Biomedical subjects

T Arai

Publications and source records attributed to T Arai.

At least 361 records · Page 20Linked to original sources

PubMed1997

Glial tau-positive structures lack the sequence encoded by exon 3 of the tau protein gene.

Tau protein comprises six distinct isoforms defined by the presence or absence of sequences encoded by alternatively spliced exon 2, 3 and 10. We have investigated immunohistochemically the expression of exon 3-derived fragment (E-3) of tau protein in brains of patients with Alzheimer's disease (AD) and other neurodegenerative diseases in which the abnormal accumulation of tau protein takes place. In AD, a subset of neurofibrillary tangles, neuropil threads and dystrophic neurites in senile plaques were stained positively with an anti-E-3 antibody. In sharp contrast, glial tau-positive structures, such as astrocytic plaques and oligodendroglial coiled bodies, were negative for E-3 in all cases examined in this study. This is the first report to discriminate tau-positive inclusions in glial cells from those in neurons at the molecular level.

Aged↗

PubMed1997

The effect of hypothermia on H2O2 production during ischemia and reperfusion: a microdialysis study in the gerbil hippocampus.

The changes in the extracellular concentration of hydrogen peroxide (H2O2) in gerbil hippocampus during ischemia and reperfusion were investigated by microdialysis coupled with fluorometry of dichlorofluorescin oxidation. In a normothermic condition (37.5 degrees C), a transient forebrain ischemia for 5 or 10 min produced a significant increase in hippocampal H2O2 immediately after the start of ischemia. The duration of this elevation after reperfusion was significantly shorter in gerbils subjected to 5 min of ischemia than in those subjected to 10 min of ischemia. Hypothermia at both 34 degrees C and 30 degrees C inhibited the increase in the H2O2 concentration during ischemia and reperfusion in gerbils subjected to 5 min of ischemia. In gerbils subjected to 10 min of ischemia, hypothermia delayed the onset of the increase in the H2O2 concentration and shortened the duration of the elevated H2O2 concentration. Hypothermia improved the histological outcome in the hippocampal CA1 neurons 7 days after ischemia. These findings suggest that the suppression of H2O2 production in ischemia and reperfusion is a possible mechanism of brain protection by hypothermia.

Animals↗

PubMed1997

A subset of senile dementia with high incidence of the apolipoprotein E epsilon2 allele.

There is a subset of very elderly patients with senile dementia in whom abundant neurofibrillary tangles are present, mainly in the hippocampal region, without a significant number of senile plaques. In a retrospective neuropathological examination of 239 dementia patients, 14 were found to have this type of senile dementia. The apolipoprotein E epsilon2, epsilon3, and epsilon4 allele frequencies in this patient group were 0.39, 0.50, and 0.11, respectively. Such a high frequency of the epsilon2 allele suggests that this type of dementia is distinct from Alzheimer's disease not only from a neuropathological but also from a genetic viewpoint.

Aged↗

PubMed1997

Interferon alpha induces disorder of lipid metabolism by lowering postheparin lipases and cholesteryl ester transfer protein activities in patients with chronic hepatitis C.

The effect of recombinant interferon alpha 2a (rIFN-alpha2a) on serum lipoprotein metabolism was assessed in 39 patients with chronic viral hepatitis C. rIFN-alpha2a was administered intramuscularly at a dose of 9 x 10(6) U/d for 2 weeks and then for 3 times a week over 6 months. The serum cholesterol concentration significantly decreased one week after rIFN-alpha2a administration. Approximately 67% of this decrease was attributed to the reduction of high-density lipoprotein (HDL)-cholesterol; a decrease in HDL2-cholesterol was more evident. By contrast, serum triglyceride levels, largely derived from very-low density lipoprotein (VLDL), significantly increased following rIFN-alpha2a treatment. Lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activities in the postheparin plasma were reduced by 75.7% and by 79.4%, respectively, and decreases in plasma cholesteryl ester transfer protein (CETP) activity and its protein mass were also observed. However, prothrombin time was ameliorated by rIFN-alpha2a, suggesting that the decrease in LPL, HTGL, and CETP activities may not be due to a reduction in protein synthesis by the liver. Simple correlation analysis demonstrated that the changes in LPL activity before and after 2 weeks of treatment with rIFN-alpha2a showed a significant negative correlation with changes in serum triglyceride and VLDL-triglyceride and a positive correlation with changes in HDL-cholesterol and HDL2-cholesterol. These results suggest a major contribution of reduced LPL activity with regard to the lipoprotein disorders. In conclusion, rIFN-alpha2a treatment on patients with chronic hepatitis C causes marked changes in serum lipoprotein metabolism associated with decreases in LPL, HTGL, and CETP activities.

Adult↗

PubMed1997

Mevalonic acidemia: first case of Japan.

Mevalonic acidemia is a rare metabolic disorder due to mevalonate kinase deficiency which affects the biosynthesis of cholesterol and nonsterol isoprenes. We report the first case of Japan. The clinical course is characterized by intrauterine growth retardation, postnatal growth failure, intractable diarrhea, liver dysfunctions and death at three months of age. Dysmorphic features including triangular face, protrusion of forehead, hypertelorism, low set ears and micrognathism were noted. High mevalonic acid level was found by GC/MS.

Fatal Outcome↗

PubMed1997

Tc-99m-MIBI scintigraphy for detecting parathyroid adenoma and hyperplasia.

We performed scintigraphy with technetium-99m-methoxyisobutylisonitrile (MIBI) in 10 patients with parathyroid adenoma (7 lesions) or hyperplasia (9 lesions). Correlation between an amount of accumulation of MIBI and histological types of the lesions were evaluated with special reference to an amount of oxyphilic cell in the lesions. Selected lesions were also evaluated for mitochondrial density by electromicroscopy and showed increased mitochondrial density in the oxyphilic cells. All lesions equal to or above 220 mg showed positive scintigraphic results despite differences in cell types. Undetected lesions were all equal to or below 100 mg. The scintigraphic results for 2 lesions with abundant oxyphilic cells were both positive although those for 11 lesions with abundant chief cells only 6 were positive, probably because these lesions were smaller in the hyperplasia group. In conclusion, MIBI uptake in parathyroid lesions was not dependent on the cell type but either on the size or functional state of the lesions.

Adenoma↗

PubMed1997

Scan findings of various myocardial SPECT agents in a case of amyloid polyneuropathy with suspected myocardial involvement.

A 31-year-old male having familial amyloid polyneuropathy underwent a Tc-99m(V)-DMSA study to evaluate the myocardial involvement. The patient also underwent T1-201, I-123-BMIPP and I-123-MIBG myocardial SPECT studies to evaluate blood perfusion, fatty acid metabolism and sympathetic function of the heart, respectively. Tc-99m(V)-DMSA SPECT showed uptake to the myocardium indicating myocardial involvement of amyloidosis. Both T1-201 and I-123-BMIPP studies showed normal uptake indicating normal blood perfusion and fatty acid metabolism but I-123-MIBG SPECT showed no uptake to the heart, indicating severe impairment of sympathetic function.

3-Iodobenzylguanidine↗

PubMed1997

Multiple haemorrhagic brain metastases from papillary thyroid cancer.

We report a 40-year-old woman, who initially developed cerebellar symptoms, with multiple hemorrhagic brain metastases from a papillary thyroid cancer. Intracranial masses gave heterogeneous high signal on T1-weighted and T2-weighted images, hemosiderin rims on the latter. Some of the tumors showed contrast enhancement. Metastatic thyroid cancer is a consideration in a patient with multiple hemorrhagic masses.

Brain↗

PubMed1997

Hemispatial sunglasses: effect on unilateral spatial neglect.

OBJECTIVE: To investigate whether using glasses shaded on the non-neglected side would lead to less unilateral neglect during pencil-and-paper activities. DESIGN: Descriptive study of ten patients. One remarkable case is described in detail. SETTING: Rehabilitation medicine department in an urban general hospital. PATIENTS: Ten hemiplegic patients showing left unilateral neglect during pencil-and-paper activities. INTERVENTION: Use of glasses in which the right half of each lens was shaded by a darker lens like those used in sunglasses. MAIN OUTCOME MEASURES: For unilateral neglect: (1) deviation from marking the middle of a 20-cm horizontal line; (2) number of lines left unmarked on the left hand portion of a page of 40 randomly oriented lines; (3) degree of failure to copy a representation of a cube. RESULTS: Among the ten patients, improvement was mixed for each of the three outcome measures. One patient, however, demonstrated dramatic and lasting improvement in functional activities by wearing the hemispatial sunglasses. CONCLUSION: Hemispatial sunglasses appear to have a potentially specific effect on visual neglect in certain patients with right hemispheric lesions. Further investigation is necessary to determine the nature of this effect and its scope of applicability.

Adult↗

PubMed1997

Effects of photoperiod and aging on locomotor activity rhythms in the onion fly, Delia antiqua.

At photoperiods longer than 8h per 24h, adults of the day-active onion fly Delia antiqua showed a major peak of locomotor activity in the late photophase and also bursts of activity induced by lights-on or lights-off. At shorter photoperiods the activity peaks fused. After transfer from long photoperiods to constant darkness (DD), the rhythm free-ran, but only the major peak persisted. This suggests that only the major peak is controlled by the circadian pacemaker. At long photoperiods, the daily phase of the major peak occurred progressively later with age. As a result, the activity at short photoperiods often shifted from photophase to scotophase in old flies. The free-running period (tau) also changed with age; tau was shorter than 24h until 14-20 days after eclosion and thereafter became longer, but a few individuals repeated changes in tau. The phase delay of locomotor activity with age in D. antiqua would be attributable to the increase in tau.

Journal Article↗

PubMed1997

Histological diagnosis of amniotic fluid embolism by monoclonal antibody TKH-2 that recognizes NeuAc alpha 2-6GalNAc epitope.

This study evaluates whether immunohistochemical staining using antibody TKH-2 is presented as a sensitive method for the histological diagnosis of amniotic fluid embolism (AFE). TKH-2 is the sensitive antibody clearly directed to sialyl Tn, NeuAc alpha 2-6GalNAc and reacts with meconium- and amniotic fluid-derived mucin-type glycoprotein. Formalin-fixed, paraffin-embedded maternal lung tissue sections were obtained from four cases of patients showing AFE, and four women uninvolved with AFE served as control. Specimens were stained using the streptavidin-biotin-immunoperoxidase method. The results of immunostaining were compared with those of hematoxylin-eosin (H&E) or a conventional Alcian blue stain. Remarkable positive TKH-2 stainings were observed easily within the pulmonary vasculature in patients with AFE syndrome. AFE can be easily missed on H&E sections. Compared with TKH-2 staining, Alcian blue staining also may be insufficient to show intravascular mucin in the maternal lung sections. TKH-2 immunostaining is the sensitive method to detect meconium- and amniotic fluid-derived mucin in the lung sections of patients with AFE syndrome.

Adult↗

PubMed1997

Expression of the MDR1 and MDR3 gene products in acute and chronic leukemias.

We performed immunocytochemistry to detect mdr1 and mdr3 P-glycoproteins (P-gps) in 81 patients with acute and chronic leukemia, using the mdr1 P-gp-specific monoclonal antibody (MoAb) MRK16, and the mdr3 P-gp-specific MDR3M. Immunoreactivity for the mdr1 gene product was positive in 27 out of 81 (33%) patients. Immunoreactivity with the anti-mdr3 P-gp MoAb was positive in 20 out of 81 (25%) patients. Of 54 patients with acute leukemia, 17 (31%) were positive for mdr1 P-gp and 8 (15%) for mdr3 P-gp. A high proportion (60%) of patients with chronic lymphocytic leukemia (CLL) were mdr3 P-gp positive. Of the patients with granular-lymphocyte proliferative disorder (GLPD), a chronic T-cell or natural killer cell leukemia, 8/17 (47%) were positive for mdr1 P-gp and 6/17 (35%) for mdr3 P-gp. Of 23 patients with chronic leukemia (CLL and GLPD), 10 (37%) were positive for mdr1 P-gp and 12 (44%) for mdr3 P-gp. To clarify the function of the mdr3 P-gp, we examined the intracellular rhodamine123 (Rh123) levels of mdr1 P-gp-negative and mdr3 P-gp-positive leukemic cells from patients with acute lymphocytic leukaemia, on the addition of 10 microM cyclosporin A (CyA). The addition of CyA led to significant increases in intracellular Rh123 levels in mdr1 P-gp-negative and mdr3 P-gp-positive leukemic cells. Results of the assay for dye efflux suggested that the mdr3 P-gp has a role in drug resistance, and functional drug-efflux capacity. In 31 acute leukemia patients at initial diagnosis, mdr1 or mdr3 P-gp expression correlated significantly to an outcome of complete remission (CR). In 54 acute leukemia patients, exposure to precytotoxic agents correlated significantly to expression, with a significant higher number of patients mdr1 or mdr3 P-gp positive than negative. In the 54 patients with acute leukemia, mdr1 P-gp expression correlated to mdr3 P-gp expression significantly (p=0.0007). In the 27 patients with chronic leukemia (CLL and GLPD), mdr1 and mdr3 P-gp expression did not correlate to exposure to precytotoxic agents, nor did mdr1 P-gp expression correlate to mdr3 P-gp expression. It may be speculated that precytotoxic agents induced mdr1 and mdr3 P-gp expression in acute leukemia; however, in chronic leukemia, both P-gps were expressed independently of exposure to precytotoxic agents.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed1997

Beta-estradiol protects hippocampal CA1 neurons against transient forebrain ischemia in gerbil.

Beta-estradiol has been considered to be a neurotrophic agent, but its in vivo effect on gerbils with transient forebrain ischemia has not yet been demonstrated. In the first set of the present experiments, we infused beta-estradiol at a dose of 0.05 or 0.25 microg/day for 7 days into the lateral ventricles of normothermic gerbils starting 2 h before 3-min forebrain ischemia. Beta-estradiol infusion at a dose of 0.25 microg/day prevented significantly the ischemia-induced reduction of response latency time as revealed by a step-down passive avoidance task. Subsequent light and electron microscopic examinations showed that pyramidal neurons in the hippocampal CA1 region as well as synapses within the strata moleculare, radiatum and oriens of the region were significantly more numerous in gerbils infused with beta-estradiol than in those receiving saline infusion. Beta-estradiol at a dose of 1.25 microg/day was ineffective and occasionally increased the mortality of experimental animals. Since the total brain content of exogenous beta-estradiol at 12 h after forebrain ischemia was estimated to be less than 145 ng, the second set of experiments focused on the neurotrophic action of beta-estradiol at concentrations around 100 ng/ml in vitro. Beta-estradiol at concentrations of 1-100 ng/ml facilitated the survival and process extension of cultured hippocampal neurons, but it did not exhibit any significant radical-scavenging effects at the concentration range. On the other hand, 100 microg/ml of beta-estradiol, even though failing to support hippocampal neurons in vitro, effectively scavenged free radicals in subsequent in vitro studies, as demonstrated elsewhere. These findings suggest that beta-estradiol at a dose of 0.25 microg/day prevents ischemia-induced learning disability and neuronal loss at early stages after transient forebrain ischemia, possibly via a receptor-mediated pathway without attenuating free radical neurotoxicity.

Animals↗

PubMed1997

Suppression of cholinergic activity via the dopamine D2 receptor in the rat striatum.

The effect of dopamine (DA) D2 receptor on extracellular choline (Ch) and acetylcholine (ACh) levels in rat caudate-putamen (striatum) was investigated by means of microdialysis. The systemic, intraperitoneal (i.p.), injection of (+/-)-2-(N-phenylethyl-N-propyl) amino-5-hydroxytetralin (N-434), a specific DA D2 receptor agonist decreased striatal ACh release in a dose-dependent manner and the i.p. injection of sulpiride, a specific DA D2 receptor antagonist, increased the ACh release in a dose-dependent manner. In contrast, extracellular Ch levels were increased by the agonist and decreased by the antagonist. An increased Ch uptake was observed in sulpiride-treated rats and a decreased Ch uptake was observed in N-434-treated rats. The effects of the D2 agonist on extracellular Ch, ACh and Ch uptake were completely antagonized by the D2 antagonist. These results suggest clearly an inhibition of ACh release by D2 receptor activation, contrasting with previous findings on DA-ACh interaction. The inverse relationship between extracellular Ch and ACh reflects a change in the Ch uptake owing to a change in cholinergic neuron activity via the D2 receptor mechanisms.

Acetylcholine↗

PubMed1997

Regulation of dopamine D1 and D2 receptors on striatal acetylcholine release in rats.

The effects of dopamine (DA) D1 and D2 receptors on striatal acetylcholine (ACh) releases were investigated by in vivo microdialysis. All drugs were applied via dialysis membrane directly to the striatum. The levels of ACh release were increased by 10(-4) M SKF38393, a D1 receptor agonist. Although 10(-4) M SCH23390, a D1 receptor antagonist, exhibited an increase in the levels of ACh release, the agonist (10(-4) M) induced-increase in the levels of ACh release was suppressed by coperfusion of the antagonist (10(-4) M). In contrast, the levels of ACh release were decreased by the D2 receptor agonist, N-434, in a dose-dependent manner (10(-4) M to 10(-7) M) and increased by the D2 receptor antagonist, sulpiride, in a dose-dependent manner (10(-5) M to 10(-7) M). The agonist (10(-5) M) induced-decrease in the levels of ACh release was suppressed by coperfusion of the antagonist (10(-4) M). Coperfusion of D1 (10(-4) M) and D2 (10(-5) M) agonists blocked both effects of respective drug alone. In order to clarify the effect of endogenous DA, two drugs with different mechanisms for enhancing DA concentration in the synaptic cleft, the DA release-inducer methamphetamine, and the DA uptake inhibitor nomifensine were perfused separately. Both (10(-4) M to 10(-5) M) produced a dose- and a time-dependent decrease in the levels of ACh release. Significant higher levels of ACh release were observed in the striatum of the 6-hydroxydopamine (8 micrograms/10 microliters)-treated rats with significant depletion of striatal DA content. These results suggest that in striatal DA-ACh interaction ACh release, as cholinergic interneuron's activity, is tonically inhibited via the D2 receptor, mainly by dopaminergic input, and the D1 receptor probably modifies the effect of the D2 receptor indirectly.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1997

Covalent binding of a reactive metabolite derived from propranolol and its active metabolite 4-hydroxypropranolol to hepatic microsomal proteins of the rat.

Repeated administration of propranolol (PL) to rats causes the inhibition of cytochrome P450-2D (P450-2D) enzyme. We recently found that 4-hydroxypropranolol (4-OH-PL) was biotransformed to 1,4-naphthoquinone (1,4-NQ) by superoxide (SO) anions in medium containing rat liver microsomes and NADPH and proposed that the binding of the quinone to P450-2D apoproteins might be one of mechanisms for the enzyme inhibition [Narimatsu et al. (1995) Chem. Res. Toxicol. 8, 721-728]. In this study, we have searched for possible sources of SO for the conversion of 4-OH-PL to 1,4-NQ in rat liver microsomes and determined the radioactivity covalently bound to microsomal proteins after incubation of radioactive PL and 4-OH-PL with rat liver microsomes. Elimination of 4-OH-PL from a mixture containing microsomes and NADPH was suppressed by carbon monoxide. Antibodies raised to P450-2B1 and -3A2 partially, and antibody against NADPH-cytochrome P450 reductase (fp2) markedly suppressed the reaction. 1,4-NQ was formed concomitantly with 4-OH-PL elimination by a reconstituted preparation of fp2. Binding studies using naphthalene ring (NR)- and side chain (SC)-radiolabeled PL and 4-OH-PL showed that radioactivity covalently bound to microsomal proteins was much higher from 4-OH-PL than from PL for the NR-labeled compounds, but higher from PL than from 4-OH-PL for the SC-labeled compounds. These results suggest that the 4-OH-PL formed from PL by P450-2D enzyme is converted to 1,4-NQ with loss of the side chain, and the 1,4-NQ accounts for most of the radioactivity covalently bound to microsomal proteins, including the P450-2D enzymes. The SO for conversion of 4-OH-PL to 1,4-NQ is supplied mainly by fp2 with some contribution by P450 enzymes.

Adrenergic beta-Antagonists↗

PubMed1997

Evidence for the involvement of docosahexaenoic acid in cholinergic stimulated signal transduction at the synapse.

[4,5-3H]Docosahexaenoic acid ([3H]DHA) or [9,10-3H]palmitic acid ([3H]PAM) was infused intravenously for 5 min to awake, adult male rats before and after treatment with arecoline (15 mg/kg, i.p.), a cholinergic agonist. Animals were killed 15 min post-infusion, the brains were rapidly removed and subcellular fractions were obtained after sucrose density centrifugation. In control animals, [3H]DHA and [3H]PAM were incorporated into the synaptosomal fractions, representing 50%-60% of total membrane label. Most remaining membrane label (30%-40%) was in the microsomal fraction. Both fractions contained the synaptic marker synaptophysin. The remaining 10% of radioactivity was in the myelin and mitochondrial fractions. Arecoline significantly increased [3H]DHA entry into the synaptosomal fractions by 100% and into the microsomal fraction by 50%. In these fractions 60%-65% of the [3H]DHA was in phospholipid, the rest corresponding to free fatty acid and diacylglycerol. In contrast, arecoline did not change [3H]PAM incorporation into any brain fraction. These results demonstrate that plasma [3H]DHA incorporation is selectively increased into synaptic membrane phospholipids of the rat brain in response to cholinergic activation. The increased incorporation of DHA but not of PAM into synaptic membranes in response to cholinergic stimulation indicates a primary role for DHA in phospholipid mediated signal transduction at the synapse involving activation of phospholipase A2 and/or C.

Animals↗

PubMed1997

High-density lipoproteins from probucol-treated patients have increased capacity to promote cholesterol efflux from mouse peritoneal macrophages loaded with acetylated low-density lipoproteins.

To elucidate the anti-atherogenic effect of probucol, high-density lipoprotein (HDL) was isolated from probucol-treated patients (n = 14) and compared with that from control subjects (n = 12). The HDL obtained from probucol-treated patients was low in cholesteryl ester (CE) in comparison with that from control subjects (21.3 +/- 3.9 mol per cent vs. 27.6 +/- 3.2 mol% of total lipids. P < 0.001), and the peak diameters of patients' HDL were significantly smaller than those of control subjects on 4-30% non-denaturing polyacrylamide gradient gel electrophoresis (10.6 +/- 0.6 nm vs. 12.1 +/- 0.4 nm, P < 0.001). These data may be explained by the increased cholesteryl ester transfer protein (CETP) activities of probucol-treated patients (129 +/- 12% of control subjects, P < 0.001). The in vitro ability of HDL to remove CE from lipid-laden macrophages induced by incubation with acetylated low-density lipoprotein (Ac-LDL) was studied. The small and CE-poor HDL obtained from probucol-treated patients had a greater capacity to promote CE efflux from macrophages than did control HDL (59.8 +/- 6.9% vs. 44.2 +/- 5.4%, P < 0.01). Furthermore, the ability of HDL to promote cholesterol efflux correlated negatively with the CE content and particle diameter of HDL (r = -0.561 and r = -0.583 respectively; P < 0.01). When the inhibitory effect of HDL on the incorporation of [14C]-oleate into cellular cholesteryl ester was compared, the HDL from patients and control subjects inhibited CE formation to a similar extent. The enhanced ability of probucol-treated patients' HDL may, therefore, be involved in the acceleration of hydrolysis of the CE pool in macrophages. Taken together, we conclude that CETP plays a crucial role in making HDL more active in its anti-atherogenic function by reducing CE and making HDL smaller, and that probucol may enhance reverse cholesterol transport by activating CE transfer in vivo. The current study demonstrated, for the first time, that HDL modified by enhanced CETP activity in vivo is potentially anti-atherogenic.

Adult↗