Monoreactive high affinity and polyreactive low affinity rheumatoid factors are produced by CD5+ B cells from patients with rheumatoid arthritis.

In patients with rheumatoid arthritis (RA), circulating CD5+ B lymphocytes, but not CD5- B lymphocytes, are increased in number and size, exist in an activated state, spontaneously proliferate, and secrete Ig that binds to the Fc fragment of IgG. By constructing continuous mAb-secreting cell lines from CD5+ B lymphocytes, the properties and dissociation constants (Kd) of these antibodies were determined. Two types of rheumatoid factors (RFs) with discrete reactivities were produced. The first type is polyreactive and binds with relatively low affinity (Kd, 10(-5) mol/liter) to the Fc fragment of IgG. These antibodies are similar to those produced by CD5+ B cells from healthy subjects. The second type of RF is monoreactive and binds with higher affinity (Kd, 10(-7) mol/liter) to the Fc fragment of IgG. These latter autoantibodies are produced by CD5+ B cells of RA patients, but not healthy subjects. Long-term longitudinal studies are needed to determine the role of these two types of RFs in the pathogenesis of RA

Effects of Antiepileptic Drugs on GABA Responses and on Reduction of GABA Responses by PTZ and DMCM on Mouse Neurons in Cell Culture

The mechanisms of action of antiepileptic drugs effective against generalized absence seizures (antiabsence AEDs) remain uncertain. Antiabsence AEDs are generally effective against seizures induced in experimental animals by pentylenÉtÉtrazol (PTZ) and methyl-6,7-dimethoxy-4-ethyl-Β-carboline-3-carboxylate (DMCM), drugs which reduce GABAergic inhibition. Thus, antiabsence AEDs have been suggested to enhance GABAergic inhibition. We studied the effects of several AEDs on GABA responses recorded from mouse spinal cord neurons grown in primary dissociated cell culture. Four antiabsence AEDs were included: ethosuximide (ESM), dimethadione (DMO), sodium valproate (VPA), and diazepam (DZP). Two experimental AEDs, CGS 9896 and ZK 91296, with anticonvulsant action against PTZ- or DMCM-induced seizures were also included. Possible effects of the antiabsence and experimental AEDS on PTZ- and DMCM-induced inhibition of GABA responses were also evaluated. PTZ and DMCM revers-ibly reduced GABA responses in a concentration-dependent manner. PTZ complÉtÉly inhibited GABA responses at 10 mM (IC 50 of 1.1 mM), whereas DMCM-induced inhibition of GABA responses reached a plateau level of 39% of control values at 1 p.M (IC 50 of 33 nM). ESM (1,200 ΜM), DMO (6 mM), VPA (200 u.M), CGS 9896 (2 ΜM), and ZK 98% (2 Μ M ) did not alter GABA responses. DZP enhanced GABA responses in a concentration-dependent manner. The inhibition of GABA responses produced by PTZ 1 mM was unaltered by ESM (600 Μ M ), DMO (6 mM), CGS 9896 (1 Μ M), or ZK 9896 (1 ΜM)- Coapplication of VPA (200 ΜM) and PTZ (1 mM) slightly enhanced the PTZ effect. DZP (> 10 nM), however, reversed the PTZ-induced reduction of GABA responses. The DMCM (250 nM) inhibition of GABA-responses was unaltered by ESM (600 Μ.M), DMO (2 mM), or VPA (200 ΜM). CGS 9896 (2 Μ M ) and ZK 91296 (2 ΜM), however, antagonized the DMCM effect. DZP (> 10 nM) significantly reversed the DMCM-induced inhibition of GABA responses. The lack of effect of VPA, ESM, and DMO on postsynaptic GABA responses suggests that direct enhancement of postsynaptic GABA action is not a common mechanism of action of antiabsence AEDs. The AEDs DZP, CGS 98%, and ZK 912% all reversed DMCM, but not PTZ, reduction of GABA responses, suggesting that these AEDs blocked DMCM seizures by acting at benzodiazepine receptors. However, since only DZP enhanced GABA responses, it is unclear how CGS 98% and ZK 912% blocked PTZ seizures. Key Words: Anticonvulsants–GABA–Neuron culture–Cell culture–Spinal cord neurons–Convulsants. RESUMEN Los mecanismos de accidn de las medicaciones antiepilÉpticas eficaces contra los ataques generalizados de ausencia (AEDs antiausencia) permanecen inciertos. Los AEDs antiausencia son, generalmente, eficaces contra ataques experimentales inducidos por el pentilentetrazol (PTZ) y el metil-6,7-dimetoxy-4-etil-Pcarbolina-3-carboxilato (DMCM) en animates, medicaciones que reducen la inhibiciÓn GABAÉrgica. Hemos estudiado los efectos de varios AEDs sobre respuestas-GABA registradas en las neuronas de la mÉdula espinal de ratones que habian crecido en cultivos de cÉlulas primarieas disociadas. Cuatro AEDs antiausencia fueron incluidos: etoxusimida (ESM), dimetadiona (DMO), valproato sÓdico (VPA) y diazepan (DZP). TambtÉn se incluyeron dos AEDs experimentales, CGS 9896 y ZK 912%, con acciÓn anticonvulsiva contra los ataques inducidos por PTZ o DMCM. TambiÓn se valoraron los posibles efectos de los AEDs antiausencia y experimentales sobre el PTZ y la inhibiciÓn de las respuestas-GABA inducidas por el DMCM. El PTZ y el DMCM redujeron las respuestas-GABA de modo reversible y dependiendo de sus concentraciones. El PTZ inhibiÓ cmpleta-mente las respuestas-GABA a 10 mM (IC 50 de 1.1 mM) mientras que la inhibitiÓn de las respuestas GABA inducida por el DMCM alcanzÓ un nivel estable del 39% de los valores control con 1 Μ. M (IC 50 de 33 mM). La ESM (1200 Μ.M), la DMO (6 mM), el VPA (200 Μ M ), el CGS 98% (2 Μ M) y el ZK 98% (2 Μ M) no alteraron las respuestas-GABA. El DZP aumentÓ las respuestas GABA de una manera concentraciÓn-dependiente. La inhibition de las respuestas-GABA producidas por el PTZ (1 mM), no se altero con las ESM (600 Μ M), la DMO (6 mM), el CGS 98% (1 Μ M) o el ZK 98% (1 Μ .M). La co-aplicacion de VPA (200 Μ M) y el PTZ (1 mM) aument6 ligeramente los efectos del PTZ. Sin embargo el DZP (10 nM) revirtiÓ significativamente la inhibition de las respuestas GABA inducidas por el DMCM. La falta de efectos de CPA, ESM y DMO sobre las respuestas GABA post-sinÁpticas sugiere que el incremento de la acciÓn GABA post-sinÁptica no es un mecanismo comÚn de actuatiÓn de las AEDs antiausencia. Todas las AEDs DZP, CGS 98% y ZK 912% revirtieron la reduction de las respuestas GABA producidas por el DMCM pero no las inducidas por el PTZ lo que sugiere que estos AEDs bloquean los ataques DMCM actuando sobre los receptores de la benzodiazepina. Sin embargo, puesto que el incremento de las respuestas GABA sÓlÓ se produce por el DZP, permanece todavia sin aclarar el por quÉ el CGS 98% y el ZK 912% bloquean los ataques producidos por el PTZ. ZUSAMMENFASSUNG Der Wirkmechansimus von Antiepileptika gegen generalisierte Absencen ist unklar. Antiabsencemittel sind generell wirkungs-voll gegen PTZ- und Methyl-6,7-Dimethoxy-4-Äthyl-P-Carbolin-Β-Carboxylat (DMCM) induzierte tierexperimentelle AnfÄlle, also von Medikamenten, die die GABA-erge Inhibition reduzieren. Es wurde vermutet, daß Antiabsencemittel die GABA-erge Inhibition verstÄrken. Wir untersuchten die Wirkung von verschiedenen Antiepileptika auf GABA-Antworten in spinalen MÄuseneuronen, die in Zellkulturen gew-achsen waren. Es wurden 4 Absencemittel untersucht: Ethosux-imid (ESM), Dimethadion (DMD), Sodium Valproat (VPA) und Diazepam (DZP). ZusÄtzlich wurden 2 experimentelle Antiepileptika, CGS 98% und ZK 912%, die gegen PTZ0 oder DMCM-induzierte AnfÄlle wirkungsvoll sind, eingeschlossen. Mogliche Wirkungen der Antiabsence- und experimentellen Antiepileptika auf PTZ- und DMCM-induzierte Hemmung der GABA-Antworten wurden ebenfalls ausgewertet. PTZ und DMCM zeigten eine konzentrationsabhÄngige reversible Reduktion der GABA-Antworten. PTZ zeigte eine komplette Hemmung der GABA-Antworten bei 10 mM (IC 50 1,1 mM), DMCM-Hemmung der GABA-Antworten zeigte ein Plateau von 39% der Kontroll-werte bei 1 uJtf (ICJO von 33 mAfl. ESM (1200 uJtf), DMD (6 mM), VPA (200 Μ M), CGS 98% (2 Μ M) und ZK 98% (2 Μ M) anderten nicht die GABA-Antworten. DZP verstarkte die GABA-Antworten konzentrationsabhangig. Die durch PTZ (1 mM) hervorgerufene Hemmung der GABA-Antworten war bei ESM (600 Μ M), DMD (6 mM), CGS 98% (1 mAO und ZK 3836 (1 mM) unverÄndert. ZusÄtliche Anwendung von VPA (200 mM) und PTZ (1 mM) verstÄrkten geringfÜgig den PTZ-Effekt. DZP (10 nM) kehrte die durch PTZ hervorgerufene Reduktion der GABA-Antworten um. Die durch DMCM (250 nM) hervorgerufene Hemmung der GABA-Antworten war durch ESM (600 Μ .M), DMD (2 mM) und VPA (200 Μ M ) unbeeinflusst. CGS 98% (2 Μ M) und ZK 912% (2 Μ M ) antagonisierten die DMCM-Wirkung. DZP (>10 nM) kehrte die durch DMCM-induzierte Hemmung der GABA-Antworten um. Das Fehlen einer Wirkung von VPA. ESM und DMD auf die postsynaptischen GABA-Antworten legen nahe, daß eine direkte VerstÄrkung der postsynaptischen GABA-Aktion kein gemeinsamer Mechanis-mus der Antiabsencemittel darstellt. Die Antiepileptika DZP, CGS 98% und ZK 912% kehrten die DMCM-Wirkung auf die GABA-Antworten um, jedoch nicht die von PTZ, was vermuten lapt, daß diese Antiepileptika die DMCM-AnfÄlle Über die Wirkung an den Benzodiazipin-Rezeptoren verhinderte. Da jedoch nur DZP GABA-Antworten verstarkte, ist unklar, in welcher Weise CGS 98% und ZK 912% die PTZ-AnfaUe ver-hinderten.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65188/1/j.1528-1157.1989.tb05275.x.pd

The Genetic Signature of Sex-Biased Migration in Patrilocal Chimpanzees and Humans

A large body of theoretical work suggests that analyses of variation at the maternally inherited mitochondrial (mt)DNA and the paternally inherited non-recombining portion of the Y chromosome (NRY) are a potentially powerful way to reveal the differing migratory histories of men and women across human societies. However, the few empirical studies comparing mtDNA and NRY variation and known patterns of sex-biased migration have produced conflicting results. Here we review some methodological reasons for these inconsistencies, and take them into account to provide an unbiased characterization of mtDNA and NRY variation in chimpanzees, one of the few mammalian taxa where males routinely remain in and females typically disperse from their natal groups. We show that patterns of mtDNA and NRY variation are more strongly contrasting in patrilocal chimpanzees compared with patrilocal human societies. The chimpanzee data we present here thus provide a valuable comparative benchmark of the patterns of mtDNA and NRY variation to be expected in a society with extremely female-biased dispersal

High-Resolution Sonography: A New Technique to Detect Nerve Damage in Leprosy

Mycobacterium leprae, which causes leprosy, infects peripheral nerves resulting in functional impairment, ulcer formation and stigmatizing deformities. Early diagnosis of nerve involvement is important to avoid nerve related complications. We used non-invasive, high-resolution sonography (US) and color Doppler (CD) imaging to study the ulnar (UN), median (MN), lateral popliteal (LP) and posterior tibial (PT) nerves in 20 leprosy patients and compared 30 healthy Indian controls. The nerves were significantly thicker in the patients (p<0.0001 for each nerve). One of the key signs of leprosy is the presence of enlarged nerves. The kappa for clinical palpation and nerve enlargement by sonography was 0.30 for all examined nerves. Increased neural vascularity, the sign of inflammation was observed in 26% (39/152) of nerves by CD imaging. Increased CD was observed in multiple nerves in 3 of 4 patients with type 2 reaction. Significant correlation was observed between clinical parameters of grade of thickening, sensory loss and muscle weakness and US abnormalities of nerve echotexture, endoneural flow and cross-sectional area (p<0.001). We conclude that sonography is a better diagnostic tool to predict nerve damage as compared to clinical assessment. Nerve damage was sonographically more extensive and was observed in nerves considered clinically normal

Preliminary Clinical Evaluation of Short Fiber-Reinforced Composite Resin in Posterior Teeth: 12-Months Report

This preliminary clinical trial evaluated 12 month clinical performance of novel filling composite resin system which combines short fiber-reinforced composite resin and conventional particulate filler composite resin in high stress bearing applications. A total of 37 class I and II restorations (compound and complex type) were placed in 6 premolars and 31 molars. The restorations were reviewed clinically at 6 months (baseline) and 12 months using modified USPHS codes change criteria for marginal adaptation, post-operative sensitivity, pulpal pain and secondary caries criteria. Photographs and x-rays were obtained for restorative analysis. Results of 12 months evaluation showed 5 restorations having little marginal leakage (B score) and 1 patient had minor pulpal symptom and post-operative sensitivity (B score). No secondary caries or bulk fracture was detected. The majority of restorations exhibited A scores of the evaluated criteria. After 12 months, restorations combining base of short fiber reinforced composite resin as substructure and surface layer of hybrid composite resin displayed promising performance in high load bearing areas

Tetraspanin CD151 is a novel prognostic marker in poor outcome endometrial cancer

BACKGROUND: Type II cancers account for 10% of endometrial cancers but 50% of recurrence. Response rates to chemotherapy at recurrence are poor and better prognostic markers are needed to guide therapy. CD151 is a small transmembrane protein that regulates cell migration and facilitates cancer metastasis. High CD151 expression confers poor prognosis in breast, pancreatic and colorectal cancer. The prognostic significance of tetraspanin CD151 expression in poor outcome endometrial cancers was evaluated, along with oestrogen receptor (ER), progesterone receptor (PR), p53, human epidermal growth factor receptor -2 (HER-2), and CD 151 staining compared with α6β1, α3β1 integrins, and E-cadherin. METHODS: Tissue microarray constructed from 156 poor outcome endometrial cancers, tested with immunohistochemistry and staining correlated with clinicopathological data were used. A total of 131 data sets were complete for analysis. RESULTS: Expression of CD151 was significantly higher in uterine papillary serous and clear cell carcinoma than in grade 3 endometrioid carcinoma, sarcoma or carcinosarcoma (P<0.001). In univariate analysis, age, stage, histology type and CD151 were significant for both recurrence free (RFS) and disease specific survival (DSS). In multivariate analyses, CD151 was significant for RFS and DSS (P=0.036 and 0.033, respectively) in triple negative (ER, PR and HER-2 negative) tumours (88/131). The HER-2, p53, ER and PR were not prognostic for survival. There was strong concordance of CD151 with E-cadherin (98%), but not with α6β1 (35%), α3β1 staining (60%). CONCLUSION: The CD151 is a novel marker in type 2 cancers that can guide therapeutic decisions. CD151 may have an important role in tumourigenesis in some histology types

Sex differences in rheumatoid arthritis: more than meets the eye...

Sex differences in the prevalence of autoimmune diseases such as rheumatoid arthritis (RA) are well described, but the literature is not as clear about sex differences in RA disease course and prognosis. A recent study from a very large cross-sectional international cohort demonstrated slightly worse levels of disease activity and function in female patients with RA, compared with men. These findings are discussed in the context of our evolving knowledge of sex differences in the expression of this prototypic autoimmune disease, both in terms of the actual disease activity level, the effects that the disease has on physical function, and our ability accurately to measure these aspects

Presence of Mycoplasma fermentans in the bloodstream of Mexican patients with rheumatoid arthritis and IgM and IgG antibodies against whole microorganism

<p>Abstract</p> <p>Background</p> <p>Increasing evidence incriminates bacteria, especially <it>Mycoplasma fermentans</it>, as possible arthritogenic agents in humans. The purpose of this study was to investigate <it>M. fermentans </it>in the bloodstream of patients with rheumatoid arthritis.</p> <p>Methods</p> <p>Two hundred and nineteen blood samples from patients with rheumatoid arthritis, systemic lupus erythematosus, antiphospholipid syndrome, and healthy individuals were screened by bacterial culture and direct PCR in order to detect mycoplasmas; IgM and IgG against <it>M. fermentans </it>PG18 were also detected by ELISA and Immunoblotting assays in patients with rheumatoid arthritis and healthy individuals.</p> <p>Results</p> <p>Blood samples from patients with antiphospholipid syndrome and healthy individuals were negative for mycoplasma by culture or direct PCR. In blood samples from patients with systemic lupus erythematosus were detected by direct PCR <it>M. fermentans </it>in 2/50 (2%), <it>M. hominis </it>in 2/50 (2%) and <it>U. urealyticum </it>in 1/50 (0.5%). In patients with RA <it>M. fermentans </it>was detected by culture in 13/87 blood samples and in 13/87 by direct PCR, however, there was only concordance between culture and direct PCR in six samples, so <it>M. fermentans </it>was detected in 20/87(23%) of the blood samples from patients with RA by either culture or PCR. Antibody-specific ELISA assay to <it>M. fermentans </it>PG18 was done, IgM was detected in sera from 40/87 patients with RA and in sera of 7/67 control individuals, IgG was detected in sera from 48/87 RA patients and in sera from 7/67 healthy individuals. Antibody-specific immunoblotting to <it>M. fermentans </it>PG18 showed IgM in sera from 35/87 patients with RA and in sera from 4/67 healthy individuals, IgG was detected in sera from 34/87 patients and in sera from 5/67 healthy individuals.</p> <p>Conclusion</p> <p>Our findings show that only <it>M. fermentans </it>produce bacteremia in a high percentage of patients with RA. This finding is similar to those reported in the literature. IgM and IgG against <it>M. fermentans </it>PG18 were more frequent in patients with RA than healthy individuals.</p

Local Extinction in the Bird Assemblage in the Greater Beijing Area from 1877 to 2006

Recent growth in industrialization and the modernization of agricultural activities, combined with human population growth, has greatly modified China’s natural environment, particularly in the vicinity of large cities. We compared avifauna checklists made between 1877 and 1938 with current checklists to determine the extent of local bird extinctions during the last century in the greater Beijing area. Our study shows that of the 411 bird species recorded from 1877–1938, 45 (10.9%) were no longer recorded from 2004–2006. Birds recorded as ‘rare’ in 1938 were more likely to have disappeared in subsequent years. Migrant status also influenced the probability of local bird extinction with winter migrants being the most affected class. Moreover, larger birds were more likely to have disappeared than smaller ones, potentially explained by differential ecological requirements and anthropogenic exploitation. Although our habitat descriptions and diet classification were not predictors of local bird extinction, the ecological processes driving local bird extinction are discussed in the light of historical changes that have impacted this region since the end of the 1930 s. Our results are of importance to the broader conservation of bird wildlife

Quantifying the Spatial Dimension of Dengue Virus Epidemic Spread within a Tropical Urban Environment

Global trends in population growth and human redistribution and movement have reshaped the map of dengue transmission risk, exposing a significant proportion of the world's population to the threat of dengue epidemics. Knowledge on the relative contribution of vector and human movement to the widespread and explosive nature of dengue epidemic spread within an urban environment is limited. By analyzing a very detailed dataset of a dengue epidemic that affected the Australian city of Cairns we performed a comprehensive quantification of the spatio-temporal dimensions of dengue virus epidemic transmission and propagation within a complex urban environment. Space and space-time analysis and models allowed derivation of detailed information on the pattern of introduction and epidemic spread of dengue infection within the urban space. We foresee that some of the results and recommendations derived from our study may also be applicable to many other areas currently affected or potentially subject to dengue epidemics