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T Nakamoto

Publications and source records attributed to T Nakamoto.

At least 37 records · Page 2Linked to original sources
PubMed2000

Area under the plasma concentration-time curve of inorganic fluoride following sevoflurane anesthesia correlates with CYP2E1 mRNA level in mononuclear cells.

BACKGROUND: Because the amount of inorganic fluoride released after anesthesia with sevoflurane depends on the dose of administered sevoflurane and cytochrome P450 (CYP) 2E1 activity in the liver, a reliable and noninvasive probe for CYP2E1 would be useful for predicting plasma inorganic fluoride levels after anesthesia. In this study, the authors evaluated the relation between plasma concentration of inorganic fluoride after sevoflurane anesthesia and CYP2E1 mRNA level in mononuclear cells. METHODS: Twenty patients (American Society of Anesthesiologists physical status I), aged 20-68 yr undergoing body surface surgery with general anesthesia with sevoflurane were enrolled. One milliliter of blood was obtained before administration of sevoflurane and mononuclear cells were obtained. Levels of CYP2E1 mRNA in mononuclear cells were measured by competitive reverse transcription polymerase chain reaction with a specific primer and competitor for CYP2E1 mRNA. RESULTS: There was a significant correlation between level of CYP2E1 mRNA in mononuclear cells and the area under the plasma concentration-time curve of plasma inorganic fluoride from the beginning of sevoflurane administration to infinity in uninduced and uninhibited patients (r2 = 0.56; P < 0.01). CONCLUSIONS: Area under the plasma concentration-time curve of inorganic fluoride after sevoflurane anesthesia correlates with CYP2E1 mRNA in mononuclear cells in peripheral blood.

Adult↗
PubMed2000

CIZ, a zinc finger protein that interacts with p130(cas) and activates the expression of matrix metalloproteinases.

p130(cas) (Cas) is a docking protein that contains an SH3 domain and multiple tyrosine residues. p130(cas) is located at focal adhesions, is tyrosine phosphorylated in response to integrin stimulation, and is thought to transmit signals, via c-Crk and other proteins, for the remodeling of actin stress fibers and cell movement. In a search for the ligands of the SH3 domain of p130(cas) by far-Western screening, we cloned a novel protein named CIZ (for Cas-interacting zinc finger protein). CIZ consists of the following: a putative leucine zipper; a serine/threonine-rich region; a proline-rich sequence; five, six, or eight Krüppel-type C(2)H(2) zinc fingers; and the glutamine-alanine repeat. CIZ binds Cas in cells and is located in the nucleus and at focal adhesions. We showed that CIZ is a nucleocytoplasmic shuttling protein, by using the transient interspecies heterokaryon formation assay. In order to search for the targets of CIZ in nucleus, we determined the DNA binding consensus of CIZ as (G/C)AAAAA(A) by cyclic amplification and selection of targets analysis. The consensus-like sequences are found in several promoters of matrix metalloproteinases (MMPs), which are the enzymes used to degrade the extracellular matrix proteins. CIZ binds to a consensus-like sequence in the MMP-1 (collagenase) promoter. Overexpression of CIZ upregulates the transcriptions from MMP-1, MMP-3 (stromelysin), and MMP-7 (matrilysin) promoters, and this transactivation was enhanced in the presence of Cas. Furthermore, the stable overexpression of CIZ promoted the production of MMP-7 in culture medium. In summary, CIZ, a novel zinc finger protein, binds Cas, is a nucleocytoplasmic shuttling protein, and regulates the expression of MMPs.

Amino Acid Sequence↗
PubMed2000

Microscopic polyangiitis that presented liver dysfunction prior to noted renal manifestations.

In microscopic polyangiitis (MPA), renal manifestations are very common as first symptoms. Here, we report a case of MPA which presented liver dysfunction prior to noted renal manifestations. A 58-year-old woman was hospitalized because of a fever for 8 weeks. A laboratory examination revealed marked elevation of alkaline phosphatase and gamma-glutamyl transpeptidase, while blood urea nitrogen and creatinine levels remained normal. Although apparent renal dysfunction developed in this case soon after hospitalization, physicians should be aware of the variety of clinical manifestations in MPA. Moreover, antineutrophil cytoplasmic autoantibodies were found to be helpful for diagnosing MPA.

Female↗
PubMed2000

Gene therapy for murine renal cell carcinoma using genetically engineered tumor cells to secrete interleukin-12.

To determine the possibility of gene therapy for renal cell carcinoma (RCC) using interleukin-12 (IL-12), we prepared genetically engineered murine RCC cells (Renca) which secrete IL-12 and evaluated the usefulness of these cells as a tumor vaccine. The IL-12 gene was transduced using MFG retroviral vector. The in vitro characteristics of transfectants--i.e., cell proliferation and expression of surface antigens--were then examined. In vivo tumorigenicity was assessed by subcutaneously injecting each type of cell in syngenic BALB/c mice. For the challenge experiments, the mice rejecting previously injected Renca IL-12 cells were rechallenged with parental cells. To determine the antitumor effect at remote sites, mice were injected with parental cells into the left flank, and then either Renca IL-12 or parental cells were inoculated into the opposite site on day 0 or 1. The transfected cells can secrete 146.7 ng/ml/10(6)cells/48 hr of IL-12, as confirmed here by bioassay. The in vitro characteristics of the transfectants were not altered, but in vivo tumorigenicity was significantly reduced. Of the 21 mice that rejected Renca IL-12 cells, 9 failed to develop tumors after the challenge with parental cells. In the mice treated with Renca IL-12 as a vaccine, both number and tumor volume of the mice that developed tumors at remote sites were reduced. IL-12 secreting Renca cells conferred both protective immunity to parental cells and delay of tumor growth at remote sites, indicating that IL-12 secreting Renca cells are a feasible candidate for use in gene therapy of RCC.

Animals↗
PubMed2000

Anti-tumor effect of murine renal cell carcinoma cells genetically modified to express B7-1 combined with cytokine secreting fibroblasts.

Recently, many experiments have shown that the expression of the costimulatory molecule B7-1 on tumor cells can induce tumor-specific immunity. These results suggest that tumor cells modified to express costimulatory molecules can be used as a potential tumor vaccine. For this purpose, we transduced B7-1 gene into renal adenocarcinoma cells of spontaneous origin (Renca) in BALB/c mouse using the retroviral vector system. Our results indicated that approximately 60% of cells expressed B7-1 gene product using the retroviral vector system, and that B7-1 transduction did not affect the expression of MHC molecules on tumor cells nor the in vitro growth rate of tumor cells, but only in vivo tumorigenicity. As for the antitumor effect on the remote site, there were no significant differences among parental Renca, Renca lac Z and Renca B7-1 sublines, although tumors grew a little more slowly in the mice injected with Renca B7-1 cells as a vaccine. Even if the growth of tumors was significantly delayed in the mice treated by Renca B7-1 as a vaccine combined with the injection of BALB/c3T3 IL-12 near to the tumor on the same or following day, no significant antitumor effects were observed when the Renca B7-1 cells were injected as a vaccine compared with cytokines near the vaccine site. These results indicated that B7-1 gene transduction can decrease the tumorigenicity of murine renal cell carcinoma cells, but fails to induce sufficient antitumor response when it is used as a tumor vaccine. It is necessary to develop immunogenicity, by such means as irradiation or a combination of appropriate cytokines, to stimulate effective tumor immunity in a therapeutic setting.

3T3 Cells↗
PubMed2000

Endoscopic subureteral glutaraldehyde cross-linked collagen injection for the treatment of secondary vesicoureteral reflux: comparison with primary vesicoureteral reflux in adults.

PURPOSE: We assessed the effectiveness of endoscopic subureteral glutaraldehyde cross-linked collagen injection for treating vesicoureteral reflux in patients with vesicoureteral disorders. MATERIALS AND METHODS: All 51 ureters studied had grade II or greater vesicoureteral reflux. We treated 18 patients (24 refluxing ureters) with secondary and 17 adults (27 refluxing ureters) with primary vesicoureteral reflux. The primary group served as controls to establish normal urination. A total of 14 patients with secondary vesicoureteral reflux had a low compliant autonomous bladder, including 11 with myelodysplasia and 3 after pelvic surgery and radiotherapy. One patient had an unstable bladder due to cerebral palsy and 3 had anatomical abnormalities of the urinary tract. We evaluated the estimated reflux-free rate in the secondary and adult primary vesicoureteral reflux groups. RESULTS: Repeat injection was required in 24 ureters because of recurrent reflux. Average injected volume in the secondary and primary groups was 2.72 and 2.88 ml. per refluxing unit, respectively. The estimated reflux-free rate after the initial injection decreased gradually to about 35% in each group, while 12 and 24 months after the last injection it remained constant at 70% in the secondary group but decreased from 84.7% to 62.1% in the primary group. The percent of late recurrence was higher in the primary group. CONCLUSIONS: Long-term efficacy of the endoscopic correction of vesicoureteral reflux in the secondary group was similar to that in the primary group. Thus, endoscopic subureteral glutaraldehyde cross-linked collagen injection is useful for treating complicated secondary vesicoureteral reflux as a minimally invasive procedure. It is considered optional treatment of primary vesicoureteral reflux to avoid long-term prophylactic treatment.

Absorbable Implants↗
PubMed2000

Invasive bladder cancer after cyclophosphamide administration for nephrotic syndrome--a case report.

We report a case of invasive bladder cancer after cyclophosphamide administration for nephrotic syndrome, and briefly discuss the association of bladder cancer and cyclophosphamide. A 6-year-old boy, who was diagnosed as having nephrotic syndrome, was treated with oral administration of prednisolone and cyclophosphamide for 4 years, receiving a total dose of 49.5 g cyclophosphamide. At age 27, a gross hematuria with bloody clots appeared and he presented with postrenal renal failure. He underwent a radical cystourethrectomy and ileal conduit for stage a pT3a pN0 M0 transitional cell carcinoma of the bladder. He was not given any adjuvant treatments because of his renal insufficiency, and he died from the disease 14 months after radical surgery.

Adult↗
PubMed1999

p130(Cas), an assembling molecule of actin filaments, promotes cell movement, cell migration, and cell spreading in fibroblasts.

p130(Cas) (Cas) is an adaptor molecule which becomes tyrosine phosphorylated by v-Src- or v-Crk-triggered transformation and several physiological stimuli, such as cell attachment to fibronectin. We previously generated mice lacking Cas and demonstrated that Cas functions as an assembling molecule of actin filaments. To further explore Cas role in cellular function, we established Cas-deficient and Cas-re-expressing fibroblasts and compared their behaviors in response to several biological stimuli. We found that Cas-deficient fibroblasts showed significant defects in cell movement after mechanical wounding and in cell migration toward fibronectin as compared with Cas-re-expressing cells. In addition, when plated on fibronectin-coated dishes, Cas-deficient cells exhibited a significant delay in cell spreading as compared with Cas-re-expressing cells albeit that protein-tyrosine phosphorylation was similarly induced. These results demonstrated that Cas functions as a molecule promoting cell movement, cell migration, and cell spreading and suggest that Cas would be implicated in various physiological and pathological processes, such as would healing, chemotaxis, and tumor invasion.

Actin Cytoskeleton↗
PubMed1999

Propofol decreases the clearance of midazolam by inhibiting CYP3A4: an in vivo and in vitro study.

OBJECTIVE: To examine the effect of propofol on the pharmacokinetics of midazolam in vivo and to elucidate the mechanism of the pharmacokinetic changes of midazolam by propofol with the use of human liver microsomes and recombinant CYP3A4. METHODS: In an in vivo, double-blind randomized study, 24 patients received 0.2 mg/kg midazolam and either 2 mg/kg propofol (propofol group) or placebo (placebo group) for induction of anesthesia. In the propofol group, continuous infusion of propofol at 9 mg/kg/h was started immediately after the bolus infusion of propofol and was maintained for an hour. In the placebo group the same dose of soybean emulsion as a placebo was given and infused intravenously for an hour instead of propofol. In an in vitro study the effect of propofol on the metabolism of midazolam was studied with human liver microsomes and recombinant CYP3A4. RESULTS: In the propofol group the mean clearance of midazolam was decreased by 37% (P = .005) and the mean elimination half-life was prolonged by 61% (P = .04) compared with the placebo group. The mean plasma concentrations of 1'-hydroxymidazolam were lower in the propofol group than in the placebo group at 5, 10, 15, 20, and 30 minutes after midazolam was administered (P < .05). The mean (+/-SD) Michaelis-Menten constant for midazolam 1'-hydroxylation by human liver microsomes was 5.6 +/- 3.3 micromol/L. The formation of 1'-hydroxymidazolam was competitively inhibited by propofol, and the mean inhibition constant was 56.7 +/- 16.6 micromol/L. The mean Michaelis-Menten constant and mean inhibition constant values for midazolam 1'-hydroxylation by recombinant CYP3A4 were 4.0 micromol/L and 61.0 micromol/L, respectively, consistent with the mean values obtained from human liver microsomes. CONCLUSION: Propofol decreases the clearance of midazolam, and the possible mechanism is the competitive inhibition of hepatic CYP3A4.

Adult↗
PubMed1999

Fentanyl inhibits metabolism of midazolam: competitive inhibition of CYP3A4 in vitro.

Fentanyl decreases clearance of midazolam administered i.v., but the mechanism remains unclear. To elucidate this mechanism, we have investigated the effect of fentanyl on metabolism of midazolam using human hepatic microsomes and recombinant cytochrome P450 isoforms (n = 6). Midazolam was metabolized to l'-hydroxymidazolam (l'-OH MDZ) by human hepatic microsomes, with a Michaelis-Menten constant (K(m)) of 5.0 (SD 2.7) mumol litre-1. Fentanyl competitively inhibited metabolism of midazolam in human hepatic microsomes, with an inhibition constant (Ki) of 26.8 (12.4) mumol litre-1. Of the seven representative human hepatic P450 isoforms, CYP1A2, 2A6, 2C9, 2C19, 2D6, 2E1 and 3A4, only CYP3A4 catalysed hydroxylation of midazolam, with a K(m) of 3.6 (0.8) mumol liter-1. Fentanyl competitively inhibited metabolism of midazolam to l'-OH MDZ by CYP3A4, with a Ki of 24.2 (6.8) mumol litre-1, comparable with the Ki obtained in human hepatic microsomes. These findings indicate that fentanyl competitively inhibits metabolism of midazolam by CYP3A4.

Anesthetics, Intravenous↗
PubMed1999

Drug-associated cholelithiasis: a case of sulindac stone formation and the incorporation of sulindac metabolites into the gallstones.

A case of drug-associated cholelithiasis (sulindac chlecystohepatolithiasis) in a 63-yr-old woman is reported. The patient was admitted to our hospital to undergo treatment for rheumatoid arthritis of 20 yr duration. She was treated with nonsteroidal anti-inflammatory drugs (NSAID: sulindac). Two months later, she presented with right upper quadrant pain. Diagnostic studies including ultrasonography (US), computed tomography (CT) and endoscopic retrograde cholangiography (ERC), led to the diagnosis of cholecystohepatolithiasis. She underwent cholecystectomy and choledochotomy with an extraction of intrahepatic stones. The intrahepatic stones were light yellow in color with a claylike appearance. Unexpectedly, an infrared spectroscopic analysis of the stone showed it to consist of sulindac metabolites. In addition, the dilated segment of the intrahepatic bile duct naturally returned to its normal size after the discontinuation of the drug administration. This is the first reported case of sulindac stone formation in the bile duct. No similar problems with other NSAIDs have been reported previously.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

Effects of caffeine on the bones of aged, ovariectomized rats.

Caffeine is a substance which many people consume in their daily life. Caffeine's effects on bone are still controversial. Using ovariectomized rats, the present study was conducted to determine to what extent caffeine intake affects the mechanical properties, bone minerals and histology. Aged rats were divided into 2 groups after ovariectomy. Group 1 was fed a 20% protein diet as a control, and group 2 was fed a 20% protein diet supplemented with caffeine (2 mg/100 g body weight). The respective diets were fed to the rats of each group for 90 days. Rats were then killed by heart puncture, blood was collected, and femurs were removed. In 1 group of femurs paraffin cross-sections were made at the midshaft of each bone. Total width, cortical width, total cross-sectional bone area of the midshaft, and the number of osteocytes in randomly selected areas were measured. Another group of bones was subjected to three-point bending testing until failure. Bones were then pulverized and Ca, P, Mg, Zn, Sr, Si, hydroxyproline and hexosamine contents and crystallite size were measured. Various mechanical properties, except modulus of elasticity, in the caffeine group were consistently 7-23% lower than the noncaffeine controls. Yield strain in the caffeine group was significantly less than in the noncaffeine controls. Zinc, Sr, and crystallite size of bone showed a significant decrease in the caffeine group, whereas Si contents significantly increased. Our current results indicate that routine intake of caffeine in the elderly should be regarded with some caution.

Aging↗
PubMed1999

Effects of caffeine on heart mitochondria in newborn rats.

Caffeine consumption has been implicated in the development of cardiovascular disease. Therefore, in the present study, litters of rats were combined upon birth, and 8 pups were randomly assigned to each dam. Dams with pups were divided into 2 groups: group 1 received a 20% protein diet as a control, and group 2 received the 20% protein diet supplemented with caffeine (4 mg/100 g body weight). Pups from both groups were killed on days 11 and 15. Transmission electron microscopy revealed swollen, disrupted, degenerating mitochondria and intracellular edema in the hearts of rats in the caffeine groups when compared with those of the controls. Plasma Cu concentration was significantly decreased. These results indicate that early exposure to caffeine through maternal milk adversely affects cardiac mitochondria of rat pups and may be associated with decreased plasma Cu levels. It is unclear whether these results apply to the human infant. Interspecies extrapolation from rat to human must be made with caution.

Animals↗
PubMed1999

Combined effects of caffeine and prostaglandin E2 on the proliferation of osteoblast-like cells (UMR106-01).

BACKGROUND: The general public widely consumes caffeine (1,3,7-trimethylxanthine), which is contained in various foods, beverages and over-the-counter medications. We have shown previously that caffeine intake could affect bone metabolism in vivo. METHODS: Because prostaglandin E2 (PGE2) is shown to be elevated in the periodontally diseased site, the possible interaction between caffeine and PGE2 was investigated in the present study using UMR106-01 rat osteoblast-like cells in vitro. RESULTS: Although neither 0.1 mM caffeine nor 0.1 microg/ml of PGE2 alone showed any inhibitory effects on cell proliferation, the combination of caffeine and PGE2 showed significant inhibition. However, in order to have inhibitory effects, both caffeine and PGE2 had to be present at least 72 or 96 hours in the medium. Addition of the endogenous PGE2 synthesis inhibitor, indomethacin, showed no effects on cell proliferation. Neither cAMP-inducing agent IBMX (0.01 mM and 0.1 mM) nor forskolin (0.001 mM) inhibited cell proliferation, but combined with PGE2 these agents strongly inhibited proliferation as was observed with the combination of caffeine and PGE2, suggesting possibly that the increase of intracellular cAMP concentration plays an important role in the inhibitory effects of cell proliferation. CONCLUSIONS: The present data for the first time demonstrate the possible implication of routine caffeine intake in the acceleration of pathological conditions of periodontitis. Thus, we propose that chronic caffeine intake is one of the possible risk factors in the advancement of pathology in the periodontitis patient. Further research in this area is warranted.

1-Methyl-3-isobutylxanthine↗
PubMed1999

Modulation of carbachol-induced Cl(-) currents and fluid secretion by isoproterenol in rat submandibular acinar cells.

The effects of muscarinic and beta-adrenergic agonists on Cl(-) currents in acinar cells were investigated to clarify their role in the regulation of fluid secretion in rat perfused submandibular glands. Additions of isoproterenol (IPR) at 10(-8) to 10(-6) M and 8-(4-chlorophenylthio)-cyclic AMP (CPT-cAMP) at 10(-3) M to the perfusate suppressed carbachol (CCh; 10(-6) M)-induced fluid secretion. IPR and CPT-cAMP also diminished CCh-induced oscillatory Cl(-) current and increased CCh-stimulated non-oscillatory Cl(-) current. Propranolol blocked the effect of IPR on fluid secretion. IPR did not modulate the CCh-induced increase in intracellular concentration of calcium ions and intracellular pH in isolated cells. Propranolol blocked IPR-induced changes in Cl(- )currents, while propranolol itself increased CCh-induced K(+) current and reduced CCh-induced oscillatory Cl(-) current. Increasing external osmolarity with 50 mM sucrose abolished IPR-enhanced non-oscillatory Cl(-) current. Neither CCh-induced oscillatory Cl(-) current nor IPR-induced suppression of the oscillatory Cl(-) current was influenced by the hypertonicity. Perfusion of the gland with the hypertonic solution did not affect the IPR-induced suppression of fluid secretion. These results suggest that IPR induces the suppression of CCh-induced oscillatory Cl(-) current and potentiation of the non-oscillatory Cl(-) current via an increase in cyclic AMP level, and that suppression of the oscillatory Cl(-) current by IPR may contribute to the inhibition of fluid secretion from submandibular glands.

Adrenergic beta-Agonists↗