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Biomedical subjects

T Arai

Publications and source records attributed to T Arai.

At least 217 records · Page 12Linked to original sources

Effects of ion channel modulators in the influx and efflux of Tc-99m-MIBI.

Possible involvement of cell membrane ion transport systems in the uptake and extrusion of Tc-99m-MIBI was investigated by using various buffers with or without Na+ and Ca++, and ion transport inhibitors in a tumor cell line. The ion transport modulators dimethyl amiloride (DMA), verapamil, flunarizine and monensin were used. The uptake of Tc-99m-MIBI was significantly increased in all buffers containing either Na+ or Ca++ alone or none of them. There was significantly increased uptake of Tc-99m-MIBI especially in buffers without Na+. Verapamil, a L-type Ca++ channel blocker, increased Tc-99m-MIBI uptake in all buffers. Flunarizine, which inhibits Na+/ Ca++ channels, caused significantly increased accumulation of Tc-99m-MIBI only in buffer containing both Na+ and Ca++. Monensin, a sodium ionophore, significantly increased uptake of Tc-99m-MIBI. DMA, a potent Na+/H+ antiport inhibitor, significantly inhibited the uptake of Tc-99m-MIBI in all buffers. In conclusion, Tc-99m-MIBI behaves like Na+ during its uptake and extrusion. Extrusion of Tc-99m-MIBI may involve both verapamil- and flunarizine-sensitive pathways.

Adrenal Cortex Neoplasms↗

A high incidence of apolipoprotein E epsilon4 allele in middle-aged non-demented subjects with cerebral amyloid beta protein deposits.

We examined the apolipoprotein E (ApoE) genotypes of 19 middle-aged non-demented subjects with cerebral amyloid beta protein (Abeta) deposits, and compared the results with those of 16 patients with sporadic Alzheimer's disease (AD) and those of 34 age-matched controls. The frequency of the ApoE epsilon4 allele was higher (P = 0.0256) in these 19 subjects (0.211) than in controls (0.059), and was close to that in AD patients (0.281). This result suggests that middle-aged non-demented subjects with cerebral Abeta deposits are at high risk of developing AD, and that the diffuse Abeta deposits in these cases represent an early stage of AD pathology. We speculate that in the majority of late-onset sporadic AD patients, cerebral Abeta deposition commences when these patients are in their forties or fifties, and that the pathological process progresses gradually, taking 20 to 30 years for clinical manifestation of dementia.

Adult↗

Ischaemic complication following obliteration of unruptured cerebral aneurysms with atherosclerotic or calcified neck.

We report three cases of ischaemic complications following direct surgery of unruptured cerebral aneurysms having necks with atherosclerotic or calcified walls. Among 30 patients we treated directly for unruptured aneurysm over the last 4 years, 6 had 8 such aneurysms. Atherosclerotic or calcified neck was a major contributor to postoperative ischaemic sequelae in our recent series of unruptured aneurysms treated surgically, and common technical problems during surgery seemed to have caused ischaemic complications in the 3 patients reported here. In this report, attention is given to ischaemic complications in the treatment of such aneurysms.

Aged↗

Angiomyofibroblastoma arising from the fallopian tube.

BACKGROUND: Angiomyofibroblastoma is a rare tumor that occurs most commonly in the vulva and vagina. CASE: A 28-year-old woman, gravida 1, para 1, presented with secondary infertility. Pelvic ultrasound showed a multicystic mass that further imaging found to be septated and extended to the umbilicus. At laparotomy, a 25 x 14 x 4 cm mass originating from the left fallopian tube and the tube were excised. Pathologic examination confirmed an angiomyofibroblastoma of the fallopian tube. CONCLUSION: Angiomyofibroblastomas can occur in the fallopian tube and should be differentiated from more aggressive angiomyxoma.

Adult↗

Primary undifferentiated small cell carcinoma of the esophagus.

We histologically examined undifferentiated small cell carcinoma of the esophagus from 21 patients and used immunohistochemical methods for detection of chromogranin A and p53, bcl-2, and Rb oncoproteins. Nine (43%) of the 21 carcinomas consisted solely of undifferentiated cells, but heterogeneous components of in situ or invasive squamous cell carcinoma or mucoepidermoid carcinoma were observed in the other 12 (57%) tumors. Squamous cell carcinoma in situ was observed in the mucosa adjacent to the main tumor in 7 (50%) of the 14 resected esophageal specimens. An admixture of invasive squamous cell carcinoma and undifferentiated carcinoma was observed in 4 (19%) of the 21 tumors, and mucoepidermoid carcinoma was noted in one case. Chromogranin A staining yielded a positive reaction in two (10%) undifferentiated components but was negative in all heterogeneous components. Multiple sites of p53 immunopositivity were seen in the undifferentiated component of 17 (81%) of the 21 tumors, as well as in the in situ or invasive squamous cell carcinoma or mucoepidermoid carcinoma components of 9 (75%) of 12 tumors. Seven (33%) of the 21 tumors showed positive bcl-2 immunoreactivity in the small cell component, but all of the heterogeneous components were negative. Rb protein immunoreactivity was observed in the small cell component of one (5%) case and in 9 (75%) of the 12 heterogeneous components. Six (86%) of the seven in situ squamous cell carcinoma components were positive for Rb protein. Eighteen (86%) of the 21 patients died within 24 months of diagnosis. Two patients (10%) who survived for more than 24 months had received chemotherapy.

Aged↗

Increased serum and urinary neopterin in nephrotic syndrome indicate cell-mediated immune dysfunction.

T-cell-mediated immune disturbances are likely but not certain to cause the nephrotic syndrome. Because neopterin (NP) production is closely related to activation of cell-mediated immunity, we addressed the question by measuring serum NP concentrations and urinary NP/creatinine (Cr) ratios, as well as by assessing interstitial lymphocyte and monocyte infiltration in the kidney and activation of the same cell types in peripheral blood. Finally, we observed whether urinary NP/Cr ratios in nephrotic syndrome are changed by steroid therapy. Seventy-four patients with primary glomerulonephritis were divided into 4 groups based on presence or absence of nephrotic syndrome and presence or absence of mesangial proliferation and expansion. Serum and urinary NP concentrations were measured chromatographically. Infiltrating cells in the kidney were identified by immunohistochemistry, and activation of peripheral blood cells was examined by fluorescent surface marker antibodies and flow cytometry. Irrespective of the pathohistology of glomeruli, nephrotic groups showed significantly higher urinary NP/Cr ratios and serum NP concentrations. Nephrotic groups also exhibited more activation of T cells in peripheral blood than did nonnephrotic groups or a healthy control group. Serum NP did not correlate with extent of interstitial renal infiltrates. Steroid therapy decreased urinary NP/Cr ratios in steroid-responsive patients, but not in steroid-resistant patients. Increased serum NP concentrations and urinary NP/Cr ratios may reflect disordered cell-mediated immunity in the nephrotic syndrome, irrespective of glomerular histology or interstitial cell infiltration.

Adult↗

Neuroprotective effect of mild hypothermia cannot be explained in terms of a reduction of glutamate release during ischemia.

An exogenous glutamate injection into the hypothermic hippocampal CA1 during 5-min ischemia produced the same extent of extracellular glutamate levels as observed in the normothermic CA1 during 5-min ischemia; however, neuronal death was not induced in the hypothermic CA1. Glutamate is released excessively into the extracellular space during ischemia, and is thought to induce brain injury by its neurotoxicity. It has been reported that the massive glutamate release is reduced by mild hypothermia, and it has been proposed that the reduction of ischemia-induced glutamate release exerts the neuroprotective effect on postischemic neuronal death. In the present study, to determine whether the neuroprotective effect of mild hypothermia on postischemic hippocampal CA1 neuronal death is due to the reduction of ischemia-induced glutamate release, gerbils were subjected to 5-min ischemia under hypothermic condition at 31 degrees C and were simultaneously injected exogenously with L-glutamate, so that the hypothermic CA1 around a microdialysis probe was exposed to the same extracellular glutamate levels as seen during normothermic ischemia, and the histological outcome was examined. An injection with 1 mM L-glutamate into the hypothermic CA1 during 5-min ischemia produced a similar extent of increased glutamate (17-fold increase) to that observed in the normothermic CA1 during 5-min ischemia (16-fold increase). However, neuronal death was not induced in the hypothermic CA1. This result indicates that the neuroprotective effect of mild hypothermia cannot be explained in terms of a reduction of glutamate release during ischemia.

Animals↗

Bis-N-nitroso-caged nitric oxides: photochemistry and biological performance test by rat aorta vasorelaxation.

Three new caged nitric oxides (NOs)-BNN3, BNN5Na, and BNN5M were tested for biological use. BNNs have a strong ultraviolet (UV) absorption band (lambda(max): 300 nm, epsilon: 13.5 mM(-1) cm (-1)) extended to 420 nm and produce NO upon irradiation with 300-360 nm light in quantum yields about 2. A photoexcited BNN molecule yields two NOs with time constants of less than 10 ns for phase 1 and less than 20 micros for phase 2 at 37 degrees C, suggesting usefulness of BNNs for measuring in vivo and in vitro fast NO reactions. Upon irradiating with UV light, caged nitric oxides-loaded rat aortic strips maintained in a state of active tonic contraction effectively relaxed ( < 3 microM BNN5M loading solution concentration). BNN3 is incorporated in the lipid membrane. BNN5Na, insoluble in organic solvents but water soluble, localizes in the water phase. BNN5M, is muscle-cell-permeable and hydrolysed to BNN5Na to remain in cytosol. BNNs were thermally stable and demonstrated no observable toxicity.

Animals↗

Measurement of total nitric oxide metabolite (NO(x)(-)) levels in vivo.

The measurement of the total level of nitric oxide (NO) metabolite (NO(x)(-)) by microdialysis has recently been used to assess the production of NO in the in vivo brain [D. Luo, S. Knezevich, S.R. Vincent, N-Methyl-D-aspartate-induced nitric oxide release: an in vivo microdialysis study, Neuroscience, 57 (1993), 897-900; K. Ohta, N. Arai, M. Shibata, J. Hamada, S. Komatsumoto, K. Shimazu, Y. Fukuuchi, A novel in vivo system for consecutive measurement of brain nitric oxide production combined with the microdialysis technique, Neurosci. Lett., 176 (1994), 165-168; K. Shintani, S. Kanba, T. Nakai, K. Sato, G. Yagi, R. Kato, M. Arai, Measurement by in vivo microdialysis of nitric oxide release in the rat cerebellum, J. Psychiatr. Neurosci., 3 (1994), 217-221; H. Togashi, K. Mori, K. Ueno, M. Matsumoto, N. Suda, H. Saito, M. Yoshika, Consecutive evaluation of nitric oxide production after transient cerebral ischemia in the rat hippocampus using in vivo brain microdialysis, Neurosci. Lett., 240 (1998), 53-57]. Although several methods are available for detecting NO(x)(-) levels in dialysates, these methods are either not sensitive enough or require expensive experimental equipment. The method described herein provides a convenient and sensitive procedure for determining NO(x)(-) levels in dialysates. This method is useful for the in vivo study of NO production from various brain regions in various pathological conditions, and can be applied to other tissues.

Animals↗

Simulation of the daily sunlight illumination pattern for bacterial photo-hydrogen production.

Methods of illumination to simulate the daily sunlight irradiation pattern were studied in relation to photohydrogen production using the photosynthetic bacterium Rhodobacter sphaeroides RV. Three illumination patterns were compared, in which the light intensity was changed in 1, 3, or 6 steps. As a control, outdoor experiments were also carried out over a 3-d period in Tsukuba, August 1996. Outdoors, hydrogen production by Rba. sphaeroides RV was dependent on the sunlight intensity: the total volume of hydrogen produced per day varied from 14 to 28 l.m(-2), while the total light energy ranged from 5.5 to 6.4 kWh.m(-2). d(-1). The maximum hydrogen production rate was 2.8 l.m(-2).h(-1) under a 4.5-cm light path and the average light energy conversion efficiency was 1.1%. Indoors, the hydrogen production rate was found to be independent of the mode of illumination among the three patterns employed. The maximum hydrogen production rate was 3.3 l.m(-2).h(-1) with a light energy conversion efficiency of 1.0%, and it was concluded that the single-step illumination method provides an appropriate simulation of sunlight. Saturation of hydrogen production occurs during high light intensity around noon and this plays a key role in the simulation.

Journal Article↗

A comparison of the plasma fructose concentrations in dogs and cats and changes in the fructose concentrations in dogs following intravenous administration of fructose.

The plasma concentrations of fructose, glucose, free fatty acids (FFA) and triglycerides (TG) were measured in dogs and cats. Changes in these concentrations were investigated in dogs by an intravenous fructose tolerance test (IVFTT) at a dose of 0.1 g/kg body weight. Fructose concentrations in the plasma of dogs were significantly higher than those of cats. There was no significant difference in plasma glucose concentrations between dogs and cats. Plasma FFA concentrations decreased and TG concentrations increased after feeding in both dogs and cats. During the IVFTT, the plasma fructose concentrations in the dogs increased rapidly to a peak by 2 min and then decreased to half of the peak by 5 min after the administration of fructose. Administration of fructose resulted in an increase in the plasma TG concentrations and reduced plasma FFA concentrations in the dogs. Only 4%, of the administered fructose was detected in the urine of dogs following IVFTT. Plasma fructose was considered to be rapidly absorbed and metabolized in both dogs and cats. However, as with glucose metabolism, there appear to be some differences in fructose metabolism between dogs and cats.

Animals↗

Effects of in vivo soluble selectin gene introduction of lps-induced leukocyte accumulation in the murine lung.

The selectin family adhesion molecules exert a crucial role in accumulation of leukocytes at the site of inflammation. To test the biological effects of soluble selectin on lung inflammation, we introduced an expression plasmid vector of soluble selectin gene via HVJ-liposome into a murine model of LPS-induced lung injury. The myeloperoxidase activity in LPS-injected mice was suppressed by the in vivo injection of soluble P-selectin gene relative to control mice. On the contrary, soluble E- or L-selectin genes did not exert suppressive effects. Our observations suggest that P-selectin plays a crucial role in the initial steps of lung inflammation, and exogenous introduction of soluble P-selectin by in vivo gene transfer method may be a useful strategy for regulating inflammation of the lung.

Animals↗

Introduction of plasmid DNA and oligonucleotides into lung epithelial cells by the hemagglutinating virus of Japan (HVJ)-liposome method.

The hemagglutinating virus of Japan (HVJ) fused with liposomes provides a unique transfection vehicle with characteristics of both virus vector and liposome. Here we investigate the efficiency and safety of the HVJ-liposome technique in delivering foreign genes and oligonucleotides into the lung of the Wistar rat. A plasmid vector containing the Escherichia coli beta-galactosidase (beta-gal) gene and the chicken beta-actin promoter was transfected via the trachea using the HVJ-liposome method. Cytochemical staining showed expression of exogenous beta-gal activity in airway epithelial cells, alveolar macrophages, and alveolar type II cells. This activity persisted at least 28 days after administration of the genes. FITC-labeled oligonucleotides also were introduced into the same types of lung cells as those expressing beta-gal. After instillation of HVJ-liposome, anti-HVJ antibodies were detected in the sera of the rats, but even after repeated administration of HVJ-liposome, no marked histopathologic change was observed while exogenous beta-gal expression was detected in pulmonary cells.

Actins↗

Retrovirus vectors designed for efficient transduction of cytotoxic or cytostatic genes.

It is difficult to establish stable packaging cell lines producing retrovirus vectors for the expression of anti-oncogenes with cytotoxic or cytostatic potential, because these genes would also affect the growth of the packaging cell lines. To overcome this problem, we designed a transcriptional unit pBabeLPL for vector RNA production, in which the transcription of the exogenous genes is completely suppressed by the presence of a preceding insertion containing the puromycin resistance gene (puro) and a poly(A) addition signal. This insertion is flanked by a tandem pair of loxP, and is designed to be excised after the introduction of Cre recombinase, when transcription of the exogenous gene will be started from the 5'-LTR. The transcriptional unit car- rying LacZ or p53 as the exogenous gene was introduced into a previously constructed prepackaging cell lines PtG-S2, in which the expression of VSV-G is also designed to be initiated by the introduction of Cre recombinase, while the gag-pol gene is expressed continuously. After the introduction of Cre recombinase by an adenovirus vector, LacZ- or p53-expressing VSV-G-pseudotyped retrovirus vectors with the designed structure were produced at high virus titers. The p53 virus was shown to be able to transduce p53 into the entire population of several human cancer cell lines and to induce their growth arrest at the G1 phase, indicating that this vector-producing system will be advantageous for human gene therapy.

Adenoviridae↗

Changes in testicular transferrin concentrations measured by enzyme immunoassay after FSH administration to beagle dogs.

A sensitive enzyme immunoassay (EIA) was developed for transferrin (Tf) in the canine testis, as an effective marker of Sertoli cell function. Tf was purified from male dog serum by DEAE-Affi-Gel Blue chromatography and gel filtration. Rabbits were immunized with the Tf, and anti-dog Tf antibody was purified from the rabbit serum by affinity chromatography as primary antibody for EIA. Peroxidase-conjugated goat anti-dog Tf antibody was used as the secondary antibody for microtitre plate double-antibody EIA. The EIA was applied to measurement of testicular Tf concentrations in five normal beagle dogs. All of the dogs were given five injections of 2 mg porcine pituitary FSH at 12 h intervals, and testicular biopsy was performed. The testicular tissue was used for EIA of Tf. The optimum dilutions of the primary and secondary antibodies for the standard curves of canine Tf were 1: 4000 and 1: 1000, respectively. The limits of sensitivity of our EIA were between 30 ng Tf/plate-well and 2500 ng/well. The intra- and inter-assay coefficients of variation, and the recovery rate were 8.6, 7.6 and 86.0%, respectively. Before FSH administration, the mean +/- SEM Tf concentration in the testis of normal dogs was 357 +/- 31 ng/mL. At 12 h after the final FSH administration, Tf concentrations were significantly increased (p < 0.5) when compared with values before the start of treatment. Thus, Tf in the canine testis, measured by our EIA, appears capable of serving as a marker of Sertoli cell function.

Animals↗

Primary adenocarcinoma of the duodenum in the elderly: clinicopathological and immunohistochemical study of 17 cases.

Seventeen cases of primary duodenal adenocarcinoma occurring in the elderly (older than 65 years) were examined to clarify their clinicopathological features and biological behavior. The mean age was 77.4 years (range, 66-104), and there was no appreciable difference in the incidence between the sexes (female: male ratio, 8: 9). Thirteen patients had tumors located in the first portion of the duodenum, three in the second portion and one in the third portion. Grossly, there were three varieties of lesions: six polypoid, four flat-elevated and seven ulcerative-invasive. Sixteen cases showed well-differentiated adenocarcinoma, three of which were difficult to distinguish from adenoma, and one was poorly differentiated adenocarcinoma. Three of 16 tumors had poor differentiation in the invasive area, whereas mucosal lesions were well differentiated. Eight tumors had invaded the duodenal wall with occasional involvement of the pancreas. Immunohistochemistry demonstrated p53 protein overexpression in two intramucosal (22.2%) and five invasive (62.5%) cancers. In the intramucosal area the mean Ki-67-positive rate (PR) of the tumors with distant metastasis was significantly higher than that of the tumors without metastasis (46.0 vs 31.6%; P < 0.05), while there was no significant difference in the association between PR and gross feature or depth of the tumors. Clinical follow-up showed three of the five patients with invasive cancer died of carcinoma within 28 months. Compared with published data from other investigators, the results of the present study indicate a proximal shift of duodenal carcinoma in the elderly. Furthermore, it is concluded that invasive duodenal adenocarcinomas with high PR should be considered as potentially aggressive tumors, although their histology may indicate a high degree of differentiation.

Adenocarcinoma↗

A high-fat diet aggravates tubulointerstitial but not glomerular lesions in obese Zucker rats.

BACKGROUND: Despite a large body of evidence that manipulation of dietary fat alters glomerular lesions, reports regarding the effects of dietary fat on tubulointerstitial lesions are limited. Obese Zucker rats (OZR) spontaneously develop glomerular and tubulointerstitial lesions in association with hyperlipidemia. We sought to elucidate the effects of dietary fat on glomerular and tubulointerstitial lesions in OZR versus lean Zucker rats (LZR) and to assess the involvement of macrophages in the development of these lesions. METHODS: We fed LZR and OZR either a low- (1%) or high-fat (20%) diet. After 30 weeks of the specified diet, the creatinine clearance (Ccr) and renal histology as well as plasma lipid concentrations were examined. For morphological evaluation, glomerular sclerosis (GSI) and tubulointerstitial indices (TII) were each determined by a point-counting method. Infiltrating macrophages were stained immunohistochemically using an avidin-biotin complex technique. RESULTS: The high-fat diet increased the plasma low-density lipoprotein concentration in OZR. Both low- and high-fat OZR groups had higher GSI and TII than LZR receiving either diet. The high-fat diet aggravated TII but not GSI or Ccr in OZR; conversely, high fat intake worsened GSI and Ccr but not TII in LZR. Tubulointerstitial macrophages were most prominent in the high-fat OZR group, followed by the low-fat OZR group. Glomerular macrophages were similar in number in all groups. CONCLUSIONS: The manipulation of dietary fat has diverse effects on the kidney. A high-fat diet aggravated macrophage-mediated tubulointerstitial lesions in OZR, whereas in LZR, the diet induced glomerulosclerosis.

Albuminuria↗