Polyarthritis and bone lesions complicating traumatic pancreatitis in two children.

The association of bone lesions, polyarthritis and cutaneous nodules with pancreatic disease is being recognized and reported more frequently. In adults all forms of pancreatitis and carcinoma of the pancreas have been involved, but in the few children described these complications have been associated with acute traumatic pancreatitis. This paper describes two cases of acute traumatic pancreatitis in which polyarthritis and limb pains were noted after 2 to 3 weeks. In one child osteolytic lesions and periostitis were seen on roentgenograms 7 weeks after the onset of pancreatitis. In the other child minor roentgenographic changes were not seen until 5 months after the onset; however, bone scans showed clear-cut abnormalities after 1 month. Almost complete resolution could be expected within a year. Serum lipase and amylase concentrations remained elevated during the acute illness. Disseminated fat necrosis is apparently related to the excess amounts of circulating lipase.     

Pretreatment of rats with anticollagen IgG renders them resistant to active type II collagen arthritis

Intravenous administration of 24 mg of affinity-purified rat anticollagen IgG induced a polyarthritis in recipient rats within 48 hr. This polyarthritis was transient and hind paw diameters returned to normal values within 12 days. IgG and C3 could be detected on the articular cartilage by immunofluorescence up to 16 days after antibody administration. Administration of 24 mg of rat anticollagen IgG to these antibody-treated rats did not induce a second phase of polyarthritis. In addition, recovered rats that had been pretreated with antibody were resistant to arthritis when Type II collagen was administered intradermally. In these rats, serum anticollagen IgG levels were significantly lower than in control rats which were not treated with antibody. Pretreatment of rats with anticollagen IgG did not have an effect on the severity or the incidence of adjuvant-induced arthritis. In addition, pretreatment of rats with anticollagen IgG did not have an effect on the development of a humoral response to ovalbumin.     

抗RA33抗体与幼年特发性关节炎的诊断意义

目的：通过检测幼年特发性关节炎（JIA）患者血清中的抗RA33抗体,了解抗RA33抗体与幼年特发性关节炎的临床诊断价值。方法：采用酶联免疫固相分析检测81例JIA患儿（女19名,男62名,平均年龄8.6岁,平均病程1.4年）血清中抗RA33抗体、RF,同时以55例儿童系统性红斑狼疮（SLE）等其他关节性疾病或病毒感染患者和49例健康儿童作为对照组。阴阳性结果判断均采用试剂盒推荐的临界值。结果：81例JIA患儿中抗RA33抗体阳性率为11.11%（9/81）,RF阳性率为12.35%（10/81）,特异性均为91.35%;JIA组与正常对照组抗RA33抗体阳性率比较有统计学意义（P〈0.05）,与其他关节性疾病对照组比较差异无显著性（P〉0.05）。JIA组中抗RA33抗体的检出与RF无相关性（P〉0.05）;在JIA各亚型中抗RA33抗体主要存在于全身型和多关节型,各占33.3%和25.0%,RF则只出现于多关节型,占62.5%。两者比较有显著性差异（P〈0.05）。81例JIA患儿中共有18例关节出现影像学改变,其中4例抗RA33抗体阳性（22.2%）,与未发生影像学改变的JIA患儿比较无显著性差异（P〉0.05）。结论：抗RA33抗体尚不能作为JIA早期诊断的新的可靠性指标,抗RA33抗体主要见于全身型和多关节型,对JIA的分型有指导意义。     

Propylthiouracil hypersensitivity with circumstantial evidence for drug-induced reversible sensorineural deafness: a case report.

Severe adverse reactions to propylthiouracil occur in 1-5% of patients. Three major side effects, namely agranulocytosis, hepatotoxicity and drug-induced hypersensitivity, have been described though these syndromes are not distinct entities and there can be overlaps in the clinical manifestations. The drug-induced hypersensitivity may be an immune-mediated reaction with multiorgan involvement in which a combination of polyarthritis, cutaneous vasculitis and fever is common. We report a patient with propylthiouracil-induced hypersensitivity with an unusual combination of high spiking fever, migratory polyarthritis, reversible sensorineural deafness, normochromic normocytic anaemia, leucocytosis and hepatotoxicity associated with polyclonal activation of multiple autoantibodies. This case illustrates the highly variable clinical manifestations of the syndrome. The prompt recovery upon withdrawal of the drug indicates the importance of early diagnosis.     

Benorylate in Management of Still's Disease

The present recommended dose of benorylate is not satisfactory for the management of children suffering from inflammatory polyarthritis. A starting dose of 200 mg/kg/day should be used, and the salicylate level checked at seven days and the dosage adjusted to give an anti-inflammatory effect—that is, a blood salicylate level of between 25 and 30 mg/100 ml. Once a satisfactory level has been achieved, this dosage should be maintained with occasional monitoring of the salicylate level. The paracetamol level does not need to be estimated as it tends to follow the salicylate level, provided that liver function is normal; thus it is quite safe to monitor only the salicylate level. Given in an adequate dosage, benorylate seems to be an acceptable salicylate preparation for use in juveniles suffering from chronic polyarthritis.     

Gene transfer in Mycoplasma arthritidis: transformation, conjugal transfer of Tn916, and evidence for a restriction system recognizing AGCT.

Mycoplasma arthritidis is a rat pathogen causing a severe polyarthritis. The study of its pathogenic mechanisms has been hampered by the lack of genetic systems for use with M. arthritidis. Described here are procedures for genetic transformation of M. arthritidis and conjugal transfer of Tn916 from an enterococcal donor to M. arthritidis. The location of Tn916 insertion sites in the mycoplasmal chromosome was random, suggesting that Tn916 may be useful as an insertional mutagen in this organism. Additionally, a restriction and modification system was identified which presented a strong barrier to gene transfer. For transformation, the restriction system was circumvented by using DNA that was modified in vitro with the appropriate site-specific methylase (AluI).     

Arboviruses associated with human disease in Australia

Mosquito-borne arboviruses are an important public health issue in Australia. The alphaviruses Ross River and Barmah Forest virus are widespread and active annually, and cause debilitating polyarthritis. The flaviviruses Murray Valley encephalitis, Kunjin and Japanese encephalitis virus are restricted in distribution and activity but may cause life-threatening illness, and dengue viruses are active in some areas.     

Anti-inflammatory, antiarthritic and analgesic activity of a herbal formulation (DRF/AY/4012)

Anti-inflammatory, antiarthritic and analgesic effect of a herbal product (DRF/AY/4012) was evaluated in animal models. Herbal product treatment induced a dose dependent anti-inflammatory activity in acute inflammatory models (carrageenin and egg-albumin induced rat hind paw edema). It also elicited promising anti-inflammatory activity in chronic inflammatory models (cotton pellet granuloma and Freund's adjuvant induced polyarthritis in rats). Further, the product inhibited the increased level of serum lysosomal enzyme activity viz. serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase and the lipid peroxidation in liver. In Freund's adjuvant induced polyarthritis, herbal product reduced the increased level of hydroxy proline, hexosamine and total protein content in edematous tissue. The product also exhibited mild to moderate analgesic activity in acetic acid induced writhing in mice. The LD50 value of the herbal product was more than 16 gm/kg by oral route in mice. The product has distinct advantages over the existing agents and deserves further developmental studies.     

Altered signalling thresholds in T lymphocytes cause autoimmune arthritis

The development of spontaneous autoimmunity in inbred strains of rodents has allowed us to investigate the molecular basis of chronic inflammatory disease in ways that would not be possible in humans. Recently, two new mouse models of autoimmune inflammatory polyarthritis have been reported that demonstrate how alterations in signalling thresholds sufficient to perturb central T-cell tolerance lead to inflammatory arthritis. These mice provide new insights into the complexities of what may turn out to be a heterogeneous group of diseases that we call rheumatoid arthritis. They will also provide unique tools for dissecting precisely how chronically activated T cells contribute to the effector phase of arthritis through mechanisms that may be less dependent on antigen receptor signalling.     

Effect of intraperitoneal administration of Streptococcus group A and its cell fractions on the development of adjuvant arthritis in rats

The effect produced by the intraperitoneal injection of live and heat-killed group A streptococci, the fractions of their cell walls (both intact and sonicated) and cytoplasm was studied on 450 white rats with experimental adjuvant arthritis (AA). The injection of live streptococci into rats with AA decreased the swelling of joints (by 70-80% in the second half of the experiment), reduced the titers of rheumatoid-like factor (RLF), and inhibited the development of polyarthritis. The use of heat-killed streptococci gave a less pronounced antiarthritic effect, while the fraction of streptococcal cell walls, similarly to live streptococci, decreased the swelling of joints (by 27-64%); at the same time a considerable drop in the titers of RLF was observed in 3 experiments, and the development of polyarthritis was registered in 38% of the test animals and in 62% of the control animals. In rats with AA the cytoplasm not subjected to ultracentrifugal purification decreased the swelling of joints (by 21-50%) and the titers of RLF. In this case the development of polyarthritis was observed in 48% of the test animals and in 70% of the control animals.     

Haptoglobin groups and rheumatoid arthritis

Haptoglobin types were determined in 200 patients with rheumatoid arthritis (RA) subdivided according to sex and familial occurrence of polyarthritis. A highly significant excess of the Hp2 gene was found among patients with a family history of polyarthritis, more pronounced among males. The possible association between Hp2 and predisposition for increased immune reactivity is discussed.     

CERNA2: A predictor for clinical progression and poor prognosis in cervical carcinoma

Competing long noncoding RNA 2 (lncRNA 2) for microRNA let-7b (CERNA2) has emerged as an important regulator of tumorigenesis and cancer progression but the clinical value and regulatory function of CERNA2 is yet to be investigated in cervical carcinoma. In our study, we found the CERNA2 expression was obviously increased in cervical carcinoma tissues compared with adjacent normal cervical tissues. In addition, we observed that metastatic lymph nodes exhibited high levels of CERNA2 expression in contrast to primary cervical carcinoma tissues. Furthermore, high CERNA2 expression was associated with advanced clinical stage, lymph node metastasis, distant metastasis poor histological grade, and short overall survival in cervical carcinoma patients. Moreover, high CERNA2 expression acted as an independent unfavorable predictor for overall survival in cervical carcinoma patients. The cell migration and invasion assays in vitro suggested that knockdown of CERNA2 remarkably inhibited cell migration and invasion in cervical carcinoma. In conclusion, CERNA2 functions as an oncogenic lncRNA and may be as a potential therapeutic target in cervical carcinoma.     

Obituaries

Pseudotumour cerebri is a disorder characterized by elevated intracranial pressure in the absence of hydrocephalus and intracranial mass lesions. The cause of this disease remains obscure but has been related to diverse underlying conditions. We report a patient with pseudotumour cerebri, polyarthritis, urticaria, hypocomplementemia and cryoglobulinemia. Serial lumbar punctures were unsuccessful in lowering the cerebrospinal fluid (CSF) pressure. A trial of prednisone, 40 mg daily for 4 weeks, resulted in clinical improvement but was ineffective in lowering the CSF pressure. Circulating immune complexes and complement activation may have played a role in the development of increased intracranial pressure. Cryoglobulinemia should be added to the list of disorders associated with pseudotumour cerebri.     

Human parvovirus B19 transgenic mice become susceptible to polyarthritis

Human parvovirus B19 (B19) often causes acute polyarthritis in adults. In this paper, we analyzed nucleotide sequences of the B19 genome of patients with rheumatoid arthritis (RA), and then introduced the nonstructural protein 1 (NS1) gene of B19 into C57BL/6 mice that had a genetic origin not susceptible to arthritis. The transgenic mice developed no lesions spontaneously, but were susceptible to type II collagen (CII)-induced arthritis. B19 NS1 was expressed in synovial cells on the articular lesions that were histologically characteristic of granulomatous synovitis and pannus formation in cartilage and bone. Serum levels of anti-CII Abs and TNF-alpha increased in NS1 transgenic mice to the same levels as those of DBA/1 mice, which were susceptible to polyarthritis. Stimulation with CII increased secretion of Th1-type- and Th2-type cytokines in NS1 transgenic mice, indicating that a nonpermissive H-2(b) haplotype in the wild type of C57BL/6 mice can be made susceptible to polyarthritis through the expression of NS1. This study is the first to show that a viral agent from the joints in humans can cause CII-induced arthritis resembling RA.     

Isolation of Yersinia Enterocolitica from a Dog with Chronic Enteritis

During recent years, Yersinia enterocolitica has been isolated from humans and various animal species in connection with intestinal disorders, such as acute ileitis and appendicitis. Cases of septicaemia, polyarthritis and erythema nodosum have also been described (Mollaret & Destombes 1964, Nilehn 1969, Winblad 1969, Lassen 1972, Langford 1972). Y. enterocolitica has been isolated most frequently from chinchillas and hares, but sporadic isolations from deer, cow, horse, rabbit, goat and dog have been reported (Langford, Krogstad et al. 1972). In Norway, an outbreak of the disease in a goat herd is the only described case of yersiniosis among animal species (Krogstad et al.). A case of chronic enteritis in a dog from which Y. enterocolitica was isolated is presented in the following.     

SIRT1 and c-Myc Promote Liver Tumor Cell Survival and Predict Poor Survival of Human Hepatocellular Carcinomas

The increased expression of SIRT1 has recently been identified in numerous human tumors and a possible correlation with c-Myc oncogene has been proposed. However, it remains unclear whether SIRT1 functions as an oncogene or tumor suppressor. We sought to elucidate the role of SIRT1 in liver cancer under the influence of c-Myc and to determine the prognostic significance of SIRT1 and c-Myc expression in human hepatocellular carcinoma. The effect of either over-expression or knock down of SIRT1 on cell proliferation and survival was evaluated in both mouse and human liver cancer cells. Nicotinamide, an inhibitor of SIRT1, was also evaluated for its effects on liver tumorigenesis. The prognostic significance of the immunohistochemical detection of SIRT1 and c-Myc was evaluated in 154 hepatocellular carcinoma patients. SIRT1 and c-Myc regulate each other via a positive feedback loop and act synergistically to promote hepatocellular proliferation in both mice and human liver tumor cells. Tumor growth was significantly inhibited by nicotinamide in vivo and in vitro. In human hepatocellular carcinoma, SIRT1 expression positively correlated with c-Myc, Ki67 and p53 expression, as well as high á-fetoprotein level. Moreover, the expression of SIRT1, c-Myc and p53 were independent prognostic indicators of hepatocellular carcinoma. In conclusion, this study demonstrates that SIRT1 expression supports liver tumorigenesis and is closely correlated with oncogenic c-MYC expression. In addition, both SIRT1 and c-Myc may be useful prognostic indicators of hepatocellular carcinoma and SIRT1 targeted therapy may be beneficial in the treatment of hepatocellular carcinoma.     

Changes in rat leukocyte populations in peripheral blood, spleen, lymph nodes, and synovia during Erysipelas bacteria-induced polyarthritis.

Kinetics of leukocyte subsets were followed for several weeks in rats suffering from polyarthritis induced by experimental infection with erysipelas bacteria (Erysipelothrix rhusiopathiae, serovar 2, strain T28). A marked leukocytosis was found in peripheral blood, and, with some delay, in the synovia and draining lymph nodes of affected joints. In the lymphoid organs tested considerable blast formation of lymphoid cells with a paucity of polymorphonuclear granulocytes was found, while the latter represented the majority of leukocytes in acutely inflamed joints. Cells isolated from spleen showed only moderate and transient alterations in proportions of subpopulations during the first week after inoculation of erysipelas bacteria. In contrast, cells isolated from synovia of inflamed joints and draining lymph nodes displayed more intense and longer lasting alterations: In arthritic animals, the proportion of MHC class II-positive lymphocytes generally increased and remained elevated at least during the first three weeks of the disease. Spontaneous release of IL-2 from cells isolated up to 20 days post induction of the arthritis indicated a considerable activation of lymphocytes in vivo. Interestingly, with exception of synovia, the relative amount of T-lymphocytes including their major CD4+ and minor CD8+ subsets showed little alteration during the course of the disease. Much more pronounced were the rapidly and the extent the membrane Ig-positive B-lymphocytes increased in the synovia as well as in the lymph nodes. Thus, B-lymphocytes may be of particular relevance for elucidating pathomechanisms of erysipelas polyarthritis.     

Mycoplasma capricolum in an Outbreak of Polyarthritis and Pneumonia in Goats

An outbreak of polyarthritis, pneumonia and mastitis was encountered in a herd of goats in northern Sweden. The most obvious clinical sign was lameness, progressing to recumbency. Necropsy revealed fibrinous and suppurative polyarthritis and in some kids interstitial pneumonia. Mycoplasmas were isolated from joints and lungs and also from the udder of a mastitic goat. The strains were identified as Mycoplasma capricolum, although extensive cross-reactions with antiserum against mycoplasma strain F38 was noted.     

Association of MHC and rheumatoid arthritis. Regulatory role of HLA class II molecules in animal models of RA: studies on transgenic/knockout mice

Human leucocyte antigen (HLA) class II molecules have been shown to be associated with predisposition to rheumatoid arthritis (RA). We generated HLA-DR and DQ transgenic mice that lacked endogenous class II molecules to study the interaction between the DR and DQ molecules and define the immunologic mechanisms in rheumatoid arthritis. Using collagen-induced arthritis (CIA) as an experimental model for inflammatory polyarthritis, we show that both DQ and DR are involved in predisposition or resistance to arthritis. Our studies suggest that polymorphism in DQB1 genes may determine predisposition to RA while the DRB1 polymorphism may dictate severity/protection of the disease. These mice provide powerful tools to develop immunotherapeutic protocols.     

The persistence of Ureaplasma and its arthritogenic action in the experimental infection of rabbits

In the experimental intraperitoneal infection of rabbits with U. urealyticum, serotype VIII, transitory polyarthritis with immunomorphological characteristics different from those of human rheumatoid arthritis has been shown to develop in the animals. The pathological process develops simultaneously with Ureaplasma infection. U. urealyticum persists in the body of infected rabbits during 12 weeks of observation. The mechanism of the resorption process in the bone tissue of joints, running similarly to periosteocytic osteolysis, is discussed.