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Biomedical subjects

T Arai

Publications and source records attributed to T Arai.

At least 307 records · Page 17Linked to original sources

Body-cavity-based lymphoma in an elderly AIDS-unrelated male.

Body-cavity-based lymphoma (BCBL) is a recently described subtype of human non-Hodgkin's lymphoma characterized by the localization of neoplastic cells exclusively in the body cavities. BCBL is found most commonly in AIDS patients, and is known to be highly associated with Kaposi's sarcoma-associated herpes virus (KSHV). We describe here a case of BCBL that occurred in a 101-year-old man. He was successively treated with etoposide, but died 8 months after the diagnosis of BCBL. No lymphoma masses were noted at pre- and postmortem examinations. KSHV was demonstrated in large numbers in the neoplastic cells using semiquantitative PCR analysis. Although there have been four brief reports of HIV negative BCBL, the present case is the first for which the detailed clinical course and response to chemotherapy have been recorded.

Aged↗

Molecular cloning of cDNA for p10, a novel protein that increases in the regenerating legs of Periplaneta americana (American cockroach).

Previously, we purified a protein with a molecular mass of 10 kDa (p10) that increases transiently during the regeneration of legs in the nymphal American cockroach Periplaneta americana, and showed that it is localized exclusively in the cytosol and on the external side of the newly formed epidermis of the regenerating legs [Nomura, A. et al. (1992) Int. J. Dev. Biol. 36, 391-389]. We isolated p10 cDNA and analyzed the expression of the p10 gene. The results indicated that p10 is synthesized as a precursor protein with a putative prosegment including a signal sequence at its N-terminal. The deduced amino acid sequence of p10 showed 53% and 47% identities with those of A10 (a Drosophila antennal protein) and CLP-1 (a moth, Cactoblastis cactorum labial palp protein), respectively. Expression of the p10 gene was shown to be significantly enhanced in regenerating Periplaneta legs. Immunoblotting analysis revealed that p10 was expressed not only in the regenerating legs, but also in the antennae and heads of nymphal and adult cockroaches.

Amino Acid Sequence↗

Cloning of cDNA for regenectin, a humoral C-type lectin of Periplaneta americana, and expression of the regenectin gene during leg regeneration.

We isolated cDNA for regenectin, a C-type lectin of the American cockroach (Periplaneta americana), and analysed expression of the regenectin gene in the regenerating legs. Regenectin was found to be a member of the Periplaneta lectin-related protein family. We found that the regenectin gene was expressed specifically in the epidermal cells of the newly formed regenerating legs. Together with our previous results, these results suggest that regenectin is synthesized by epidermal cells, secreted into the regenerating leg saccule, and assembles around myoblasts to form leg muscle fibers in situ.

Amino Acid Sequence↗

Measurement of the extracellular H2O2 in the brain by microdialysis.

This paper reports on the protocol for the determination of H2O2 in the brain using in vivo microdialysis coupled with fluorometry of dichlorofluorescin oxidation. We applied this protocol to monitor changes in the concentration of H2O2 in the brain, in vivo, during ischemia and reperfusion. Using this method, changes in the level of H2O2 in the brain during ischemia and reperfusion were effectively determined. The present protocol provides a novel tool to study the production of reactive oxygen species in the brain.

Animals↗

A comparison of the activities of certain enzymes related to energy metabolism in leukocytes in dogs and cats.

The activities of Na+,K(+)-ATPase in plasma membrane, of cytosolic enzymes and of glutamate dehydrogenase (GlGD) in mitochondria were measured in leukocytes (WBC) from dogs and cats to clarify the differences in energy metabolism in these cells. Feline WBC had significantly higher activities of hexokinase (HK), pyruvate kinase (PK) and LDH with pyruvate as substrate than did canine WBC. Canine WBC had significantly higher activities of glucokinase (GK) and GlDH than did feline WBC. Feline WBC had unique characteristics of energy metabolism in that the activities of the cytosolic enzymes under anaerobic conditions were significantly higher than those in canine WBC. It therefore appears that there are distinct differences in glucose-metabolism in WBC between dogs and cats. WBC enzyme activities are considered to reflect the metabolic state in the whole body of the animal. It is therefore suggested that changes in the activities of certain glycolytic enzymes in WBC may be useful as a diagnostic indicator in some types of metabolic disease in dogs and cats.

Alanine Transaminase↗

Dipyridamole and dilazep suppress oxygen radicals in puromycin aminonucleoside nephrosis rats.

BACKGROUND: Reactive oxygen species (ROS) are involved in the pathophysiology of puromycin aminonucleoside (PAN) nephrosis. To elucidate further the role of radicals in PAN nephrosis and the to determine the particular radical species scavenged by dipyridamole (DPM) and dilazep (DZ), we applied chemiluminescence and electron spin resonance (ESR) techniques. METHODS: Chemiluminescence of glomeruli, which were isolated on day 7 from rats injected with 100 mg kg-1 PAN, was measured with or without scavengers. The inhibitory effects of DPM and DZ on hydroxyl radical adduct formation in the Fenton's reaction were evaluated using ESR. RESULTS: Chemiluminescence was greater in glomeruli from rats with PAN nephrosis than in the the glomeruli of control rats. This increase was suppressed by superoxide dismutase, catalase, dimethylthiourea and also by DPM and DZ. ESR indicated that DPM and DZ inhibited hydroxyl radical adduct formation with a second-order rate constant of 2.9 x 10(10) and 1.6 x 10(10) (mol L(-1) s(-1) respectively, similar to that of dimethylthiourea. CONCLUSION: DPM and DZ scavenge hydroxyl radicals, thereby alleviating PAN nephrosis.

Animals↗

Effects of inhalation anaesthetics on the release of acetylcholine in the rat cerebral cortex in vivo.

By analysing the EEG, reticular multi-unit activity and behavioural changes, we have classified general anaesthetics into three groups: central nervous system (CNS) depressant, CNS excitant and epileptogenic agents. Changes in CNS neural activity are associated with alteration in transmitter release. We have attempted to clarify the actions of widely used inhalation anaesthetics, such as isoflurane (CNS depressant), nitrous oxide (CNS excitant) and sevoflurane (epileptogenic) on acetylcholine (ACh) release in the cerebral cortex using brain microdialysis. ACh release was suppressed by isoflurane and sevoflurane in a dose-related manner but recovered on wash-out. There were no significant differences between the effects of sevoflurane and isoflurane at the same MAC values. In contrast, ACh release was enhanced significantly by nitrous oxide. These findings indicate that the response of the cortical cholinergic cells to different anaesthetics reflects their neurophysiological characteristics, that is whether they stimulate or suppress CNS neurones.

Acetylcholine↗

Effect of xenon on central nervous system electrical activity during sevoflurane anaesthesia in cats: comparison with nitrous oxide.

We have compared the effects of xenon and nitrous oxide on central nervous system (CNS) electrical activity during sevoflurane anaesthesia in cats by recording the electroencephalogram (EEG), multi-unit activity of the midbrain reticular formation (R-MUA) and somatosensory evoked potentials (SEP). Basal anaesthesia with 2% and 5% sevoflurane was used. With 2% sevoflurane, 70% xenon initially produced rhythmic slow waves which were followed by bursts of high-amplitude sharp waves interrupted by low amplitude slow waves on the EEG. Xenon induced an initial increase, followed by a decrease in R-MUA. Nitrous oxide 70% decreased the amplitude of the EEG activity which was associated with an increase in R-MUA. Xenon suppressed the amplitude of both the initial positive and negative deflections of the SEP to a greater extent than nitrous oxide. With 5% sevoflurane anaesthesia, both anaesthetics increased the frequency of spikes on the EEG and facilitated R-MUA. These findings indicate that xenon has a stimulatory action on CNS background activity and a suppressive action on CNS reactive capability which is more potent than that of nitrous oxide.

Anesthetics, Combined↗

Isoflurane and sevoflurane augment norepinephrine responses to surgical noxious stimulation in humans.

BACKGROUND: Suppression of hypertensive response to noxious stimulation by volatile anesthetics may be a result of suppression of the stimulation-induced norepinephrine response or that of the cardiovascular response to catecholamines, or both. The suppression of the cardiovascular response is established, but that of norepinephrine response has not been confirmed. The authors hypothesized that the suppression of cardiovascular response but not that of norepinephrine response plays a major role in suppressing the noxious stimulation-induced hypertensive response by volatile anesthetics. METHODS: Forty healthy donors for living-related liver transplantation were allocated to four groups: receiving 1.2% (end-tidal) isoflurane in oxygen and nitrogen, 2.0% isoflurane, 1.7% sevoflurane, or 2.8% sevoflurane. The intraoperative plasma norepinephrine and epinephrine concentrations, arterial blood pressure and pulse rate were measured for the first 15 min of surgery and were compared with the preoperative values. RESULTS: Norepinephrine and epinephrine concentrations both increased intraoperatively in all four groups. The values of maximum increase and area under the concentration-versus-time curve of norepinephrine were greater in the high dose groups of both anesthetics. The intraoperative blood pressure did not differ by different doses of anesthetics, and the degree of increase of blood pressure was not proportional to the plasma catecholamine concentrations. CONCLUSION: The effects of isoflurane and sevoflurane on the surgical noxious stimulation-induced norepinephrine response were inversely proportional to the dose. The suppression of noxious stimulation-induced blood pressure response by anesthetics that were studied may be the result of suppression of the responses of vascular smooth muscle and myocardium to catecholamines.

Adult↗

Changes in the brain monoamine metabolism in acute liver failure produced by ischemia-reperfusion injury in rats.

OBJECTIVE: To investigate the relationship between behavioral alterations and changes in monoaminergic systems provoked by ischemia-reperfusion liver injury in rats. DESIGN: Prospective, randomized, controlled animal study. SETTING: University animal laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: Acute liver failure was induced by occlusion of the left portal vein and the hepatic artery for 90 mins. Twenty animals were subjected to the behavioral examination. The brain water content was measured in 12 animals. Forty-two animals were used for the evaluation of brain monoamine turnover. Half of animals in each experiment were subjected to the ischemic operation. MEASUREMENTS AND MAIN RESULTS: A step-through passive avoidance test was used for the behavioral evaluation 48 hrs after the ischemic operation. Then, plasma concentrations of amino acids were determined. The brain water content was measured with the dry weight method. The brain monoamine turnover was evaluated by the depletion of norepinephrine and dopamine induced by alpha-methyl-p-tyrosine, or the accumulation of 5-hydroxyindoleacetic acid induced by probenecid. In the plasma analysis performed 48 hrs after the operation, marked damage was found in animals subjected to liver ischemia. Injured rats demonstrated impairment in the passive avoidance test. The plasma concentrations of branch-chain amino acids were decreased, and the plasma concentrations of aromatic amino acids were increased. However, the brain water content was not changed by liver ischemia. The turnover of both norepinephrine in the cerebral cortex and dopamine in the striatum was decreased. The turnover of 5-hydroxytryptamine in the cerebral cortex was increased markedly. CONCLUSION: In liver injury caused by liver ischemia, the excitatory neurotransmission by norepinephrine and dopamine is depressed and the inhibitory neurotransmission mediated by 5-hydroxytryptamine is facilitated, especially in the telencephalon.

Amino Acids↗

Dexamethasone aggravates ischemia-induced neuronal damage by facilitating the onset of anoxic depolarization and the increase in the intracellular Ca2+ concentration in gerbil hippocampus.

The Ca2+ mobilization across the neuronal membrane is regarded as a crucial factor in the development of neuronal damage in ischemia. Because glucocorticoids have been reported to aggravate ischemic neuronal injury, the effects of dexamethasone on ischemia-induced membrane depolarization, histologic outcome, and changes in the intracellular Ca2+ concentration in the gerbil hippocampus were examined in vivo and in vitro. The effects of metyrapone, an inhibitor of glucocorticoid synthesis, were also evaluated. Changes in the direct-current potential shift in the hippocampal CA1 area produced by transient forebrain ischemia for 2.5 minutes were compared among animals pretreated with dexamethasone (3 microg, intracerebroventricularly), metyrapone (100 mg/kg, intraperitoneally), and saline. The histologic outcome was evaluated 7 days after ischemia by assessing the delayed neuronal death in the hippocampal CA1 pyramidal cells of these animals. A hypoxia-induced intracellular Ca2+ increase was evaluated by in vitro microfluorometry in gerbil hippocampal slices, and the effect of dexamethasone (120 microg/L in the medium) on the cytosolic Ca2+ accumulation was examined. The effect in a Ca2+-free ischemialike condition was also investigated. Preischemic administration of dexamethasone reduced the onset latency of ischemia-induced membrane depolarization by 22%, and aggravated neuronal damage in vivo. In contrast, pretreatment with metyrapone improved the histologic outcome. The onset time of the increase in the intracellular concentration of Ca2+ provoked by in vitro hypoxia was advanced in dexamethasone-treated slices. The Ca2+-free in vitro hypoxia reduced the elevation compared with that in the Ca2+-containing condition. Treatment with dexamethasone facilitated the increase on both the initiation and the extent in the Ca2+-free condition. Aggravation of ischemic neuronal injury by endogenous or exogenous glucocorticoids is thus thought to be caused by the advanced onset times of both the ischemia-induced direct-current potential shift and the increase in the intracellular Ca2+ concentration.

Animals↗

Evaluation of focal cerebral ischemia in rats by magnetic resonance imaging and immunohistochemical analyses.

Correlation of focal ischemia-induced brain damage evidenced by magnetic resonance imaging (MRI) and by staining with microtubule-associated protein 2 (MAP2) was studied in rats. Ischemia was produced by transient occlusion of the middle cerebral artery (MCAO). The damage was assessed at 6 to 8 hours after MCAO and 1 week later. The area of damage assessed by MRI agreed with that by MAP2 staining at 6 to 8 hours after MCAO, which was smaller (P < 0.001) than that defined by MAP2 staining 1 week after MCAO. Glial staining indicated that glial infiltration affected the signal intensity of MRI in the area of damage.

Animals↗

Postischemic enhancements of N-methyl-D-aspartic acid (NMDA) and non-NMDA receptor-mediated responses in hippocampal CA1 pyramidal neurons.

Glutamate receptor-mediated responses were investigated by using a whole-cell recording and an intracellular calcium ion ([Ca2+]i) imaging in gerbil postischemic hippocampal slices prepared at 1, 3, 6, 9, 12, and 24 hours after 5-minute ischemia. Bath application of N-methyl-D-aspartic acid (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), and kainate showed that NMDA-, AMPA- and kainate-induced currents were enhanced in postischemic CA1 pyramidal neurons at 1 to 12 hours after 5-minute ischemia. NMDA and non-NMDA receptor-mediated excitatory postsynaptic currents (EPSC) were examined in postischemic CA1 pyramidal neurons at 3 hours after 5-minute ischemia to confirm whether synaptic responses are enhanced in the postischemic CA1 pyramidal neurons. The amplitudes of NMDA- and non-NMDA-receptor-mediated EPSC were enhanced in the postischemic CA1 pyramidal neurons. NMDA-, AMPA-, and kainate-induced [Ca2+]i elevations were also examined to determine whether the enhancement of currents is accompanied by the enhancement of [Ca2+]i elevation. The enhancements of NMDA-, AMPA-, and kainate-induced [Ca2+]i elevations were shown in the postischemic CA1. These results indicate that NMDA and non-NMDA receptor-mediated responses are persistently enhanced in the CA1 pyramidal neurons 1 to 12 hours after transient ischemia, and suggest that the enhancement of glutamate receptor-mediated responses may act as one of crucial factors in the pathologic mechanism responsible for leading postischemic CA1 pyramidal neurons to irreversible neuronal injury.

Animals↗

Quantification of modified amyloid beta peptides in Alzheimer disease and Down syndrome brains.

To gain insights into the different forms of modified amyloid beta peptides (A beta) in the Alzheimer disease (AD) and Down syndrome (DS) brain, we used two-site ELISAs with antibodies specific for isomerized (i.e. A beta with L-isoaspartate at positions 1 and 7) and pyroglutamate-modified (i.e. A beta beginning with pyroglutamate at position 3) forms of A beta to quantitate the levels of these different A beta peptides in formic acid extracts of AD and DS frontal cortex. Despite variations in the proportions of distinct forms of A beta in AD and DS frontal cortex, the major species of A beta in these samples were A betaN3(pyroGlu)-42 as well as A beta x-42 (where x is a residue at position 2 or less in A beta), whereas isomerized A beta was a minor species. Further, the levels of isomerized and pyroglutamate-modified forms of A beta terminating at amino acid 42 were higher than those ending at amino acid 40. The abundance of the distinct forms of A beta reported here in formic acid extracts of AD and DS frontal cortex suggests that these A beta species could play important roles in the deposition of A beta in AD and DS brains.

Aged↗

Detection of lung lesions and lymph nodes with 201Tl SPET.

The aim of this study was to characterize lung lesions by means of the uptake, retention and washout of 201Tl, and to quantify the sensitivity of 201Tl SPET (single photon emission tomography) in detecting mediastinal and hilar lymph nodes. A total of 68 patients with lung lesions (tumours and inflammation) underwent both helical computed tomography (CT) and 201Tl SPET examinations. Uptake, retention and washout parameters were calculated from early and delayed 201Tl SPET by drawing regions of interest over the primary lesion and the background of the lung. The findings on 201Tl SPET were compared with those on CT and surgical findings. A significant difference in the retention index (RI) was observed between primary malignant and benign lesions. In detecting lymph nodes, the sensitivity, specificity and negative predictive value were 83%, 60% and 90% respectively for early 201Tl SPET, and 50%, 80% and 80% respectively for delayed 201Tl SPET. 201Tl SPET with semi-quantitative analysis, especially RI, helps to differentiate between malignant and benign lung lesions. Lymph nodes larger than 1 cm on CT but not showing 201Tl uptake could be considered non-metastatic lesions.

Adult↗

Detection of lung and chest tumours using 99Tcm-tetrofosmin: comparison with 201Tl.

The aim of this study was to assess the usefulness of 99Tcm-tetrofosmin for detecting tumours of the lungs and adjacent structures and to compare the results with those for 201Tl. In the 18 patients studied, there were 30 lesions in total. Dual-isotope SPET acquisitions were performed 10 min and 3 h after the administration of 99Tcm-tetrofosmin and 201Tl. Image quality and semi-quantitative parameters were evaluated for both tracers. All lesions were detected by the two radiopharmaceuticals on both the early and delayed images. In seven patients, the image quality of 99Tcm-tetrofosmin was better than that of 201Tl. For the detection of metastatic lymph nodes, the delayed 201Tl and the early 99Tcm-tetrofosmin images were superior. No significant difference was observed between the uptake ratios of the two tracers. 99Tcm-tetrofosmin showed significantly (P < 0.001) higher washout than 201Tl from both the lesions and normal lungs, although washout of 201Tl from normal lungs was significantly higher than that from the lesions. In conclusion, 99Tcm-tetrofosmin may be helpful for detecting tumours of the lungs and adjacent structures, but has limited applicability in differentiating between malignant and benign tumours and may not be used instead of 201Tl to detect malignant tumours of the lungs.

Adenocarcinoma↗

Pathological characteristics of gastric carcinomas in the very old.

A total of 69 gastric carcinomas of very old people (aged > or = 85) were collected and pathologically analyzed in comparison with those of young to middle-aged (30-39) and elderly (65-69) people, with special attention to their phase. In the very old, almost all (34/35) carcinomas in the early phase belonged to well-differentiated categories. In the advanced phase, half of them (17/34) were classified into poorly differentiated categories when determined from the predominant pattern, but a well-differentiated pattern almost always coexisted in the superficial site. Thus, the gastric carcinomas in the very old may principally develop as well-differentiated carcinomas which then progress to poorly differentiated carcinomas with time, in contrast to those of the young to middle-aged, most of which emerged from the very early phase as poorly differentiated lesions. The gross features of the carcinomas were also in line with these histological observations. The carcinomas of the elderly showed distinct similarity to those of the very old. The results suggest that poorly differentiated carcinomas of the young to middle-aged and the old may be better classified and analyzed separately in view of the generally recognized etiological (e.g., specifically close causal relationship with environmental factors of the intestinal-type carcinoma of the old) and biological (e.g., practically no tendency for hematogenous metastasis of the diffuse-type carcinoma of the young to middle-aged) differences, although in the General Rules for Gastric Cancer Study of Japan, both are placed in the same category, por (por2).

Adenocarcinoma↗

Antitumor effect of a neutralizing antibody to vascular endothelial growth factor on liver metastasis of endocrine neoplasm.

Distant metastasis of gastrointestinal endocrine neoplasm is resistant to currently available treatments. Because hematogenic metastasis is dominant, anti-angiogenic drugs are expected to be a novel therapy for this neoplasm. In the present study, the therapeutic effect of vascular endothelial growth factor neutralizing antibody (VEGFAb) on liver metastasis of an endocrine neoplasm was investigated experimentally. Cecal transplantation into nude mice of small pieces of EN-1, a xenotransplanted human intestinal endocrine neoplasm, resulted in liver metastasis. A treated group (n = 19) received 100 micrograms/mouse of VEGFAb intraperitoneally on alternate days from day 10 after tumor transplantation, and the control group (n = 19) received saline. Five of the 19 control mice died of tumor progression, of which 2 could not be evaluated. The cecal tumor weighed 6316 +/- 2333 mg (n = 17) in the control group and 1209 +/- 837 mg (n = 19) in the treated group (P < 0.01) 6 weeks after transplantation. Liver metastasis developed in 16 of 17 control mice and in 2 of 19 treated mice (P < 0.01). The VEGF level of the whole cecal tumor in the control group was significantly higher than that in the treated group (305.1 +/- 174.1 vs. 54.7 +/- 41.2 mg; P < 0.001). VEGFAb did not cause any body weight loss (28.52 +/- 1.63 in the control vs. 28.44 +/- 1.71 g in the treated group). These results indicate that VEGFAb may be a novel therapeutic agent for endocrine neoplasm with distant metastasis.

Aged↗