[Cyclosporin A reverses steroid-resistance induced by P-glycoprotein in patients with SLE].
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ATP Binding Cassette Transporter, Subfamily B, Mem↗
Biomedical subjects
T Ota
Publications and source records attributed to T Ota.
[Comparison between intermittent antegrade warm blood cardioplegia and cold crystalloid cardioplegia in patients performed reoperation for valvular heart disease].
The purpose of this study was to compare the postoperative cardiac function and systemic effects between intermittent antegrade warm blood cardioplegia and cold crystalloid cardioplegia in patients performed reoperation for chronic acquired valvular heart disease. Group I consisted of 4 patients who underwent intermittent antegrade warm blood cardioplegia (MVR in 1, MVR + TAP in 2, DVR + TAP in 1), and Group II consisted of 5 patients who underwent intermittent antegrade cold crystalloid cardioplegia (MVR + TAP in 3, TVR in 2). There were no significant differences found between the two groups in operation time, perfusion time, aortic cross clamp time, spontaneous beating rate after declamping and reperfusion time. Also doses of inotropes required during weaning was almost the same for the both groups. But 24 hours after surgery, smaller doses of inotropes (4.4 +/- 2.1 gamma/kg/min) were required for Group 1, while larger doses (7.8 +/- 2.8 gamma/kg/min) were required for Group 2 (p < 0.05). As for the postoperative complications, none was noted in Group 1, while multiple organ failure in 2, hyperbilirubinemia in 2 and complete atrioventricular block in 1 patient was noted in Group 2. The above results suggest that, for reoperations of valvular heart disease, intermittent antegrade warm blood cardioplegia is a useful and reliable method with optimum myocardial protection as well as favorable systemic effects.
Adult↗
[Echo-guided extirpation of huge left atrial myxoma].
A 41-year-old male undergoing outpatient therapy for hypertension was to have a mass in the left atrium by echocardiography for screening. Transesophageal echocardiography did not identify the attachment of the tumor. The optimal approach to the tumor was determined depending on the findings of intraoperative echocardiography which well visualized the attachment of the tumor. The tumor, a large myxoma filling the most inner space of the left atrium, was extirpated via incisions in the right atrium and interatrial septum. Intraoperative echocardiography is an extremely useful method to determine the optimal approach for tumor resection. It is especially useful in cases of left atrial myxoma which has an unclear attachment on preoperative examination.
Adult↗
[Detection of anti-IgA alloantibody in a case of non-hemolytic transfusion reaction].
A 59-year-old man with myelodysplastic syndrome exhibited unticaria, dyspnea, fever, and hypotension immediately after the start of platelet concentrate (PC) transfusion on the 15th day of hospitalization. On the 17th and 21st day of hospitalization, the patient exhibited severe unticaria resembling that of erythroderma after the start of PC transfusion. Anti-IgA IgG antibody was detected by enzyme-linked immunosorbent assay (ELISA) on the 28th day of hospitalization. Anti-IgA (purified from pooled human plasma) was detected by Western blotting. The patient's IgA level was normal. No antibodies against HLA or platelet-specific antigens were detected in serum. The patient had no reaction to administration of washed PC. These findings suggest that anti-IgA antibody might have been responsible for the nonhemolytic transfusion reaction in this patient.
Antibodies, Anti-Idiotypic↗
[A study on the efficacy of combination chemoendocrine therapy consisting of cyclophosphamide, adriamycin, UFT, and tamoxifen for advanced or recurrent breast cancer].
The efficacy of the combination chemoendocrine therapy CAUT against advanced and recurrent breast cancer was examined. One course of this therapy lasted 3 weeks and consisted of adriamycin (i.v.) at 30 mg/m2 on day 1, cyclophosphamide (p.o.) at 65 mg/m2 and UFT (p.o.) at 300 mg/m2 on days 1-14, and tamoxifen (p.o.) at 20 mg/body on days 1-21. Twenty patients were enrolled, of whom 19 were eligible including seven with advanced cancer and 12 with recurrent cancer. One patient achieved CR, ten PR, three NC, and five PD, for a response rate of 58% (95% CI: 29-87%). The response rates according to type of lesion were 73% (8/11) for the soft tissue, 38% (3/8) for the bone, 20% (1/5) for the lungs and pleura, and 50% (2/4) for the liver. Adverse events with a severity of grade 3 or more included a reduction in WBC in six patients (31.6%), a reduction in RBC in one (5.3%), alopecia in four (21.1%), and severe general fatigue in one (5.3%). One patient experiencing a grade 4 reduction in WBC, and one of five patients experiencing a grade 3 reduction with a fever, recovered after treatment with G-CSF. The other four patients recovered following suspension of administration. This therapy is considered useful, exhibiting a high response rate and relatively slight adverse effects.
Adult↗
Crosslinking of CD44 on rheumatoid synovial cells augment interleukin 6 production.
CD44 is a ubiquitous molecule also known as hyaluronic acid or homing receptor. However, its cellular functions and its role in inflammation, for example rheumatoid synovitis, are currently unknown. Here we propose a novel function for CD44. Using synovial cells from patients with rheumatoid arthritis (RA), we demonstrated that CD44 crosslinking and binding to hyaluronan augmented IL-6 production. Briefly, we found that (a) rheumatoid synovial cells highly expressed CD44; (b) crosslinking of CD44 augmented IL-6 production and its mRNA transcription; (c) hyaluronan, especially when fragmented, also increased IL-6 production; and (d) CD44 activated the transcription factor activator protein-1 and CAMP-responsive element binding protein. These results indicate that the adhesion of RA synovial cells to matrices such as hyaluronic acid through CD44 could activate transcription factor, resulting in cytokine production. We therefore propose that the function of adhesion molecules as a signaling molecule may be pivotal in the pathogenesis of inflammation, including RA synovitis.
Arthritis, Rheumatoid↗
[Left and right atrial masses in a 67-year-old man with lone atrial fibrillation].
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Aged↗
Water channel AQP-1 in the primary cell culture of rat peritoneum.
To analyze the regulation of water channels in the peritoneum, we tried to establish a primary mesothelial cell culture system. Male Sprague-Dawley rats weighing about 250 g were anesthetized, and 10 mL of phosphate-buffered saline (PBS) containing 0.25% trypsin and 1 mmol/L ethylenediamine tetraacetic acid (EDTA) was infused into the peritoneal cavity for 15 minutes. Sediments from the recovered fluid were cultured in medium M199 supplemented with 10% fetal bovine serum (FBS). The culture was succeeded 4-6 times before experiments commenced. After exposure to the test medium, RNA was extracted and subjected to reverse transcriptase polymerase chain reaction (RT-PCR) for 10-19 cycles, then was measured by Southern blot analysis with a digoxin-labeled probe. Cultured cells were positively stained with mouse monoclonal anti-cytokeratin antibody, confirming their characteristics as mesothelial cells. Aquaporin-1 (AQP-1) message in the cultured cells increased with increases in glucose and mannitol concentrations when beta-actin message was used as an internal control. Tranexamic acid effected no change in AQP-1 message in the cultured mesothelial cells. This system offers potential as a simple approach to test the effects of osmolytes, cytokines, and vasoactive hormones on aquaporin expression and water transport in the peritoneum.
Animals↗
Human AIM-1: cDNA cloning and reduced expression during endomitosis in megakaryocyte-lineage cells.
The rat AIM-1 gene encoding an Aurora- and Ipl1-like midbody-associated protein serine/threonine kinase has a mitotic regulator function playing a key role in the onset of cytokinesis during mitosis. This report presents a cDNA sequence and megakaryocytic differentiation-dependent expression profile of the human AIM-1 gene. The nucleotide sequences of the human AIM-1 were identified from cDNAs of three cell lines, including cervical carcinoma HeLa cells, colorectal tumor SW480 cells, and normal human diploid skin fibroblast NHDF cells, and no mutation was found. The expression levels of AIM-1 transcript were markedly reduced during differentiation into megakaryocytic cell lineage in human leukemia cells induced by 12-o-tetradecanoyl-phorbol-13-acetate (TPA), suggesting that the downregulation of AIM-1 contributes to the differentiation by repeated duplication of DNA without cytokinesis (endomitosis).
Amino Acid Sequence↗
Multinuclearity and increased ploidy caused by overexpression of the aurora- and Ipl1-like midbody-associated protein mitotic kinase in human cancer cells.
Aurora- and Ipl1-like midbody-associated protein (AIM-1) is a serine/ threonine kinase that is structurally related to Drosophila aurora and Saccharomyces cerevisiae Ipl1, both of which are required for chromosome segregation. A kinase-negative form of AIM-1 inhibits the formation of cleavage furrow without affecting nuclear division, indicating that the gene controls entry into cytokinesis during M phase in mammalian cells. A human gene that encodes the protein AIM-1 was overexpressed in colorectal and other tumor cell lines. The regulation of AIM-1 expression was cell cycle dependent in normal and tumor cells, and the maximum accumulation was observed at G2-M. Exogenous overexpression of wild-type AIM-1 produced multinuclearity in human cells, suggesting that the excess amount of AIM-1 had a dominant-negative effect on the overexpressing cells. In long-term culture of AIM-1-overexpressing cells, multiple nuclei in a cell were occasionally fused, and then an increased ploidy and aneuploidy were induced. Thus, the overexpression of AIM-1 in colorectal tumor cell lines is thought to have a causal relationship with multinuclearity and increased ploidy. Cytokinesis error caused by AIM-1 overexpression is a major factor in the predisposition of tumor cells to the perturbation of chromosomal integrity that is commonly observed in human neoplasia. Thus, defects of pathways essential for mitotic regulation are important during human cancer development.
Amino Acid Sequence↗
Kainic acid-induced neuronal loss and glial changes in the hippocampal CA3 of p53-deficient mouse.
We examined kainic acid (KA)-induced neuronal death and changes in glial cells in p53-deficient (p53-/-) and wild-type (p53+/+) mice which were CBA and C57BL/6 background. The p53-/- mouse exhibited a KA-induced loss of CA3 pyramidal neurons similar to that in wild-type mouse. Before neuronal death, c-Jun protein was expressed, phosphorylated and translocated into several nuclei of CA3 pyramidal neurons. In p53-/- mouse, microglial activation was slightly faster and more continuous after 1-7 days than that in p53+/+ mouse. On the other hand, p53-/- astrocytes were relatively resistant to KA cytotoxicity, and marked astrocytosis also occurred after 7 days. These observations suggest that p53-null mutation may influence the activation and proliferation of glial cells rather than neuronal death.
Animals↗
Citrus auraptene exerts dose-dependent chemopreventive activity in rat large bowel tumorigenesis: the inhibition correlates with suppression of cell proliferation and lipid peroxidation and with induction of phase II drug-metabolizing enzymes.
In our previous short-term experiment, Citrus auraptene inhibited the development of azoxymethane (AOM)-induced aberrant crypt foci, which are precursor lesions for colorectal carcinoma. In the present study, the possible inhibitory effect of dietary administration of auraptene was investigated using an animal colon carcinogenesis model with a colon carcinogen AOM. Male F344 rats were given s.c. injections of AOM (15 mg/kg body weight) once a week for 3 weeks to induce colon neoplasms. They also received diets containing 100 or 500 ppm auraptene for 4 weeks in groups of "initiation" feeding, starting 1 week before the first dosing of AOM. The diets containing auraptene were also given to rats for 38 weeks in groups of "postinitiation" feeding. At the termination of the study (38 weeks), dietary administration of auraptene caused dose-dependent inhibition in AOM-induced large bowel carcinogenesis. Auraptene feeding during the initiation phase reduced the incidence of colon adenocarcinoma by 49% at 100 ppm (P = 0.099) and 65% at 500 ppm (P = 0.0075). Auraptene administration during the postinitiation phase inhibited the incidence of colon adenocarcinoma by 58% at 100 ppm (P = 0.021) and 65% at 500 ppm (P = 0.0075). Also, the multiplicity of colon carcinoma was significantly reduced by initiation feeding at a dose level of 500 ppm (P < 0.01) and postinitiation feeding at a level of 100 and 500 ppm (P < 0.05 and P < 0.01, respectively). Feeding of auraptene suppressed the expression of cell proliferation biomarkers (ornithine decarboxylase activity and polyamine content) in the colonic mucosa and reduced the production of aldehydic lipid peroxidation [malondialdehyde and 4-hydroxy-2(E)-nonenal]. In addition, auraptene increased the activities of Phase II drug-metabolizing enzymes (glutathione S-transferase and quinone reductase) in the liver and colon. These findings suggest that the inhibitory effects of auraptene on AOM-induced colon tumorigenesis at the initiation level might be associated, in part, with increased activity of Phase II enzymes, and those at the postinitiation stage might be related to suppression of cell proliferation and lipid peroxidation in the colonic mucosa.
Aldehydes↗
Alteration of proteins regulating apoptosis, Bcl-2, Bcl-x, Bax, Bak, Bad, ICH-1 and CPP32, in Alzheimer's disease.
Recently, apoptosis has been implicated in the selective neuronal loss of Alzheimer's disease (AD). Apoptosis is regulated by the B cell leukemia-2 gene product (Bcl-2) family (Bcl-2, Bcl-x, Bax, Bak and Bad) and the caspase family (ICH-1 and CPP32), with apoptosis being prevented by Bcl-2 and Bcl-x, and promoted by Bax, Bak, Bad, ICH-1 and CPP32. In the present study, we examined the levels of these proteins in the membranous and cytosolic fractions of temporal cortex in AD and control brain. In the membranous fraction, the levels of Bcl-2 alpha, Bcl-xL, Bcl-x beta, Bak and Bad were increased in AD. In the cytosolic fractions, the level of Bcl-x beta was increased, while Bcl-xL, Bax, Bak, and Bad and ICH-1L were unchanged. CPP32 was not detected in AD or control brain. These findings demonstrate a differential involvement of cell death-regulatory proteins in AD and suggest that Bak, Bad, Bcl-2 and Bcl-x are upregulated in AD brains.
Age Factors↗
Heparan sulfate proteoglycan on endothelium efficiently induces integrin-mediated T cell adhesion by immobilizing chemokines in patients with rheumatoid synovitis.
OBJECTIVE: To clarify the role of heparan sulfate proteoglycan (HSPG) and chemokines in integrin-mediated T cell adhesion to endothelial cells in the synovium of patients with rheumatoid arthritis (RA). METHODS: Endothelial cells were purified from RA synovium. Expression of heparan sulfate, chemokines, and adhesion molecules on the endothelium was assessed by immunohistochemical analysis or flow cytometry. The effects of chemokines and heparan sulfate on T cell adhesion to RA endothelium were estimated with relevant antibodies and signaling inhibitors. Production of chemokines from synovial T cells was detected by Northern blotting and enzyme-linked immunosorbent assay. RESULTS: The endothelium in RA synovium highly expressed HSPG. The soluble form of chemokines, macrophage inflammatory protein 1beta (MIP-1beta), induced T cell adhesion to the endothelial cells. When MIP-lalpha and MIP-1beta were immobilized on RA endothelial cells, a more efficient integrin-mediated adhesion of T cells was induced compared with their soluble form. The induced T cell adhesion was reduced by pretreatment with either heparitinase, anti-MIP-lalpha antibody, or anti-MIP-lbeta antibody, indicating that these chemokines were bound to heparan sulfate on the cells. T cell adhesion was also inhibited by pertussis toxin, wortmannin, and cytochalasin B. MIP-lalpha and MIP-1beta were found on vessels in RA synovium in vivo, which were spontaneously produced from T cells purified from RA synovium. CONCLUSION: Endothelial cells in RA synovium characteristically express HSPG, which is involved in T cell integrin triggering by "posting" chemokines, which are produced by synovial T cells, and by "relaying" them to their receptors on T cells, which activate G protein-dependent phosphoinositide 3-kinase and actin-dependent integrin triggering.
Arthritis, Rheumatoid↗
Relationship between skeletal uptake of 99mTc-HMDP and bone mineral density in elderly women.
The relationship between bone mineral density in elderly women and the pattern of skeletal uptake of 99mTc-HMDP, especially in regard to skull uptake, was investigated. The whole-body skeletal uptake (WBSU) and whole-body skeletal tracer distribution patterns were studied in 86 disease-free women on bone scintigraphy with 99mTc-hydroxy-methylene-diphosphonate (HMDP). Bone scans were quantified by setting regions of interest (ROI) and bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry in all patients. WBSU and the skeletal distribution pattern were compared with bone mineral densities of the entire skeleton as well as selected regions. WBSU was high in the elderly and negatively correlated with regional bone mineral densities (r = -0.403 to -0.534). Among the regions, uptake by the skull increased with age more than in other regions in women and had the highest negative correlation with the bone mineral density. The skull uptake correlated negatively with total body BMD (r = -0.583) and with lumbar BMD (r = -0.561, p < 0.0001). Our results show that increased radionuclide uptake in bone scintigraphy, especially skull uptake was associated with decreased bone mineral density in elderly women, so that, increased skull uptake in elderly women would be a scintigraphic sign of post-menopausal or senile osteopenia.
Absorptiometry, Photon↗
Interleukin-6 may play an important role in thrombopoiesis: a case of leukemic transformation from myelodysplastic syndrome.
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Blood Platelets↗
Effects of CD-832, a new calcium antagonist, on intracranial pressure in anesthetized dogs.
Effects of a new calcium antagonist, CD-832, on intracranial pressure (ICP), vertebral blood flow (VBF) and common carotid blood flow (CCBF) were investigated in dogs and the results were compared with findings for nifedipine and diltiaem. Dogs were anesthetized with sodium pentobarbital and a 20-gauge needle was inserted into the cisterna magna for ICP determination. Mean arterial blood pressure (MBP), heart rate (HR), CP, VBF and CCBF were measured before and during the continuous intravenous infusion of CD-832 (0.3, 1 and 3 microg/kg/min), nifedipine (0.1, 0.3 and 1 microg/kg/min) or diltiazem (1, 3 and 10 microg/kg/min). Although the three drugs caused a comparable hypotension, differences were evident in effects of these agents on ICP, VBF and CCBF. Nifedipine and diltiazem but not CD-832 significantly increased ICP, VBF and CCBF. These results suggest that CD-832 is a unique calcium antagonist which does not increase ICP during hypotension. Because the most evident side effects of calcium antagonists are caused by vasodilation and include headache and flushing, CD-832 may possibly be useful to treat subjects with hypertension or angina pectoris.
Anesthesia↗
Effect of flunitrazepam on sleep and memory.
Flunitrazepam's (FNZ) effect on sleep and memory 1 mg and 2 mg was investigated in 6 healthy volunteers (mean age 21.5 +/- 0.8 years) by polysomnography (PSG) and memory testing. A PSG was recorded on each study night. Memory testing was done before sleep (40 min after taking FNZ or placebo), and after waking (560 min after medication). Rapid eye movement (REM) latency was found to be prolonged on the FNZ 2 mg night (FNZ2N) compared to the baseline night (BN). Percentage of stage 2 sleep was increased in the FNZ2N as compared to BN, while REM percentage on both FNZ nights did not significantly differ from BN. The number of total REM and REM density were decreased in the FNZ2N compared to BN. Memory testing showed significant differences between before sleep and after waking on the FNZ2N. There was a significant correlation between the degree of impairment on memory testing and the rate of reduced REM density, but there was no significant correlation between degree of impairment on memory testing and the rate of increased non-REM sleep on the FNZ2N. The results of this study suggest that impairments in memory result from the dose of FNZ, and that there is a possibility of a relationship between memory disturbance and REM sleep suppression caused by this benzodiazepine.
Adult↗