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Biomedical subjects

S Imai

Publications and source records attributed to S Imai.

At least 55 records · Page 3Linked to original sources

[Effect of percutaneous transvenous mitral commissurotomy for the preservation of sinus rhythm in patients with mitral stenosis].

OBJECTIVES: Atrial fibrillation is frequently associated with mitral stenosis and is considered to be an unfavorable factor for the long-term prognosis. The efficacy of percutaneous transvenous mitral commissurotomy(PTMC) was examined for the preservation of sinus rhythm in patients with mitral stenosis after PTMC. METHODS: Long-term clinical data after PTMC were obtained from 71 patients who had undergone PTMC from March 1989 to September 1999. Eighteen patients in sinus rhythm before PTMC were divided into two groups: the SR group(n = 5) who remained in sinus rhythm, and the Af group(n = 13) who showed change from sinus rhythm to persistent or paroxysmal atrial fibrillation after PTMC. RESULTS: Age, sex, mitral valve area(1.4 +/- 0.3 vs 1.2 +/- 0.3 cm2), mean mitral pressure gradient(14.3 +/- 5.5 vs 12.6 +/- 5.9 mmHg), mean left atrial pressure(15.9 +/- 7.6 vs 19.0 +/- 7.7 mmHg), left ventricular end-diastolic pressure(7.5 +/- 2.8 vs 9.3 +/- 3.9 mmHg), left ventricular end-diastolic volume index(77 +/- 13 vs 82 +/- 14 ml/m2), left ventricular ejection fraction(60 +/- 6% vs 55 +/- 4%) and cardiac output(5.1 +/- 0.4 vs 4.9 +/- 0.8 l/m2) before PTMC were not different between the two groups. Changes in mean mitral pressure gradient, mean left atrial pressure and cardiac output immediately after PTMC were not different statistically. Mitral valve area immediately after PTMC was significantly greater in the SR group compared to the Af group(2.3 +/- 0.3 vs 1.8 +/- 0.3 cm2, p < 0.05). The change in mitral valve area was also greater in the SR group(1.0 +/- 0.2 vs 0.6 +/- 0.4 cm2, p < 0.05), but there was no statistical difference in the percentage change of mitral valve area between before and immediately after PTMC(SR group 78 +/- 35% vs Af group 50 +/- 35%). End-diastolic pressure, end-diastolic volume index and ejection fraction immediately after PTMC were not statistically different. CONCLUSIONS: The final mitral valve area immediately after PTMC in the patients with mitral stenosis in sinus rhythm, but not the changes of mean mitral pressure gradient, mean left atrial pressure or cardiac output, is important for the maintenance of sinus rhythm.

Adult↗

[Whole-body MR imaging for evaluation of bone marrow cellularity in aplastic anemia].

The aim of this study was to investigate the usefulness of whole-body MRI(WB-MRI) in the evaluation of cellularity in bone marrow and the distribution of fatty marrow in aplastic anemia. WB-MRI was performed on five patients with aplastic anemia who ranged in age from 62 to 70 years of age, and on four controls with malignant lymphoma who ranged in age from 59 to 67 years. Coronal images were obtained using a body coil with an FOV of 48 cm x 48 cm, and with both fast short T1 inversion recovery(STIR) and spin-echo T1-weighted(T1-WI) in three regions: (1) head to thorax, (2) abdomen to pelvis, and (3) lower extremities. The findings on WB-MRI were compared with those of histological studies of bone marrow at the sternum and the posterior iliac crest. The results were as follows: (1) there was a correlation between the cellularity of histological studies of bone marrow and signal intensity on WB-MRI; (2) WB-MRI could detect the activity of bone marrow; and (3) in a comparison of signal intensity in aplastic anemia and control subjects, there were differences of signal intensity in the central marrow.

Aged↗

[Significance of soluble thrombomodulin in the coronary circulation of patients with coronary artery disease].

OBJECTIVES: The relationship between plasma levels of soluble thrombomodulin, a probable marker for endothelial damage, and the severity of coronary atherosclerosis was investigated. METHODS: Plasma soluble thrombomodulin levels were evaluated in 160 patients(mean age 62 +/- 11 years) who underwent coronary angiography. Blood samples were obtained from the peripheral vein, ostium of the left coronary artery and coronary sinus. The levels of plasma thrombomodulin were measured by enzyme-linked immunosorbent assay. The change of thrombomodulin level in the coronary circulation (delta TM) was calculated as the coronary sino-arterial difference. Patients were classified into four groups according to the number of diseased vessels, and the severity of coronary atherosclerosis was evaluated with the modified Gensini score. RESULTS: Coronary sinus levels of thrombomodulin were significantly higher in the two or more vessel disease(VD) groups than in the no or one VD groups(p < 0.05). delta TM were significantly higher in the 2VD than in the 0VD groups(p < 0.05), and higher in the 3VD than in the 0VD or 1VD groups(p < 0.05). delta TM showed positive correlation with Gensini score for left coronary arteries(r = 0.347, p < 0.0001). CONCLUSIONS: The increment of thrombomodulin across the coronary circulation was significantly correlated with the severity of coronary atherosclerosis, suggesting a close association between the progression of coronary atherosclerotic stenosis and damage to the endothelial surface.

Aged↗

[Measurements of cerebral blood flow by the noninvasive microsphere method with 123I-IMP and fan beam collimator: comparison with the continuous arterial blood sampling method].

PURPOSE AND METHODS: The noninvasive microsphere (NIMS) method quantifies cerebral blood flow with N-isopropyl-p-[123I]-iodoamphetamine (123I-IMP) without blood sampling of a patient, but when a fan beam collimator is used for collecting raw data in single photon emission computed tomography (SPECT), the procedure is complicated because we have to change the collimator. In phantom and clinical studies we investigated the validity of using a fan beam collimator in collecting planar and SPECT raw data. RESULTS: The phantom study suggested that using a fan beam collimator for planar imaging was feasible because of the image magnification rate and the count rate. Mean cerebral blood flow (mCBF) values obtained by the NIMS method with the fan beam collimator were compared with mCBF simultaneously estimated from the conventional continuous arterial blood sampling (microsphere: MS) method in twenty patients with ischemic cerebral vascular diseases. There was good correlation (y = 1.033x + 8.004, r2 = 0.729, p < 0.01) in mCBF between the fan beam NIMS method and the MS method. CONCLUSION: In conclusion, this method for the measurement of CBF was acceptable for routine clinical studies.

Brain Ischemia↗

The biological activity of ABA-1-like protein from Ascaris lumbricoides.

The elevation of non-specific IgE (total IgE) in Ascaris infection can be seen one week after infection, and reaches a peak after approximately two weeks. It has been reported that ABA-1 protein is the main constituent in the pseudocoelomic fluid of Ascaris suum. To investigate the effect of the ABA-1-like protein from Ascaris lumbricoides (ALB), the cDNA was cloned by reverse transcriptase polymerase chain reaction, using original primers based on the consensus sequences of ABA-1 and TBA-1, that is an ABA-1-like protein from Toxocara canis. The clone was sequenced, we constructed the recombinant polyprotein of ALB (rALB14 and rALB7) based on the ALB sequence, and rALB was administrated to BALB/c mice. Fourteen days after inoculation with rALB14 which is the full length of ALB, the elevation of total IgE which we supposed to contain non-specific IgE was observed, and the results were as we expected. Furthermore, in an in-vitro experiment, we confirmed that the spleen cells proliferated when stimulated by rALB14 and concanavalin A. Therefore, the whole conformation of ALB is considered to be involved in the elevation of non-specific IgE, and is involved in the activation of T cells.

Allergens↗

Modulation of NMDA- and (+)TAN-67-induced nociception by GABA(B) receptors in the mouse spinal cord.

The present study was designed to investigate the effect of a selective GABA(B) receptor agonist baclofen on the pain-like nociceptive behavior (scratching, biting and licking) induced by intrathecal (i.t.) injection of N-methyl-D-aspartate (NMDA) or (+)TAN-67, the enantiomorphs of 2-methyl-4aalpha-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12aalpha-octahydro-quinolino[2,3,3g]isoquinoline (TAN-67), in the mouse. NMDA (0.05-0.2 microg/mouse) given i.t. immediately caused nociception in a dose-dependent manner. The nociception was significantly antagonized by i.t. co-injection with dizocilipine (0.1-1.0 microg/mouse), a non-competitive NMDA receptor antagonist. I.t. co-injection with baclofen (37.5-150 ng/mouse) significantly reduced the NMDA-induced nociceptive behavior in a dose-dependent fashion. The inhibition produced by baclofen was completely reversed by a selective GABA(B) receptor antagonist 2-hydroxysaclofen (0.15 and 0.3 microg/mouse). An i.t. injection of (+)TAN-67 at doses of 3.75-15 microg/mouse elicited a long-lasting and a dose-related nociception. The nociceptive behavior induced by (+)TAN-67 given i.t. was markedly suppressed by i.t. co-injection with baclofen (3-30 ng/mouse), and the inhibitory effect of baclofen was prevented by i.t. injection of 2-hydroxysaclofen (1 and 3 microg/ mouse). In addition, the (+)TAN-67-induced nociception was also attenuated by i.t. co-injection with dizocilipine (0.1-1.0 microg/mouse). These results suggest that spinal GABA(B) receptors may be implicated in the expression of nociception elicited by i.t. injection of either NMDA or (+)TAN-67 in the mouse.

Analgesics↗

Epstein-Barr virus lacking glycoprotein gp85 cannot infect B cells and epithelial cells.

To evaluate whether the BXLF2 gene of Epstein-Barr virus (EBV), which codes gp85 protein, is essential for infection of B cells and epithelial cells, we analyzed the infectivity of an EBV recombinant lacking gp85. The cells that were infected with the BXLF2-disrupted virus were unable to express gp85 proteins that could be detected by mouse monoclonal antibody E1D1, specific for gp85/gp25 complexes. The BXLF2-disrupted EBV had the ability to attach to, but not infect, B cells. On the other hand, the same virus failed to bind to and infect NU-GC-3, a human gastric adenocarcinoma cell line that is susceptible to EBV infection. The results indicate that the gp85 is used for infection of not only B cells but also epithelial cells and suggest that the gp85 is necessary for attaching the virus to epithelial cells.

Animals↗

A HER2/NEU-derived peptide, a K(d)-restricted murine tumor rejection antigen, induces HER2-specific HLA-A2402-restricted CD8(+) cytotoxic T lymphocytes.

We have identified an H-2K(d)-binding peptide, HER2p780 (PYVSRLLGI), derived from murine HER2/neu (HER2), that can induce HER2-specific murine cytotoxic T lymphocytes (CTL). Weekly vaccination of BALB/c mice by syngeneic dendritic cells pulsed with HER2p780 peptide, entirely common to murine and human HER2, suppressed growth of pretransplanted HER2-expressing syngeneic tumors. A HER2-expressing human cancer cell line SKOV3 transfected with murine H-2K(d) cDNA could also be lysed by HER2p780-specific murine CTLs, indicating that human HER2-expressing cancer cells can process and present the cognate peptide in the context of H-2K(d). Since H-2K(d) and HLA-A2402 molecules have similar anchor motifs, the possibility of inducing HER2-specific CTL activity with HER2p780 in HLA-A2402 individuals was examined. CD8(+) CTL clones specific for HER2-expressing cancer cell lines were established from peripheral blood lymphocytes with HLA-A2402 by repeatedly sensitizing with peptide-pulsed autologous dendritic cells as well as peripheral blood mononuclear cells. Detailed analysis of their specificity revealed that the cytotoxicity of CTL clones is specific for the cognate peptide with HLA-A2402 restriction. The results suggest that HER2p780 is a unique peptide that may function as a tumor rejection antigen peptide in HLA-A2402 individuals, as it was directly proven here to function in a murine tumor system.

Animals↗

Possible site of action of TAK-637, a tachykinin NK(1) receptor antagonist, on the micturition reflex in guinea pigs.

TAK-637((aR,9R)-7-[3,5-bis(trifluoromethyl)benzyl]-8,9,10, 11-tetrahydro-9-methyl-5-(4-methylphenyl)-7H-[1,4]diazocino[2,1-g] [1,7]naphthyridine-6,13-dione) is a novel tachykinin NK(1) receptor antagonist that has been shown to inhibit the micturition reflex in guinea pigs. The aim of this study was to clarify its mechanism of action in guinea pigs. TAK-637 inhibited the spinal vesico-vesical reflex induced by electrical stimulation of the proximal cut end of the pelvic nerve in spinal animals, but not bladder contractions induced by electrical stimulation of the distal cut end of the nerve. Furthermore, TAK-637 had no effect on carbachol- or electrical field stimulation-induced contractions of isolated bladder muscle strips in an organ bath, whereas drugs used for abnormally frequent micturition inhibited both contractions. These results suggest that TAK-637 inhibits the micturition reflex by acting, at least in part, on the spinal cord, and its mechanism of action clearly differs from those of antimuscarinics or spasmolytics.

Animals↗

PCCX1, a novel DNA-binding protein with PHD finger and CXXC domain, is regulated by proteolysis.

We identified a novel gene PCCX1 that encoded a nuclear protein carrying a PHD finger, a CXXC domain, and an acidic region. The CXXC domain was found to be sufficient for binding to DNA. The acidic region exhibited a high transactivation ability, but the full-length protein was inactive due to regions which inhibited the acidic region, including the C-terminal region. We examined the expression of PCCX1 during cellular aging and immortalization of SV40-transformed human fibroblasts. PCCX1 mRNA was expressed constitutively through stages of cellular aging and immortalization, but at the protein level, a shorter form lacking the C-terminal region appeared as the cells approached crisis. These results suggested that PCCX1 was activated by proteolytic cleavage, which removed the C-terminal inhibitory region.

Amino Acid Sequence↗

Effects of TAK-637, a tachykinin receptor antagonist, on the micturition reflex in guinea pigs.

The effects of a new tachykinin NK(1) receptor antagonist, (aR, 9R)-7-[3,5-bis(trifluoromethyl)benzyl]-8,9,10, 11-tetrahydro-9-methyl-5-(4-methylphenyl)-7H-[1,4]diazocino[2,1-g] [1, 7]naphthyridine-6,13-dione (TAK-637), on the micturition reflex were compared with those of drugs used for abnormally frequent micturition or incontinence. TAK-637 showed a characteristic effect on the distension-induced rhythmic bladder contractions in guinea pigs. The systemic administration of TAK-637 decreased the number but not the amplitude of the distension-induced rhythmic bladder contractions. A similar effect was observed in animals in which the spinal cord had been severed. TAK-637 also inhibited the micturition reflex induced by topical application of capsaicin onto the surface of bladder dome. From these results, it is concluded that TAK-637 inhibits sensory transmissions from the bladder evoked by both physiological and nociceptive stimuli by blocking tachykinin NK(1) receptors, possibly at the level of the spinal cord. On the other hand, the other drugs such as oxybutynin, tolterodine, propiverine, and inaperisone showed no effects on the frequency of the distension-induced rhythmic bladder contractions but decreased the contraction amplitude. Therefore, TAK-637 may represent a new class of drugs, which would be effective for abnormally frequent micturition without causing voiding difficulties due to decreased voiding pressure.

Animals↗

PEBP2alphaA/CBFA1 mutations in Japanese cleidocranial dysplasia patients.

Cleidocranial dysplasia (CCD) is an autosomal dominant human bone disease whose genetic locus has been located on chromosome 6p21, where the PEBP2alphaA/CBFA1 gene essential for osteogenesis also maps. Previously, several heterozygous mutations in PEBP2alphaA/CBFA1 were found in CCD patients. In this study, we identified six different types of mutations in PEBP2alphaA/CBFA1 in Japanese CCD patients. Four cases were similar to those reported previously: two were nonsense mutations in the Runt domain, one was a hemizygous deletion, and the other was a missense mutation in the Runt domain which abolished the DNA-binding activity of Runx2/PEBP2alphaA/CBFA1. The remaining two mutations were novel: one had a heterozygous gt-to-tt mutation at the splice donor site (gt) between the exon3-intron junction, which resulted in abnormal exon3 skipping, and the other had a mutation in exon7, which led to the introduction of a translational stop codon in the middle of the transactivation domain. Thus, defects in either the DNA-binding domain or transactivation domain of Runx2/PEBP2alphaA/CBFA1 can cause CCD. The results not only provide a strong genetic evidence that mutations involving in PEBP2alphaA/CBFA1 contribute to CCD, but also provide a useful tool to study how Runx2/PEBP2alphaA/CBFA1 plays its pivotal role during osteoblastic differentiation.

Amino Acid Substitution↗

Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase.

Yeast Sir2 is a heterochromatin component that silences transcription at silent mating loci, telomeres and the ribosomal DNA, and that also suppresses recombination in the rDNA and extends replicative life span. Mutational studies indicate that lysine 16 in the amino-terminal tail of histone H4 and lysines 9, 14 and 18 in H3 are critically important in silencing, whereas lysines 5, 8 and 12 of H4 have more redundant functions. Lysines 9 and 14 of histone H3 and lysines 5, 8 and 16 of H4 are acetylated in active chromatin and hypoacetylated in silenced chromatin, and overexpression of Sir2 promotes global deacetylation of histones, indicating that Sir2 may be a histone deacetylase. Deacetylation of lysine 16 of H4 is necessary for binding the silencing protein, Sir3. Here we show that yeast and mouse Sir2 proteins are nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylases, which deacetylate lysines 9 and 14 of H3 and specifically lysine 16 of H4. Our analysis of two SIR2 mutations supports the idea that this deacetylase activity accounts for silencing, recombination suppression and extension of life span in vivo. These findings provide a molecular framework of NAD-dependent histone deacetylation that connects metabolism, genomic silencing and ageing in yeast and, perhaps, in higher eukaryotes.

Acetylation↗

A novel human HER2-derived peptide homologous to the mouse K(d)-restricted tumor rejection antigen can induce HLA-A24-restricted cytotoxic T lymphocytes in ovarian cancer patients and healthy individuals.

A mouse HER2-derived peptide, HER2p63 (A) (TYLPANASL), can induce K(d)-restricted mouse cytotoxic T lymphocytes (CTL) and also function as a tumor rejection antigen in an in vivo assay. Since the anchor motif of mouse K(d) for peptide binding has much similarity to that of human HLA-A2402, we asked if human HER2p63 (T) (TYLPTNASL) could induce HER2-specific CTL in HLA-A2402-positive individuals. Peripheral blood mononuclear cells (PBMC) of HLA-A2402-positive individuals were sensitized in vitro with HER2p63-pulsed autologous dendritic cells prepared from PBMC. CTL clone derived from these specifically lysed HER2-expressing cell lines bearing HLA-A2402. Cytotoxic activity of the CTL clone against the HER2-expressing cell line bearing HLA-A2402 was blocked by antibodies against CD3, CD8, HLA-A24 or MHC class I, and was also inhibited by the addition of excess HER2p63-pulsed C1R bearing HLA-A2402. Killer cells were generated from PBMC of seven healthy individuals and five ovarian cancer patients, all of HLA-A2402 type, by in vitro sensitization with HER2p63-pulsed autologous antigen presenting cells. These killer cells selectively lysed HER2-expressing SKOV3 transfected with HLA-A2402 cDNA, indicating high immunogenicity of HER2p63 in all 12 individuals examined.

Animals↗

Lytic Epstein-Barr virus infection in the synovial tissue of patients with rheumatoid arthritis.

OBJECTIVE: To evaluate the existence of Epstein-Barr virus (EBV) infection in the synovial tissue of patients with rheumatoid arthritis (RA). METHODS: Synovial tissues were obtained at synovectomy or arthroplasty from 32 patients with RA and 30 control patients with osteoarthritis (OA). EBV DNA was detected by Southern blot hybridization and/or polymerase chain reaction (PCR) amplification. To localize the EBV-infected cells, tissue sections were studied by RNA in situ hybridization (ISH) for the EBV-encoded small RNA 1 (EBER-1), by DNA ISH for the Bam HI W region of EBV DNA, and by immunohistochemistry for EBV lytic proteins BZLF1 and gp350/220. RESULTS: EBV DNA was detected by PCR in 15 of the 32 samples from RA patients (47%), but in none of those from the 30 OA patients (P < 0.01). Of the 15 PCR-positive samples, 9 contained >1 EBV copy/1,000 cells (referred to as EBV 2+), and 6 contained 1 copy/1,000-5,000 cells (EBV 1+). Among the 9 EBV 2+ samples, 3 were also positive for EBV DNA by Southern blot hybridization, 5 were positive for EBER-1 by RNA ISH, and 3 were positive for EBV DNA by DNA ISH. Immunohistochemical analysis showed positive signals in all samples for BZLF1 and in 7 samples for gp350/ 220. In each examination, the positive signals were detected not only in lymphocytes, but also in synovial lining cells. CONCLUSION: EBV was frequently detected in the synovial tissue of RA patients. The infected cells were both lymphocytes and synovial cells, and expressed EBV proteins associated with virus replication. These findings suggest that EBV may play a role in the pathogenesis of RA.

Adult↗

Rapid-growing carcinosarcoma of the esophagus arising from intraepithelial squamous cell carcinoma: report of a case.

A case of carcinosarcoma arising from the intraepithelial spreading area of esophageal squamous cell carcinoma (SCC) is reported herein. A 64-year-old man was referred to our hospital for investigation of a sore throat and dysphagia. An endoscopic examination revealed a 2. 5-cm polypoid mass in the mid-esophagus. Esophagograms taken 1 month prior to consultation by our hospital and just before surgery revealed marked change within a period of less than 2 months from a 2-cm sessile elevated mass to a 4-cm polypoid mass with a lobular appearance. The resected specimen contained two lesions in the esophagus. The larger one measured 4.0 x 2.0 x 2.0 cm and had a pedunculated polypoid shape, while the smaller one, measuring 1 cm in diameter, was a plateau-type elevated lesion located 3 cm distal from the larger mass. Histologically, the distal smaller lesion was diagnosed as primary SCC associated with a high frequency of intraepithelial spread, while the larger polypoid mass was composed of spindle-shaped sarcomatous cells, arising from the intraepithelial spread of SCC. To our knowledge, this is the only reported case of esophageal carcinosarcoma arising from an area of intraepithelial spread of SCC that showed such surprisingly rapid growth.

Carcinoma in Situ↗

Expression of glucocorticoid receptor beta in lymphocytes of patients with glucocorticoid-resistant ulcerative colitis.

BACKGROUND & AIMS: Recently, the glucocorticoid receptor beta (hGRbeta) was suggested to play a role as a dominant negative regulator for determining glucocorticoid response. The aim of this study was to clarify whether reverse-transcription polymerase chain reaction (RT-PCR) analysis of hGRbeta messenger RNA (mRNA) can predict the response to glucocorticoids in patients with ulcerative colitis. METHODS: Total RNA obtained from peripheral blood mononuclear cells (PBMCs) of 23 patients with ulcerative colitis and 20 healthy volunteers was reverse transcribed; the resulting complementary DNA was amplified using specific primers for hGRalpha and hGRbeta. Protein expression of hGR in PBMCs was confirmed by immunoprecipitation-Western blot analysis. RESULTS: The expression of hGRalpha mRNA (477 base pairs) was detected in all patients and all healthy volunteers. In contrast, a hGRbeta mRNA (366 base pairs) was detected in 1 (9.1%) of 11 glucocorticoid-sensitive patients, 10 (83.3%) of 12 glucocorticoid-resistant patients, and 2 (10%) of 20 healthy volunteers. The positive rate of hGRbeta mRNA in the resistant group was significantly higher than that in the sensitive group (P = 0.0019). The hGRbeta band could be detected by immunoprecipitation-Western blotting in hGRbeta mRNA-positive patients. CONCLUSIONS: The results show that the expression of hGRbeta mRNA in PBMCs examined by RT-PCR may serve as a novel predictor of glucocorticoid response in ulcerative colitis.

Adolescent↗