Biomedical subjects

F Takayama

Publications and source records attributed to F Takayama.

At least 55 records · Page 3Linked to original sources

PubMed1998

Variation of monoamines and their metabolite contents in the cerebrospinal fluid of conscious rats.

To study the circadian rhythm of the monoamine and metabolite contents, cerebrospinal fluid was taken from the cisterna magna through a polyethylene catheter tube every 4 hr in the conscious rat. Norepinephrine and 3-methoxy-4-hydroxy-phenylglycol were found to describe a rhythm with the maximal content occurring during the dark phase and the minimal content occurring during the light phase. Dopamine levels increased significantly during the light phase compared with the dark phase. These results, given that cerebrospinal fluid can be taken chronically from conscious rats, indicate that our present method may be suitable for estimating changes in brain monoamine and metabolite contents.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1998

Papillary thyroid carcinoma: MR diagnosis of lymph node metastasis.

PURPOSE: The purpose of this study was to ascertain the usefulness of MR imaging in the diagnosis of nodal metastasis of papillary thyroid carcinoma and to establish the most indicative MR criteria of metastasis. METHODS: Pathologic records and MR images in 50 patients with papillary thyroid carcinoma were reviewed. Each neck was divided into four nodal levels, so that 200 nodal levels were assessed in all. The maximum of the minimum transverse diameters of the lymph nodes on each nodal level measured on MR images and the certainty of metastasis as determined by a head and neck radiologist on the basis of morphologic aspects were compared with the pathologic findings by using receiver operating characteristic curves. The presence or absence of cystic nodes on each nodal level was also evaluated. RESULTS: Metastasis was found on 87 (44%) of the nodal levels in 34 (68%) of the patients. A cystic node was identified on 33 (17%) of the nodal levels in 13 (26%) of the patients and was seen only on positive nodal levels. Morphologic diagnosis by the radiologist was better than that obtained by measurement. With the combined criteria of a cystic node or a node of 13 mm or more for the maximum of the minimum transverse diameters, specificity was 100% with an 82% accuracy and always indicated metastasis (100% positive predictive value). However, 41% of the metastatic nodes were missed with this criterion (59% sensitivity). CONCLUSION: MR imaging was useful for diagnosing metastatic nodes; a nodal diameter threshold of 13 mm or the presence of a cystic node strongly indicated metastasis from papillary thyroid carcinoma.

Adult↗

PubMed1998

Immunohistochemical detection of imidazolone and N(epsilon)-(carboxymethyl)lysine in aortas of hemodialysis patients.

The modification of long-lived proteins with advanced glycation endproducts (AGEs) has been hypothesised to contribute to the development of pathologies associated with uremia. Imidazolone and N(epsilon)-(carboxymethyl)lysine (CML) are common epitopes of AGE-modified proteins. Imidazolone is a reaction product of arginine with 3-deoxyglucosone (3-DG) which is markedly accumulated in uremic serum. CML is produced by glycoxidation, and represents a marker of oxidative stress. The specificity of anti-imidazolone antibody that we had developed was further examined using ELISA. The antibody reacted only with imidazolone derived from 3-DG and arginine, but did not react at all with the other imidazolone-like compounds such as reaction products of glyoxal, methylglyoxal, glucosone with arginine or a reaction product of 3-DG with creatine. Further, to determine if AGEs are involved in the development of atherosclerosis in hemodialysis (HD) patients, we studied the localisation of imidazolone and CML in the aortas obtained from HD patients by immunohistochemistry using the anti-imidazolone and anti-CML antibodies. Imidazolone and CML were localised in all atherosclerotic aortic walls of the HD patients. In conclusion, imidazolone and CML are localised in the characteristic lesions of atherosclerosis in HD patients. These results strongly suggest that imidazolone produced by 3-DG, and CML produced by glycoxidation may contribute to the development of atherosclerosis in uremic patients.

Aged↗

PubMed1997

Assessment of parotid masses: which MR pulse sequences are optimal?

The objective of this paper is to determine which MR pulse sequences are optimal for delineation of lesion and predicting pathologic nature of lesion with signal intensity. A prospective study was performed in 53 parotid masses (39 benign and 14 malignant lesions) in 53 patients. Signal intensity of lesion was visually assessed and lesion/parotid contrast-to-noise ratios were measured. On visual assessment, detection sensitivity was 100% for nonenhanced nonfat-suppressed T1-weighted images, 91% for nonfat-suppressed fast spin-echo (FSE) T2-weighted images, 83% for gadolinium-enhanced fat-suppressed T1-weighted images, and 75% for fat-suppressed FSE T2-weighted images. The highest contrast-to-noise ratios were obtained with nonenhanced T1-weighted images. Hypointensity of lesion relative to the parotid gland on nonfat-suppressed FSE T2-weighted images was seen in 11 of 14 malignancies, 12 of 15 Warthin tumors, and two of 18 pleomorphic adenomas. Cystic portion of hyperintensity on nonenhanced T1-weighted images was solely seen in benign tumors (n = 11). Thus, the highest accuracy (81%) (79% sensitivity and 82% specificity) for predicting malignancy was obtained with a criterion of hypointensity on nonfat-suppressed FSE T2-weighted images plus absence of cystic portion of hyperintensity on nonenhanced T1-weighted images. Nonenhanced T1-weighted images combined with nonfat-suppressed FSE T2-weighted images is optimal for delineation of lesion and prediction of pathologic nature of parotid masses.

Adolescent↗

PubMed1997

[Detection and characterization of free radicals, radical scavenging activity, and lipid peroxides in cerebral ischemia-reperfusion injury by electron spin resonance and chemiluminescence high-performance liquid chromatography].

During the ischemia-reperfusion period, the hypoxanthine-xanthine oxidase system simultaneously generates superoxide (O2-). O2- has an extremely short half-life, as it rapidly undergoes Fenton-type reactions in the presence of iron and yields highly cytotoxic hydroxyl radicals (.OH). Oxygen-derived free radicals are induced as a contributing cause of cellular injury in several neurological disorders, including cerebral infarction and aging. Cerebral injury by ischemia-reperfusion following middle cerebral artery occlusion could be useful experimental model for studying cerebral injury induced by free radicals. Thiobarbituric acid reactants generally indicate lipid peroxidation associated with cellular damage caused by free radicals. Phosphatidylethanolamine hydroperoxide (PEOOH) is the primary peroxidative product of phosphatidylethanolamine, which is the most important functional lipid in the membrane. Plasma PEOOH levels appear to be a reliable indicator of cerebral damage caused by ischemia-reperfusion and other oxidative stress. Recently, an electron spin resonance (ESR) spectrometer was used in the detection of free radicals, in vivo and in vitro using 5,5'-dimethyl-1-pyrroline-N-oxide (DMPO) as the radical-trapping reagent. Moreover, there are reports the electron spin resonance-computed tomography (ESR-CT) images of the cephalic region of rats for locating regions of pathological change are related to free radicals in the brain.

Animals↗

PubMed1996

Effects of long-term treatment with dicyclic, tricyclic, tetracyclic, and noncyclic antidepressant drugs on monoamine oxidase activity in mouse brain.

1. The individual long-term effects of the antidepressant drugs zimeldine, viloxazine, imipramine, amitriptyline, nortriptyline, maprotiline, or nomifensine, on brain mitochondrial monoamine oxidase (MAO) activity, were studied in mice that were given daily intraperitoneal injections (30 mg/kg) of these reagents for 4 weeks. 2. Both the A-form (MAO-A) and B-form (MAO-B) of MAO were inhibited after long-term administration of all the drugs except nortriptyline (MAO-A was not affected) and maprotiline (neither MAO-A nor MAO-B were affected). 3. Kinetic analysis showed a significant decrease in Vmax values, and an increase in K(m) values for MAO-B during treatment. 4. All seven drugs are competitive inhibitors of MAO-A, noncompetitive inhibitors of MAO-B, and were more potent in vitro for MAO-B. 5. MAO-A was inhibited by the following drugs (in ascending order of potency) : nortriptyline, amitriptyline, imipramine, maprotiline, zimeldine, nomifensine, and viloxazine. 6. MAO-B was inhibited by the following drugs (in ascending order of potency): nortriptyline, imipramine, maprotiline, amitriptyline, zimeldine, nomifensine, and viloxazine.

Animals↗

PubMed1996

Lipo-PGE1, prostaglandin E1 incorporated in lipid microspheres, protects injury of the liver caused by warm ischemia reperfusion.

Effects of Lipo-PGE1, prostaglandin E1 incorporated in lipid microspheres on liver injury caused by ischemia reperfusion were investigated. Lipo-PGE1 (10 micrograms/kg or 3 micrograms/kg) or vehicle was gradually injected twice via portal vein 5 min prior to induction of ischemia and reperfusion. Rats died within 2 d after liver ischemia of 90 min from the group receiving injection of vehicle alone. Lipo-PGE1 had its most profound effect on the survival of animals subjected to liver ischemia followed by reperfusion when given in two doses, one prior to ischemia, and another prior to reperfusion. Lipo-PGE1 markedly suppressed both the increases in plasma PCOOH (phosphatidyl-choline hydroperoxide) levels and the leakage of GOT, GPT, and LDH from the liver during the ischemia reperfusion. These findings suggest that Lipo-PGE1 may have therapeutic applications in treatment of hepatic injury.

Alanine Transaminase↗

PubMed1996

In vivo EPR detection and imaging of endogenous nitric oxide in lipopolysaccharide-treated mice.

Nitric oxide (NO), a simple diatomic free radical, is known to play a critical physiological role in diverse organisms. An iron complex, with N-(dithiocarboxy)sarcosine (Fe-DTCS), has a high affinity for endogenous NO and can trap, stabilize, and accumulate it. The stable NO adduct thus formed is detectable at room temperature with electron paramagnetic resonance (EPR) spectrometry. We report in vivo EPR imaging of endogenous NO, trapped by an Fe-DTCS complex, in the abdomen of a live mouse. To our knowledge, this is the first report on EPR imaging of endogenous free radicals produced in vivo. This EPR imaging method will be useful for the noninvasive investigation of the spatial distribution of NO in pathologic organs or tissues.

Animals↗

PubMed1996

Effect of fluvoxamine on 5-hydroxytryptamine uptake, paroxetine binding sites and ketanserin binding sites in the Japanese monkey brain and platelets, in vivo and in vitro.

We investigated the in vitro effects of fluvoxamine on 3H-paroxetine binding and 3H-monoamine uptake in monkey cerebral cortex in comparison with those of other antidepressants. Fluvoxamine selectively inhibited 3H-5-hydroxytryptamine (5-HT) uptake and 3H-paroxetine binding. However, it did not alter 3H-norepinephrine or 3H-dopamine uptake. In addition, we examined the effects of chronic treatment with fluvoxamine (5 mg/kg per day, p.o.) on 5-HT uptake sites that bind 3H-paroxetine and 5-HT2 receptors that bind 3H-ketanserin, in monkey brains and platelets. Chronic treatment with fluvoxamine affected neither the paroxetine binding sites nor the kentanserin binding sites of the brains and platelets. These results suggest that long-term treatment with fluvoxamine does not affect either the 5-HT uptake sites or 5-HT2-receptors of 5-HT neurons in monkey brain in spite of its strong inhibitory effect on 5-HT uptake in vitro.

Animals↗

PubMed1996

Effects of bifemelane on muscarinic receptors and choline acetyltransferase in the brains of aged rats following chronic cerebral hypoperfusion induced by permanent occlusion of bilateral carotid arteries.

Cerebral hypoperfusion was chronically induced in aged rats via permanent bilateral occlusion of common carotid arteries (2VO). Marked reduction of the Bmax value of the muscarinic receptors (mAChR) in both the cortex and striatum and the Vmax value of choline acetyltransferase (ChAT) activity in the cortex, hippocampus and striatum were observed as compared with those of control aged rats. No significant changes in mAChR and ChAT activity were observed between young control rats and young 2VO rats. One month post-surgery in aged rats, daily doses of bifemelane (10 mg/kg) or aniracetam (50 mg/kg) were administered orally over a 4-week period. Administration of bifemelane significantly increased Bmax values and decreased apparent Kd values for 3H-quinuclidinyl benzilate (QNB) in mAChR in the striatum. Chronic administration of bifemelane or aniracetam also enhanced ChAT activity in the cortex, hippocampus and striatum. In particular, administration of bifemelane resulted in a significant increase in Vmax values of ChAT in all three brain regions, while no significant change in K(m) values for ChAT was observed. These results suggest that bifemelane is responsible for this activity, thereby enhancing the functioning system of CNS cholinergic neurons of cerebral hypoperfused aged rats.

Age Factors↗

PubMed1995

Importance of hepatovenous back-perfusion for maintenance of liver viability during the Pringle manoeuvre.

The role of hepatovenous back-perfusion in maintaining hepatic viability was investigated during inflow occlusion (Pringle manoeuvre) of the pig liver. The study compared two ischaemia procedures of 60 min duration: hepatic inflow occlusion and inflow plus outflow occlusion (vascular exclusion). Each procedure was carried out in six pigs and liver tissue perfusion, energy metabolism, lipid peroxidation and 7-day survival were assessed. Although all pigs survived after inflow occlusion, five of six died after vascular exclusion (P < 0.01). Exclusion induced a significant decrease in perfusion to 15.3 per cent of the value before ischaemia compared with 32.4 per cent after hepatic inflow occlusion alone (P < 0.01). Although cellular adenosine 5'-triphosphate levels were significantly decreased by ischaemia in both groups, the fall was less in pigs with inflow occlusion alone (to 55 per cent of the preclamp value) than in those with exclusion (to 24 per cent of the preclamp value) (P < 0.01). The plasma phosphatidylcholine hydroperoxide level rose immediately after reperfusion in pigs with exclusion, while the level remained constant after inflow occlusion alone. There is a fundamental difference between the two ischaemia procedures: back-perfusion from the vena cava contributes to the maintenance of liver function during inflow occlusion.

Adenosine Triphosphate↗

PubMed1995

[Protective effects of LipoPGE1, prostaglandin E1 incorporated in lipid microspheres, against liver injury caused by ischemia-reperfusion].

Effect of LipoPGE1 on liver injury caused by ischemia-reperfusion were compared with that of PGE1-CD, cyclodextrin clathrated PGE1, in rats. LipoPGE1 (10 micrograms/kg) and PGE1-CD (10 micrograms/kg) were gradually injected into the portal vein 5 min both prior to ischemia and prior to reperfusion. In only the group receiving injections of vehicle alone, rats died within 2 days after the episode of 90-min liver ischemia. The survival rate of all rats treated with LipoPGE1 was higher than that of rats who received vehicle alone, which indicates that LipoPGE1 pretherapy improved the survival of rats after liver ischemia-reperfusion. LipoPGE1 markedly suppressed elevations of GOT, GPT, and LDH, lipid peroxide and aromatic amino acid levels in the plasma caused by ischemia-reperfusion of the liver. When animals were given a single dose of LipoPGE1 prior to reperfusion, LipoPGE1 also suppressed elevations of GOT, GPT, LDH and lipid peroxide levels caused by 30-min of liver ischemia followed by 12-hr reperfusion. These suppressive effects with LipoPGE1 were stronger than those of PGE1-CD. These findings suggest that LipoPGE1 may have therapeutic applications in the treatment of hepatic injury.

Alprostadil↗

PubMed1995

Effect of long-term fluvoxamine treatment on endogenous serotonin uptake inhibitor-like substance in monkey cerebrospinal fluid.

We found that substances present in monkey cerebrospinal fluid (CSF) could inhibit [3H]-paroxetine binding in monkey brain preparations. The molecular weight of one of these inhibitory substances was approximately 2000, which is in agreement with earlier studies using human CSF. We also found that the inhibitory effect of the substances present in monkey CSF on [3H]-paroxetine binding decreased after 8 weeks of chronic fluvoxamine (5 mg/kg day, p.o.) treatment. These results suggest that the ability of a drug to decrease the activity of endogenous 5-HT uptake modulators may related to its antidepressive effects.

Animals↗

PubMed1995

[Study on the anti-dementia therapies for rats with a unilateral basal forebrain lesion--serial changes of the cholinergic markers' activities and event-related potentials after the administration of bifemelane hydrochloride or autotransplantation of the vagal nodosal ganglion].

Using rats with a unilateral lesion in the nucleus basalis magnocellularis (NBM), we examined electrophysiologically the therapeutic effects of bifemelane (BIF) and autotransplantation of the vagal nodosal ganglion (X) on the event-related potential (P300) serially for 4 weeks, and also neurochemically their effects on cholinergic markers--the specific binding of 3H-QNB (quinuclidinyl benzilate) on muscarinic acetyl-choline receptor (mAChR) and the activities of acetylcholinesterase (AChE) and choline acetyltransferase (CAT). The latency of P300 was continuously delayed and its amplitude remained low voltage until 4 weeks in the NBM-lesioned rats (No-Tx group). Whereas the latency and amplitude returned to normal after 2-3 weeks in the rats given daily intraperitoneal injection of 15 mg/kg BIF (BIF group) and autotransplanted ones (X group). The cortical CAT and AChE levels on the lesion side did not recover until 4 weeks in No-Tx group, but the CAT levels recovered after 3 weeks in both BIF and X group; the AChE levels, after 1 week in BIF group and after 3 weeks in X group. The cortical mAChR on the lesion side was within or more than normal range in all rats. These results might indicate as follows: 1) Compensatory postsynaptic process such as cortical mAChR increase and AChE decrease occurred after acute cholinergic depletion. 2) Administration of BIF and X autotransplantation recovered cortical CAT and AChE levels and normalized cholinergic neuronal activity of P300.

Acetylcholinesterase↗

PubMed1994

Effect of methylprednisolone on plasma lipid peroxidation induced by lipopolysaccharide.

The effects of methylprednisolone succinate (MP) on plasma lipid peroxidation, plasma SOD activity and superoxide production in polymorphonuclear leukocytes (PMNs) induced by lipopolysaccharide (LPS) were examined in rats in vivo and in vitro. In rats subjected to LPS treatment, plasma phosphatidylcholine hydroperoxide (PCOOH) levels significantly increased, and the plasma Cu,Zn-SOD activity decreased by about 75%. When rats were given 30 mg/kg of MP intravenously, MP suppressed the elevation of plasma PCOOH levels and partially inhibited the decrease in plasma Cu,Zn-SOD activity. MP also suppressed PMA-induced superoxide production in PMNs primed by LPS. In in vitro experiments, low concentrations of MP had no effect on NADPH-dependent lipid peroxidation, but 4 mM MP produced 50% inhibition. MP had little effect on PMA-induced superoxide production in PMNs primed by LPS. Moreover, MP had no radical-trapping effect on superoxide, hydroxyl radical and stable DPPH radical. These results suggest that the suppressive effect of plasma lipid peroxidation by MP is not due to radical-trapping effects or preventive anti-oxidation, but may involve the suppression of the lipid chain reaction in liver membrane resulting from PMA-induced superoxide anions generated by PMNs.

Animals↗

PubMed1994

Effect of diclofenac, a non-steroidal anti-inflammatory drug, on lipid peroxidation caused by ischemia-reperfusion in rat liver.

The present study investigated the effects of diclofenac sodium (Dic Na) on lipid peroxidation (LPO) and liver injury in ischemia-reperfused rat. LPO was estimated from the levels of phosphatidylcholine hydroperoxide (PCOOH), a primary peroxidative product of phosphatidylcholine. Hepatic ischemia-reperfusion induced significant elevation of plasma PCOOH and caused liver injury in rats. Rats were treated daily with Dic Na or alpha-tocopherol (alpha-toc.), p.o., for 5 days and once at 1 hr prior to induction of ischemia. Both substances prevented LPO from decreasing the plasma PCOOH level, and they significantly suppressed the elevation of serum GOT and LDH, in a dose-dependent manner. Dic Na was able to scavenge the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH), but did not show radical-trapping ability for superoxide anion (O2-) or hydroxyl radicals (.OH), nor a suppressive ability for the NADPH-dependent LPO of microsomes. In contrast, alpha-toc. trapped both DPPH and O2-, but not .OH, and it inhibited the NADPH dependent LPO in vitro. These results suggest that Dic Na may suppress liver injury caused by ischemia-reperfusion through stable radical scavenging and the inhibition of superoxide production in activated phagocytes, both of which may restrain the induction and progression of oxidative stress.

Animals↗

PubMed1994

Developmental changes in and hormonal modulation of epidermal growth factor concentration in the rat submandibular gland.

Developmental changes in the hormonal effects on the concentration of epidermal growth factor (EGF) in the rat submandibular gland were investigated. The level of EGF in the gland gradually increased with age from 4 up to 8 weeks of age; thereafter it increased markedly, reaching a plateau level at 12 weeks of age in both male and female rats. A significant sex difference in EGF levels was observed between 8 and 14 weeks, the level in the males being approximately twice as high as that in the females at 12 and 14 weeks of age. Castration of male rats decreased EGF to about the same level as that of control females. Treatment of castrated rats with testosterone propionate (TP) restored EGF to the levels in control male rats. Ovariectomy and/or administration of oestradiol-17 beta to ovariectomized rats had no apparent effect on EGF concentration. These findings indicate that the sex difference in EGF concentration can be attributed to the level of endogenous androgens. In addition, hypophysectomy of male rats caused a remarkable decrease in submandibular gland EGF to about 7% of the normal level. This reduction was significantly, although not completely, restored by the administration of TP, triiodothyronine (T3) or GH. Moreover, giving TP with T3 or with GH or both together had additive effects on the increase in EGF levels in hypophysectomized rats. These results provide evidence that EGF in the submandibular gland is regulated multihormonally by at least TP, T3 and GH.

Aging↗

PubMed1994

The multiple hydroperoxides of choline phospholipids occurring in plasma after ischemia-reperfusion in rat liver.

Since phosphatidylcholine is a primary membrane component, and its peroxidation may result in disruption and dysfunction of the biomembrane, we used phosphatidylcholine hydroperoxide (PCOOH) as an index of oxidative-stress-related injury. We detected the occurrence of PCOOH in both liver and plasma from rats subjected to hepatic ischemia-reperfusion, and demonstrated that liver and plasma PCOOH levels reflect the extent of liver injury. However, the accuracy in measuring PCOOH levels, particularly in blood samples, is still in question since PCOOH may be rapidly eliminated by phospholipase A2 enzymes, which are widespread, easily activated, and have a preference for oxidized glycerophospholipids. When PCOOH levels were determined, using high-performance liquid chromatography to detect chemiluminescence (CL), the plasma samples showed a broad CL peak that began to elute at the same time as in the liver samples, but lasted longer. The peak appeared to contain hydroperoxides from multiple lipid classes. In addition to PCOOH, the hydroperoxides of sphingomyelin and lysophosphatidylcholine (SPHOOH and LPCOOH) were identified in the plasma of rats subjected to ischemia-reperfusion using thin layer chromatography separation and subsequent visualization, infrared spectroscopy, and hydrolysis under mild alkaline conditions. These results indicate that the occurrence of SPHOOH and LPCOOH, as well as PCOOH, may reflect liver damage related to ischemia-reperfusion.

Animals↗