Possible rheumatoid arthritis subtypes in terms of rheumatoid factor,depression, diagnostic delay and emotional expression: an exploratory case-control study

Introduction

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathology of rheumatoid arthritis (RA), particularly as vulnerable personality types are exposed to chronic stress. Emotions are powerful modulators of stress responses. However, little is known about whether patients with RA process emotions differently to matched controls. In this study we: 1) assessed whether the trait emotional intelligence (trait EI) scores of patients with RA differ from healthy controls at the facet level; 2) explored any subgroups in RA, in terms of trait EI and common risk factors.

Methods

A total of 637 patients with RA were compared to 496 controls on the trait EI Questionnaire (TEIQue). RA subgroups were explored in terms of trait EI, rheumatoid factor status (RF+/-), depression and time from onset of symptoms until diagnosis (diagnostic delay).

Results

The RA group rated themselves lower on Adaptability, Stress-management, Emotion management, Self-esteem, Sociability, Assertiveness, Impulsiveness and Well-being, and higher on Empathy and Relationships than healthy controls. The RF- subtype reported more time with depression (25.2 vs. 11.3 months), a longer diagnostic delay (3.0 vs. 1.7 years), and greater emotional expression (5.15 vs. 4.72), than the RF+ subtype. These differences were significant at the P <0.05 level, but not following strict Bonferroni corrections and should therefore be treated as indicative only. RF- patients with a longer diagnostic delay reported depression lasting three times longer (42.7 months), when compared to three other subtypes (11.0 to 12.7 months).

Conclusions

RA patients and controls differ in their emotion-related personality traits, as operationalized by trait EI. These differences may make people with RA more susceptible to chronic stress and HPA-axis dysregulation. RA may be a highly heterogeneous illness where at least two subtypes may be characterized by personality, psychiatric and immunological differences. RF- status, as well as diagnostic delay and emotional expression, may predict future risk of depression. Research on the causes of RA could benefit from a systems science approach.     

Oligomeric protein structure networks: insights into protein-protein interactions

Background  

Protein-protein association is essential for a variety of cellular processes and hence a large number of investigations are being carried out to understand the principles of protein-protein interactions. In this study, oligomeric protein structures are viewed from a network perspective to obtain new insights into protein association. Structure graphs of proteins have been constructed from a non-redundant set of protein oligomer crystal structures by considering amino acid residues as nodes and the edges are based on the strength of the non-covalent interactions between the residues. The analysis of such networks has been carried out in terms of amino acid clusters and hubs (highly connected residues) with special emphasis to protein interfaces.     

Oncolytic poxviruses

The latest data on selection and construction of poxviruses capable of specifically lysing tumor cells of different genesis, inducing antitumor immunity and apoptosis of malignant cells are discussed. The review concerns several directions: virus attenuation, insertion of immunomodulatory protein genes, and anti-tumor protein genes. Thymidine kinase and viral growth factor genes make the greatest contribution to the virus attenuation as their inactivation results in the virus inability to replicate in non-dividing cells, thereby contributing to increased selectivity with respect to tumor cells. Among the immunomodulatory proteins, interleukins 2, 12, and granulocyte-macrophage colony-stimulating factor proved to be most promising for oncolytic virotherapy. An attempt to use p53 protein gene expressed by vaccinia virus for addressed apoptosis of tumor cells was reported. The use of the double and triple viral recombinants carrying genes of multidirectional action seems to be most promising. Encouraging results were obtained using vaccinia virus in the oncotherapy with prodrugs and angiogenesis inhibitors. At present, two poxviral strains are undergoing Phase III clinical trials as anti-tumor preparations in the USA.     

Lymphoid regulation of the proliferative stage in regeneration of the intestines and esophagus of rats

After the removal of a half of small intestine in the rats, the lymphocytes acquired the ability to stimulate the mitotic activity of crypts of the small intestine, large intestine and oesephagus in syngenic recipients. The ratio of mitotic phases in the experimental animals suffered no changes, the number of cells in the crypts increased reliably thus suggesting the true stimulation of proliferation. The lymphocytes of pseudooperated rats had no such ability.     

Principle of the supramolecular stacking of the cellular deoxyribonucleoprotein complex

Using cytofluorimetry with acridine orange staining and a modified thermal denaturation technique of cellular DNP, it has been shown that chromatin melting profiles of normal human nuclei (from lymphocytes and granulocytes) have distinct regularities. It is believed that these regularities reflect specific supramolecular chromatin organization. Parallel comparative analysis performed using electrophoretic fractionation and isoelectric focussing of nuclear proteins has revealed that: 1) peculiarities of chromatin melting profiles are independent of the quantity and molecular weights of chromatin proteins; 2) the lack of principal differences in chromatin melting profiles and the data on isoelectric points of nuclear proteins of granulocytes and lymphocytes from the same patient indicate that specific supramolecular organization of DNP-complex depends on the chromatin protein charge.     

Melting profiles for lymphocyte chromatin of healthy subjects and Down's disease patients obtained by the technic of cellular DNA absorption in ultraviolet light

Integral values of optical density (E260) were obtained for lymphocyte nuclei from normal people and those suffering from Down's syndrome during the melting of cells in media of varying ionic strength (0.15 M NaCl - control; 0.015, 0.0015 and 0.00015 M NaCl - experimental). The differences in E260 were obtained only during the melting of cells in 0.15 M NaCl. In lymphocytes from normal people, the distinctly reproducible hyperchromic effect was detected from 78 degrees (up to 35--40%), reaching the plateau by 96 degrees C (P less than 0.01). In identical conditions, the hyperchronic effect on aneuploid cells was revealed only after 98 degrees C (P less than 0.01). The data presented confirm the authors' concept of the greater condensation of aneuploidic genome.     

Characteristics of liver regeneration and growth in 3-week-old mice of different strains]

Three-week mice of C57BL strain are characterized by low proliferative activity of hepatocytes during normal growth of the liver. Hepatocytes of mice of this strain also had low proliferative activity 44 hours after partial hepatectomy (16%). Mice of the same age, but of other strains (mongrel, CBA, CC57BR) had higher mitotic indices both during normal growth and during regeneration (42; 70 and 60%, respectively). This peculiarity in the mitotic activity of hepatocytes of mice of different strains was also present 7 days after the beginning of the experiment. The data obtained indicated the genetic determination of the level of proliferative activity of hepatocytes.     

Morphogenic Regulation of Pathotoxin Synthesis in Cochliobolus carbonum

The fungus Cochliobolus carbonum causes leaf spot disease of maize. Highly virulent isolates of the pathogen produce a host-selective, peptide toxin that is active against susceptible genotypes of maize. Prior to infection, spores must germinate and differentiate appressoria, structures specialized for leaf penetration. Analysis of spore germination fluids by plasma desorption mass spectrometry, which allowed detection of as little as 0.5 ng toxin, revealed that spores induced to form appressoria in vitro synthesized and released the toxin at a time coincident with maturation of appressoria. Spores incubated under conditions that did not induce appressorium formation failed to produce toxin. These observations indicate that synthesis of the host-selective toxin, which is essential for successful pathogenesis of maize by C. carbonum, is regulated by infection-related morphogenesis.     

Dynamics of the activity of the normal mouse spleen killers after partial splenectomy

The activity of natural killers from the mouse spleen was determined by 51Cr clearance from labeled target cells (YAC-1) at different times after resection of the two-thirds of the spleen. In the early periods after operation, there was a decrease in the natural cytotoxic activity of splenocytes followed by a relatively rapid rise for 8 days until the maximum exceeding the cytotoxicity of intact spleen cells was reached. However, the total lytic potential of the regenerating spleen did not return to normal during 28 days.