Toshio Ushiyama

Cytokine production in the infrapatellar fat pad: another source of cytokines in knee synovial fluids

Background: Recent studies have shown that adipose tissue is an endocrine organ that releases various cytokines. Objective: To investigate the production of growth factors and proinflammatory cytokines in infrapatellar fat pad specimens. Methods: Infrapatellar fat pad tissues were obtained from patients during knee surgery. Protein levels of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), tumour necrosis factor (TNF)α, and interleukin (IL)6 in homogenised tissues were measured by an enzyme immunoassay. Gene expressions for those cytokines were examined by reverse transcription-polymerase chain reaction (RT-PCR). Localisation of bFGF and VEGF was evaluated by immunohistochemistry and in situ hybridisation. Results: Infrapatellar fat pads were found to contain various protein levels of bFGF, VEGF, TNFα, and IL6. Further, gene expressions for these cytokines were detected by RT-PCR. Immunohistochemistry and in situ hybridisation showed that the expressions of both bFGF and VEGF were localised in immature adipocytes, interstitial undifferentiated mesenchymal cells, and vascular endothelial cells. Conclusion: The production of bFGF, VEGF, TNFα, and IL6 in the infrapatellar fat pad was demonstrated. Although synovial cells and articular chondrocytes are thought to be primary sources of cytokines found in knee synovial fluids, the results suggest that they may also originate from this fat pad.

Changes in the incidence and prevalence of rheumatoid arthritis in Kamitonda, Wakayama, Japan, 1965–1996

OBJECTIVE To evaluate secular trends in the incidence and prevalence of rheumatoid arthritis (RA) in Japan. METHODS The incidence and prevalence of RA were determined in a longitudinal population based study in the Kamitonda district, Wakayama, Japan, from 1965 to 1996. RESULTS In the study area consisting of about 3000 inhabitants, 16 incident cases, satisfying definite RA by the Rome criteria were detected during the study period. The age and sex adjusted incidence in both men and women combined and the age adjusted incidence in women significantly decreased (p<0.025 and p<0.01, respectively). The age and sex adjusted prevalence in all inhabitants tended to decrease (p<0.1), and the age adjusted prevalence in women significantly declined (p<0.025). In men, however, neither incidence nor prevalence showed significant change. CONCLUSIONS The decline of incidence and prevalence of female RA may be reducible to some environmental changes preferentially occurring more obviously in Japanese women than in men. Because the use of oral contraceptives has been extremely low in Japan, the decline should be explained by other factors.

Association of oestrogen receptor gene polymorphisms with age at onset of rheumatoid arthritis

OBJECTIVE In view of the possible role of oestrogens in the pathogenesis of rheumatoid arthritis (RA), this study investigated the association between oestrogen receptor (OR) gene polymorphisms and RA. METHODS Pvu II and Xba I restriction fragment length polymorphisms of the OR gene were analysed in 70 male and 240 female patients with RA, and in 300 male and 350 female controls. The absence or presence of restriction sites were represented as P, p (Pvu II ) or X, x (Xba I ). The distribution of OR genotypes was compared between the RA and control subjects by sex. RA patients were divided into subgroups according to their OR genotypes, then the age at onset, seropositivity, and rheumatoid nodule positivity were compared between the subgroups. RESULTS The OR genotype frequency of distribution did not have significant differences between the male RA and male controls nor between the female RA and female controls. In women with RA, there was a significant difference of age at onset between the subgroups (uncorrected p=0.047, corrected p=0.94). Female patients with the OR genotype PPxx (homozygote of Px) tended to have developed RA at a younger age, whereas those with PPXX and ppxx (lack of Px haplotype) developed RA at an older age. In men with RA, there was no association between the OR genotype and age at onset. In seropositivity and rheumatoid nodule positivity, there was no significant difference between subgroups for either sex. CONCLUSIONS Some variants of the OR gene are related to the onset of RA in women in certain age periods, suggesting the role of the interaction between the OR gene and serum concentrations of oestrogen at the onset of the disease.

Polymorphic CAG repeats of the androgen receptor gene and rheumatoid arthritis

OBJECTIVE In view of the possible role of androgens in the pathogenesis of rheumatoid arthritis (RA), this study investigated the association between repeat lengths of CAG microsatellites of the androgen receptor (AR) gene and RA. METHODS The number of CAG repeats in exon 1 of the AR gene was determined in 90 men and 276 women with RA, as well as in 305 male and 332 female controls. RESULTS The male RA patients tended to have shorter repeats than the male controls (22.5 versus 23.1, p=0.07), whereas the female RA patients had similar repeats to the female controls (22.7 versus 22.9, p=0.17). Patients of both sexes were divided into younger and older age at onset groups, and compared with younger and older controls. Younger onset male RA patients had significantly shorter CAG repeat lengths than the younger male controls (21.8 versus 23.2, p=0.007) or the older onset male RA patients (21.8 versus 23.2, p=0.04). Older onset male RA and both younger and older onset female RA patients had similar CAG repeat lengths when compared with their controls. Neither seropositivity nor rheumatoid nodule positivity had a significant relation with CAG repeat lengths. CONCLUSION Shorter CAG repeats of the AR gene, presenting high levels of transactivation activity, are related to younger age onset male RA, suggesting the possible role of androgens as a modulating factor.

Perforated Appendicitis Causing Thigh Emphysema: A Case Report

We report a case of thigh emphysema resulting from perforated appendicitis. The patient was an 83-year-old man who had no apparent abdominal signs and was initially misdiagnosed as having psoas abscess. Magnetic resonance imaging of the pelvis revealed appendicitis, and a barium enema showed a leakage of enhanced contrast material from the appendix region down into the thigh. A retroperitoneal perforation of the retrocaecal appendix without peritonitis was diagnosed. The patient underwent an appendectomy and curettage of the retroperitoneal and psoas muscle spaces, as well as the thigh. He recovered gradually, though the abscess had extended into the hip joint and resulted in osteomyelitis, requiring an additional procedure of resection arthroplasty. The patient fully recovered with no signs of infection one year postoperatively.

Sociodemographic factors and failure of hip arthroplasty

Abstract To identify the sociodemographic and lifestyle factors related to development of aseptic loosening after a cemented total hip arthroplasty (THA), 151 consecutive primary THAs performed at a single hospital in a rural district of Japan, at a mean follow-up of 7.5 years, were reviewed. Based on the medical records collected during hospital admission for THA, in which sociodemographic and lifestyle backgrounds had been recorded by the nurse, answers regarding residence, education, employment, engagement in agricultural work, marital status, family members living together, religion, recreational activity, smoking, and alcohol intake were analyzed in relation to the development of loosening, using a multivariate Cox proportional hazards model. With adjustment for cementing technique, diagnosis, age, and sex, agricultural work had a significant relation with prosthetic loosening (relative risk =2.85, P=0.03). Restriction of physical work in agriculture for patients undergoing THA should be considered.Résumé Afin d’identifier les habitudes de vie et les facteurs sociodemographiques relies au developpement d’un descellement aseptique apres une arthroplastie totale scellee de la hanche (THA), ont été recensées 151 THA primaires consécutives realisees dans un hopital de region rurale au Japon, avec observation moyenne de 7.5 annees. Sur la base des dossiers médicaux des patients admis pour une THA, dans lesquels des données avaient été recueillies en entrevue par les infirmieres sur les facteurs sociodemographiques et sur les habitudes de vie (type de residence, education, emploi, activites agricoles, etat civil, cohabitation des membres de la famille, religion, activites récreatives, consommation de tabac et d’alcool), ces donnees furent analysées en relation avec le developpement d’un descellement, a l’aide du Modèle de regression a effet proportionnel et a variantes multiples de Cox. Apres ajustements en fonction de la technique de scellement, du diagnostic, de l’age et du sexe, une relation significative entre le descellement et l’engagement dans des activites agricoles a été trouvée (risque relatif=2.85, P=0.03). Des restrictions au niveau du travail physique agricole devraient etre envisagees pour les personnes ayant subi une THA.

Gene expressions of antiinflammatory mediators in THR retrieved interfacial membranes.

We investigated gene expression of antiinflammatory mediators in the interfacial membranes retrieved at hip revision arthroplasty using reverse transcription-polymerase chain reaction (RT-PCR). Levels of RT-PCR products were compared with those of synovial tissue from patients with osteoarthrosis or rheumatoid arthritis. Antiinflammatory mediators such as type II interleukin (IL)-1 receptor, IL-4, IL-10, IL-1 receptor antagonist, and transforming growth factor-beta 1 (TGF-beta 1) were expressed in the interfacial membrane. In interfacial tissue, the level of IL-10 was lower, but that of the IL-1 receptor antagonist higher than in diseased synovial tissue.

Spinal degenerative lesions and spinal ligamentous ossifications in ancient Chinese populations of the Yellow River Civilization

Rheumatological diseases, whether inflammatory or degenerative, are ubiquitous among modern Asian people but very few palaeopathological studies have been performed in Asia on this subject. Since 1996, we have been carrying out a palaeoepidemiological survey of rheumatic diseases in ancient Chinese and Japanese skeletal populations. Findings on the spinal column in ancient Chinese populations (ca. 5000 bc–ad 1644) in Henan Province (centre of the Yellow River Civilization) are reported in this study. The examined number of the people over 20 years old was 365 (185 males, 169 females and 11 unsexed). Of these, 248 were young adults, 98 were middle adults and 19 were old adults. Crude prevalence (number/100) in total population of vertebral osteophytosis/facet osteoarthritis was 17.5/7.7, 17/3.7 and 44.6/21.1 at the cervical, thoracic and lumbar spine, respectively. That of ossified anterior longitudinal ligament (OALL) or Forestiers disease was around 3 at each of the cervical, thoracic and lumbar spine. Ossification of the posterior longitudinal ligament (OPLL) of the cervical spine was observed in five out of 114 skeletons with cervical spine preserved, while it did not exist in any thoracic and lumbar segment. Ossification of the ligamentum flavum (OLF) was predominantly observed in the thoracic spine, the crude prevalence of which was 36.7. Overall spinal degenerative lesions seemed to have been more prevalent and spinal ligament ossifications less prevalent in ancient Chinese populations than in modern people. None of the inflammatory lesions like rheumatoid spondylitis, as well as seronegative spondyloarthropathies, were detected. This is the first palaeopathological study in which the prevalence of OPLL and OLF, the two clinically important spinal ligamentous ossifications causing myelopathy in modern mankind, was surveyed in ancient skeletons. Copyright

Increased rate of hysterectomy in women undergoing surgery for osteoarthritis of the knee

We performed a case-controlled study to determine whether previous gynecological surgery is associated with severe osteoarthritis (OA) of the knee, the hip or the spine, as well as mild OA of the knee. Patients who underwent surgical treatment for OA were defined as having severe OA. Patients with knee pain and radiographic grade 2 OA in a tibiofemoral joint on the Kellgren and Lawrence scale were defined as having mild knee OA. An increased rate of hysterectomy was observed in the severe knee OA group after adjustment for age and number of children, or even after adjustment for body mass index. Hysterectomy in this group was most often performed for myoma uteri. Patients with mild knee OA tended to have previous hysterectomy. From the results, we speculate that certain subsets of OA which often take a progressive course might be related to hysterectomy.

Association of CYP17 with HLA-B27-negative seronegative spondyloarthropathy in Japanese males.

Susceptibility genes for seronegative spondyloarthropathy (SNSA) other than HLA‐B27 remain unclarified. Sex hormones are implicated in the pathogenesis of SNSA. Cytochrome P450c17a (CYP17) is a key regulator of androgen biosynthesis, and a single nucleotide polymorphism (SNP) in the 5′‐untranslated region of the CYP17 gene (CYP17), −34C > T, is associated with variety of diseases. We have investigated the association between the CYP17 SNP and SNSA in Japanese males. Genomic DNA was extracted from 149 Japanese male SNSA patients and 380 controls. The CYP17 SNP was genotyped using polymerase chain reaction‐restriction fragment length polymorphism analysis. Allelic and genotypic frequencies of the SNP were compared between SNSA patients and controls, and within SNSA patients. We also computed haplotype frequencies using an expectation‐maximization algorithm, analyzed the difference between SNSA and control groups, and examined the potential association of other known SNPs in the CYP17 gene. The frequency of the −34T allele was significantly increased in HLA‐B27‐negative SNSA, but not in total or HLA‐B27‐positive SNSA when compared to controls. The T allele was more prevalent in HLA‐B27‐negative SNSA than in HLA‐B27‐positive SNSA, and the T/T genotype was over‐represented in HLA‐B27‐negative SNSA. Haplotype analysis did not demonstrate more significant association. The CYP17 SNP is associated with SNSA in HLA‐B27‐negative Japanese males.