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Biomedical subjects

S Imamura

Publications and source records attributed to S Imamura.

At least 91 records · Page 5Linked to original sources

Mitogen-inducible SIPA1 is mapped to the conserved syntenic groups of chromosome 19 in mouse and chromosome 11q13.3 centromeric to BCL1 in human.

Sipa1, previously called Spa1, is transcriptionally induced in the murine lymphoid cells following mitogenic stimulation and encodes a protein with a domain related to Rap1 GTPase activating protein (Rap1GAP) at the N-terminus and to PEST sequences followed by a leucine zipper motif at the C-terminus. Herein mouse genomic Sipa1, which consisted of 16 exons, was cloned. Gene linkage analysis using (BXD) recombinant inbred strains indicated that Sipa1 was mapped to the most centromeric region of chromosome 19 syntenic with the long arm of human chromosome 11. Human SIPA1 cDNA exhibited a striking homology to that of mouse throughout the entire region, with the overall identity being 90% at the amino acid level. Human genomic clones, which hybridized with both mouse and human SIPA1 cDNA but not with RAP1GAP cDNA, were then isolated. Fluorescence in situ hybridization (FISH) analysis using the human genomic clones indicated that SIPA1 was indeed mapped to chromosome 11q13, most likely to the 11q13.3 subregion. It was further indicated by double-color FISH that SIPA1 was located in the centromeric neighborhood of CCND1/ PRAD1, a presumed BCL1 oncogene.

Animals↗

Loss of biological activity due to Glu-->Arg mutation at residue 11 of the B subunit of cholera toxin.

Since it has been reported that a single amino acid mutation of Gly-->Arg in the CAGYC region of the beta chain of human thyroid stimulating hormone (hTSH) was responsible for congenital isolated TSH deficiency, and that the same amino acid substitution in this site of hTSH and human chorionic gonadotropin (hCG) introduced by site-directed mutagenesis resulted in loss of activity, the authors studied the role of glutamic acid at position 11 (Glu-11) from the N-terminus of the B subunit of cholera toxin (CT), which corresponds to the glycine in the CAGYC region of the beta chain of hTSH and hCG. A mutant CT constructed by site-directed mutagenesis in which Glu-11 was replaced by Arg (CT-E11R) did not induce either morphological changes or accumulation of cytosolic cyclic AMP in Chinese hamster ovary cells, although it formed the holotoxin AB5, retained the ability to bind to GM1-ganglioside and showed ADP-ribosyltransferase activity. Weak assembly of the B subunits in mutant CT-E11R demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under non-heating conditions might explain the loss of biological activity.

Amino Acid Substitution↗

Age-related changes in the compound action potentials of the eighth nerve in guinea pigs.

The eighth nerve compound action potential (CAP) in 95 guinea pigs was measured using click stimuli to investigate age-related changes in their neural auditory thresholds. The animals were separated into three groups: group A (n = 43, 86 ears; 2-4 months old); group B (n = 29; 58 ears, 13-15 months old); and group C (n = 23; 46 ears, 23-25 months old). With increasing age, a gradual elevation of CAP thresholds was clearly seen among the three groups. The negative peak (N1) latencies of the CAP were prolonged, and the N1 amplitudes of the CAP decreased. There were significant differences in N1 latencies among the three groups and in N1 amplitudes between groups A and B, and between groups A and C. However, the rate of decline of the thresholds as well as the input-output function curves of the CAP varied in some of the oldest animals, suggesting that there were some individual differences in degenerative aging processes of the auditory system.

Acoustic Stimulation↗

Human melanoma cells generate leukotrienes B4 and C4 from leukotriene A4.

We examined the synthesis of leukotrienes (LTs) in human melanoma cells in order to assess the function of LTs in human melanocytes. LTA4 hydrolase, which catalyzes the conversion of LTA4 to LTB4, was detected in the supernatant of cultured human melanoma (MeWo) cells and melanoma cells obtained from patients. Immunoblotting analysis using an antihuman LTA4 hydrolase antibody showed LTA4 hydrolase to be a 70-kDa protein in both MeWo and melanoma cells. Considerable activity of LTC4 synthase, which catalyzes the conversion of LTA4 to LTC4, was detected in the microsomal fraction of both MeWo and melanoma cells. The HPLC profile of the LTC4 synthase reaction products revealed that LTC4 was the main product. LTD4 was not detected under these conditions, indicating that the microsomal fraction of human melanoma cells lacks the membrane-bound gamma-glutamyl transferase that converts LTC4 to LTD4. LTC4 synthase activity was inhibited by the addition of MK-886, and was not altered by treatment with N-ethylmaleimide or 1-chloro-2,4-dinitrobenzene. These results indicate that the enzyme responsible for the conversion of LTA4 to LTC4 in human melanoma cells is LTC4 synthase rather than a nonspecific or microsomal glutathione-S-transferase. These results also suggest that human melanoma cells can generate LTB4 and LTC4 from LTA4, and that this process is catalyzed by two enzymes: LTA4 hydrolase and LTC4 synthase.

Dinitrochlorobenzene↗

Flow cytometry analysis of the Fas ligand expression of activated lymph node T-cells.

There is increasing evidence for the role of the Fas/Fas ligand interaction in the immunoregulation of T-cells. We studied the expression of the Fas ligand (FasL) in activated peripheral T-cell in vitro, and its relation to autonomous cell death by flow cytometry. Following the stimulation of lymph node T-cells with anti-CD3 and rIL2, the mRNA level of FasL increased more than four times during the first 2 days over the level before stimulation. The surface expression of FasL was observed on 27% of the population at day 2 after stimulation and increased to approximately 50% at day 3. Kinetic analysis by flow cytometry, however, indicated that all T-blasts transformed during activation did not express FasL. FasL expression became evident simultaneously with the termination of cell expansion. Since cells remained viable (> 90%) at day 3 as judged by trypan blue-exclusion, cell membranes expressing FasL were supposed to be still intact. Concomitantly with FasL-expression, spontaneous DNA fragmentation was observed. These observations support the idea that autonomous Fas/FasL interaction mediates apoptosis in activated peripheral T-cells as demonstrated in T-cell hybridoma or established T-cells.

Animals↗

The relationship between orthostatic dizziness and hypotension in male medical students.

We carried out a questionnaire survey regarding symptoms of orthostatic dysregulation (OD) and administered the Schellong test (orthostatic test) to 123 normal male medical students aged 21-29 years to investigate the relationship between orthostatic dizziness and hypotension. OD was identified in 15 (12.2%) of the subjects based on the questionnaire results. Orthostatic dizziness was noted in 40.7% of the subjects (50/123). The occurrence of orthostatic dizziness was most significantly related to systolic pressure decrease during the procedure for the Schellong test. These results suggest that the testing procedure introduced by Schellong can be useful, and clinically applicable to the assessment of orthostatic dizziness, since it presents the advantage of being simple enough to carry out in clinical practice.

Adult↗

Prenatal determination of human platelet antigen type 4 by DNA amplification of amniotic fluid cells.

To predict a fetus at risk for neonatal alloimmune thrombocytopenia (NATP) caused by human platelet antigen (HPA)-4 incompatibility, we applied a sequence-specific polymerase chain reaction (PCR-SSP). We were able to determine the HPA-4 genotype of three infants at risk using amniotic fluid cells without the need for fetal blood sampling. The HPA-4 genotypes of amniotic fluid cells determined in this way were completely concordant with the genotype and phenotype of infants' venous blood samples obtained after delivery. Therefore, this technique is also convenient to a fetus at risk in the antenatal management of NATP induced by HPA-4 incompatibility.

Adult↗

The relationship between psychosomatic factors and orthostatic dysregulation in young men.

We carried out a questionnaire survey regarding symptoms of orthostatic dysregulation and administered the Japanese Edition of the Cornell Medical Index-Health Questionnaire (JCMI) and the Yatabe-Guilford Personality Test (Y-G test) to 151 male medical students (mean age, 24.6 yr). Orthostatic dysregulation was identified in 19 (12.5%) of the subjects based on the questionnaire results. The percentage classed as types III (possible neurotic) and IV (probable neurotic) according to the health questionnaire was 47.3% in the 19 with orthostatic dysregulation and 8.9% in the controls (n = 78). The percentage classed as types B and E, suggestive of emotional or psychological disturbance according to the personality test, was 42.1% in those with orthostatic dysregulation and 8.9% in the controls. These differences were significant (P < 0.01). These results suggest that psychosomatic factors influence the occurrence of orthostatic dysregulation in young men.

Abdominal Pain↗

Identification of novel cadherins expressed in human melanoma cells.

Cadherin molecules are essential for tissue morphogenesis and are also related to cancer invasion and metastasis. Although normal melanocytes express E- and P-cadherin, the activity and expression of E- and P-cadherin in melanoma cells are still unknown. We measured the homophilic adhesion activity of human normal epidermal melanocytes and the melanoma cell lines MeWo and A375. The melanoma cells showed stronger homophilic adhesion activity than did the melanocytes, despite the lower expression of E- and P-cadherin in the melanoma cells. This result suggested that melanoma cells expressed other types of homophilic adhesion molecules. Using degenerate primers to amplify multiple cadherin subtypes, we performed a polymerase chain reaction (PCR) with the first strand of cDNAs generated by reverse transcription of the mRNAs of the melanoma cells, and we isolated two known cadherin fragments, N-cadherin and PC42, and six novel cadherin fragments, cadherins ME1-ME6. The reverse transcriptase-PCR using specific primers of cadherins including E-, P-, and N-cadherins, PC42, and cadherins ME1-ME6 revealed that the melanoma cells expressed more kinds of cadherin molecules than did the melanocytes. Such cadherins may play an important role in melanoma cell-cell adhesion.

Amino Acid Sequence↗

An alanine to proline mutation in the 1A rod domain of the keratin 10 chain in epidermolytic hyperkeratosis.

We report a mutation in a case of epidermolytic hyperkeratosis that results in a proline for alanine substitution in the residue position 12 of the 1A subdomain of the keratin 10 chain (codon 158). The disease phenotype is consistent with the inappropriate substitution of a proline near the beginning of the rod domain, because it is likely to seriously disrupt the structural organization of coiled-coil molecules within keratin intermediate filaments. Mutations/substitutions in this position have not been reported in any keratin disease. Position 12 is an alanine in all intermediate filament chains, and lies in the outer b heptad position of the coiled-coil. In vitro peptide interference assembly assays revealed that substitutions that alter residue size or charge at this position primarily interfere with keratin filament elongation.

Adolescent↗

An autopsy case of angioimmunoblastic T-cell lymphoma with a high content of epithelioid cells in the lymph node: immunohistochemical and genomic analyses.

A 79-year-old female developed red papulonodular eruptions on her extremities, facial erythema, generalized lymphadenopathy and high fever. Histopathology of an affected lymph node showed the features of angioimmunoblastic T-cell lymphoma with a high content of epithelioid cells. She died about two years after the onset despite therapy. Genomic Southern blotting and immunostaining of the lymph nodes were performed twice. In August of 1993, Southern blotting did not show any rearrangement of the immunoglobulin or the T-cell receptor (TCR) gene. Small or medium-sized lymphoid cells were positive for CD4 or CD8 (CD4:CD8 = 2:1). However, in September of 1994 (at autopsy), rearrangements of TCK C beta 1, J beta 2 and J gamma genes were observed. Small or medium-sized lymphoid cells were positive for CD4, but negative for CD8. Several large cells were positive for Latent Membrane Protein 1 (LMP1) of the Epstein-Barr virus (EBV). Our results proved that selective oligoclonal proliferation of tumor cells (probably CD4+) accompanied the disease progress.

Aged↗

Progressive decrease in hair diameter in Japanese with male pattern baldness.

Fifty-six Japanese with male pattern baldness were evaluated for changes in their hair diameters over three years. The mean hair diameter significantly decreased each year. The average decrease was 1.1 microns per year. Although the percentage of vellus hair increased by 3.6% over three years, this increase rate was lower than that found in Caucasians. To precisely examine the change in hair diameter, the mean distribution of this diameter was investigated. At the beginning of the study, clear peaks were observed at 95 microns in the twenties and 45 microns in the fifties. The number of thicker hairs decreased and the high frequency peak shifted to a thinner hair diameter over 3 years. To quantify the change in the distribution of hair diameter, the percentage of hairs of more than 60 microns was examined. There was a statistically significant 5.61% decrease in the percentage of hairs with a diameter of more than 60 microns over three years. Our findings suggest that the progression of male pattern baldness in Japanese is slower than that of Caucasians and that the percentage of hairs of more than 60 microns is a sensitive index to evaluate the progression of male pattern baldness and the effects of hair growth or hair loss preventive agents.

Adult↗

Foot ulcer due to arteriovenous malformation: report of a case.

A 41-year-old woman had erosive eruptions surrounded by irregularly shaped pigmentation on the lateral aspect of her right foot, where she had noted gradually increasing warmth and pain for 10 years. The eruptions waxed and waned without complete healing, and an ulcer which had formed one year previously did not respond to topical treatments. Arteriography performed on the right lower extremity disclosed multiple diffuse arteriovenous malformations in the right lower leg and foot. The ulcer was treated by bed rest, surgical debridement, and topical application of bucladesine sodium ointment. After three months, the ulcer healed, leaving a shallow scar and pigmentation.

Administration, Cutaneous↗

Involvement of tumor necrosis factor-alpha, interleukin-1 beta, interleukin-8, and interleukin-1 receptor antagonist in acute lung injury caused by local Shwartzman reaction.

A local Shwartzman reaction (LSR) was prepared in rabbit lung as a model of acute lung injury. To induce LSR, intratracheal injection of lipopolysaccharide (LPS) 10 micrograms into the lower lobe of the right lung, followed 24 h later by i.v. injection of LPS (10 micrograms/kg). In the lung with the LSR, myeloperoxidase activity, representing neutrophil accumulation, peaked at 1-2 h and was sustained for 48 h after challenge with i.v. LPS. The lung water content peaked at 12 h, and decreased gradually. Histological findings showed diffuse interstitial widening, intra-alveolar leukocyte infiltration with hemorrhage, and alveolar exudate formation. The production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-8 (IL-8), and IL-1 receptor antagonist (IL-1 Ra) in the lung was analyzed. TNF-alpha first elevated and peaked at 0.5 h (66.5 +/- 16.7 ng/g.lung), subsequently, IL-1 beta and IL-8 increased and peaked at 2 h (17.8 +/- 3.4 ng/g.lung and 336.9 +/- 49.6 ng/g.lung, respectively). IL-1Ra was present even before the challenge, and the production increased to show a dual peak (0.5 h, 1.5 +/- 0.2 micrograms/g.lung; and 2 h, 1.6 +/- 0.1 micrograms/g.lung), and a large concentration of IL-1Ra was sustained for 48 h. Immunohistochemistry showed that the cellular source of these cytokines was alveolar macrophages and infiltrating neutrophils. Thus, disclosing the kinetics of the generation of cytokines led to a better understanding of their roles, namely TNF-alpha as an initiator, IL-1 and IL-8 as amplifier and effector, and IL-1Ra as regulator of the intensity of acute inflammation.

Animals↗

Clinicopathologic study of leptomeningeal carcinomatosis involving the temporal bone.

The temporal bone pathology of a 71-year-old man with bilateral sensorineural hearing loss and facial paralysis caused by diffuse metastatic leptomeningeal carcinomatosis is described. The origin of this malignant disease was an extremely rare entity, a transitional cell carcinoma of the renal pelvis. Histopathologic study of the temporal bone demonstrated that tumor cells filled the internal auditory meatus, infiltrated into the Rosenthal's canals, and reached the scala tympani of the basal turn of the bilateral cochleas. The vestibulocochlear nerve and facial nerve trunks in the internal auditory meatus had been destroyed by the bilateral tumor invasion. Case reports of temporal bone metastases of leptomeningeal carcinomatosis published since 1965 were reviewed. In leptomeningeal carcinomatosis, it is suggested that tumor cells infiltrate the internal auditory meatus of both ears simultaneously from the cerebrospinal fluid, involving the seventh and eighth nerve trunks, and then cause bilateral sensorineural hearing loss and facial paralysis.

Aged↗