Search PubMed⌕ Search

Biomedical subjects

S Imamura

Publications and source records attributed to S Imamura.

At least 109 records · Page 6Linked to original sources

Clinical observations on acute low-tone sensorineural hearing loss. Survey and analysis of 137 patients.

We retrospectively analyzed the clinical records of 137 patients who were treated at our clinic for acute low-tone sensorineural hearing loss of unknown cause over a period of 8 years. The analyses of the clinical records indicated the following clinical characteristics: female preponderance; peak incidence during the fourth decade of life; frequent accompanying tinnitus, sensation of ear fullness, and/ or autophony; suspicion of bilateral involvement; and association with autonomic imbalance. The hearing in most of the patients completely recovered, but some selected patients experienced fluctuating hearing loss or progression to Meniere's disease. Our results suggest that a subgroup of patients with severe initial hearing loss should be carefully followed up, although it is difficult to predict the outcome of this disorder.

Acute Disease↗

Electrophysiologic effects of nitrous oxide, a volatile anesthetic, in dogs following myocardial infarction in comparison with other anesthetics.

The present study was undertaken to examine the electrophysiologic effects of nitrous oxide in the dog heart after inducing myocardial infarction, and to compare these with those of other anesthetics. Myocardial infarction was produced by two-stage ligation of the left anterior descending coronary artery in dogs. Seven days after ligation, bipolar electrodes were sutured on the ventricular surface of the infarcted and normal regions for applying electrical stimulation or recording ventricular activation. Ventricular activation time and QT interval on the bipolar electrocardiogram and PQ interval from the standard limb lead II were measured during atrial pacing. Nitrous oxide 80% did not significantly prolong ventricular activation time, PQ interval or QT interval. However, halothane 1 minimum alveolar concentration (MAC), thiopental 5 and 10 mg/kg and fentanyl 30 microg/kg did prolong ventricular activation time; thiopental and fentanyl prolonged the QT interval. Nitrous oxide did not potentiate the effects of fentanyl. Therefore, electrophysiologic effects of nitrous oxide are much weaker compared with those of thiopental, fentanyl or halothane.

Anesthetics, Inhalation↗

Evoked potentials in patients with chronic respiratory insufficiency.

P300, somatosensory evoked potential (SEP) and brainstem auditory evoked potential (BAEP) are widely used neurophysiological methods for objectively evaluating cognitive, somatosensory and brainstem auditory functions. We studied the P300, SEP and BAEP in 17 patients with chronic respiratory insufficiency (PaO2:58.2 +/- 7.0 mmHg; mean +/- SD) and 15 age-matched healthy subjects (PaO2: 84.4 +/- 11.3 mmHg). The latency and amplitude of P300, the N9 latency, N9-N13 and N13-N20 interpeak latencies (IPL) in SEP, wave I latency and I-V IPL in BAEP were compared between the patients and controls. The P300 latency, N9-N13 and N13-N20 IPLs in SEP in the patients were significantly prolonged compared to the controls. In contrast, the amplitude of P300, N9 latency in SEP, wave I latency and I-V IPL in BAEP were not significantly different between the patients and controls. These results suggest that chronic respiratory insufficiency influences the cognitive and somatosensory functions, and indicate that there is a selective vulnerability of evoked potentials to this condition.

Aged↗

Werner's syndrome--chromosome analyses of cultured fibroblasts and mitogen-stimulated lymphocytes.

Two cases of Werner's syndrome are reported. Fibroblasts derived from both patients revealed reduced population doubling numbers. Chromosomal analyses for fibroblasts from both patients and lymphocytes from one patient revealed that chromosomal aberrations occur frequently and randomly. Although some of the chromosomal aberrations involved sites where tumour suppressor genes have been mapped, neither of our patients demonstrated malignancy. Chromosomal aberration at one critical site may not be sufficient to induce cancer or additional factors may be necessary.

Cell Culture Techniques↗

Mosaic expression of uncein and 180-kDa bullous pemphigoid antigen in generalized atrophic benign epidermolysis bullosa.

Immunofluorescence microscopy of epidermodermal junction components in serial cryosections from the perilesional skin of a patient with generalized atrophic benign epidermolysis bullosa (GABEB) showed broken line-like staining of both BPAG2 (180-kDa bullous pemphigoid antigen) and uncein (antigen of 19-DEJ-1 monoclonal antibody), whereas integrin alpha 6 and laminin 5 were continuously expressed along the basement membrane zone. Immunoelectron microscopy revealed a mosaic distribution of the BPAG2/uncein positive and negative cells. BPAG2, a candidate protein of GABEB, probably has a close connection with uncein, and anchoring filament component.

Adult↗

In vivo evidence of the critical role of cadherin-5 in murine vascular integrity.

Vascular endothelial cell-cell adhesion is crucial for the regulation of vascular functions and is associated with many circulatory disorders. We isolated a rat monoclonal antibody (VECD1) recognizing the mouse vascular endothelial cell adhesion molecule and found that it inhibited vascular endothelial cell-cell association. We sequenced a full-length cDNA of the antigen that was identical to mouse cadherin-5. L-cells transfected with its cDNA acquired cell-cell adhesiveness, and these transfectants reacted with VECD1 at cell-cell contact areas. We studied the role of mouse cadherin-5 in vascular functions. The addition of VECD1 antibody to a cultured vascular endothelial cell line (F-2) caused the detachment of each cell. Although normal F-2 cells formed tubular structures on Matrigel, VECD1 disturbed the tubulogenesis. VECD1 also increased the permeability through the F-2 cell layer. To clarify the in vivo function of mouse cadherin-5, we intraperitoneally injected the hybridomas producing VECD1 into adult mice. Severe venous stasis and subcutaneous hemorrhage were induced within several days after the injection, resulting in the early death of the animals. These findings are evidence of an essential role of cadherin-5 in the regulation of vascular endothelial cell-cell adhesion in vivo.

Abdominal Muscles↗

Molecular cytogenetic diagnosis of Williams syndrome.

Williams syndrome (WS) is characterized by distinct facial changes, growth deficiency, mental retardation, and congenital heart defect (particularly supravalvular aortic stenosis), associated at times with infantile hypercalcemia. Molecular genetic studies have indicated that hemizygosity at the elastin locus (7q11.23) causes WS. The purpose of this study was to confirm that this regional deletion, involving the elastin locus, is the cause of WS in Japan, and to clarify the correlation between the phenotype and the elastin locus. Thirty-two patients with WS and thirty of their relatives were examined by fluorescent in situ hybridization (FISH), using the WS chromosome region (WSCR) probe. All patients had cardiovascular disease (100%), 30 had typical WS facial changes (94%), 31 had mental retardation or developmental delay (97%), 16 were small-for-date at birth (50%), 14 had short stature (44%), and 13 had dental anomalies (41%). No relatives showed any manifestation of WS. Hemizygosity for a region of 7q11.23, involving the elastin locus, was found in all WS patients, but was not found in the 30 relatives.

Adolescent↗

CD34+ hematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to GM-CSF+TNF alpha.

Human dendritic cells (DC) can now be generated in vitro in large numbers by culturing CD34+ hematopoietic progenitors in presence of GM-CSF+TNF alpha for 12 d. The present study demonstrates that cord blood CD34+ HPC indeed differentiate along two independent DC pathways. At early time points (day 5-7) during the culture, two subsets of DC precursors identified by the exclusive expression of CD1a and CD14 emerge independently. Both precursor subsets mature at day 12-14 into DC with typical morphology and phenotype (CD80, CD83, CD86, CD58, high HLA class II). CD1a+ precursors give rise to cells characterized by the expression of Birbeck granules, the Lag antigen and E-cadherin, three markers specifically expressed on Langerhans cells in the epidermis. In contrast, the CD14+ progenitors mature into CD1a+ DC lacking Birbeck granules, E-cadherin, and Lag antigen but expressing CD2, CD9, CD68, and the coagulation factor XIIIa described in dermal dendritic cells. The two mature DC were equally potent in stimulating allogeneic CD45RA+ naive T cells. Interestingly, the CD14+ precursors, but not the CD1a+ precursors, represent bipotent cells that can be induced to differentiate, in response to M-CSF, into macrophage-like cells, lacking accessory function for T cells. Altogether, these results demonstrate that different pathways of DC development exist: the Langerhans cells and the CD14(+)-derived DC related to dermal DC or circulating blood DC. The physiological relevance of these two pathways of DC development is discussed with regard to their potential in vivo counterparts.

Antigens, CD1↗

Keratin 9 point mutation in the pedigree of epidermolytic hereditary palmoplantar keratoderma perturbs keratin intermediate filament network formation.

Keratins form an intracellular keratin filament network in keratinocytes. Point mutations in the epidermal keratins could lead to the disruption of keratin filament formation, developing skin diseases such as epidermolytic hereditary palmoplantar keratoderma (EHPPK). We found a G to A transition in keratin 9 (K9) cDNA, resulting in the substitution of glutamine for arginine at 162, in all patients of a pedigree of EHPPK. Transfection into MDCK cells and DJM-1 cells revealed that the plasmid CMX vector containing normal keratin 9 cDNA showed normal keratin network formation, whereas the vector with a G to A point mutated keratin 9 cDNA showed disrupted keratin filaments with droplet formation in the cells. These results indicate that the point mutation seen in our patients had a dominant-negative effect on keratin network formation.

Amino Acid Sequence↗

The human OX40/gp34 system directly mediates adhesion of activated T cells to vascular endothelial cells.

Fresh leukemic cells from patients with adult T cell leukemia (ATL) and some ATL-derived T cell lines show adhesion to human umbilical vein endothelial cells (HUVECs) mainly through E-selectin, but a proportion of this binding remains unaffected by the addition of combinations of antibodies against known adhesion molecules. By immunizing mice with one of such cell lines, we established monoclonal antibodies (mAbs), termed 131 and 315, that recognize a single cell surface antigen (Ag) and inhibit the remaining pathway of the adhesion. These mAbs did not react with normal resting peripheral blood mononuclear cells (PBMC) or most of the cell lines tested except for two other human T cell leukemia virus type I (HTLV-I)-infected T cell lines. After stimulation with phytohemagglutinin (PHA), PBMC expressed Ag 131/315 transiently, indicating that these mAbs define a T cell activation Ag. Western blotting and immunoprecipitation revealed that Ag 131/315 has an apparent molecular mass of 50 kD. Expression cloning was done by transient expression in COS-7 cells and immunological selection to isolate a cDNA clone encoding Ag 131/315. Sequence analysis of the cDNA indicated that it is identical to human OX40, a member of the tumor necrosis factor/nerve growth factor receptor family. We then found that gp34, the ligand of OX40, was expressed on HUVECs and other types of vascular endothelial cells. Furthermore, it was shown that the adhesion of CD4+ cells of PHA-stimulated PBMC to unstimulated HUVECs was considerably inhibited by either 131 or 315. Finally, OX40 transfectants of Kit 225, a human interleukin 2-dependent T cell line, were bound specifically to gp34 transfectants of MMCE, a mouse epithelial cell line, and this binding was blocked by either 315 or 5A8, an anti-gp34 mAb. These results indicate that the OX40/gp34 system directly mediates adhesion of activated T cells or OX40+-transformed T cells to vascular endothelial cells.

Animals↗

Characterization of p53 gene mutations in basal-cell carcinomas: comparison between sun-exposed and less-exposed skin areas.

Mutations in the p53 gene in 32 basal-cell carcinomas (BCC) developed in Japanese patients were identified by the polymerase chain reaction and single-strand-conformation polymorphism analysis, followed by sequencing the DNA. Among 16 BCC developed in continuously sun-exposed areas, 6 tumors showed 7 base substitutions, most of which were G:C to A:T transitions, mainly at the dipyrimidine sites. Seven out of 16 BCC developed in less-exposed areas showed 8 base substitutions, but the majority (75.0%) of them were transversions. These results suggest that the mutation in the p53 gene plays a significant role in the tumorigenesis of BCC developed in less-exposed areas as well as those in sun-exposed areas in Japanese patients. There must be therefore causative factors other than UV irradiation for BCC in less-exposed areas.

Aged↗

[Reliability of the evaluation of the active sweat gland density on the dorsum of the foot using the silastic impression mold technique].

The evaluation of the density of the active sweat gland on the dorsum of the foot induced by iontophoresis of 1% pilocarpine was made repeatedly using the silastic impression mold technique in 83 subjects (52 normal volunteers: 24 subjects younger than 50 years of age and 28 subjects 50 years of age or older, 20 men and 32 women: 20 diabetic patients and 11 patients with other neurological disorders), from 12 to 82 years of age, and the reliability of such evaluation was assessed. After 8 to 14 days following the first evaluation, the second one was performed. The reliability was expressed as an intra-class correlation. The intra-class correlation was greater in the subjects 50 years of age or older (0.909) than in the subjects younger than 50 years of age (0.653). It was similar between males (0.921) and females (0.803). On the other hand, it was less in diabetic patients (0.543) than in the normal volunteers (0.857) and patients with other neurological disorders (0.809). The silastic impression mold technique is widely applicable in evaluating the sweat gland function. However, it should be kept in mind that the reliability is variable among the groups defined clinically and that it is low in the diabetic patients.

Adolescent↗

The relationship between orthostatic dysregulation and the orthostatic test in dizzy patients.

The orthostatic test was administered to 134 dizzy patients (37 males and 97 females) who were identified as having orthostatic dysregulation from December 1990 through November 1994. The mean age of the male and female patients was 42.5 and 44.6 years, respectively, and the peak age decade was the 50s. Among the questionnaire items for orthostatic dysregulation, orthostatic dizziness was the most frequent major symptom and occurred in 116 of the patients (86.6%). Fatigue was the most frequent minor symptom and was found in 97 (72.4%). The incidence of positive orthostatic test results in the patients with orthostatic dysregulation (50.7%) was significantly higher (P < 0.01) than that in the control subjects (27.8%). There was also a significant difference (P < 0.01 or P < 0.05) between systolic pressure decrease during the orthostatic test procedure in the patients with orthostatic dysregulation and that in the control subjects. These results suggest that autonomic imbalance as reflected by the orthostatic dysregulation questionnaire and orthostatic test results is closely related to the occurrence of dizziness or vertigo.

Adolescent↗

Immunolocalization of peptide 19 and other calcium-binding proteins in the guinea pig cochlea.

Calcium ions are known to play critical roles in a variety of cochlear functions. The distributions of a number of calcium binding proteins that regulate calcium ion levels within the cochlea have previously been described. In this report we extend and refine previous reports of the distribution of immunostaining for calmodulin, calbindin, and calretinin and show for the first time the distribution for peptide 19. There were longitudinal and radial gradients of immunostaining for peptide 19 within outer hair cells that appeared to match previously described gradients of efferent innervation of these cells. Gradients of immunostaining for calbindin within outer hair cells were in the opposite directions, which suggests that levels of this protein are correlated with afferent innervation density and perhaps the abundance of subsurface cisternae. No gradients were seen in the distributions of cells stained for calmodulin and calretinin, which included sensory cells and supporting cells respectively. All ganglion cells were stained for calmodulin but the other proteins appeared to be present in limited ganglion cell subpopulations. In addition to staining of sensorineural elements, antisera to all compounds but peptide 19 showed immunostaining of cells within the lateral wall and the spiral limbus. The results suggest that the proteins under study are involved in a wide variety of calcium-regulated functions within the cochlea. Knowledge of the unique distribution of each of the compounds should facilitate further studies of their roles in cochlear function.

Animals↗

Leukotriene A4 hydrolase in peripheral leukocytes of patients with atopic dermatitis.

We examined the enzymatic activity of leukotriene (LT) A4 hydrolase, which catalyzes the conversion of LTA4 to LTB4, in peripheral leukocytes of patients with atopic dermatitis. The patients were divided into three categories (severe, moderate and mild) on the basis of clinical severity. The LTA4 hydrolase activities in the supernatant fraction of peripheral blood polymorphonuclear leukocytes (PMN) were significantly higher in preparations of cells from severe atopic dermatitis patients (123.94 +/- 16.61 pmol/10(6) cells per min) than in those from moderate (49.03 +/- 9.43 pmol/ 10(6) cells per min; P < 0.01) and mild (28.75 +/- 11.42 pmol/10(6) cells per min; P < 0.01) atopic dermatitis patients and normal controls (15.14 +/- 1.74 pmol/10(6) cells per min; P < 0.01). LTA4 hydrolase activities were also higher in peripheral blood mononuclear cells (PBMC) from severe atopic dermatitis patients (27.81 +/- 8.28 pmol/10(6) cells per min) than in those from moderate (11.31 +/- 2.11 pmol/10(6) cells per min; P < 0.05) and mild (6.16 +/- 2.62 pmol/10(6) cells per min; P < 0.05) atopic dermatitis patients and normal controls (11.17 +/- 0.83 pmol/10(6) cells per min; P < 0.05). LTA4 hydrolase activities in PMN were reduced after improvement of the disease in eight patients with severe or moderate atopic dermatitis. These results suggest that LTA4 hydrolase, which synthesizes LTB4, plays a significant role in the pathogenesis and development of atopic dermatitis.

Adolescent↗

High frequency class switching of an IgM+ B lymphoma clone CH12F3 to IgA+ cells.

We have developed an efficient in vitro class switching system using a subclone (CH12F3) of the IgM+ CH12.LX lymphoma cell line. CH12F3 cells switched from surface IgM+ cells to surface IgA+ cells at a high frequency (50%) after 72 h stimulation with IL-4, transforming growth factor (TGF)-beta and CD40L. No other class isotype-producing cells were detected, indicating that the CH12F3 clone is exclusively committed to IgA isotype switching. To understand the molecular basis of the isotype commitment, we studied the methylation profiles of I region promoters and I region transcription of CH12F3 cells. No germline transcripts other than those from the I alpha region were detected and only the I alpha promoter was demethylated in uninduced CH12F3 cells. TGF-beta, CD40L and IL-4 synergistically induced efficient switch recombination in CH12F3 cells, suggesting that the three stimulations up-regulate different steps of switch recombination in isotype-committed B cells such as CH12F3 cells. Stimulation of CH12F3 cells by IL-4 or TGF-beta, but not by CD40L, induced transient but complete methylation of the I alpha region. TGF-beta and CD40L, but not IL-4, increased the amounts of germline alpha transcripts. We found that the extents of methylation and the amounts of germline transcripts do not necessarily correlate with the efficiency of recombination in induced CH12F3 cells. These results led to the proposal that switch recombination can be separated into at least two phases, i.e. commitment and recombination. The roles of IL-4, TGF-beta and CD40L in the two phases are discussed.

Animals↗

Developmentally regulated expression of the PD-1 protein on the surface of double-negative (CD4-CD8-) thymocytes.

PD-1, a member of the Ig superfamily, was previously isolated from an apoptosis-induced T cell hybridoma 2B4.11 by subtractive hybridization. Expresson of the PD-1 mRNA is restricted to thymus in adult mice. Using an anti-PD-1 mAb (J43), we examined expression of the PD-1 protein during differentiation of thymocytes in normal adult, fetal and RAG-2(-/-) mice with or without anti-CD3 mAb stimulation. While PD-1 was expressed only on 3-5% of total normal thymocytes, approximately 34% of the CD4(-)CD8(-) double-negative (DN) fraction are PD-1(+) cells with two distinct expression levels (low and high). PD-1(high) thymocytes belonged to TCR gammadelta lineage cells. In the DN compartment of the TCR alphabeta lineage, PD-1 expression started at the low level from the CD44(+)CD25(+) stage and the majority of thymocytes expressed PD-1 at the CD44(-)CD25(-) stage in which the thymocytes express TCR beta chains. The anti-CD3epsilon antibody administration augmented the PD-1 expression as well as the differentiation of the CD44(-)CD25(+) DN cells into the CD44(-)CD25(-) DN stage, not only in normal mice but also in RAG-2-deficient mice. The fraction of the PD-1(low) cells in the CD4(+)CD8(+) double-positive (DP) compartment was very small (<5%) but increased by stimulation with the anti-CD3 antibody, although the total number of DP cells was drastically reduced. The results show that PD-1 expression is specifically induced at the stages preceding clonal selection.

Aging↗