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Biomedical subjects

H Aono

Publications and source records attributed to H Aono.

At least 37 records · Page 2Linked to original sources

Monoclonal expansion of synoviocytes in rheumatoid arthritis.

OBJECTIVE: To examine whether synoviocytes from patients with rheumatoid arthritis (RA) have a stronger growth ability than those from patients with osteoarthritis (OA), and to determine whether these synoviocytes clonally expand in situ. METHODS: Synovial tissues from 13 RA patients and 4 OA patients were cultured, and their ability to form colonies in soft agarose was examined. RA and OA synoviocytes were also examined in varying concentrations of fetal calf serum (FCS)-containing medium to test the effects of FCS on colony formation. DNA was extracted from clones with colony-forming ability in nonpannus lesions and from synoviocytes in pannus lesions. Restriction fragment length polymorphism (RFLP) analysis was used to examine phosphoglycerate kinase 1 (PGK-1) gene patterns. Production of cytokines by these cells was also assessed. RESULTS: All 13 RA synoviocytes exhibited colony formation, whereas none of the 4 OA synoviocytes did. This tendency was also seen with all of the concentrations of FCS examined, although growth varied in a dose-dependent manner. In contrast to OA synovial clones, cloned RA synoviocytes obtained from colonies exhibited a partial RFLP PGK-1 gene pattern, suggesting that the clones originated from monoclonal cells. Of note, 3 of 7 noncloned synoviocytes from pannus lesions exhibited a monoclonal pattern. Pannus cells produced high levels of transforming growth factor beta and platelet-derived growth factor. CONCLUSION: These findings suggest that synoviocytes with a strong growth ability are present in the rheumatoid synovium, and that these cells expand monoclonally, particularly in pannus lesions.

Adult↗

Extracellular human T cell leukemia virus type I tax protein stimulates the proliferation of human synovial cells.

OBJECTIVE: The present study was designed to investigate whether the proliferation of normal synovial cells from patients with meniscus injury is stimulated by human T cell leukemia virus type I (HTLV-I) Tax protein. METHODS: The effect of Tax protein on the proliferation of synovial cells was evaluated using a 3H-thymidine incorporation assay. Production of cytokines was determined by enzyme-linked immunosorbent assay. Nuclear factor kappaB (NF-kappaB) DNA binding activity and the transcription of several NF-kappaB-mediated genes was detected by electrophoretic mobility shift assay and reverse transcriptase-polymerase chain reaction. RESULTS: The proliferation of synovial cells, as well as their expression of tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor, and interleukin-6, was significantly enhanced by extracellular Tax at concentrations of 2.5 pM to 25 nM. In contrast, extracellular bacterial extract did not change the cytokine expression or the proliferation of these cells. Proliferation of synovial cells induced by Tax protein may be due to activated expression of several cytokines and protooncogenes that contain NF-kappaB regulatory sequences. CONCLUSION: Our results suggest that extracellular Tax can regulate the expression of endogenous cellular genes in synovial cells and may contribute to the NF-kappaB-mediated synovial hyperplasia.

Cell Division↗

Calcium disodium ethylenediaminetetraacetate-chelated lead as a predictor for subclinical lead neurotoxicity: follow-up study on gun-metal foundry workers.

OBJECTIVES: To examine if chelated lead was a more predictive indicator of the subclinical effect of lead on conduction velocities of faster or slower nerve fibers as compared with blood lead (BPb). METHODS: Distribution of conduction velocities (DCV) in large myelinated fibers of the sensory median nerve was measured twice at a 1-year interval in 17 male gun-metal foundry workers with BPb concentrations of 22-59 (mean 40.2) microg/dl and a mobilization yield of lead into urine (MPb) by calcium disodium ethylenediaminetetraacetate of 0.15-2.09 (mean 1.19) mg/24 h for the 1st year and in 20 healthy males (controls). RESULTS: Yearly changes in the conduction velocities of faster fibers were significantly correlated with the corresponding change in MPb (P < 0.05) but not with that in BPb (P > 0.05). In ten workers showing an increase in MPb during the 1-year period (0.44 mg/24 h on average) the conduction velocities of faster fibers were decreased significantly, resulting in the values being significantly lower in all the workers combined than in the controls (P < 0.05). On the other hand, in the remaining workers, who showed a lesser extent of reduction in MPb (0.08 mg/24 h on average), the DCV did not change (P > 0.05). CONCLUSION: Chelated lead might be a more predictive indicator of the effect of lead on the conduction velocities of faster fibers than blood lead.

Adult↗

Stress responses in three different anesthetic techniques for carbon dioxide laparoscopic cholecystectomy.

STUDY OBJECTIVE: To evaluate and compare the stress hormone responses during laparoscopic cholecystectomy during general anesthesia, general anesthesia supplemented by fentanyl, and general anesthesia combined with epidural anesthesia. DESIGN: Prospective, randomized clinical study. SETTING: Operating rooms at a municipal hospital. PATIENTS: 52 ASA physical status I and II patients. INTERVENTIONS: Anesthesia was induced slowly with sevoflurane and nitrous oxide (N2O) in oxygen (O2) by mask. Endotracheal intubation was facilitated with intravenous (i.v.) vecuronium 0.1 mg/kg. In 17 patients, anesthesia was maintained with sevoflurane and 50% N2O in O2. For another 18 patients, fentanyl 4 micrograms/kg was administered after endotracheal intubation, and anesthesia was maintained with sevoflurane and 50% N2O in O2. The remaining 17 patients received thoracic epidural anesthesia (1% mepivacaine in an 8 ml bolus followed by a continuous infusion of 1% mepivacaine, 3 ml/hr) after endotracheal inturbation, and general anesthesia was maintained with sevoflurane and 50% N2O in O2. End-tidal sevoflurane concentrations were adjusted to maintain mean arterial pressure between 70% and 100% of preinduction values. MEASUREMENTS AND MAIN RESULTS: Venous blood was sampled for measurements of cortisol and catecholamines (epinephrine and norepinephrine) immediately before and 30 minutes after surgical incision. Cortisol levels increased in all three anesthesia techniques. Both catecholamines increased in patients receiving general anesthesia only; catecholamines did not increase significantly in patients receiving general anesthesia combined with epidural anesthesia; in patients receiving general anesthesia supplemented with fentanyl, both catecholamines increased significantly, but the degree of increase in norepinephrine was less than that in the general anesthesia only group. CONCLUSIONS: The fentanyl supplemented group received relatively small doses insufficient to inhibit an increase in catecholamines. Thoracic epidural anesthesia depressed the sympathetic response presumably by blocking afferent sympathetic pathways under the conditions of this study. However, it did not attenuate an increase in cortisol, one of the hypothalamic-pituitary-adrenal stress hormones, during carbon dioxide laparoscopic cholecystectomy in our study. This action may be due to the inability of epidural anesthesia to block phrenic nerves that can convey noxious surgical stimulation to the central nervous system.

Anesthesia, Epidural↗

[Study on blood glucose control of subjects with borderline type abnormality in 75 G oral glucose tolerance test values. The establishment of a high risk group on the basis of yearly observations].

SUBJECTS AND METHODS: 227 of subjects with a 2-hour plasma glucose concentration of 120-199 mg/dl were selected from 413 participants who had two or more 75 g OGTT in health examinations from 1987-1995. From these subjects we established 8 groups according to initial 2-hour plasma glucose concentration 120-199 mg/dl stratified by 10 mg/dl, and calculated the total percentages of participants whose 2-hour plasma glucose concentration reached 200 mg/dl or greater over a 1-8 years (2.7 +/- 1.7 years, mean +/- SD) observation period. In 36 subjects who were tested annually over a four year period (4 times), the mean values of their 4 values were analyzed for relationships to coefficients of variation of the 2-hour plasma glucose. RESULTS: By stratified groups (from lowest to highest) of those with an initial plasma glucose concentration of 120-159 mg/dl, 7.4%, 12.1%, 16.1%, and 15.0% attained values of 200 mg/dl and higher, respectively in 1-8 years. On the other hand, 29.6%, 29.6%, 39.1%, and 47.4% of those with an initial plasma glucose concentration of 160-199 mg/dl moved to a diabetic type after 1-8 years, respectively. The percentages of those who ended up with levels of 200 mg/dl and greater at 2-hours tended to increase in subjects whose initial 2-hour plasma glucose concentration was over 160 mg/dl in comparison with patients below that initial level. CONCLUSIONS: From these results, it appears that subjects with 160-199 mg/dl 2-hour glucose concentration, which is considered a borderline status, are at high risk for future abnormal levels (> 200 mg/dl at 2-hours) and should be managed as a high risk level group for prevention of diabetes.

Blood Glucose↗

Accumulation of soluble Fas in inflamed joints of patients with rheumatoid arthritis.

OBJECTIVE: To examine the concentration of the soluble form of the Fas molecule (sFas) in the serum and synovial fluid of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: The concentration of sFas in the serum of 15 normal subjects and in the synovial fluid and serum of 45 RA patients and 13 OA patients was determined. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and the level of several cytokines in serum and synovial fluid were also determined. RESULTS: The synovial fluid concentration of sFas was higher in RA than in OA patients (P < 0.005). The synovial fluid level of sFas correlated weakly with serum levels of CRP (r = 0.541), the ESR (r = 0.499), and with synovial fluid levels of interleukin-2 (IL-2) receptor (r = 0.544), IL-6 (r = -0.529), and intercellular adhesion molecule 1 (r = 0.514). Reverse transcription-polymerase chain reaction analysis revealed that synovial cells and infiltrating mononuclear cells expressed sFas messenger RNA in RA patients. CONCLUSION: Our data suggest that accumulation of sFas in the joint cavity of RA patients may inhibit apoptosis and exacerbate the inflammatory process.

Aged↗

Tenosynovial nodulosis in a patient infected with human T cell lymphotropic virus I.

We describe a 45-year-old man who presented with multiple nodules along the tendons of the scapular region, the elbows, wrists, forearms, thighs, and ankles. The patient was a carrier of human T cell lymphotropic virus I (HTLV-I), which was probably transmitted from his mother; his mother also had polyarthritis. Histopathologically, the nodules consisted of numerous, small, fibrinoid masses. The synovium adjacent to the tendon sheath was hyperplastic, with fibrinoid necrosis mimicking rheumatoid synovium. However, synovitis was not present inside the adjacent joint. HTLV-I proviral DNA was detected in the cells of the nodule, in tenosynovial cells, and in peripheral blood lymphocytes, but not in skin fibroblasts. In situ reverse transcription assay showed a high quantity of tax/rex messenger RNA in the proliferating lining cells. Based on these features, we classified this case as an atypical manifestation of HTLV-I-associated arthropathy associated with fibrinoid nodules resulting from chronic tenosynovitis.

Carrier State↗

Characterisation of fibroblast-like cells in pannus lesions of patients with rheumatoid arthritis sharing properties of fibroblasts and chondrocytes.

OBJECTIVE: To better understand the characteristics of synoviocytes located in the rheumatoid arthritis (RA) pannus. METHODS: One cell line, termed PSC, was cloned from RA pannus lesions. Phenotypic analysis was done by contrast microscopy, indirect immunostaining, and safranin O staining. Transcription of several protooncogenes and matrix degrading enzymes was evaluated. The expression of mRNA for collagen II was detected by in situ hybridisation. The ability of anchorage independent growth was assessed by soft agarose culture. RESULTS: PSCs showed a high transcription of protooncogenes c-fos, c-myc and c-jun. They also expressed mRNA for matrix degrading enzymes, such as collagenase, cathepsin B, and cathepsin L. Anchorage independent growth assay demonstrated that PSCs formed colonies in soft agar culture. Phenotypic analysis showed that this fibroblast-like PSC was stained intensely with anti-vimentin and anti-fibroblast antibody. In situ reverse transcriptase assay showed that the cell line expressed type II collagen mRNA. CONCLUSION: Alternative fibroblast-like cells were identified in the pannus lesion of RA sharing properties of fibroblasts and chondrocytes. These findings suggest that this fibroblast-like cell derived from pannus lesions may contribute to the destruction of the cartilage in RA.

Aged↗

Heart disease deaths on death certificates re-evaluated by clinical records in a Japanese city.

In order to estimate the number of deaths from ischemic heart disease (IHD) in a Japanese city, we reevaluated heart disease deaths among residents aged 25-74 years by examining their clinical records. During the 2-year period from 1987 to 1988, 271 deaths among this population were attributed to heart disease. The recorded underlying cause of death was IHD in 96 cases, heart failure in 123 cases, and other heart disease in 52 cases. Re-evaluation of the cause of death yielded 57 cases of acute myocardial infarction (AMI), 85 cases of sudden death, 37 cases of heart disease other than IHD, and 63 cases of non-heart disease. In the remaining cases, there was insufficient information for evaluation. According to some autopsy studies, about 50% of sudden deaths are due to IHD. Thus, 50% of the number of sudden death cases may be added to the total number of IHD deaths. Accordingly, the total number of IHD deaths may have been 100, ie, 57 cases of AMI plus 43 cases of sudden death. The difference between the number of IHD deaths after re-evaluation and the number for which IHD was recorded as the underlying cause was small, with the former only 4% higher than the latter. The number of false-positives was equal to the number of false-negatives, and hence the number of IHD deaths recorded in this area seems to be close to the actual figure. We speculate that more accurate death certification will result in a decrease in the total number of deaths attributable to heart disease, as in 23% of deaths attributed to heart disease the underlying cause of death was not in fact heart disease.

Adult↗

Prevalence of risk factors for coronary heart disease among Dominicans in the Dominican Republic: comparison with Japanese and Americans using existing data.

Risk factors of coronary heart disease (CHD) in Dominicans were compared with those of Japanese and Americans for the presumption of prevalence of CHD in about 2000 persons. Dominican adults aged 20 through 76 years were medically examined in 1993. Data of nationally representative Japanese and Americans which included serum lipid levels were compared. Total cholesterol levels(TCH) in Dominicans were lower than those in Americans. High-density lipoprotein cholesterol levels in Dominicans were lower than those in Japanese and Americans. The prevalence of hypertension and current smoking rates in Dominicans were similar to that of Americans and lower than that of Japanese. TCH in Americans have substantially been declining and those in Japanese were inadequate for preventing CHD. The prevalence of CHD in Dominicans may be lower than that of Americans viewed from the recent levels of main risk factors. Community wide health programs have spread to people with hypertension a decrease in the incidence of CHD should occur.

Adult↗

[Reevaluation of heart disease deaths on death certificates and trends for ischemic heart disease mortality during the last five years in Oita city].

To evaluate heart disease deaths and clarify trends for ischemic heart disease (IHD) mortality during the last five years in Oita City, we reevaluated causes of death on death certificates. In 1993, there were 253,000 people aged 25-74 in Oita City. In this population age group, there were 1,996 deaths from January 1992 through December 1993. Our subjects were 982 deaths recorded as caused by heart disease and IHD related diseases. Subjects were reevaluated on the basis of physician's interview, clinical records and police records. This IHD reevaluation was conducted by the WHO MONICA criteria. The death certificates identified 321 heart disease deaths, of which there were 80 (24.9%) acute myocardial infarctions (AMI), 22 (6.9%) other IHD, 180 (56.1%) heart failures, and 39 (12.1%) other heart diseases. The remaining 61 deaths were caused by other diseases. After reevaluation, 40 'definite' AMI and 60 'possible' AMI were recognized through the MONICA criteria, 86 sudden deaths (SD) which were defined as, 'death within 24 hours of the onset of acute symptoms and without clear signs suggesting what disease was the cause,' were also classified. Assuming that 50% of SD were due to IHD, according to some postmortem autopsy studies, aged-standardized IHD mortality per 100,000 for males was 38.3 per year and for females 17.3 per year in this period. Both mortality rates, 31% for males and 38% for females, were higher than IHD mortality statistics. Moreover, in comparison with IHD mortality estimated by reevaluation of heart disease in Oita City in 1987-88, age-standardized IHD mortality per 100,000 for males has remained basically stable, increasing from 37.8 to 38.4 during the last five years. On the other hand, mortality for females has increased from 11.2 to 17.3. Our results suggest that mortality from IHD actually was about 30% more than mortality statistics, and does not show a declining trend as mortality statistics have stated.

Adult↗

[Effect of injection speed on sensory blockade in spinal anesthesia with 0.5% hyperbaric tetracaine].

We investigation the effect of injection speed on sensory blockade in spinal anesthesia. Forty two female patients, scheduled for total abdominal hysterectomy, were allocated randomly to 3 groups of 14 each according to the injection speed of 0.5% hyperbaric tetracaine: Group F (fast; injection speed > or = 0.2 ml.s-1), Group M (moderate; 0.1 < injection speed < 0.2 ml.s-1) and Group S (slow; injection speed < or = 0.1 ml.s-1). Spinal puncture was performed via the median approach at the L3-4 interspace with the patient in a lateral position. The maximum level of sensory blockade was assessed by means of the pin-prick method in the midline 3, 5, 10, 20, 30, 60 minutes after injection. In Group F, the level of sensory blockade became higher quickly (within 5 min), but anesthetic effects were not so satisfactory. And, in this group, there were more patients with dyspnea than in other groups. We speculate that the turbulence made by fast injection in subarachnoid space caused unsatisfactory effects. In Group S, anesthetic level was becoming higher also 20 or 30 min after injection. The fixation of anesthetics requires about 30 min. In our opinion, anesthetics injected slowly were diluted less by CSF, and the actual baricity of them was higher, and this made the difference within 30 min. In Group M, anesthetic effects and patient's condition were stable. We suppose that this injection speed (0.1-0.2 ml.s-1) is suitable for spinal anesthesia.

Adult↗

Amelioration of type II collagen induced arthritis in rats by treatment with thymulin.

OBJECTIVE: To investigate the effects of thymulin (serum thymic factor + Zn2+) in collagen induced arthritis (CIA) in rats. METHODS: SD rats were immunized with bovine type II collagen plus Freund's incomplete adjuvant, and thymulin was administered intraperitoneally on the first day of first immunization. We determined the level of serum thymulin by rosette inhibition assay. Effects of thymulin on CIA rats were estimated by measuring the extent of hind paw edema, the level of serum anti-type II collagen antibody, and changes in histopathological features of the affected joints. RESULTS: Serum thymulin levels in CIA rats were significantly lower than in untreated rats. Thymulin diminished hind paw swelling and onset of arthritis compared with control rats. The serum anti-type II collagen antibody level was also reduced by thymulin. Histopathological examination showed inhibition of granulation tissue and new bone formation after injection of thymulin. CONCLUSION: Our results suggest thymulin plays a significant role in the onset and development of CIA in rats. Our data indicate thymulin may be therapeutically effective in preventing the development of rheumatoid arthritis.

Animals↗

Therapeutic effect of the anti-Fas antibody on arthritis in HTLV-1 tax transgenic mice.

We have recently demonstrated Fas-mediated apoptosis in the synovium, of patients with rheumatoid arthritis (RA) and suggested that it may be one factor responsible for the regression of RA. To examine whether the induction of apoptosis caused by anti-Fas mAb may play a potential role as a new therapeutic strategy for RA, we investigated the effect of anti-Fas mAb (RK-8) on synovitis in an animal model of RA, the human T cell leukemia virus type I (HTLV-1) tax transgenic mice. We report here that administration of anti-Fas mAb into mice intra-articularly improved the paw swelling and arthritis within 48 h. Immunohistochemical study and in vitro culture studies showed that 35% of synovial fibroblasts, 75% of mononuclear cells, and some of polymorphonuclear leukocytes infiltrating in synovium underwent apoptosis by anti-Fas mAb. In situ nick end labeling analysis and electron microscope analysis clearly showed that many cells in synovium were induced apoptosis by anti-Fas mAb administration. However, local administration of anti-Fas mAb did not produce systemic side effects. Results demonstrated that administration of anti-Fas mAb in arthritic joints of the HTLV-1 tax transgenic mice produced improvement of arthritis. These findings suggest that local administration of anti-Fas mAb may represent a useful therapeutic strategy for proliferative synovitis such as RA.

Alanine Transaminase↗

Activation of transcription factor NF-kappa B in human synovial cells in response to tumor necrosis factor alpha.

OBJECTIVE: To examine whether nuclear factor kappaB (NF-kappaB) is activated in cultured synovial cells in response to tumor necrosis factor alpha (TNFalpha) and to investigate the correlation between NF-kappaB activation and synovial cell proliferation. METHODS: Activation of NF-kappaB was detected by electrophoretic mobility shift assay. The transcription of several NF-kappaB-dependent genes was evaluated by reverse transcriptase polymerase chain reaction and transient expression assay using human immunodeficiency virus-long terminal repeat chloramphenicol acetyltransferase. Proliferative activity was determined by measurement of 3H-thymidine incorporation. RESULTS: Stimulation of synovial cells with TNFalpha activated NF-kappaB and subsequent transcription of several genes. Treatment of synovial cells with N-acetyl-L-cysteine (NAC), an antioxidant agent, inhibited TNFalpha-induced NF-kappaB activation and transcription. Moreover, NAC also inhibited synovial cell proliferation induced by TNFalpha. CONCLUSION: Our results suggest that NF-kappaB plays a pivotal role in synovial cell activation by TNFalpha. Thus, suppression of NF-kappaB could be a potential therapeutic modality for synovitis such as that of rheumatoid arthritis.

Acetylcysteine↗

Induction of Fas-dependent apoptosis in synovial infiltrating cells in rheumatoid arthritis.

Apoptosis is a feature of the synovium of rheumatoid arthritis (RA). We have recently shown that RA synoviocytes were susceptible to anti-Fas mAb and undergo apoptosis in vitro. To investigate whether infiltrating mononuclear cells also undergo Fas-dependent apoptosis, double-labeling techniques combined with immunohistochemical examination with anti-CD3 mAb and the TdT-mediated dUTP-blotin nick end labeling (TUNEL) method to detect apoptotic cells, or in situ RT assay to detect Fas mRNA, were performed using frozen tissue sections. We also examined the in vitro induction of Fas-dependent apoptosis in freshly isolated synovium infiltrating mononuclear cells (SIM), synovial stromal cells (SSC) and peripheral blood lymphocytes (PBL) using tissues from nine patients with RA and three with osteoarthritis (OA). The results showed expression of Fas antigen and apoptotic cells in a number of CD3-bearing cells in RA synovial tissues. In vitro treatment with anti-Fas mAb produced a significant apoptosis of RA SIM and SSC, while none of PBL, and neither SIM nor SSC from OA exhibited apoptosis. Moreover, approximately 50% of CD4+, CD3+ and CD45RO+ cells, and > 90% of Fas-expressing cells of RA SIM underwent apoptosis in response to anti-Fas mAb, as detected by flow cytometry. Our results suggest that RA synovial infiltrating lymphocytes acquire high susceptibility to anti-Fas mAb and undergo apoptosis. Such a phenomenon of infiltrating T cells in RA synovium may play an important pathophysiological role and suggest a possible therapeutic effect for anti-Fas mAb in RA.

Aged↗

[Clinical features and prognosis of facial palsy and hearing loss in patients with Ramsay Hunt syndrome].

Clinical studies were performed on 325 patients with Ramsay Hunt syndrome who were treated in the Facial Nerve Clinic at Ehime University Hospital between 1976 and 1995. The clinical manifestations of Ramsay Hunt syndrome were various. Three major symptoms, auricular vesicles, facial paralysis and vestibulo-cochlear dysfunction, were found in 57.6% of the patients although these symptoms did not always appear simultaneously. Auricular vesicles appeared before (19.3%), during (46.5%), or after (34.2%) the onset of facial paralysis. Hearing loss was observed subjectively in only 20% but objectively in 48.2% of the patients. Hearing loss appeared before (34.3%), during (34.3%), or after (31.3%) the onset of facial paralysis. Complete recovery from facial paralysis was achieved in 52.4% of the patients. Good recovery of the facial nerve function was achieved in patients who had zoster vesicles or vestibulo-cochlear dysfunction preceding the development of facial paralysis. Complete recovery of hearing was also achieved in 45.4% of the patients, and the recovery was better in patients having light hearing loss, less than 35dB. The patients younger than 16 years old showed better recovery from both facial paralysis and hearing loss than the patients older than 60 years. Glossopharyngeal nerve or vagal nerve paralysis concomitant with facial paralysis was found in 8 (2.5%) patients. The outcome of glossopharyngeal nerve paralysis was good but that of the vagal nerve was poor.

Adolescent↗