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Biomedical subjects

T Nakai

Publications and source records attributed to T Nakai.

At least 127 records · Page 7Linked to original sources
PubMed1998

Longterm effects of hepatic arterial interleukin-2-based immunochemotherapy after potentially curative resection of colorectal liver metastases.

BACKGROUND: Our previous study of hepatic arterial infusion of interleukin-2 (IL-2)-based immunochemotherapy demonstrated a high response rate of patients with unresectable liver metastases. In this study, we applied this therapy to the prevention of liver recurrence in patients who underwent potentially curative resection of liver metastases. STUDY DESIGN: A pilot study was conducted of 18 patients with liver metastases from primary colorectal cancer who underwent potentially curative liver resection followed by adjuvant immunochemotherapy. The regimen consisted of a weekly hepatic arterial infusion of IL-2 (1.4-2.1 X 10(6) U) and 5-fluorouracil (250 mg) and a bolus of mitomycin C (2-4 mg) for 6 months. RESULTS: Among 18 patients, 14 are still alive with a median postoperative survival of 52 months (as of April 1998). The 5-year overall survival rate was 75%. Although recurrent cancer developed in 6 of the 18 patients, no patients had recurrence in the residual liver. This complete prevention of liver recurrence is believed to have contributed to the high 5-year survival rate (75%) as compared with the survival rate of patients treated with surgery alone (average, 30%-40%) or with several other forms of adjuvant therapy. CONCLUSIONS: Interleukin-2-based immunochemotherapy is useful in combination with liver resection for the prevention of liver recurrence in colorectal cancer patients with liver metastases. A multicenter randomized trial is recommended.

Adult↗
PubMed1998

A novel method to immobilize bioactive substances on hydrophobic surfaces using a polymerizable cationic lipid.

We have successfully developed a novel method to stably immobilize bioactive substances that have anionic groups, such as heparin and succinylated collagen (SC), on hydrophobic surfaces through ionic complexation using a polymerizable cationic lipid, diallyl(dioleyl)ammonium bromide (DADOA). It is composed of a hydrophobic part consisting of long hydrocarbon chains and a hydrophilic head with double bonds which render it polymerizable. Analysis of the modification with DADOA and heparin suggested that the modification formed a thin layer, roughly 60 nm in thickness, as a result of the spontaneous deposition of DADOA and heparin dissolved in water, through the hydrophobic interaction between DADOA and the surface and the ionic complexation between DADOA and heparin. The heparin deposition and its rate of release in plasma were 1.5 microg/cm2 and 0.0017 U/cm2/min, respectively. Cytotoxicity test results showed that the polymerization of the deposited DADOA rendered the modified surface stable and noncytotoxic. Further, antithrombogenicity and cell attachability test results demonstrated that heparin and SC were effectively immobilized on hydrophobic surfaces through ionic complexation. This method has proved useful for the modification of the hydrophobic surfaces of medical devices because the modification process can be performed under aqueous conditions without the use of organic solvents which induce crazing/cracking of plastic casings.

Allyl Compounds↗
PubMed1998

Changes in tissue oxygen tension caused by contrast media injected into the femoral artery of the dog.

PURPOSE: To document changes in tissue oxygen tension as measured directly in an area perfused with contrast medium. MATERIAL AND METHODS: Changes in tissue oxygen tension in response to the injection of ionic and non-ionic contrast media into the femoral arteries were measured in the femoral adductor (proximal) and gastrocnemius (distal) muscles of 8 dogs. Amidotrizoic-acid and iopamidol were injected in two different iodine concentrations (370 mg I/ml and 185 mg I/ml respectively) and tissue oxygen tension in the proximal and distal muscles was monitored continuously using polarographic needle electrodes. RESULTS AND CONCLUSION: A transient decrease and subsequent increase of muscle tissue oxygen tension were observed after the injection. The extent of these changes depended on the concentration and osmolality of the medium. To minimize changes in peripheral tissue oxygen tension, contrast media with low osmolality and low concentration are recommended for femoral angiography.

Angiography↗
PubMed1998

An increase in apparent affinity for sucrose of mung bean sucrose synthase is caused by in vitro phosphorylation or directed mutagenesis of Ser11.

A mutational analysis of mung bean (Vigna radiata Wilczek) sucrose synthase was performed by site-directed mutagenesis of the recombinant protein expressed in Escherichia coli, in which two different acidic amino acid residues (Asp or Glu) were introduced at Ser11 (S11D, S11E). Only the wild-type enzyme (Ser11) was phosphorylated in vitro by a Ca(2+)-dependent protein kinase from soybean root nodules, suggesting that this is the specific target residue in mung bean sucrose synthase. The apparent affinity for sucrose was increased in this phosphorylated enzyme and also in the S11D and S11E mutant enzymes, although the affinities for UDP-glucose and fructose were similar in the wild-type, phosphorylated wild-type, and mutant enzymes. These results suggest that a monoanionic (1-) side chain at position 11 mimics the Ser11-P2- residue to bind and cleave sucrose for the synthesis of UDP-glucose. Since the S11E mutant enzyme showed the lowest K(m) (sucrose) and the highest catalytic efficiency of the recombinant proteins, the enzymic properties of this S11E mutant were further characterized. The results showed that replacement of Ser11 with Glu11 modestly protected the sucrose synthesis activity against phenolic glycosides and altered the enzyme nucleotide specificity. We postulate that the introduction of negative charge at Ser11 is possibly involved in the enzymatic perturbation of sucrose synthase.

Amino Acid Sequence↗
PubMed1998

Effects of sevoflurane and isoflurane on renal function and on possible markers of nephrotoxicity.

BACKGROUND: Low-flow sevoflurane anesthesia is associated with increasing circuit concentrations of compound A, which is nephrotoxic in rats, but the effect of compound A and low-flow sevoflurane anesthesia on renal function in humans is unclear. The authors compared the effects of high- and low-flow sevoflurane and isoflurane anesthesia on renal function and on several possible markers of nephrotoxicity in humans. METHODS: Forty-two patients without preexisting renal disease underwent either low-flow isoflurane (1 l/min, n = 14), low-flow sevoflurane (1 l/min, n 14), or high-flow sevoflurane (6 l/min, n = 14) anesthesia for body-surface-area surgery scheduled to last at least 4 h. Twenty-four-hour urinary excretion of N-acetyl-beta-glucosaminidase (NAG), beta2-microglobulin, protein, glucose, blood urea nitrogen (BUN), and serum creatinine concentrations were measured before and after anesthesia. RESULTS: There were no differences in blood urea nitrogen, creatinine, and creatinine clearance among the three groups after anesthesia. Increased urinary N-acetyl-beta-glucosaminidase excretions were seen in the low-flow and high-flow sevoflurane groups, but not in the low-flow isoflurane group (P < 0.01). Ten patients in the low-flow sevoflurane group had 24-h urinary excretion of protein that exceeded the normal ranges after anesthesia, but only one patient in the isoflurane and none in the high-flow sevoflurane groups had this. CONCLUSIONS: Low-flow sevoflurane anesthesia was associated with mild and transient proteinuria. However, the observed proteinuria was not associated with any changes in blood urea nitrogen, creatinine, and creatinine clearance in these patients with no preexisting renal disease.

Acetylglucosaminidase↗
PubMed1998

Dexamethasone modulates the expression of endothelin-1 and -A receptors in A7r5 vascular smooth muscle cells.

Endothelin-1 (ET-1) is synthesized and released by vascular smooth-muscle cells (VSMCs). Glucocorticoids induce the release of ET-1 from VSMCs into the medium. We investigated whether glucocorticoids modulate ET-1 action by an autocrine production of ET-1 in A7r5 VSMCs. Dexamethasone (100 nM) stimulated the release of ET-1 into the medium. Treatment with 100 nM dexamethasone for 24 h reduced the peak increase of intracellular free Ca2+ induced by ET-1 (100 nM) by 50%, an effect that was dose-dependently inhibited by the specific ET(A)-receptor antagonist FR139317. Scatchard plots of [125I]-ET-1 binding revealed that dexamethasone reduced the number of maximal ET-1 binding sites without altering their binding affinity. FR139317 reversed the decrease in ET-1 binding capacity induced by dexamethasone. Northern blot analysis revealed that dexamethasone increased the level of prepro-ET-1 messenger RNA (mRNA) and decreased the level of ET(A)-receptor mRNA. FR139317 prevented the decrease in the level of ET(A)-receptor mRNA induced by dexamethasone. Results indicate that dexamethasone downregulates ET(A) receptors in A7r5 VSMCs at the mRNA level, in part by the autocrine production of ET-1.

Animals↗
PubMed1998

Long-term alcohol effects on hepatic phosphoglucomutase activities in relation to posttranslational modification of the protein.

ADP-ribosylation is a posttranslational protein modification catalyzed by two classes of enzymes: mono-ADP-ribosyltransferase and poly-ADP-ribose polymerases. We previously demonstrated that long-term alcohol intake remarkably enhanced an endogenous ADP-ribosylation of a 58 kDa protein in rat liver and also identified the 58 kDa protein as phosphoglucomutase (PGM). To assess biological significance of this phenomenon, we tested the effects of long-term alcohol intake on PGM activities in connection with posttranslational modification of the protein. ADP-ribosylation of PGM was mono- rather than poly-ADP-ribosylation. Also, nonenzymatic binding of ADP-ribose was excluded. It was of note that ADP-ribosylation of exogenous PGM was remarkably increased by adding rat liver plasma membranes, and that the extent of the increase was greater in alcohol-fed rats than in pair-fed controls. Furthermore, PGM activities were significantly increased after long-term alcohol intake concomitant with increased ADP-ribosyltransferase activities toward PGM. In view of the variety of roles of PGM in the liver, such as carbohydrate metabolism and Ca2+ homeostasis, it is tempting to speculate that increased ADP-ribosylation of PGM may play a role in long-term alcohol effects on hepatocytes.

ADP Ribose Transferases↗
PubMed1998

Metastatic tumor thrombus attached to a pacemaker electrode.

We present a patient with a large tumor embolus attached to a pacemaker electrode leading to multiple pulmonary emboli. At postmortem examination, this thrombus was composed of clusters of well-differentiated squamous cell carcinoma intermingled with fibrin. Tumor involvement was not evident in the myocardium, endocardium, or epicardium. The primary tumor was discovered in the lower intrathoracic esophagus. Tumor microemboli from the esophageal primary lesions may have accumulated around the pacemaker electrode due to turbulent flow in this region, producing a large and friable tumor embolus.

Aged↗
PubMed1998

Expression of mRNA coding for four catecholamine-synthesizing enzymes in human adrenal pheochromocytomas.

OBJECTIVE: To understand the molecular mechanisms by which catecholamine synthesis is controlled in pheochromocytomas--tumors that synthesize and release catecholamines, which are related to various clinical manifestations of the condition. METHODS: We measured the concentrations of mRNA coding for the catecholamine-synthesizing enzymes tyrosine hydroxylase, aromatic L-amino acid decarboxylase (AADC), dopamine beta-hydroxylase (DBH) and phenylethanolamine N-methyl transferase (PNMT) and for the catecholamine contents in 12 pheochromocytomas and 12 normal adrenal medullas. RESULTS: The mean content of total catecholamine and the beta-actin mRNA expression in the pheochromocytomas were almost the same as those in the normal adrenal medullas. However, the tyrosine hydroxylase, AADC and DBH mRNA concentrations in the pheochromocytomas were greater than those of the normal adrenal medullas. Conversely, the PNMT mRNA concentration in the pheochromocytomas was lower than that in the normal adrenal medullas. These differences are responsible for the difference in the proportions of catecholamines between pheochromocytomas and normal adrenal medullas. The constitutive expression of the catecholamine-synthesizing enzyme mRNAs varied in magnitude among the pheochromocytomas, and the tyrosine hydroxylase mRNA expressions correlated with the contents of total catecholamine in the tumors (r=0.964, P<0.0001). CONCLUSIONS: These findings indicate that catecholamine production in pheochromocytomas is primarily controlled by the level of gene expression.

Adrenal Gland Neoplasms↗
PubMed1998

Identification and initial characterization of stathmin by the differential display method in nerve growth factor-treated PC12 cells.

The differential display of mRNA is a new strategy to identify genes that are differentially expressed under altered conditions. We applied this method to determine differential gene expression in the rat pheochromocytoma cell line during differentiation induced by nerve growth factor (NGF). Three different mRNA species were isolated, and their differential expression was confirmed by RT-PCR. One of the mRNA species was identified as stathmin, a 19 kDa cytosolic protein attracting increasing interest for its role in signal transduction. In the NGF-treated PC12 cells, the expression of stathmin mRNA increased in a time-dependent manner, as assessed by northern blot analysis and RT-PCR. We also assessed by northern blot analysis how the expression of stathmin mRNA was altered in human pheochromocytomas (n = 5) compared with that in normal adrenal medulla tissue (n = 5). The mRNA concentrations were found to be significantly greater in the pheochromocytomas than in the normal tissues. It has been shown that stathmin mRNA concentrations are increased in various tumor cells. As pheochromocytomas are well-differentiated tumors of neural origin, it is not unexpected that stathmin mRNA is overexpressed in these tumors. Stathmin was isolated and identified as a differentially expressed gene by the differential display method in PC12 cells during differentiation induced by NGF. In addition, stathmin mRNA was found to be overexpressed in human pheochromocytomas. The mechanisms responsible for the up-regulation of stathmin mRNA during differentiation of PC12 cells and the significance of its overexpression in human pheochromocytomas remain to be determined.

Adrenal Gland Neoplasms↗
PubMed1998

[Validation of dissolution testing: evaluation of vibration levels of dissolution apparatuses].

The collaborative study participated by seven laboratories was carried out to develop a dissolution standard for evaluating vibration levels of dissolution apparatuses using enteric-coated granules of cefalexin (EG). Dissolution apparatuses could be divided into two groups according to their vibration levels and the dissolution test results of EG by the rotating basket method at 50 rpm. The critical value of acceleration was about 0.05 m/s2. The upper limit of normal dissolution rates of EG was calculated from the results of the rotating basket method at 50 rpm obtained from low vibration apparatuses. All high vibration apparatuses used in this study were distinguished by the limit from low vibration apparatuses, although most of them were not distinguished by current USP calibrators. These results suggest that EG would be useful as a calibrator for detection of apparatuses on high vibration levels.

Calibration↗
PubMed1998

[Genetic polymorphism of human CYP2E1: new allels detected in exons and exon-intron junctions].

Cytochrome P450-2E1 (CYP2E1) is a major component of the microsomal ethanol-oxidizing system (MEOS) and is also involved in the metabolism of a variety of foreign compounds including carcinogens. It has been shown that there is an interindividual variation in the expression of human hepatic CYP2E1. Gene-environmental interactions have been suggested to account for the difference. In this study, we screened nine exons of the human CYP2E1 gene for detecting allelic variants in genomic DNA samples obtained from 115 Japanese controls, 96 Japanese alcoholics and 124 American control subjects. A novel missense mutation in exon 2 (V72L) was found in Japanese controls, and another missense mutation in exon 8 (D394G) was detected in American Caucasians. In addition, two novel silent mutations in exon 6 (T303T) and exon 8 (F420F) were found in Japanese controls and alcoholics. Especially the silent mutation in exon 8 was highly polymorphic among three population groups. The mutation in exon 2 (V72L) was detected only in Japanese controls, but not in alcoholics although it shows no significant difference. Gene frequency of the silent mutation in exon 8 was significantly higher in Japanese than American Caucasians (34.8% vs 21.0%, p < 0.02). Our data indicated that nucleotide replacement in the open reading frame is no major factor responsible for alcoholism. However, functional significance of the two novel missense mutations remains to be detailed.

Alcoholism↗
PubMed1997

Effect of a protein phosphatase inhibitor, okadaic acid, on thrombomodulin expression in cultured human umbilical vein endothelial cells.

We examined the effects of okadaic acid, a potent specific inhibitor of protein phosphatases 1 and 2A, on the expression of thrombomodulin (TM), a cell surface anti-thrombotic glycoprotein, on cultured human umbilical endothelial cells. Okadaic acid (2.5-10 nM) significantly increased TM antigen levels in parallel with its cofactor activity for thrombin-dependent protein C activation. Incubation of cells with 10 nM okadaic acid for 18 h induced an approximately 240% up-regulation of TM antigen levels that was accompanied by an increase in TM mRNA levels. Co-incubation of cells with okadaic acid and dibutyryl cyclic AMP further increased TM antigen levels. Furthermore, the effect of cAMP on TM expression was augmented by the pretreatment of cells with 10 nM okadaic acid for 18 h. These results provide evidence for the involvement of protein phosphatase in the cellular regulatory mechanisms for TM expression, which is distinct from that by cAMP.

Blotting, Northern↗