Biomedical subjects

S Shimada

Publications and source records attributed to S Shimada.

At least 127 records · Page 7Linked to original sources

PubMed1998

Increased transcription of glutamate-aspartate transporter (GLAST/GluT-1) mRNA following kainic acid-induced limbic seizure.

Expression of mRNA for glutamate-aspartate transporter (GLAST/GluT-1/EAAT1) was studied in the brain of the rat which presented recurrent limbic seizure following systemic administration of kainic acid (KA) by in situ hybridization and Northern blot analysis. The expression of GLAST mRNA was markedly increased after 12 h and peaked after 48 h in animals which demonstrated limbic seizure. The induction of the mRNA were observed in the small non-neuronal cells in the hippocampus, especially around CA3 region and hilus. In contrast, there was no change in GLAST mRNA levels in KA injected seizure-free animals. These findings suggest that GLAST mRNA is induced by seizure and increased extracellular glutamate levels during seizure may be important for induction of GLAST mRNA.

ATP-Binding Cassette Transporters↗

PubMed1998

Circadian variation of myocardial ischemia in patients with unstable angina pectoris secondary to fixed and/or spastic coronary narrowing.

We investigated the circadian variation of myocardial ischemia in patients with unstable angina using a 24-hour 12-lead electrocardiographic monitoring system with computer analysis. The circadian variation of ischemic attacks in patients who had ST elevation showed a similarity to that of the onset of acute myocardial infarction and most of these patients had vasospasm without organic stenosis; no similarity was seen in patients with organic stenosis.

Aged↗

PubMed1998

MK-801 blocks monoamine transporters expressed in HEK cells.

(+)-MK-801 is known to be a specific non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors. However, besides having an anticonvulsant effect, this compound possesses a central sympathomimetic effect and an anxiolytic-like action, raising the possibility that (+)-MK-801 might affect monoamine uptake systems. To elucidate this possibility, we investigated the effects of (+)-MK-801 on monoamine transporters expressed in HEK cells. (+)-MK-801 significantly inhibited the uptake of all three monoamine transporters in a dose-dependent manner and the inhibitions were competitive with respect to monoamines. The Ki values of (+)-MK-801 on the norepinephrine, dopamine and serotonin transporters were 3.2 microM, 40 microM and 43 microM, respectively. In addition, (-)-MK-801, a less potent antagonist of NMDA receptors, also inhibited monoamine transporters with a similar potency as that of (+)-MK-801. These results clearly indicate that MK-801, a non-competitive antagonist of NMDA receptors, competitively inhibits monoamine transporters without stereoselectivity.

ATP-Binding Cassette Transporters↗

PubMed1998

Functional analysis of CD82 in the early phase of T cell activation: roles in cell adhesion and signal transduction.

To define T cell co-stimulatory molecules that work in the early phase of T cell activation, we established monoclonal antibodies (mAb) that inhibit or enhance T cell activation by the histiocytic leukemia cell line U937. One of the mAb, 53H5, which recognized both T cells and U937, was identified to bind to CD82 by expression cloning. Functional analyses of CD82 revealed that 1) CD82 needs to exist on both T cells and U937 for the full activation of T cells; 2) CD82 expression is up-regulated on both T cells and U937 by stimulation such as CD3 ligation or treatment with phorbol 12-myristate 13-acetate; 3) overexpression of CD82 enhances both homotypic and heterotypic cell adhesion between T cells and U937; 4) CD82 signal co-stimulates T cells and the signal works synergistically with the CD28-mediated T cell co-stimulation signal; 5) in mixed leukocyte reactions using U937 as stimulator cells, CD82 overexpression on U937 correlates with the higher allogeneicity of U937 cells. These results indicate that CD82 co-stimulates T cells not only by sending intra-T cell signals that work synergistically with CD28 signals but also by inducing enhanced T cell-antigen-presenting cell interaction.

Antigens, CD↗

PubMed1998

Intestinal intraepithelial T lymphocytes. Our T cell horizons are expanding.

The alimentary tract is an essential structure for the ingesting of nutrients from the outside, and even most primitive animals have a straight tract that runs from the mouth to the anus. We come into contact with the outside world through our skin and mucous membranes. The surface area of the enteric mucous membrane, which absorbs nutrients, is enlarge through its ciliary structure, and the enteric cavity creates by far the largest external world that we come into contact with. For instance, the enteric mucosal surface of the human gastrointestinal tract covered by a single layer of epithelial cells corresponds to the size of one-and-a-half tennis courts, and the innumerable number of epithelial cells covering this mucous surface are entirely replaced by new epithelial cells in the space of just several days. Simultaneously, the fact that 60-70% of peripheral lymphocytes are congregating in the gastrointestinal tract supports the notion that the enteric mucous membrane represents an extremely dangerous locale, where numerous harmless/precarious external antigens come in through the wide array of food we injest on a daily basis, and the literally infinite amounts of normal intestinal flora intermingled from time to time with life-threatening microbes surge across. Surprisingly, approximately one out of the five cells in the intestinal epithelium are lymphocytes, most of which are ill-defined T cells having unusual, but distinctive characteristics and situated apparently so close to external antigens in the entire body. This article deals with the information that has been accumulated mainly in the past decade concerning the development, phenotypes, and possible function of these yet unacknowledged mucosal T cells that lurk in the anatomical front of the intestine.

Animals↗

PubMed1998

Complications and management of microwave coagulation therapy for primary and metastatic liver tumors.

Microwave coagulation therapy (MCT) has been widely used, both percutaneously and directly, as effective minimal invasive therapy for liver tumors. To facilitate the use of MCT, we describe the complications we have encountered, and their possible management and prophylaxis. MCT was performed for 42 patients with hepatocellular carcinoma (HCC) and for 29 with metastatic liver tumors, following which complications developed in 14.2% and 20.6% of the HCC and metastatic groups, respectively. The complications included abscess, biloma, bleeding, hepatic failure, and dissemination of cancer cells. In the HCC group, the mean value of tumor size and the clinical stage of patients with complications were significantly larger (P = 0.006) and higher (P = 0.032), respectively, than those of patients without complications. The incidence of complications increased significantly when the tumor size was more than 4cm (P = 0.008). Abscesses and bleeding were successfully treated using percutaneous drainage and interventional angiography, respectively, but as the other serious complications were not able to be treated effectively once induced, prophylaxis is important to facilitate MCT. Transcatheter cooling of the intrahepatic bile duct during MCT and the administration of an anticancer agent into the abdominal cavity are recommended to prevent biloma and dissemination, respectively. MCT is indicated for tumors less than 4 cm in diameter to reduce the risk of complications. The prophylaxis and treatment of these complications enhance the safety of MCT.

Aged↗

PubMed1998

Tetrahydropapaveroline and its derivatives inhibit dopamine uptake through dopamine transporter expressed in HEK293 cells.

Tetrahydropapaveroline (THP), an isoquinoline alkaloid, has been detected in brain and urine of Parkinsonian patients on L-dopa medication, and in the urine and brain of rats after L-dopa or acute ethanol administration. Since THP is considered to be synthesized from dopamine, it may affect dopaminergic neurons through the reuptake system, i.e. dopamine transporter (DAT). To determine whether THP has affinity for DAT, we generated a cell line which stably expresses DAT and examined whether THP and its derivatives could inhibit [3H]DA uptake in these cells. Ki of THP and three derivatives (1-benzyl-1,2,3,4-tetrahydroisoquinoline (1BnTIQ), 1-(3',4'-dibydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline (3',4' DHBnTIQ) and 6,7-dihydroxy-1-benzyl-1,2,3,4-tetrahydroisoquinoline (6,7 DHBnTIQ)) for inhibition of [3H]DA uptake were about 41, 35, 23 and 93 microM, respectively, which were similar to the Ki of 1-methyl-4-phenylpyridinium ion (MPP+) (28 microM). These results suggest that THP and its derivatives might be uptaken through DAT and be involved in Parkinson's disease and/or alcohol addiction.

Animals↗

PubMed1998

Assessment of affinities of beta-CIT, beta-CIT-FE, and beta-CIT-FP for monoamine transporters permanently expressed in cell lines.

We investigated the effects of three cocaine analogs, beta-CIT (2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane), beta-CIT-FE (2-beta-carbomethoxy-3-beta-(4-iodophenyl)-N-(2.fluoroethyl)-nortropa ne), and beta-CIT-FP (2-beta-carbomethoxy-3-beta-(4-iodophenyl)-N-(3-fluoropropyl)-n ortropane), on the uptake of [3H]dopamine(DA), serotonin(5-HT), and 1-norepinephrine (NE) using cell lines permanently expressing DA, 5-HT, and NE transporters, respectively, to determine their affinities for these three transporters. We generated cell lines stably expressing DA, 5-HT, and NE transporters, respectively, by the Chen-Okayama method, and then tested the abilities of (-)cocaine, beta-CIT, beta-CIT-FE, beta-CIT-FP, and clomipramine to inhibit the uptake of [3H]DA, 5-HT, and 2-NE. Ki values of beta-CIT, beta-CIT-FE, and beta-CIT-FP for [3H]DA, 5-HT, 1-NE uptake were 6, 29, and 33 nM, 91, 133, and 130 nM, and 28, 113 and 70 nM, respectively, whereas those of cocaine and clomipramine were 316, 581, and 176 nM and > 10,000, 437, and 851 nM, respectively. Beta-CIT, beta-CIT-FE, and beta-CIT-FP were shown to be potent DA, 5-HT, and NE uptake inhibitors. Beta-CIT and beta-CIT-FP were highly potent and selective dopamine uptake inhibitors, and therefore might be useful for imaging of DA transporter with single photon emission computed tomography (SPECT) or positron emission tomography (PET).

Animals↗

PubMed1998

Nuclear localization of brain-type glycogen phosphorylase in some gastrointestinal carcinoma.

Our previous reports have demonstrated frequent and strong expression of glycogen phosphorylase (EC 2.4.1.1) activity mainly in the cytoplasm of gastric carcinoma. Although previous studies have suggested the phosphorylase glycosyltransferase system to be in the nucleus from enzyme histochemical analyses, intranuclear localization of the phosphorylase has not been fully established. The aims of the present study are to investigate the nuclear localization of glycogen phosphorylase and to identify the isoform of phosphorylase in the nucleus of gastrointestinal carcinoma. The activity of glycogen phosphorylase in carcinoma cells corresponding to the nucleus was demonstrated using enzyme cytochemical analysis. The phosphorylase activity coincided with localization revealed by immunocytochemistry using affinity-purified specific anti-human brain-type glycogen phosphorylase antibody. The isoform expressed in the nuclei of carcinoma cells was identified as being only the brain type according to a polymerase chain reaction-based assay using RNA obtained from gastric carcinoma cells and primers specific to muscle, liver and brain types of glycogen phosphorylase. The intranuclear localization of the brain-type isoform was confirmed by immunoelectron microscopical analyses. Further investigation to examine the nuclear localization in human carcinoma tissue (145 and 25 specimens with gastric and colonic carcinoma respectively) was carried out by immunohistochemistry using specific anti-brain-type antibody. Nuclear immunostaining was observed in seven cases out of 145 gastric carcinoma. The present study is the first to clarify the nuclear localization of glycogen phosphorylase with enzymatic activity in gastrointestinal carcinoma. The isoform of the enzyme expressed in the carcinoma was identified as the brain type. These results warrant further studies on the mechanisms for transporting the large molecule of brain-type glycogen phosphorylase to nuclei and its function in the nucleus of carcinoma cells.

Brain↗

PubMed1998

Deletion pattern of the steroid sulphatase gene in Japanese patients with X-linked ichthyosis.

Most caucasian patients with X-linked ichthyosis (XLI) reportedly display large genomic deletions involving the entire steroid sulphatase (STS) gene and flanking regions. In this study, we investigated the deletion patterns of the STS gene and flanking regions in 12 unrelated Japanese patients with XLI using the polymerase chain reaction method with 10 markers, including the 5' and 3' ends of the STS gene. Eleven of the 12 patients exhibited deletion of this entire gene, whereas the twelfth patient showed no evidence of deletion. In 10 of the 12 patients, the entire region from DXS1139 to DXF22S1 was deleted, the most common deletion pattern observed in caucasian patients, indicating that there are no racial or ethnic differences.

Adolescent↗

PubMed1998

Identification of receptors and Smad proteins involved in activin signalling in a human epidermal keratinocyte cell line.

BACKGROUND: Activin A is a multifunctional protein, which is a member of the transforming growth factor-beta (TGF-beta) superfamily. Smad proteins have recently been shown to transduce signals for the TGF-beta superfamily of proteins, and Smad2 was implicated in activin signalling in Xenopus embryos. RESULTS: We identified the receptors and Smad proteins activated by activin A in a human epidermal keratinocyte cell line, HaCaT. The major activin receptors expressed on HaCaT cells were activin type II receptor (ActR-II) and activin type IB receptor (ActR-IB). We have also shown that in HaCaT cells, activin A induced the phosphorylation of Smad3 and, to a lesser extent, of Smad2. On the other hand, TGF-beta induced an efficient phosphorylation of both Smad2 and Smad3. Activin A preferentially induced the nuclear translocation of Smad3 in HaCaT cells, whereas TGF-beta strongly induced the nuclear translocation of Smad2, as well as other Smads. Moreover, a constitutively active form of ActR-IB efficiently stimulated the formation of a heteromeric complex between Smad3 and Smad4 in COS cells transfected with Smad cDNAs. CONCLUSIONS: These results suggest that activin A binds to a receptor complex of ActR-II and ActR-IB, and preferentially activates Smad3 in HaCaT human keratinocytes.

Activin Receptors↗

PubMed1998

Inhibition of myo-inositol transport causes acute renal failure with selective medullary injury in the rat.

Myo-inositol is a major compatible osmolyte in the renal medulla that is accumulated under hypertonic conditions via the Na+/myo-inositol cotransporter (SMIT). We have recently reported that SMIT is predominantly present in the thick ascending limb of Henle (TAL) and is strongly induced by acute NaCl loading, suggesting an important role of myo-inositol in this nephron segment. In the present study, we sought to examine in vivo effects of inhibition of myo-inositol transport using a transport inhibitor, 2-O, C-methylene-myo-inositol (MMI). Intraperitoneal injection of MMI caused acute renal failure in the rats. Serum creatinine and urea nitrogen were significantly increased 12 hours after MMI injection. Morphologic study revealed that the tubular cells were extensively injured in the outer medulla. A considerable number of the tubular cells were injured in the cortex as well. Immunohistochemical study for Tamm-Horsfall protein (THP), which was used for identification of the TAL cells, showed that THP-positive cells were predominantly injured. The tubular injury apparently appeared to worsen when high concentration of NaCl was injected with MMI. Administration of myo-inositol prevented acute renal failure and improved the tubular injury after MMI injection. Furthermore, supplementation of betaine, another osmolyte in the TAL cells, partially prevented the toxic effects of MMI. These results suggest that myo-inositol play a crucial role in the TAL regarding osmoregulation of the cells.

Acute Kidney Injury↗

PubMed1998

Enhanced angiotensin II stimulates renal disorders in transgenic Tsukuba hypertensive mice.

Tsukuba hypertensive mice (THMs) are transgenic mice carrying human renin-angiotensin system (RAS) genes. The aim of this study is to evaluate whether renal disorders are present in THMs. Twenty-week-old THMs and C57BL/6 mice (C57s) were used for this study. Each group consisted of 8 mice. Systolic blood pressure, urinary volume, water intake and urinary albumin excretion were measured in each mouse. Each mouse was then euthanized, and the renal glomerulosclerosis index and glomerular size were measured. Systolic blood pressure of THMs was about 40 mmHg higher than that of C57s. Urinary volume, water intake and urinary albumin excretion were significantly higher in THMs than in C57s. The renal glomerulosclerosis index and glomerular size were also significantly higher in THMs than in C57s. These results suggested that an enhanced renin-angiotensin system, including its hypertensive effects, stimulates albuminuria, renal glomerulosclerosis and glomerular hypertrophy in THMs.

Angiotensin II↗

PubMed1998

Tissue angiotensin II concentration in the heart and kidneys in transgenic Tsukuba hypertensive mice.

Tsukuba hypertensive mice (THM) are transgenic mice carrying both human renin and angiotensinogen genes, and possessing an overexpressing human renin-angiotensin system. The aim of this study is to evaluate the angiotensin II concentration in the heart and kidney in THM. Twenty-week-old male THM and control C57BL/6 mice (C57) were used. Each group consisted of 3 mice. For each mouse, systolic blood pressure, heart to body weight ratio, renal glomerular sclerosis index and angiotensin II concentration in the heart and kidney were measured. Systolic blood pressure of THM was about 40 mmHg higher than that of C57. Heart to body weight ratio and renal glomerular sclerosis index were significantly higher in THM than those in C57. The angiotensin II concentration in THM was about 4 times higher in the heart and about 5 times higher in the kidney compared with that in C57. These results suggest that accelerated tissue angiotensin II production, significant cardiac hypertrophy and renal glomerular sclerosis all occur because of hypertension.

Angiotensin II↗

PubMed1998

Novel subtyping of intestinal metaplasia in the human stomach: brain-type glycogen phosphorylase expression in the proliferative zone and its relationship with carcinogenesis.

Although reports have suggested the incomplete type of intestinal metaplasia (IM) had a close correlation with carcinoma, considerable data showed no apparent relationship between the particular type of IM and the intestinal type carcinoma. The purpose of this study was to establish a novel classification of IM using brain-type glycogen phosphorylase (BGP) from a carcinogenetic viewpoint. The only isoform expressed in gastric cancer was BGP using polymerase chain reaction analysis. We studied 136 specimens with gastric carcinoma and the adjacent IM using specific anti-BGP antibody with its correlation to subtypes of IM, proliferating cell nuclear antigen-labeling index, and various oncogene products. Brain-type glycogen phosphorylase was expressed in 80.5% of the intestinal type and 18.8% of the diffuse type of carcinoma and in 87.5% and 41.6% in the generative zone of IM adjacent to cancer foci, respectively, whereas no reactivity was observed in the normal gastric mucosa. The proportion of the positivity in the cancer and IM was significantly greater in the intestinal-type carcinoma than in the diffuse type. The expression of BGP in the generative cells of IM had no significant correlation with the conventional type of IM. Intestinal metaplasias with BGP expression were significantly higher in a proliferating state than in those without BGP, and some of them that were coexpressed accumulated p53 in the generative cells. The relationship between IM with BGP in the generative cells and intestinal-type carcinoma was apparently closer than the conventional subtype of IM and gastric cancer. Intestinal-type carcinoma might arise from some of these proliferating cells with BGP.

Gastric Mucosa↗

PubMed1998

Membranocystic lesions in a patient with cytophagic histiocytic panniculitis associated with subcutaneous T-cell lymphoma.

A 51-year-old Japanese woman had erythematous, tender subcutaneous nodules on her lower legs and buttocks, as well as fever, pancytopenia, and liver dysfunction. Histopathologic examination of the nodules showed subcutaneous T-cell lymphoma with cytophagocytosis and membranocystic lesions. Our patient was unique in having the combination of cytophagic histiocytic panniculitis due to subcutaneous T-cell lymphoma and membranocystic lesions.

Cell Membrane↗

PubMed1998

Ketamine inhibits monoamine transporters expressed in human embryonic kidney 293 cells.

BACKGROUND: Ketamine has been characterized as having psychotomimetic and sympathomimetic effects. These symptoms have raised the possibility that ketamine affects monoaminergic neurotransmission. To elucidate the relation between ketamine and monoamine transporters, the authors constructed three cell lines that stably express the norepinephrine, dopamine, and serotonin transporters and investigated the effects of ketamine on these transporters. METHODS: Human embryonic kidney cells were transfected using the Chen-Okayama method with the human norepinephrine, rat dopamine, and rat serotonin transporter cDNA subcloned into the eukaryotic expression vector. Using cells stably expressing these transporters, the authors investigated the effects of ketamine on the uptake of these compounds and compared them with those of pentobarbital. RESULTS: Inhibition analysis showed that ketamine significantly inhibited the uptake of all three monoamine transporters in a dose-dependent manner. The Ki (inhibition constant) values of ketamine on the norepinephrine, dopamine, and serotonin transporters were 66.8 microM, 62.9 microM, and 162 microM, respectively. Pentobarbital, a typical general anesthetic agent with no psychotic symptoms, did not affect the uptake of monoamines, however. Further, neither the glycine transporter 1 nor the glutamate/aspartate transporter was affected by ketamine, indicating that ketamine preferentially inhibits monoamine transporters. CONCLUSIONS: Ketamine inhibited monoamine transporters expressed in human embryonic kidney cells in a dose-dependent manner. This result suggests that the ketamine-induced inhibition of monoamine transporters might contribute to its psychotomimetic and sympathomimetic effects through potentiating monoaminergic neurotransmission.

ATP-Binding Cassette Transporters↗

PubMed1998

Relationship between gait and clinical results after high tibial osteotomy.

Thirty-two patients with primary osteoarthritis of the medial compartment of the knee were studied prospectively to assess the relationship between clinical results, limb alignment, and adduction moment of the knee. Clinical and radiographic examination and gait analyses were performed preoperatively and repeated at 6 months and at 1, 3, and 6 years after high tibial osteotomy. The preoperative peak adduction moment was high in 25 patients and low in seven. In both groups, the adduction moment of the knee decreased at 6 months after surgery but increased after that period. Alignment of the affected knee in both groups remained valgus after surgery (average femorotibial angle, 167 degrees-169 degrees). Clinical outcome in both groups improved after surgery and remained unchanged after 1 year. The peak adduction moment of the knee for the whole group significantly correlated with alignment and foot angle before and 6 years after surgery but did not correlate with stride length and walking velocity. In addition, only alignment was associated significantly with clinical results at 6 years. These results suggest that the preoperative peak adduction moment of the knee does not correlate with clinical or radiographic outcomes of high tibial osteotomy, provided sufficient valgus alignment is achieved at surgery.

Aged↗