visit.
Adult↗
Assessment of affinities of propranolol and bopindolol to membranes from COS-7 cell transiently transfected with beta-1- and beta-2-adrenoceptors using a radioligand-binding assay method.
This study was performed to assess the affinities of propranolol, bopindolol, its two metabolites (18-502, 20-785), pindolol, metoprolol, and atenolol to beta(1)- and beta(2)-adrenoceptor (beta(1)- and beta(2)-AR) subtypes using the membranes of COS-7 cells transiently expressing beta(1)- and beta(2)-AR subtypes. Radioligand-binding assays were performed and the results were compared with those (pKi or pA(2) values) obtained from the membrane-enriched fractions from the rat heart, cerebral cortex, bovine heart, tracheal smooth muscle or guinea-pig heart muscle. The pKi values of propranolol, bopindolol, its two metabolites, atenolol, pindolol and metoprolol to beta(1)-AR subtypes obtained from COS-7 cell membranes were 9.02 +/- 0.04, 7.44 +/- 0.12, 9.38 +/- 0.31, 6. 65 +/- 0.16, 5.55 +/- 0.14, 8.17 +/- 0.15 and 5.99 +/- 0.13, respectively. The rank order of pKi values for these agents to beta-(2)-ARs in COS-7 cell membranes was the same as that of beta(1)-ARs. In addition, good correlations were observed between pKi values of homogenates from various tissues and those of transfected COS-7 cell membranes to beta(1)- and beta(2)-ARs. Although good correlations were also observed between pA(2) values obtained from tracheal smooth muscle (beta(2)-ARs) and pKi values obtained from transfected COS-7 cell membranes to beta(2)-ARs, low correlation coefficient values to beta(1)-ARs were observed, however. In conclusion, these results suggested that binding characteristics of (3)H-CGP-12177 to beta-AR subtypes in these membranes from transfected COS-7 cells are similar to those from membrane fractions of various tissues.
Adrenergic beta-Antagonists↗
Role of phosphatidylinositol 3-kinase in acetylcholine-induced dilatation of rat basilar artery.
BACKGROUND AND PURPOSE: We tested the hypothesis that activation of phosphatidylinositol (PI) 3-kinase is involved in dilator responses of the basilar artery to acetylcholine in vivo. METHODS: Responses of the basilar artery were measured by the cranial window technique in anesthetized rats. To examine the role of PI 3-kinase in acetylcholine-induced calcium signaling, we measured intracellular free calcium concentration ([Ca(2+)](i)) of cultured rat basilar arterial endothelial cells using a fluorescent calcium indicator, indo 1. RESULTS: -Topical application of acetylcholine (10(-6), 10(-5.5), and 10(-5) mol/L) increased the diameter of the basilar artery by 8+/-1%, 14+/-2%, and 24+/-3%, respectively. An inhibitor of PI 3-kinase, wortmannin (10(-8) mol/L), did not change the baseline diameter of the artery. In the presence of wortmannin, acetylcholine (10(-6), 10(-5.5), and 10(-5) mol/L) dilated the artery only by 3+/-2%, 6+/-2%, and 12+/-2%, respectively. Thus, wortmannin attenuated acetylcholine-induced dilatation of the basilar artery (P<0.05 versus control). Wortmannin had no effect on dilatation of the artery in response to a nitric oxide donor, sodium nitroprusside. LY294002, another inhibitor of PI 3-kinase, also inhibited dilator response of the basilar artery to acetylcholine. Acetylcholine produced an increase in [Ca(2+)](i) of the endothelial cells. Genistein, an inhibitor of tyrosine kinase, markedly attenuated acetylcholine-induced calcium influx to the cells; however, wortmannin had no effect on acetylcholine-induced calcium changes. CONCLUSIONS: These results suggest that acetylcholine-induced dilatation of the basilar artery is mediated, at least in part, by activation of PI 3-kinase in vivo. Acetylcholine-induced [Ca(2+)](i) changes of the endothelial cells may not be mediated by activation of the kinase. PI 3-kinase as well as [Ca(2+)](i) may play an important role in the acetylcholine-induced nitric oxide production of the basilar arterial endothelial cells.
Acetylcholine↗
Fibroblast contractility: usual interstitial pneumonia and nonspecific interstitial pneumonia.
The aim of this study was to compare the function of lung fibroblasts obtained from surgically biopsied specimens of patients with idiopathic pulmonary fibrosis/usual interstitial pneumonia (UIP; n = 5), nonspecific interstitial pneumonia (NSIP; n = 5), and normal parts of surgically resected lungs (control; n = 5). The results showed that (1) fibroblasts obtained from UIP showed increased contractility compared with those obtained from NSIP or controls (UIP, 72.7 +/- 6.21%; NSIP, 32.8 +/- 5.46; controls, 28.5 +/- 3.51, p < 0.01 in UIP versus NSIP or control); (2) this increase in contractility was consistent with enhanced F-actin content in fibroblasts; (3) conditioned media from UIP fibroblast cultures enhanced control fibroblast contractility, whereas those obtained from NSIP or controls did not; (4) the 180 and 25 kD products representing the contractility in conditioned media were identified as fibronectin (ED-A domain) and TGF-beta1 by immunoblots, respectively; (5) the UIP-conditioned media contained higher amounts of fibronectin or TGF-beta 1 (fibronectin: UIP 289 +/- 47.1 ng/ml, NSIP 121 +/- 23.0, control 118 +/- 16.0; TGF-beta1: UIP 798 +/- 119 pg/ml, NSIP 246 +/- 69.1, control 247 +/- 53.6, p < 0.01 in UIP versus NSIP or control); () the contractility positively correlated with the amount of either fibronectin (r = 0.867, p < 0.001, n = 15) or TGF-beta 1 (r = 0.939, p < 0.001, n = 15), respectively. Thus, UIP fibroblasts showed greater contractility than did NSIP fibroblasts and up-regulated control fibroblasts.
Actins↗