Biomedical subjects

E Yamamoto

Publications and source records attributed to E Yamamoto.

At least 55 records · Page 3Linked to original sources

PubMed2000

Molecular characterization of two soybean homologs of Arabidopsis thaliana CLAVATA1 from the wild type and fasciation mutant.

Arabidopsis thaliana CLAVATA1 (CLV1)-like genes were isolated from the wild type and fasciation mutant of soybean (Glycine max). Two soybean homologs of CLV1, designated GmCLV1A and GmCLV1B, are similar in sequence. No missense mutations in GmCLV1A and GmCLV1B between the wild type and mutant were found. GmCLV1 was mapped at 7. 1 cM from a restriction fragment length polymorphism marker on the linkage group H of the soybean molecular map. DNA fingerprinting using bacterial artificial chromosome clones identified two contigs indicating there are two loci for GmCLV1 in the soybean genome. One locus contains GmCLV1A and the other locus contains GmCLV1A and GmCLV1B. Relative multiplex quantitative reverse transcriptase-polymerase chain reaction analysis indicates that the two genes are transcribed in all organs and at higher levels in floral apices. Differential expression patterns of the two genes suggest that the function of the two genes is slightly different in different organs.

Amino Acid Sequence↗

PubMed2000

Identification of viral induced genes in Ig+ leucocytes of Japanese flounder Paralichthys olivaceus, by differential hybridisation with subtracted and un-subtracted cDNA probes.

Up-regulated genes of leucocytes expressing immunoglobulin (Ig+ leucocytes) of hirame rhabdovirus (HRV)-infected Japanese flounder were identified by differential hybridisation, using subtracted and un-subtracted cDNA probes. Ig+ leucocytes were separated from apparently healthy and HRV-infected Japanese flounder by the magnetic beads antibody method using mouse anti-Japanese flounder Ig monoclonal antibody (mab). A cDNA library was constructed from HRV-infected Japanese flounder leucocytes, and was screened with subtracted cDNA probes enriched in genes up-regulated by HRV infection. Fifty cDNAs were isolated for further analysis. These included cDNAs coding for homologues of interferon-inducible 56K protein (IFI56), Stat3, CEF-10, RGS5, inducible poly(A) binding protein, prolylcarboxylpeptidase, basigin III (Ig superfamily), MUC-18 (Ig superfamily), proteasome-nexin 1 (SERPIN), herpes virus entry mediator (TNFR family), collagenase III, gelatinase-b, megakaryocyte stimulating factor, Rab8-interacting protein, IgM, IgD and 20 unknown cDNA clones. The majority of these identified genes are reported for the first time in fish. From leucocytes mRNA for homologues of IFI56, CEF-10, Stat3, SERPIN and inducible poly (A) binding protein expression was shown to increase following HRV infection.

Animals↗

PubMed2000

Characterization of bacterial orofacial infections using a new murine model.

We devised a new murine orofacial infection model using bacteria from odontogenic infection origins and characterized the experimental infections. In this model, bacteria were injected into the submandible of mice. Streptococcus constellatus and Peptostreptococcus micros produced a single abscess at the injection site and their abscess-forming and lethal abilities were low: the median abscess-forming dose (AF(50)) of S. constellatus and P. micros were 10(8.5-10.7)and 10(10.2-10.6)cfu/mouse, and their median lethal dose (LD(50)) were >11 and 10(10.6-11)cfu/mouse, respectively. Prevotella oralis and Fusobacterium nucleatum produced multiple abscesses and their abscess-forming and lethal abilities were strong: AF(50)of P. oralis and F. nucleatum were 10(6.0-6.4)and 10(7. 0-8.7)cfu/mouse, and their LD(50)were 10(7.0-7.7)and 10(8.3-9. 9)cfu/mouse, respectively. LD(50)of P. intermedia and P. gingivalis were 10(9.4->11)and 10(8.9-9.1)cfu/mouse, respectively. Prevotella intermedia and Porphyromonas gingivalis generated a necrotizing lesion, which progressed rapidly. We conclude that this murine model could reflect human orofacial odontogenic infections and is useful to investigate the pathogenicity of causative bacteria of such infections.

Abscess↗

PubMed2000

Risk factors for posttransfusion graft versus host disease, mediastinitis, and late cardiac tamponade in heart surgery. Survey of 119 Japanese institutions.

OBJECTIVE: Correlations and risk factors remain to be unclarified for post-heart-surgery posttransfusion graft-versus-host disease, mediastinitis, and late cardiac tamponade caused by deteriorated host-defense mechanisms due to cardiopulmonary bypass both with and without steroid usage. METHODS: We sent questionnaires to 298 Japanese cardiovascular institutions asking for institution profiles, including infection control, steroid use in cardiopulmonary bypass, and prevalence of mediastinitis, late cardiac tamponade, and posttransfusion graft-versus-host disease during 1994. The overall prevalence of posttransfusion graft-versus-host disease since the start of service (from establishment of institution to date) was also requested. RESULTS: The number of pump cases at the 119 institutions responding (40%) were 91.6 +/- 67.9 cases/institution (total = 10,904). The prevalence of mediastinitis was 1.2 +/- 1.8 and that of late cardiac tamponade 1.0 +/- 1.8%. Posttransfusion graft-versus-host disease occurred in 1 of 10,904 patients (0.01%) during 1994 at an institution where steroids and nonirradiated blood were used in surgery. The simple institutional mean prevalence of posttransfusion graft-versus-host disease since establishing institutions was 0.08 +/- 0.13%. Of the 119 institutions surveyed, 86 used steroids in all pump cases (72%); 11 institutions used steroids in a limited number of cases (9%). The institutional mean of methylprednisolone-converted steroid dose was 21.5 +/- 16.4 mg/kg (n = 119). In multivariate regression analysis, operation time (p = 0.005) for mediastinitis, steroid usage (all, limited, or no cases) (p = 0.01) and % aneurysm (p = 0.05) for late cardiac tamponade, and steroid dosage (p = 0.002) for posttransfusion graft-versus-host disease were identified as significant risk factors. CONCLUSION: Our results suggest that massive steroid administration for cardiopulmonary bypass may increase the risk of posttransfusion graft-versus-host disease and late cardiac tamponade, but not mediastinitis.

Aged↗

PubMed2000

Stenotrophomonas maltophilia endophthalmitis after intraocular lens implantation.

BACKGROUND: Stenotrophomonas maltophilia is an opportunistic, gram-negative bacillus. Endophthalmitis induced by S. maltophilia has been described in only two cases after intraocular lens implantation. We report S. maltophilia endophthalmitis in two patients with diabetes mellitus after intraocular lens implantation and compare the characteristics of the S. maltophilia-induced endophthalmitis with two previous cases. METHODS: A 68-year-old woman and a 74-year-old man with diabetes mellitus developed S. maltophilia endophthalmitis within 5 days of intraocular lens implantation. We performed intraocular lens removal and vitrectomy, which resolved the inflammation. No recurrences were found. RESULTS: Cultures grew S. maltophilia in both cases, and one of the organisms was multi-resistant. The final visual acuity was counting fingers and 0.3. The first case revealed a tractional retinal detachment during vitrectomy. CONCLUSIONS: S. maltophilia is a potential opportunistic intraocular pathogen, and the incidence of multiresistant S. maltophilia is increasing. S. maltophilia causes acute endophthalmitis, and its prognosis may not be poor unless the eye has a history of serious disease before the cataract surgery. The combined procedure of intraocular lens removal and vitrectomy was useful in resolving the inflammation and preventing recurrences.

Aged↗

PubMed2000

Clinical features of sudden hearing loss associated with a high signal in the labyrinth on unenhanced T1-weighted magnetic resonance imaging.

We report on five patients with high signals in the labyrinth on unenhanced magnetic resonance imaging who developed sudden hearing loss and vertigo. Weissman et al. (1992) suggested the possibility that such high signals were caused by hemorrhage. We assessed these patients using audiograms, caloric tests, and auditory brainstem responses to investigate the possibility of inner ear hemorrhage. Most of the patients were found to have severe and irreversible impairment of both cochlear and vestibular function. These findings were consistent with the hypothesis that their symptoms were caused by inner ear hemorrhage.

Adolescent↗

PubMed2000

A survey of expressed genes in the leukocytes of Japanese flounder, Paralichthys olivaceus, infected with Hirame rhabdovirus.

We constructed a cDNA library of Japanese flounder, Paralichthys olivaceus, leukocytes that were infected with Hirame rhabdovirus (HRV) in order to analyze some of the genes that are induced and expressed by virus infection in the immune system. Four hundred and fifty-two partial sequences representing 300 cDNA clones were obtained from the 5' and/or 3' ends of inserts derived from the Japanese flounder leukocyte cDNA library. About three-quarters of the 300 cDNA clones (217 clones, 72.3%) represented known genes in the public databases, whereas the remaining 83 (27.7%) of the clones did not show any significant homology with the sequences in the public databases. Clones matching known genes were classified into 12 categories according to their function or distribution. Only 40 (18.4%) of the 217 known genes showed homology with fish genes deposited in the database. Thirty (10%) of the clones, encoding 21 different sequences, and representing several categories, were identified as putative biodefense genes or genes associated with the immune response. Nineteen of the 21 putative biodefense or immune response-related cDNAs have not been previously reported in fish genes or cDNAs.

Amino Acid Sequence↗

PubMed2000

Mechanical properties of collagen fascicles from in situ frozen and stress-shielded rabbit patellar tendons.

OBJECTIVE: To know the effects of stress shielding on the biomechanical properties of collagen fascicles obtained from in situ frozen patellar tendons (an autograft model). DESIGN: Collagen fascicles of approximately 300 microm in diameter were obtained from in situ frozen rabbit patellar tendons and also from in situ frozen and stress-shielded ones, and their mechanical properties and fibroblast density were determined. BACKGROUND: Stress shielding changes the mechanical properties of in situ frozen patellar tendons in which there exist no fibroblasts. The mechanisms of this phenomenon have not been studied well. METHOD: Patellar tendons of both in situ frozen group and in situ frozen and stress-shielded group were frozen in situ by liquid nitrogen to kill fibroblasts. Then, in the in situ frozen and stress-shielded group, no tension was applied to the tendons for 2, 3, and 6 weeks, while normal tension was applied to the tendons of the in situ frozen group. Tensile properties of the collagen fascicles obtained from these tendons were determined using a microtensile tester, and were compared to the collagen fascicles from non-frozen, stress-shielded patellar tendons. RESULTS: Tangent modulus and tensile strength of collagen fascicles from the in situ frozen and stress-shielded group progressively decreased with the time of stress shielding; however, these decreases were much smaller than those of the fascicles obtained from non-frozen, stress-shielded tendons. Although there were few fibroblasts in the patellar tendon of the in situ frozen and stress-shielded group at 2 weeks, the modulus and strength of the fascicles from the posterior portion were significantly lower than those in the in situ frozen group. In addition, the reduction of strength caused by stress shielding was much smaller in collagen fascicles than in bulk patellar tendons. CONCLUSION: The mechanical properties of collagen fascicles in in situ frozen tendons (an autograft model) are affected by stress shielding even under acellular condition. RelevanceThe in situ frozen, stress-shielded patellar tendon is a model of augmented autografts which are clinically used for the reconstruction of injured anterior cruciate ligaments. The sub-macroscopic studies of the tendon are useful to understand the mechanisms of the reduction of graft strength and its gradual recovery observed after reconstruction.

Animals↗

PubMed2000

The virulence of mixed infection with Streptococcus constellatus and Fusobacterium nucleatum in a murine orofacial infection model.

Orofacial infections are usually polymicrobial, and it is the microbial interactions of pathogenic species that cause tissue destruction. In this study, the microbial interaction between Streptococcus constellatus and Fusobacterium nucleatum was characterized using a murine orofacial infection model. A mixture of viable S. constellatus and F. nucleatum cells (both 2 x 10(8) CFU/mouse) was injected into the submandible; as a result, all of the test mice died. In contrast, none of the experimental animals monoinjected with either S. constellatus or F. nucleatum died (P<0.001), indicating that the synergism between the two resulted in the virulence. When a mixture of viable S. constellatus cells and a culture filtrate of F. nucleatum was tested, lethality and the bacterial cell count per lesion were significantly enhanced as compared with monoinjections (P<0.02). However, the virulence of F. nucleatum was not enhanced by infection of a culture filtrate of S. constellatus. The enhancement of virulence was observed even when viable S. constellatus cells and the culture filtrate of F. nucleatum were injected at separate sites. Heat treatment of the culture filtrate of F. nucleatum did not affect the enhancement. These results indicate that a heat-stable substance(s) produced by F. nucleatum contributes to the microbial synergy of S. constellatus and F. nucleatum in orofacial infections.

Abscess↗

PubMed2000

Modified rapid urease test for Helicobacter pylori detection in relation to an immunohistochemical stain.

BACKGROUND: The rapid urease test and touch cytology have been used for the rapid detection of Helicobacter pylori infection. Recently, a modified rapid urease (MRU) test, which provides results in 20 min has been available on a commercial basis. To date, few reports have evaluated the accuracy of this test. This study evaluated the sensitivity, specificity, and accuracy of the MRU test and touch cytology to detect H. pylori in relation to the density of H. pylori infection determined semi-quantitatively by using immunohistochemical stains. METHODS: Biopsy specimens obtained from a total of 60 patients who underwent endoscopy for evaluation of gastroduodenal diseases were studied by using the MRU test, Giemsa stain for touch smear tissue and histological methods. An immunohistochemical stain was used as a standard, and the density of H. pylori infection was graded according to the number of individual bacteria seen as follows: grade 0 = 0; grade 1+ = 1-9; grade 2+ = 10-29; grade 3+ = 30-99; grade 4+ > or = 100. The severity of gastritis was evaluated histologically in each specimen and compared with the density of H. pylori infection. RESULTS: The MRU test had an overall sensitivity of 73%, specificity of 100% and accuracy of 85%. The Giemsa stain had a sensitivity of 91%, specificity of 100% and accuracy of 95%.The sensitivities of the MRU test and Giemsa stain decreased in mild H. pylori infection. In the MRU test, the sensitivity was 47% when the density of H. pylori infection was 1+, while 80-100% sensitivities were obtained when the densities of infection were > or = 2+. With the Giemsa stain, the sensitivity was 80% when the density was 1+, while the sensitivity increased to 100% when the densities were > or = 2+. The severity of gastritis determined by the Rauws scores showed a positive correlation with the density of H. pylori infection as evaluated by immunohistochemical staining. CONCLUSIONS: The MRU test had high sensitivity and specificity for moderate to severe H. pylori infection, but it may result in false-negative results in tests for mild infection. As the MRU test has the advantages of shorter incubation times and low cost, a combination of the MRU test and the Giemsa stain for touch cytology may be the most time- and cost-efficient tests in a clinical setting for the diagnosis of H. pylori infection.

Cytodiagnosis↗

PubMed2000

Histological changes in the rabbit condyle following posterolateral disk perforation.

PURPOSE: To examine changes in condylar cartilage following perforation in the posterolateral region of the articular disk of the craniomandibular joint of a rabbit. MATERIAL AND METHODS: The circular perforation in the left joint of 25 female Japanese white rabbits measured precisely one-sixteenth of a disk. Histological examination, including the immunohistochemical proliferating cell nuclear antigen (PCNA) procedure, was performed on separate sets of five rabbits each 2, 4, 8, 12, and 24 weeks postoperatively. RESULTS: Microscopic examination revealed hypertrophy of the condylar cartilage with osteophyte formation up to 8 weeks after perforation. Proliferative activity then decreased near the condylar surface as the perforation flattened. Twenty-four weeks postoperatively, the condylar surface was found to be fibrous and flattened. Positive PCNA results in cartilage cells indicated proliferation following disk perforation which peaked in the 4th week and then decreased. CONCLUSION: Disk perforation was followed initially by hypertrophy of condylar cartilage, and later by degeneration of the condylar surface. Although osteoarthritic cartilage was found 24 weeks after perforation, degeneration decreased over time. This suggests that remodelling took place after the perforation.

Animals↗

PubMed2000

Temporomandibular joint morphology and disc position in skeletal class III patients.

INTRODUCTION: The purpose of this study was to investigate the relationship between temporomandibular joint (TMJ) morphology, including discal tissue and clinical symptoms in class III dentofacial deformity patients. MATERIAL AND METHODS: Forty-four patients were examined with lateral, frontal and axial cephalograms. They were divided into two groups, consisting of a class III symmetry and a class III asymmetry group. By using magnetic resonance imaging the 88 joints could be classified into four types on the basis of disc position and shape: anteriorly displaced disc, anterior type, fully-covered type and posterior type. Furthermore, TMJ morphology was measured tomographically in the sagittal plane. RESULTS: Anteriorly displaced discs in the asymmetry group (56.8%) occurred significantly more frequently than in the symmetry group (18.2%; p <0.05). TMJ symptoms (clicking, crepitus, closed lock, pain) were seen in 17/44 joints (38.6%) of the symmetry and 24/44 joints (54.5%) of the asymmetry group, for a total of 41/88 joints (46.6%). There were no differences in joint space ratio and condyle ratio. However, the fossa ratio on the deviation side was significantly higher than on the nondeviation side in the asymmetry group (p<0.05). CONCLUSION: The incidence of internal derangement in asymmetrical class III patients is higher than in symmetrical mandibular prognathism, and this difference is associated with a difference in TMJ morphology of both sides.

Adult↗

PubMed2000

Past administration of beta-lactam antibiotics and increase in the emergence of beta-lactamase-producing bacteria in patients with orofacial odontogenic infections.

OBJECTIVE: The purpose of this study was to determine the current status of beta-lactamase-producing bacteria in orofacial odontogenic infections. STUDY DESIGN: Microbiologic data regarding purulent exudate from 111 cases with orofacial odontogenic infections were analyzed in relation to the past administration of beta-lactams. RESULTS: beta-lactamase-producing bacteria were isolated more frequently from the beta-lactam-administered group (38.5%) than from the beta-lactam-nonadministered group (10.9%; P <.005), and they were isolated more frequently as the duration of administration increased. The predominant bacteria isolated included Prevotella (the most frequent isolate), viridans streptococci, Peptostreptococcus, and Fusobacterium, and 7.1% of total isolates produced beta-lactamase. Penicillin and cefazolin worked well with beta-lactamase-nonproducing Prevotella but were remarkably affected by beta-lactamase-producing Prevotella. Cefmetazole, sulbactam/cefoperazone, and imipenem worked well against both types of Prevotella. CONCLUSIONS: beta-lactams are still suitable for the first antimicrobial therapy in the treatment of these infections. However, because past beta-lactam administration increases the emergence of beta-lactamase-producing bacteria, beta-lactamase-stable antibiotics should be prescribed to patients with unresolved infections who have received beta-lactams.

Abscess↗

PubMed2000

Bacteriologic features and antimicrobial susceptibility in isolates from orofacial odontogenic infections.

OBJECTIVE: The aim of this study was to obtain information for an effective antimicrobial therapy against orofacial odontogenic infections; such information was obtained from recent bacteriologic features and antimicrobial susceptibility data. STUDY DESIGN: The bacteriology and antimicrobial susceptibility of major pathogens in 163 patients with orofacial odontogenic infections to 7 antibiotics was examined. RESULTS: Mixed infection of strict anaerobes with facultative anaerobes (especially viridans streptococci) was observed most often in dentoalveolar infections, periodontitis, and pericoronitis. Penicillin (penicillin G) was effective against almost all pathogens, although it did not work well against beta-lactamase-positive Prevotella. Cefmetazole was effective against all test pathogens. Erythromycin was ineffective against viridans streptococci and most Fusobacterium. Clindamycin exerted a strong antimicrobial activity on anaerobes. Minocycline was effective against almost all the test pathogens. The antimicrobial activity of levofloxacin against viridans streptococci was not strong. CONCLUSIONS: An antibiotic that carries out antimicrobial activity against both viridans streptococci and oral anaerobes should be suitable for treatment of dentoalveolar infection, periodontitis, and pericoronitis. Penicillin remains effective as an antimicrobial against most major pathogens in orofacial odontogenic infections. Cefmetazole, clindamycin, and minocycline may be effective against most pathogens, including penicillin-unsusceptible bacteria.

Anti-Bacterial Agents↗

PubMed2000

An unstable trinucleotide-repeat region on chromosome 13 implicated in spinocerebellar ataxia: a common expansion locus.

Larger CAG/CTG trinucleotide-repeat tracts in individuals affected with schizophrenia (SCZ) and bipolar affective disorder (BPAD) in comparison with control individuals have previously been reported, implying a possible etiological role for trinucleotide repeats in these diseases. Two unstable CAG/CTG repeats, SEF2-1B and ERDA1, have recently been cloned, and studies indicate that the majority of individuals with large repeats as detected by repeat-expansion detection (RED) have large repeat alleles at these loci. These repeats do not show association of large alleles with either BPAD or SCZ. Using RED, we have identified a BPAD individual with a very large CAG/CTG repeat that is not due to expansion at SEF2-1B or ERDA1. From this individual's DNA, we have cloned a highly polymorphic trinucleotide repeat consisting of (CTA)n (CTG)n, which is very long ( approximately 1,800 bp) in this patient. The repeat region localizes to chromosome 13q21, within 1.2 cM of fragile site FRA13C. Repeat alleles in our sample were unstable in 13 (5.6%) of 231 meioses. Large alleles (>100 repeats) were observed in 14 (1. 25%) of 1,120 patients with psychosis, borderline personality disorder, or juvenile-onset depression and in 5 (.7%) of 710 healthy controls. Very large alleles were also detected for Centre d'Etude Polymorphisme Humaine (CEPH) reference family 1334. This triplet expansion has recently been reported to be the cause of spinocerebellar ataxia type 8 (SCA8); however, none of our large alleles above the disease threshold occurred in individuals either affected by SCA or with known family history of SCA. The high frequency of large alleles at this locus is inconsistent with the much rarer occurrence of SCA8. Thus, it seems unlikely that expansion alone causes SCA8; other genetic mechanisms may be necessary to explain SCA8 etiology.

Adult↗

PubMed2000

Agitated behavior in elderly nursing home residents with dementia in Japan.

This study is the first investigation of the frequency of agitated behaviors in elderly dementia patients in Japanese nursing homes using the Cohen-Mansfield Agitation Inventory (J. Cohen-Mansfield, 1991). Despite major differences between Japanese and American cultures, findings were highly consistent with those of previous U.S. studies. Physically aggressive behavior, although evidenced by only 10-20% of the sample, comprised the strongest factor. A separate factor for verbal agitation also emerged. The behaviors declined during the evening and night shifts. In both the Japanese and U.S. samples, wandering, general restlessness, verbal agitation such as repetitious questioning, cursing, and complaining occurred most frequently. Another 4-point scale was used to code the degree to which agitated behavior occurred during eating, dressing, bathing, and toileting for each resident. The majority of aggressive behavior occurred in relation to personal caregiving, especially in regard to bathing. Despite major cultural differences, Japanese findings paralleled previous U.S. results.

Aged↗

PubMed2000

Effects of stress shielding on the transverse mechanical properties of rabbit patellar tendons.

With the aim of studying mechanisms of the remodeling of tendons and ligaments, the effects of stress shielding on the rabbit patellar tendon were studied by performing tensile and stress relaxation tests in the transverse direction. The tangent modulus, tensile strength, and strain at failure of non-treated, control patellar tendons in the transverse direction were 1272 kPa, 370 kPa, and 40.5 percent, respectively, whereas those of the tendons stress-shielded for 1 week were 299 kPa, 108 kPa, and 40.4 percent, respectively. Stress shielding markedly decreased tangent modulus and tensile strength in the transverse direction, and the decreases were larger than those in the longitudinal direction, which were determined in our previous study. For example, tensile strength in the transverse and longitudinal direction decreased to 29 and 50 percent of each control value, respectively, after 1 week stress shielding. In addition, the stress relaxation in the transverse direction of stress-shielded patellar tendons was much larger than that of nontreated, control ones. In contrast to longitudinal tensile tests for the behavior of collagen, transverse tests reflect the contributions of ground substances such as proteoglycans and mechanical interactions between collagen fibers. Ground substances provide lubrication and spacing between fibers, and also confer viscoelastic properties. Therefore, the results obtained from the present study suggest that ground substance matrix, and interfiber and fiber-matrix interactions have important roles in the remodeling response of tendons to stress.

Animals↗

PubMed2000

Spontaneous and cytokine regulated c-fos gene expression in rheumatoid synovial cells: resistance to cytokine stimulation when the c-fos gene is overexpressed.

OBJECTIVE: To study the effect of cytokines on the transactivation of the c-fos gene in relation to the contribution of overexpression of c-fos/AP-1 in rheumatoid joint destruction. METHODS: The promoter region (-447 to +109) of the human c-fos gene was integrated upstream of the chloramphenicol acetyltransferase (CAT) reporter gene, and the effect of cytokines on the expression of the c-fos gene was studied in the rheumatoid synovial cells of early (3-4) or late (14-18) passages, in the presence or absence of cytokines, by the transient transfection assay. RESULTS: Expression of c-fos gene was enhanced by tumour necrosis factor alpha (TNF alpha) and interleukin 6 (IL6) in the synovial cells of early passage, whereas it was not enhanced in the synovial cells of late passage. The c-fos gene expression was also enhanced by 13-O-tetradecanoyl phorbol-13-acetate (TPA) in early passage but was somewhat suppressed in the late passage. It was found that the c-fos gene and c-Fos protein were both increased in the synovial cells of late passage. Similarly, c-fos gene expression was also not increased by TPA or cytokine stimulation in the stable c-fos transformants (fos-pH8) or H-ras transformed NIH3T3 cells (NIH H-ras cells) that constitutively expressed c-fos genes. CONCLUSIONS: Although TNF alpha and IL6 augmented c-fos gene expression of rheumatoid synovial cells, transactivation of c-fos gene became resistant against cytokine stimulation under prolonged expression of c-fos gene, which may impart a tumour-like characteristic to rheumatoid synovial cells.

Arthritis, Rheumatoid↗