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T Aizawa

Publications and source records attributed to T Aizawa.

At least 37 records · Page 2Linked to original sources
PubMed2001

Different effects of angiotensin II and catecholamine on renal cell apoptosis and proliferation in rats.

BACKGROUND: We have recently found that chronic infusion of angiotensin II (Ang II) into rats resulted in an impairment of renal function, whereas norepinephrine (NE) infusion did not. We investigated whether chronic infusion of Ang II and NE caused different degrees of renal cell apoptosis and proliferation. METHODS: Rats were made hypertensive via continuous infusion of either Ang II or NE for up to seven days. Renal cell apoptosis and proliferation were analyzed by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) technique and staining with antibody against proliferating cell nuclear antigen (PCNA), respectively. In some experiments, an inducer or inhibitor of heme oxygenase-1 (HO-1) was administered to investigate the possible role of HO-1 in renal cell homeostasis. RESULTS: Infusion of Ang II, but not NE, resulted in approximately a sevenfold increase in bax protein at seven days of infusion. The TUNEL assay revealed that Ang II infusion significantly increased the number of apoptotic cells, whereas NE infusion did not. TUNEL- and PCNA-positive cells were mainly seen in the tubulointerstitial region of Ang II-infused rats. Ang II induced increased positivity of TUNEL, and PCNA was blocked completely by losartan, but only partially by hydralazine. Induction of HO-1 reduced and inhibition of HO increased Ang II-induced cell proliferation. CONCLUSIONS: These data suggest that Ang II plays a pivotal role in the development of renal cell proliferation and apoptosis in the setting of hypertension. The renal HO system may modulate proliferative and pro-apoptotic effects of Ang II.

Angiotensin II↗
PubMed2001

Stent placement in the pancreatic duct prevents pancreatitis after endoscopic sphincter dilation for removal of bile duct stones.

BACKGROUND: Pancreatitis is the most serious complication of endoscopic sphincter dilation. The aim of this study was to determine whether temporary stent placement in the main pancreatic duct decreases the frequency of pancreatitis and level of hyperamylasemia. METHODS: Stents were placed in the pancreatic duct after endoscopic sphincter dilation in 40 consecutive patients with bile duct stones. Stents were removed endoscopically 3 days later. Changes in serum amylase and the frequency of pancreatitis for this group were compared with those in 92 patients who underwent sphincter dilation without pancreatic duct stent placement. RESULTS: Stent placement was successful in 38 of 40 patients. Although the difference in the frequency of pancreatitis was not significantly different between stent and control groups, there was a trend toward a decrease in pancreatitis in the stent group. The level of postprocedure hyperamylasemia was significantly less in the stent group (p < 0.05). There were no procedure-related complications. CONCLUSIONS: Temporary placement of a stent in the pancreatic duct after sphincter dilation for removal of bile duct stones has a beneficial effect in terms of postprocedure hyperamylasemia and appears to reduce the frequency of postprocedure pancreatitis.

Aged↗
PubMed2001

The genetic diversity of clinical isolates of Malassezia pachydermatis from dogs and cats.

Molecular investigation of 110 clinical isolates of non-lipid-dependent Malassezia pachydermatis from dogs and cats was carried out by random amplification of polymorphic DNA (RAPD) and chitin synthase 2 (CHS2) gene sequence analyses. The RAPD analysis indicated that the clinical isolates of M. pachydermatis constituted four distinct genetic types (A, B, C and D). Moreover, the results from CHS2 gene analysis completely agreed with those from the RAPD analyses. The clinical isolates of M. pachydermatis were obtained from normal external ears, lesions of atopic dermatitis, flea allergic dermatitis, otitis externa, pyoderma and seborrheic dermatitidis in dogs and cats. Type A consisted of 93 clinical isolates as well as the ex-neotype strain of M. pachydermatis. The isolates of type A M. pachydermatis originated from lesions of all kinds of diseases. They were predominant on dog and cat skin. The other types, B, C, and D were isolated mainly from otitis externa.

Animals↗
PubMed2001

Construction of an expression system of insect lysozyme lacking thermal stability: the effect of selection of signal sequence on level of expression in the Pichia pastoris expression system.

Expression systems of human and silkworm lysozymes were constructed using the methylotrophic yeast Pichia pastoris as a host. The leader sequence and its prepro peptide of alpha-factor (a peptide pheromone derived from yeast) and the native signal sequences of these lysozymes, were used as secretion signals. When the alpha-factor leader is used as the signal sequence, human lysozyme is secreted at a much higher level than is silkworm lysozyme. On the other hand, silkworm lysozyme, when its native signal is used, is secreted more efficiently than human lysozyme. Therefore, we expected that human lysozyme cDNA with a silkworm native signal would be secreted more efficiently than human lysozyme with its native signal. However, its level of expression was not increased. This result indicates that the native signal of silkworm lysozyme does not promote the secretion of the lysozyme, but rather alpha-factor leader inhibits the secretion. Silkworm lysozyme with the alpha-factor leader is so unstable that it could be easily attacked by some proteases and our findings suggest that the level of expression of heterologous protein with signal peptides and its stability are greatly affected by the selection of the appropriate secretion signal sequence.

Amino Acid Sequence↗
PubMed2001

Phase I study of intravenous PSC-833 and doxorubicin: reversal of multidrug resistance.

PSC-833 reverses multidrug resistance by P-glycoprotein at concentrations < or = 1000 ng / ml. A phase I study of PSC-833 and doxorubicin was conducted to determine the maximum tolerated dose and to investigate pharmacokinetics. PSC-833 was intravenously infused as a 2-h loading dose (LD) and a subsequent 24-h continuous dose (CD). Doxorubicin was infused over 5 min, 1 h after the LD. The starting dose was 1 mg / kg for both LD and CD with 30 mg / m(2) doxorubicin; these dosages were increased to 2 and 10 mg / kg and 50 mg / m(2), respectively. Thirty-one patients were treated. Nausea / vomiting was controllable with granisetron and dexamethasone. Neutropenia and ataxia were dose limiting. Steady-state concentrations of PSC-833 > 1000 ng / ml were achieved at a 2 mg / kg LD and a 10 mg / kg CD. Ex-vivo bioassay revealed that activity in serum for reversing multidrug resistance was achieved in all patients; IC(50) of P-glycoprotein expressing 8226 / Dox(6) in patients' serum was decreased from 5.9 to 1.3 microg / ml (P < 0.0001) by PSC-833 administration. Doxorubicin clearance was 24.3 +/- 13.7 (mean +/- SD) liter / h/m(2), which was lower than the 49.0 +/- 16.9 liter / h/m(2) without PSC-833 (P < 0.0001). The relationship between doxorubicin exposure and neutropenia did not differ between patients treated and not treated with PSC-833. The recommended phase II dose of PSC-833 was 2 and 10 mg / kg for LD and CD, respectively, which achieved a sufficient concentration in serum to reverse drug resistance, as confirmed by bioassay. The dose of doxorubicin should be reduced to 40 mg / m(2), not because of the pharmacodynamic interaction between PSC-833 and doxorubicin affecting hematopoiesis, but because of pharmacokinetic interaction.

Adult↗
PubMed2001

Differential effects of growth hormone and insulin-like growth factor I on human endothelial cell migration.

Effects of growth hormone (GH), insulin-like growth factor I (IGF-I), and endothelin-1 (ET-1) on endothelial cell migration and the underlying molecular mechanisms were explored using a human umbilical cord endothelial cell line, ECV304 cells, in vitro. Treatment of the cells with IGF-I or ET-1, but not GH, stimulated the cell migration. Interestingly, however, ET-1-induced, but not IGF-I-induced, migration of the cells was inhibited by GH. Both ET-1 and IGF-I caused activation of mitogen-activated protein kinase (MAPK) in the cells, and GH eliminated the MAPK activation produced by ET-1 but not that produced by IGF-I. On the other hand, migration of the cells was stimulated by protein kinase C (PKC) agonist, phorbol 12-myristate 13-acetate. ET-1 promoted PKC activity, and a PKC inhibitor, GF-109203X, blocked ET-1-induced cell migration. Although GH inhibited ET-1-induced cell migration and MAPK activity, it did not block ET-1-induced PKC activation. Thus ET-1 stimulation of endothelial cell migration appears to be mediated by PKC/MAPK pathway, and GH may inhibit the MAPK activation by ET-1 at the downstream of PKC.

Cell Line↗
PubMed2001

Impaired intramembranous bone formation during bone repair in the absence of tumor necrosis factor-alpha signaling.

Tumor necrosis factor-alpha (TNF-alpha) is known to mediate bone resorption; however, its role in osteogenesis has not been fully elucidated. In order to investigate the direct role of TNF-alpha signaling in the recruitment and differentiation of osteoblasts, two separate models of bone repair were used, marrow ablation and simple transverse fractures. These models were carried out in the tibiae of both wild-type and knock-out mice in which both TNF-alpha receptors (p55(-/-)/p75(-/-)) had been ablated. Marrow ablation is a unique model in which robust intramembranous bone formation is induced without an endochondral component, followed by remodeling and restoration of the original trabecular architecture of the bone marrow. In contrast, fracture repair proceeds concurrently through both endochondral and intramembranous processes of new bone tissue formation. In both models of bone repair, healing was delayed in the TNF-alpha receptor (p55(-/-)/p75(-/-)) deficient mice. In the marrow ablation model, young osteoblasts were recruited into the marrow space by day three in the wild-type mice, while the TNF-alpha (p55(-/-)/p75(-/-)) mice had only granulation tissue in the marrow cavity. Type I collagen and osteocalcin mRNA expressions were reduced approximately 30 and approximately 50%, respectively, of the control values in the TNF-alpha receptor ablated mice. In the fracture repair model there was almost a complete absence of the initial intramembranous bone formation on the periosteal surface in the TNF-alpha (p55(-/-)/p75(-/-)) mice. As healing progressed however, the callus tissues were greatly enlarged, and there was a delay in hypertrophy of the chondrocytes and the resorption of cartilage tissue. While during the initial period of fracture repair there was a marked reduction in the expression of both type I collagen and osteocalcin mRNAs in the TNF-alpha (p55(-/-)/p75(-/-)) mice, levels of these mRNAs were elevated by approximately 10-20% over the wild type at the later time points in the absence of endochondral resorption of the callus. The lack of inhibition of osteogenesis during endochondral resorption suggests that a different set of signals are involved in the recruitment of osteogenic cells during endochondral repair then during intramembranous bone formation. Co-culture of chondrocytes with a mesenchymal stem cell line was carried out to examine if chondrocytes themselves produced paracrine factors that promote osteogenic differentiation. These experiments demonstrated that chondrocytes do indeed produce factors that promoted osteogenic differentiation. In summary, the results presented here suggest that TNF-alpha plays a crucial role in promoting postnatal bone repair through the induction of osteoprogenitor cell recruitment or osteogenic cell activation in the context of intramembranous bone formation. These results further suggest that the signals that promote osteogenesis during endochondral bone formation are different from those involved in intramembranous bone formation.

Animals↗
PubMed2001

Effects of nipradilol, a nitric oxide-releasing beta-adrenoceptor blocking agent, on phosphoenolpyruvate carboxykinase gene transcription in a rat hepatoma cell line.

Effects of nipradilol, a beta-adrenoceptor blocker with a nitroxy moiety, on phosphoenolpyruvate carboxykinase (PEPCK) gene transcription were examined using a rat hepatoma cell line, H4IIE cells. Dexamethasone was employed as an enhancer of PEPCK gene transcription. Nipradilol, but not timolol (a beta-blocker without a nitroxy moiety), attenuated PEPCK gene transcription both in the control and the dexamethasone-treated cells. The effects of nipradilol were eradicated by methylene blue (an inhibitor of cellular guanylate cyclase). Nipradilol is a unique beta-blocker that suppresses PEPCK gene transcription in hepatocytes likely through liberation of nitric oxide and resultant activation of guanylate cyclase.

Adrenergic beta-Antagonists↗
PubMed2001

Expression of osteoprotegerin, receptor activator of NF-kappaB ligand (osteoprotegerin ligand) and related proinflammatory cytokines during fracture healing.

Fracture healing is a unique biological process regulated by a complex array of signaling molecules and proinflammatory cytokines. Recent evidence for the role of tumor necrosis family members in the coupling of cellular functions during skeletal homeostasis suggests that they also may be involved in the regulation of skeletal repair. The expression of a number of cytokines and receptors that are of functional importance to bone remodeling (osteoprotegerin [OPG], macrophage colony-stimulating factor [M-CSF], and osteoprotegerin ligand [receptor activator of NF-kappaB ligand (RANKL)]), as well as inflammation (tumor necrosis factor alpha [TNF-alpha] and its receptors, and interleukin-1alpha [IL-1alpha] and -beta and their receptors) were analyzed over a 28-day period after the generation of simple transverse fractures in mouse tibias. OPG was expressed constitutively in unfractured bones and elevated levels of expression were detected throughout the repair process. It showed two distinct peaks of expression: the first occurring within 24 h after fracture and the second at the time of peak cartilage formation on day 7. In contrast, the expression of RANKL was nearly undetectable in unfractured bones but strongly induced throughout the period of fracture healing. The peak in expression of RANKL did not correlate with that of OPG, because maximal levels of expression were seen on day 3 and day 14, when OPG levels were decreasing. M-CSF expression followed the temporal profile of RANKL but was expressed at relatively high basal levels in unfractured bones. TNF-alpha, lymphotoxin-beta (LT-beta), IL-1alpha, and IL-1beta showed peaks in expression within the first 24 h after fracture, depressed levels during the period of cartilage formation, and increased levels of expression on day 21 and day 28 when bone remodeling was initiated. Both TNF-alpha receptors (p55 and p75) and the IL-1RII receptor showed identical patterns of expression to their ligands, while the IL-1R1 was expressed only during the initial period of inflammation on day 1 and day 3 postfracture. Both TNF-alpha and IL-1alpha expression were localized primarily in macrophages and inflammatory cells during the early periods of inflammation and seen in mesenchymal and osteoblastic cells later during healing. TNF-alpha expression also was detected at very high levels in hypertrophic chondrocytes. These data imply that the expression profiles for OPG, RANKL, and M-CSF are tightly coupled during fracture healing and involved in the regulation of both endochondral resorption and bone remodeling. TNF-alpha and IL-1 are expressed at both very early and late phases in the repair process, which suggests that these cytokines are important in the initiation of the repair process and play important functional roles in intramembraneous bone formation and trabecular bone remodeling.

Animals↗
PubMed2001

An ectopic ACTH-producing carcinoid tumor localized by the measurement of ACTH in the bronchial lavage.

We report a case of an ectopic ACTH-producing carcinoid in the lung. Typical Cushingoid appearance, elevated plasma ACTH and serum cortisol, bilateral enlargement of the adrenal glands, absence of pituitary adenoma and negativity in petrosus sinus venous sampling indicated the ectopic ACTH syndrome. Venous samplings from a lung tumor which was detected by the chest X-ray, did not show any step-up of ACTH. However, ACTH concentration in the bronchoscopic lavage was as high as that in the peripheral blood. Removal of the tumor, which was an ACTH producing carcinoid, resulted in normalization of ACTH and cortisol concentrations. Measurement of ACTH in the bronchoscopic lavage was useful for the diagnosis of ectopic ACTH-producing tumor.

ACTH Syndrome, Ectopic↗
PubMed2001

Glutamate is not a major conveyer of ATP-sensitive K+ channel-independent glucose action in pancreatic islet beta cell.

Insulinotropic action of glucose can be categorized as 1) triggering of release, 2) augmentation of exocytosis elicited by Ca2+, and 3) time-dependent potentiation (TDP) of the exocytotic machinery. Glucose-induced closure of ATP-sensitive K+ (K+ATP) channel is required for the first but not for the latter two. We examined the legitimacy of a novel hypothesis that glutamate is a conveyer of the K+ATP channel-independent glucose action, using intact rat pancreatic islets. To this end, we compared glucose and cell permeable glutamate donors such as dimethylglutamate and glutamine for their potency of augmentation and TDP in the presence of diazoxide (250 micromol/l), a K+ATP channel opener. One millimolar leucine was employed as an activator of glutamate dehydrogenase (GDH) as needed. A high concentration (16.7 mmol/l) of glucose applied simultaneously with a depolarizing concentration (50 mmol/l) of K+ augmented (5.80 fold) insulin release elicited by the latter. Pretreatment of the islets with 16.7 mmol/l glucose caused TDP so that insulin release subsequently elicited by 50 mmol/l K+ alone was enhanced (4.70 fold). The augmentation and TDP caused by dimethylglutamate and glutamine (10 mmol/l each), respectively, were very weak (12% of the glucose effect utmost), and dramatically enhanced upon activation of GDH by leucine. Insulinotropic effect of the glutamate donors, but not that of 50 mmol/l K+, was eliminated by 2 mmol/l NaN3, a mitochondrial poison. Glutamate per se serves as a weakly metabolizable mitochondrial fuel, but not a direct conveyer of the K+ATP channel-independent glucose action in the islet beta cell.

Adenosine Triphosphate↗
PubMed2001

Norepinephrine inhibits glucose-stimulated, Ca2+-independent insulin release independently from its action on adenylyl cyclase.

Inhibition of insulin release by norepinephrine has been attributed to activation of ATP-sensitive K+ channels, inactivation of voltage-dependent Ca2+ channels, and inhibition of adenylyl cyclase. However, direct inhibitory action of norepinephrine at a distal site of stimulus-secretion coupling has also been suggested. To obtain more direct evidence for norepinephrine inhibition of insulin release at a distal site, we performed experiments in intact, non-permeabilized beta cells. In rat pancreatic islets, a combination of glucose, phorbol ester and forskolin under stringent Ca2+-free conditions was used as a trigger of insulin exocytosis at a distal site. Norepinephrine inhibited this Ca2+-independent insulin release in a concentration-dependent manner, with an IC50 of 50 nM. The inhibition was complete, reversible, and pertussis toxin-sensitive, and not associated with any reduction of cAMP content in the islet cells. In conclusion, norepinephrine strongly, yet reversibly, inhibits insulin release in intact beta cells at a late step of exocytosis, through pertussis toxin-sensitive, G protein-mediated mechanism(s).

Adenylate Cyclase Toxin↗
PubMed2001

[Analysis of clinical costs for inpatients with the urologic diseases in 1997].

OBJECTIVES: Because of recent increases in health care costs, reformation care cost system similar to the disease related group/prospective payment system (DRG/PPS) was attracted attention in Japan. We analyzed the costs for inpatients with urologic diseases in our institution and compared them with the costs reported in Japanese trials of DRG/PPS. MATERIALS & METHODS: Subject consisted of 363 consecutive urologic diseases inpatients treated in our hospital in the period between April 1 1997 and March 31 1998. Of these 107 had bladder tumor, 79 BPH (benign prostatic hyperplasia), 34 prostate tumor, 32 renal tumor, 17 in urinary stone (excluding cases with bladder stones) and 94 cases in others. The total hospital charge for each case was calculated, and the averages and standard deviations for each disease were analyzed. We analyzed the relationship between hospital charges for each disease, and complications, the degree of disease, age and length of stay (LOS). Health care costs are assessed in unit, each of which is the equivalent of 10 yen. RESULTS: The average of total hospital charges was 108,841.6 points for bladder tumor, 61,692.2 points for BPH, 96,825.3 points for prostate tumor, 188,459.0 points for renal tumor, and 66,052.2 points for urinary stones. The standard deviation was 99,611.3 points for bladder tumors, 16,712.9 points for BPH, 65,419.3 points for prostate tumor, 204,389.6 points for renal tumor and 30,081.7 points for urinary stone. There was a positive correlation between hospital charge and LOS in most diseases. The average hospital charges for each disease were much higher than the reimbursement charges of the trial Japanese DRG/PPS. DISCUSSION: Shortening of LOS using established clinical pathways reduces health care costs. However, in Japan, the wide range of preliminary results suggests that it may be too early to introduce the DRG/PPS system for health care cost. Furthermore nationwide investigations are needed before the introduction of the DRG/PPS system into Japanese health care reimbursement system.

Adolescent↗
PubMed2001

[Comparison of quantitative coronary arteriography using cinefilm and digital images].

OBJECTIVES: Quantitative coronary arteriography using both analog data (cinefilm) and digital data was evaluated with a stenotic vessel phantom and clinical data. METHODS: A stenotic vessel phantom using contrast medium with diameters of 2, 3, 4 and 6 mm was imaged using an X-ray image intensifier. Quantitative coronary arteriography was performed to measure reference and stenosis diameters in the phantom and under clinical conditions to measure coronary artery diameters using cinefilm and digital images. RESULTS: Both cinefilm and digital images were distorted at the peripheral image area, so errors were caused when the reference and stenosis were not in the same area. Measurements of diameters in the horizontal direction were larger than in the vertical and diagonal directions (p < 0.05). Reference diameters measured on digital images were larger than those on analog images (p < 0.0001). The difference in the real and measured reference diameter (2 and 3 mm) was less than 1% on digital images. The mean error in measurement of stenotic diameter measured on cinefilm images was 0.4-6.3% smaller for 0.5-4.5 mm diameter, but on digital images was 13% larger for 1 mm diameter, 18% larger for 0.75 mm diameter and 28% larger for 0.5 mm diameter. Under clinical conditions, the reference vessel diameter measured at the stenosis and the percentage stenosis were well correlated between the analog and digital images. CONCLUSIONS: Reference diameters of stenotic vessels are almost the same on cinefilm and digital images, but stenotic diameters under 1 mm are larger than actual size on digital images and on cinefilm images.

Analog-Digital Conversion↗
PubMed2001

Effects of nifedipine retard on heart rate and autonomic balance in patients with ischemic heart disease.

The aim of this study was to explore the effects of nifedipine retard on heart rate and autonomic balance in patients with ischemic heart disease. Fourteen patients with ischemic heart disease (12 men and two women; mean age 64 years) were administered nifedipine retard at a daily dose of 20-40 mg. Changes in heart rate and autonomic balance were studied using Holter monitoring before and after 12 weeks of nifedipine therapy Heart rate was unchanged during sleep but was higher during the day after nifedipine retard administration. The high frequency power spectrum of heart rate variability (indicating parasympathetic activity) was lower during the day after nifedipine retard therapy but was unchanged during sleep. The low frequency power to high frequency power ratio, indicating sympathetic activity was unchanged during the day and during sleep. Nifedipine retard increased the heart rate of patients with ischemic heart disease only during the day and reduced parasympathetic activity.

Aged↗
PubMed2000

Induction of heme oxygenase-1 can act protectively against cardiac ischemia/reperfusion in vivo.

Enhanced production of reactive oxygen species plays a role in myocardial injury following ischemia/reperfusion. Heme oxygenase-1 (HO-1) is a heme-catabolizing enzyme that is induced by and acts against oxidant-induced tissue injury. We examined whether HO-1 expression was regulated following ischemia and reperfusion in the rat heart. HO-1 expression increased as early as 24 h after reperfusion. Strong HO-1 expression was seen in monocytes/macrophages and myofibroblasts. Next, we examined whether the induction of HO-1 could ameliorate cardiac injury following ischemia/reperfusion. Intraperitoneal hemin injection (30 mg/kg/day) for 2 days prior to the operation resulted in an about 2.8-fold increase in HO-1 expression in the rat heart. Hemin treatment significantly decreased infarct area (6 +/- 2%) compared to the control (21 +/- 2%), which was reversed by the coadministration of an HO inhibitor in a dose-dependent manner. Our data suggest that induction of HO-1 can reduce the cardiac injury in vivo following ischemia/reperfusion.

Animals↗
PubMed2000

Application of hydrostatic pressure facilitates ex vivo adenovirus gene transfer into rabbit aortas.

We investigated whether application of hydrostatic pressure facilitates ex vivo adenovirus gene transfer into rabbit aortas. Assay of beta-galactosidase activity was performed in the aortas subjected to adenovirus encoding LacZ gene (Ad-LacZ) transfer. Application of hydrostatic pressure at 8 atmospheres during Ad-LacZ gene transfer (10(10) pfu/mL, 10 min) to aortic segments resulted in an approximately 4.5-fold increase in transgene efficiency. X-Gal staining showed predominant beta-galactosidase activity in the endothelial and the adventitial cells in the aorta subjected to pressure-supported Ad-LacZ gene transfer. Then we examined the effect of heme oxygenase-1 (HO-1), which catabolizes heme to carbon monoxide and biliverdin, by transferring adenovirus encoding HO-1 (Ad-HO-1) into rabbit aortas using this pressurization system. The Ad-HO-1-infected aortic segment showed a significantly decreased contractile response to phenylephrine compared to the Ad-LacZ-infected aortic segment. Pressure-supported adenovirus gene transfer may increase the feasibility of exploiting intraoperative adenovirus-mediated gene transfer.

Acetylcholine↗