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Biomedical subjects

N Takeuchi

Publications and source records attributed to N Takeuchi.

At least 127 records · Page 7Linked to original sources
PubMed1994

In vivo microdialysis for pharmacokinetic investigations: a plasma protein binding study of valproate in rabbits.

The use of microdialysis to study the binding of valproate (VPA) to plasma proteins was evaluated in rabbits. Prior to an in vivo microdialysis, in vitro relative recovery of VPA respectively from Ringer's solution, 5% (w/v) of albumin solution and plasma sample via a microdialysis probe was examined. The in vitro relative recovery was defined as a ratio of the VPA concentration determined in the dialysate to the free VPA concentration in the sample solution surrounding the membrane of the microdialysis probe. When the sample solution was well stirred at 700 rpm and maintained at 37 degrees C, the in vitro relative recovery of VPA was significantly different among them. It increased in the order of Ringer's solution (34.3 +/- 2.6%) > 5% (w/v) of albumin solution (25.7 +/- 4.6%) > rabbit plasma sample (15.8 +/- 1.2%). Thereafter, pharmacokinetics of VPA was determined using both microdialysis sampling via the rabbit femoral vein and collection of whole blood via the rabbit ear vein after intravenous administration of VPA at a dose of 43 mg/kg. Free concentrations of VPA in plasma were determined by ultrafiltration method as opposed to microdialysis method. There was no difference in the elimination half-life of VPA determined by microdialysis, 1.09 +/- 0.22 h, or ultrafiltration, 1.22 +/- 0.21 h. The AUC of VPA in dialysate was 15 +/- 4 micrograms.h/ml, which corresponded to 15% of that in ultrafiltrate (103 +/- 17 micrograms.h/ml). The value was in good agreement with the in vitro relative recovery of VPA from plasma sample (15.8 +/- 1.2%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

[Changes in serum lipid and lipoproteins in alloxan-diabetic rats--studies for one year].

Alloxan-diabetic rats were kept on an ordinary or 0.25% cholesterol supplemented diet for up to 12 months, and changes in the serum lipid and lipoprotein levels were examined. The diabetic rats showed IRI levels of 3-5 IU/ml, which were 1/5-1/10 that of the normal rats, and about 10 times higher serum glucose levels than the normal rats. The diabetic rats consumed 1.5-2 fold amounts of diet but their body weights were almost constant. The diabetic rats showed marked hyperlipidemia, especially in the cholesterol and triglyceride levels. The phospholipid level also increased but for a lesser extent and the c/p ratio increased. The serum lipoprotein levels increased in the diabetic rats, 5-10 times in the ordinary diet fed groups and 10-20 times in the cholesterol diet fed groups. Chylomicron, VLDL, IDL and LDL increased but HDL decreased. These changes were more significant in the diabetic rats fed the cholesterol diet. The triglyceride levels in the lipoprotein fractions increased in the diabetic rats, but the increase in cholesterol was more significant and the relative composition ratios of triglyceride decreased. The composition ratios of phospholipids, however, remained almost constant in all the lipoprotein fractions. The increase in IDL, especially cholesterol in the IDL fraction, was remarkable in the diabetic rats. The responsiveness of the diabetic rat VLDL to lipoprotein lipase (release of free fatty acids) was less than a half of that of the normal rat VLDL. In conclusion, the diabetic rats showed an increase in triglyceride but more significant increase in cholesterol in the lipoprotein fractions. These changes in serum lipid and lipoprotein levels and compositions appeared as early as 3 months after the alloxan injection and lasted for 12 months without any progress in the disturbance.

Alloxan↗
PubMed1994

Metastatic pulmonary calcification in patients with hypercalcemia: findings on chest radiographs and CT scans.

OBJECTIVE: The objective of this study was to characterize the findings on chest radiographs and CT scans in patients with metastatic pulmonary calcification due to hypercalcemia. MATERIALS AND METHODS: The chest radiographs and CT scans of seven patients with biopsy-proved metastatic pulmonary calcification were reviewed by two observers. Metastatic calcification was due to chronic renal failure (n = 4), T-cell leukemia (n = 1), multiple endocrine neoplasia type I syndrome (n = 1), and idiopathic hypercalcemia (n = 1). RESULTS: Numerous nodular opacities measuring 3-10 mm in diameter were seen on the chest radiographs in five cases, and patchy areas of parenchymal opacification were seen in two cases. Calcification of the nodules was evident in two cases. On CT scans, pulmonary nodules were present in all seven cases. These nodules were predominant in the upper lung zone in three cases, were diffuse in three cases, and were predominant in the lower lung zone in one case. Calcification of the nodules was evident on the CT scans in four of the seven cases, and calcification of vessels in the chest wall was evident in six of seven cases. Other findings on CT scans included diffuse areas of ground-glass attenuation (n = 3) and patchy consolidation (n = 2). CONCLUSION: Numerous small nodules are the most common finding on the chest radiographs of patients with metastatic pulmonary calcification. The calcific nature of the nodules is seldom obvious, however. Pulmonary nodules are also the most common finding on CT scans, where the calcific nature of the nodules is more readily apparent. Additionally, calcification is often seen in the vessels of the chest wall on CT scans. The combination of calcified nodules and calcified vessels in the chest wall on CT scans may be characteristic.

Adult↗
PubMed1994

Acute myelopathy and cerebellar signs associated with uveitis with positive serum and cerebrospinal fluid antibodies to HTLV-I.

A 55-year-old man was admitted because of weakness in the legs of a few days duration. Neurological examination revealed paraparesis, ataxia of the left limbs, superficial hypoesthesia below the T-10 dermatome level and urinary retention. The antibody titers to human T-lymphotropic virus type I (HTLV-I) were x640 in the serum and x16 in the cerebrospinal fluid (CSF). The HTLV-I gag proteins, p19, p24, p46 and p53 were identified by Western blotting analysis of the serum and CSF. The CSF contained 691 white cells/c.mm; protein, 260 mg/dl; IgG, 84 mg/dl; and IgG index, 2.49. Although the paraparesis and urinary retention disappeared within 10 days, he developed right uveitis which responded well to corticosteroid treatment. With improvement of the sensory impairment, cerebellar signs and CSF pleocytosis as well as uveitis, he was discharged eight weeks after admission. HTLV-I uveitis is a recently established disease entity. The case emphasizes the need to test blood and CSF for HTLV-I antibodies if patients developed myelopathy and cerebellar signs of acute onset, especially when associated with uveitis.

Cerebellum↗
PubMed1994

Improved method for the analysis of ascorbic acid in plasma by high-performance liquid chromatography with electrochemical detection.

We improved the analytical method for the detection of ascorbic acid in plasma by high-performance liquid chromatography (HPLC) with an electrochemical detector (ECD) to be more selective and rapid than the protocol previously used. Main improvements are as follows. Applied potential of ECD to obtain the maximal response for ascorbic acid was +450 mV versus Ag/AgCl, but it was reduced to +350 mV. In that condition, uric acid did not respond to ECD, and only ascorbic acid was detected. EDTA contained in sample extraction/stabilizing solution gave the peak after the ascorbic acid. The addition of EDTA (0.2 mM) to the mobile phase eliminated the EDTA peak. These two improvements gave the chromatogram in which the peak that appeared from the plasma sample was only ascorbic acid, and shorten the sample run time. Ascorbic acid in plasma was unstable even though the plasma was treated with methanol/EDTA: it decreased from 1.5 h at 4 degrees C. However, the treated sample, which was placed at -14 degrees C until the analysis was performed, gave the reliable ascorbic acid value at least up to 6 h. The data obtained from the HPLC-ECD method was consistent with those from the hydrazine method.

Ascorbic Acid↗
PubMed1994

Development of atherosclerosis in alloxan diabetic rats.

Rats with alloxan-induced diabetes developed severe atherosclerotic lesions when they were maintained on a 0.25% cholesterol diet for one year. The atheromatous changes developed at the aortic arch, appeared as early as 3 months after the start of the experiment, and increased thereafter. The diabetic rats also developed atherosclerosis when they were fed standard rat chow, but the area of the atheromatous lesion was about one tenth of that in rats fed the high-cholesterol diet. Normal rats did not develop atherosclerosis even when fed the high-cholesterol diet for one year. The alloxan diabetic rats showed no increase in body weight, but developed serum glucose levels as high as 600-800 mg/dl as well as high serum cholesterol levels and lower serum HDL-cholesterol levels. The development of atherosclerosis in these rats was significantly related to an increase in the serum cholesterol/phospholipid ratio, the atherogenic index (TC-HDLC/HDLC), and the serum total cholesterol level, but was not related to the serum glucose, HDL-cholesterol, triglyceride, or lipid peroxide levels. These relationships were found as early as B-16 weeks after the start of the experiment. These data suggest that the serum cholesterol/phospholipid ratio, the atherogenic index, and the total cholesterol level are important risk factors for the development of atherosclerosis in rats with alloxan diabetes.

Animals↗
PubMed1994

Decreased susceptibility of glycated very low density lipoproteins to lipoprotein lipase in vitro and prevention by glutathione.

In vitro glycation of very low density lipoprotein (VLDL) reduced the susceptibility to lipoprotein lipase (LPL) as the level of glycation increased. Addition of reduced glutathione to an incubation medium of serum and glucose interfered with glycation of serum proteins when the concentration of reduced glutathione was higher than 10 mM. At concentrations higher than 25 mM, it also significantly prevented the glycation induced reduction of fatty acid releases from VLDL by LPL. There were no such effects on glycation of serum protein and the fatty acid release from the addition of aminoguanidine. By contrast, addition of D-lysine enhanced glycation of serum proteins by glucose and further decreased fatty acid release from VLDL by LPL. From these results, it is suggested that glycation of VLDL decreases the susceptibility of VLDL to LPL. Delayed catabolism of VLDL in diabetic patients is considered partly caused by glycation of apoproteins, which renders VLDL less sensitive to LPL, in addition to the decreased LPL activity in diabetes mellitus.

Catalysis↗
PubMed1994

[End stage polycystic kidney disease: the study for upper urinary tract infection & hemorrhage into the cysts].

The results have been reviewed of 41 patients with end stage polycystic kidney disease on maintenance hemodialysis. The patients ranged in age from 34 to 83 years with an average age of 55 years and 25 patients were male, 16 were female. The duration of maintenance hemodialysis in the patients was from 1 to 200 months with an average time of 69 months. Infection of the cysts and pyelonephitis occurred 22 times in 13 patients (32%) and hemorrhage into the cysts occurred 15 times in 13 patients (32%). To control the infection, bilateral nephrectomy was required in 10 patients and 1 patient was undergone unilateral nephrectomy. Of 13 patients with the hemorrhagic cysts, 5 were undergone bilateral nephrectomy and 2 were undergone unilateral nephrectomy. Six patients died during follow up and the cause of death were 1) cardiac failure, 2) cerebral hemorrhage, 3) cardiac infarction, 4) pneumonia after nephrectomy, 5) massive bleeding after second operation for adhesive ileus due to first nephrectomy, 6) unknown. Fourteen patients but one undergone bilateral nephrectomy were followed for an average time of 70 months after nephrectomy. Such as complication due to bilateral nephrectomy, anemia occurred in 13 patients (93%) and hypotension occurred in 5 patients (33%). Bilateral nephrectomy was effective procedure in safety for end stage polycystic kidney patients with the infection and the hemorrhagic cysts because anemia and hypotension which occurred usually after bilateral nephrectomy now can be controlled goodly.

Adult↗
PubMed1993

In vitro degradation of very low density lipoprotein from diabetic patients by lipoprotein lipase.

Fatty acid release by incubation with lipoprotein lipase (LPL) in vitro from very low density lipoproteins (VLDL) obtained from diabetic patients was low compared with that from healthy subjects, though the compositions were similar in both VLDL. Percentages of the large size VLDL decreased and those of the small size VLDL increased after the incubation with LPL. At the same time, on polyacrylamide gel disk electrophoresis, the smaller catabolic products from these VLDL appeared at a similar position to that of low density lipoproteins (LDL) and at the running front where high density lipoproteins (HDL) had migrated. The amount of the small size VLDL and the LDL-like lipoproteins produced from diabetic VLDL were less than those from normal VLDL and inversely correlated with the percent decrease of the large original size VLDL. This fact suggests that VLDL from diabetic patients are poor substrates for LPL compared with normal VLDL.

Diabetes Mellitus, Type 2↗
PubMed1993

Possible role of Na+ influx in phorbol ester-induced down-regulation of protein kinase C in HL60 cells.

Amiloride, an inhibitor of Na+/H+ exchange, inhibited down-regulation of protein kinase C in HL60 cells induced by tumor-promoting phorbol ester in dose-dependent manner judging from immunoblot analysis. This inhibition was observed with regard to type I (gamma), type II (beta), and type III (alpha) isozymes of protein kinase C. On the other hand, monensin, a Na+ ionophore, accelerated the down-regulation of protein kinase C induced by phorbol ester. When we examined 22Na+ uptake by HL60 cells, the higher uptake was observed after stimulation with phorbol ester compared to the control cells and this 22Na+ uptake was strongly inhibited by the addition of amiloride. However, monensin further stimulated the 22Na+ uptake observed in phorbol ester-treated cells. These data suggest that the increase in intracellular Na+ concentration may be one of the triggers for the induction of down regulation of protein kinase C.

Amiloride↗
PubMed1993

The lectin concanavalin A stimulates a protein-tyrosine kinase p72syk in peripheral blood lymphocytes.

We report that the activation of porcine peripheral blood lymphocytes (PBL) by lectin concanavalin A (Con A) led to the increase in tyrosine phosphorylation on 84-, 72-, 55-, 40-, and 33-kDa proteins. A non-receptor protein-tyrosine kinase (PTK), p72syk (Taniguchi et al. (1991) J. Biol. Chem. 266, 15790-15796), was detected in PBL around 0.1% of total protein and distributed in both particulate and cytosolic fractions. Furthermore, Con A induced a rapid activation of p72syk within 1 min in a manner similar to the time course of Con A-induced protein-tyrosine phosphorylation. These results suggest that p72syk plays a certain role in the activation of PBL and that p72syk may be one of the major non-receptor PTKs in T cells as well as in B cells.

Animals↗
PubMed1993

Expression of perforin and membrane-bound lymphotoxin (tumor necrosis factor-beta) in virus-specific CD4+ human cytotoxic T-cell clones.

In an attempt to clarify the mechanisms of cytotoxicity mediated by CD4+ cytotoxic T lymphocytes (CTL), the expression of perforin and membrane-bound lymphotoxin (LT) (tumor necrosis factor-beta) in herpes simplex virus (HSV)-specific CD4+ human cytotoxic and noncytotoxic T-cell clones was examined. Three HSV-specific CD4+ human CTL clones that showed HLA-DR-restricted cytotoxicity and proliferative response were established. The cytotoxicity of these clones in 5-hour 51Cr release assays was found to be mediated by the directional target cell lysis and not by the release of cytotoxic soluble factors, ie, "innocent bystander" killing. Northern blot analysis showed that messenger RNAs for perforin and LT, which were both considered to be important mediators for cytotoxicity of CD8+ CTL and natural killer cells, were abundantly expressed in HSV-specific CD4+ CTL clones. Expression of perforin in the cytoplasm of CD4+ CTL clones was also detected by immunohistochemical staining using a monoclonal antibody against perforin. In addition, LT bound to the cell surface of CD4+ CTL clones was detected by flow cytometry. In contrast, little or no expression of perforin and LT was detected in three HSV-specific CD4+ noncytotoxic T-cell clones. Although the cytotoxicity mediated by lymphokine-activated killer cells was partly inhibited by addition of anti-LT antibody, it did not show any effect on the cytotoxicity of HSV-specific CD4+ CTL clones. In addition, it was found that cytotoxicity mediated by these CD4+ CTL clones was Ca2(+)-dependent. These data thus suggest that perforin and membrane-bound LT are both expressed in HSV-specific CD4+ CTL, although perforin might be the more important mediator in short-term culture.

Antibodies, Monoclonal↗
PubMed1993

Peripherally administered serotonin induces hyperglucagonemia in mice.

Peripherally administered serotonin (5-HT) induced a marked increase in the plasma glucagon level in mice. The hyperglucagonemic effects of 5-HT were completely antagonized by methysergide, ketanserin and ritanserin which have a high affinity for 5-HT2 receptors. However, the 5-HT3 receptor antagonist ICS 205-930 and MDL 72222 were without effect. These findings suggest that the activation of the peripheral 5-HT2 receptor induces the increase in plasma glucagon level and that these receptors may play a role in the release of glucagon.

Animals↗
PubMed1993

Actions of benzalkonium chloride as a potent depressant at the neuromuscular junction.

Benzalkonium chloride (BA), a positively charged surface active agent, applied (> 10 nM) in the superfusing solution, produced a concentration-dependent reduction in the amplitude of both evoked endplate potentials (EPPs) and spontaneous miniature EPPs of the frog. Voltage-clamped endplate currents (EPCs) and spontaneous miniature endplate currents (MEPCs) were also diminished in amplitude, in the presence of BA (50-140 nM), whereas their time-course and reversal potential were not obviously affected. No significant change due to the addition of 50 nM BA was observed in apparent properties of the ACh channel estimated from ACh-induced current fluctuations. In the relationship between the amplitude of ACh potentials and the net charge for iontophoretic pulses at a single junction, the principal pattern of action of BA (30-60 nM) appeared to be a parallel shift to the right. At concentrations greater than about 1 microM, BA slightly increased the resting input conductance of the non-synaptic muscle fibre membrane. It was suggested that this increase was attributable to a slight increase in Cl ion conductance of the non-synaptic membrane. These results indicate that BA effectively blocked neuromuscular transmission, acting as an ACh receptor antagonist at smaller concentrations and as a more potent blocker that acts through multiple sites at greater concentrations.

Acetylcholine↗
PubMed1993

Inhibition of homologous complement activation by the heat-stable antigen.

The murine heat-stable antigen (HSAg) is of particular interest due to its unique tissue distribution. HSAg is expressed on most thymocytes, bone marrow cells, immature B cells, and erythrocytes, but not on peripheral T and mature B cells. Although HSAg has been thought to be a differentiation antigen, its actual biological significance remains unknown except for the HSAg on antigen presenting cells. Recently, a new rat anti-HSAg mAb, R13, has been developed. Here it has been found that the mouse complement activation on mouse erythrocytes, but not the human, guinea pig or rabbit complement activations, was enhanced in the presence of the Fab fragment of R13. Affinity-purified HSAg derived from mouse erythrocytes could be passively incorporated into rabbit erythrocytes because of its molecular characteristic of glycosylphosphatidyl inositol-anchored protein. Mouse complement activation, but not guinea pig complement activation, was partially suppressed on the HSAg-incorporated rabbit erythrocytes. These findings suggest that HSAg has a homologous complement regulating activity.

Animals↗
PubMed1993

Membrane-associated lymphotoxin expression and functional analysis of lymphokine-activated killer cells derived from tumor-infiltrating lymphocytes.

The expression of a membrane-associated lymphotoxin molecule (mLT) on lymphokine-activated killer (LAK) cells obtained from 18 patients with malignant tumors and its role in the tumor cell killing mechanisms were investigated. LAK cells from tumor-infiltrating lymphocytes (TIL-LAK cells) were mainly composed of CD3-positive cells, whereas LAK cells from peripheral blood lymphocytes (PBL-LAK cells) were mainly composed of CD16- and CD56-positive cells. However, mLT was found to be expressed on TIL-LAK cells as well as PBL-LAK cells. The degree of mLT expression correlated with the killing activity of LAK cells towards L929 cells (r = 0.806, P < 0.01, n = 15), but not with that towards Daudi or K562 cells. Although the degree of mLT expression correlated with the amount of secreted lymphotoxin (LT) in the supernatant of LAK cell culture, the secreted LT itself could not account for the tumor cell killing activity of LAK cells. Polyclonal rabbit anti-LT antibody partially inhibited the killing activities of LAK cells towards L929 cells and this inhibition was found in the combination of autologous tumor cells and PBL-LAK cells. These findings suggest the possibility that the mLT-related cytotoxicity is involved in the tumor cell killing mechanisms of TIL-LAK cells as well as PBL-LAK cells.

Adult↗