Effects of forest fragmentation on avian breeding activity.

Biodiversity declines and ecosystem decay follow forest fragmentation; initially, abundant species may become rare or be extirpated. Underlying mechanisms behind delayed extirpation of certain species following forest fragmentation are unknown. Species declines may be attributed to an inadequate number of breeding adults required to replace the population or decreased juvenile survival rate due to reduced recruitment or increased nest predation pressures. We used 10 years of avian banding data, 5 years before and 4 years after fragment isolation, from the Biological Dynamics of Forest Fragments Project, carried out near Manaus, Brazil, to investigate the breeding activity hypothesis that there is less breeding activity and fewer young after relative to before fragment isolation. We compared the capture rates of active breeding and young birds in 3 forest types (primary forest, fragment before isolation, and fragment after isolation) and the proportion of active breeding and young birds with all birds in each unique fragment type before and after isolation. We grouped all bird species by diet (insectivore or frugivore) and nesting strategy (open cup, cavity, or enclosed) to allow further comparisons among forest types. We found support for the breeding activity hypothesis in insectivorous and frugivorous birds (effect sizes 0.45 and 0.53, respectively) and in birds with open-cup and enclosed nesting strategies (effect sizes 0.56 and 0.44, respectively) such that on average there were more breeding birds in fragments before isolation relative to after isolation. A larger proportion of birds in the community were actively breeding before fragment isolation (72%) than after fragment isolation (11%). Unexpectedly, there was no significant decrease in the number of young birds after fragment isolation, although sample sizes for young were small (n = 43). This may have been due to sustained immigration of young birds to fragments after isolation. Together, our results provide some of the strongest evidence to date that avian breeding activity decreases in response to fragment isolation, which could be a fundamental mechanism contributing to ecosystem decay.

Efectos de la fragmentación del bosque sobre la actividad reproductiva de las aves Resumen Les declinaciones de la biodiversidad y el deterioro de los ecosistemas van después de la fragmentación forestal; al inicio, las especies abundantes pueden volverse raras o ser extirpadas. Todavía no se conocen los mecanismos subyacentes detrás de la extirpación retrasada de ciertas especies después de la fragmentación forestal. La declinación de las especies puede atribuirse a un número inadecuado de adultos reproductivos requeridos para reemplazar a la población o a la tasa reducida de supervivencia de los juveniles debido al reclutamiento disminuido o al incremento en la presión de depredación de los nidos. Usamos diez años de datos de anillamiento de aves, cinco años antes y cuatro años después del aislamiento por fragmentación, tomados del Proyecto Dinámica Biológica de Fragmentos de Bosque realizado cerca de Manaos, Brasil, para investigar la hipótesis de actividad reproductiva que sostiene que hay una menor actividad reproductiva y menos crías después del aislamiento por fragmentación que antes del aislamiento. Comparamos las tasas de captura de aves con reproducción activa y aves juveniles en tres tipos de bosque (primario, fragmento antes del aislamiento y fragmento después del aislamiento) y la proporción de las aves juveniles y con reproducción activa con todas las aves en cada tipo de fragmento único antes y después del aislamiento. Agrupamos todas las especies de aves según su dieta (insectívora o frugívora) y su estrategia de anidación (nido abierto, cavidad o nido cerrado) para poder realizar más comparaciones entre los tipos de bosque. Las aves con dieta insectívora y frugívora (tamaño del efecto: 0.45 y 0.53, respectivamente) y aquellas con nidos abiertos y cerrados (tamaño del efecto: 0.56 y 0.44, respectivamente) respaldaron la hipótesis de la actividad reproductora de tal manera que en promedio hubo más aves reproductoras en los fragmentos antes del aislamiento que después del aislamiento. Una gran parte de las aves de la comunidad tuvieron reproducción activa antes del aislamiento por fragmentación (72%) que después del aislamiento (11%). Sorprendentemente, no hubo una disminución significativa en el número de aves juveniles después del aislamiento, si bien el tamaño de la muestra de este grupo fue reducido (n = 43). Lo anterior pudo deberse a la continua inmigración de juveniles a los fragmentos después del aislamiento. En conjunto, nuestros resultados proporcionan algunos de los indicios más claros de que la actividad reproductiva de las aves disminuye como respuesta al aislamiento por fragmentación, lo cual podría ser un mecanismo fundamental del deterioro de los ecosistemas.

A novel point mutation in the mitochondrial tRNA(Trp) gene produces a neurogastrointestinal syndrome.

We report a novel, heteroplasmic point mutation in the mitochondrial tRNA for tryptophan at position 5532. The mutation was present in all the tissues studied and segregated with the biochemical defect, with higher levels of mutation present in cytochrome c oxidase-deficient muscle fibres. The patient manifested a neurogastrointestinal syndrome with features including failure to thrive, psychomotor retardation, ophthalmoplegia, sensorineural deafness and encephalopathy together with vomiting, diarrhoea and colitis.

Assessment of antibodies to double-stranded DNA induced in rheumatoid arthritis patients following treatment with infliximab, a monoclonal antibody to tumor necrosis factor alpha: findings in open-label and randomized placebo-controlled trials.

OBJECTIVE: To compare the incidence of anti-double-stranded DNA (anti-dsDNA) antibodies in rheumatoid arthritis (RA) patients receiving either single or multiple doses of a chimeric anti-tumor necrosis factor alpha (anti-TNFalpha) antibody or placebo infusions, with or without methotrexate, in open-label, randomized, placebo-controlled trials. METHODS: Multiple sera obtained from 156 patients before and after treatment with infliximab and from 37 patients treated with placebo infusions were tested for anti-dsDNA antibodies by 3 methods: Crithidia luciliae indirect immunofluorescence test (CLIFT), a commercial Farr assay (Ortho Diagnostics radioimmunoassay [RIA]) in which the antigen source is mammalian DNA, and a Farr assay employing 125I-labeled circular plasmid DNA (Central Laboratory of The Netherlands Red Cross Blood Transfusion Service [CLB] RIA). Patients with positive findings on the CLIFT were also tested for antibodies to histones (H1-H5) and chromatin and for IgM rheumatoid factors (IgM-RFs). RESULTS: None of the RA patients had a serum sample that was positive for anti-dsDNA antibodies by the CLIFT prior to infliximab therapy. Of the 22 patients who developed a positive CLIFT result, 11 (7% of 156 exposed to infliximab) also had positive findings on the Ortho RIA at a concentration of >10 units/ml and another 8 (5%) were positive at a concentration of >25 units/ml. In all but 1 patient, the anti-dsDNA antibodies were solely of the IgM isotype. Only 1 patient had detectable anti-dsDNA antibodies by the CLB RIA. All sera containing anti-dsDNA by the CLIFT contained antibodies to chromatin, and sera from 2 patients also contained antibodies to histones. IgM-RF titers showed a significant reduction following infliximab therapy in these 22 patients. One patient developed anti-dsDNA antibodies of IgG, IgA, and IgM isotype and had positive results on both Farr assays (peaking at 22 weeks and resolving by 54 weeks); this was associated with a reversible lupus syndrome. CONCLUSION: Anti-dsDNA antibodies of IgM class are induced by infliximab therapy; the frequency is dependent on the assay method used. Only 1 of the 156 patients who were treated with infliximab developed a self-limiting clinical lupus syndrome; that patient developed high titers of anti-dsDNA antibodies of IgG, IgM, and IgA class, as detected by the CLIFT and by 2 different Farr assays.

Multicenter validation of recombinant, natural and synthetic antigens used in a single multiparameter assay for the detection of specific anti-nuclear autoantibodies in connective tissue disorders.

OBJECTIVES: We investigated the feasibility of using a single multi-parameter test based mainly on recombinant autoantigens for the detection of anti-nuclear autoantibodies, and analyzed the agreement between this test format and conventional techniques. METHODS: The presence of autoantibodies was determined by a line immunoassay (LIA) in 755 sera derived from patients with different autoimmune connective tissue disorders. All sera were previously tested by standard assays that are routinely used at the 8 participating European centers. RESULTS: The overall sensitivity and specificity of autoantibody detection by LIA was similar or higher as compared to combined conventional techniques (CCT). In particular, the detection of anti-Ro52 in systemic lupus erythematosus (SLE) sera (P = 0.004) and anti-LA in both SLE (P < 0.0009) and in Sjögren's syndrome (P < 0.0009) sera was significantly more sensitive when using LIA compared to CCT. By contrast, CCT was never more sensitive than LIA for any of the markers. CONCLUSION: The LIA is a reliable alternative to a combination of conventional techniques for the detection of specific anti-nuclear autoantibodies. The multi-parameter test also reveals autoantibody reactivities that may not be detected when only a limited number of conventional techniques are applied.

Real time signal processing in the clinical setting.

We routinely use a variety of real time signal acquisition, enhancement, and display techniques in the operating room to provide the surgeon with functional information. This enables reduction of surgical morbidity in cases which present a significant risk to the nervous system. Here we present regression based signal processing algorithms which produce considerable signal-to-noise-ratio enhancement with corresponding reduction in the time required to obtain an interpretable neurophysiological signal. We also present the approach we have applied to fault tolerance and distributed data display for our workstation cluster environment.

Anaemia of chronic disease in rheumatoid arthritis: in vivo effects of tumour necrosis factor alpha blockade.

Anaemia of chronic disease (ACD) is a common feature of active rheumatoid arthritis (RA). Inflammatory cytokines, particularly tumour necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1) and interleukin-6 (IL-6), are thought to contribute to the pathogenesis of ACD, possibly by inhibiting erythropoietin (EPO) production. In this study, we examined the in vivo effects of TNF-alpha blockade with a chimeric monoclonal antibody, cA2, on erythropoiesis in RA patients with ACD. Administration of cA2 led to a dose-dependent increase in haemoglobin levels compared to placebo and these changes were accompanied by a reduction in both EPO and IL-6 levels. The data support the notion that TNF-alpha is important in the causation of ACD, but suggest a mechanism independent of EPO suppression. Instead, TNF-alpha may act directly on bone marrow red cell precursors.

Sulphasalazine-induced autoimmune abnormalities in patients with rheumatic disease.

Sulphasalazine is a commonly used second line agent in rheumatoid arthritis (RA) and other inflammatory joint diseases and is reported to be one of the least toxic of this group of drugs. Recently a severe allergic reaction and cases of lupus-like disease have been described in patients with RA after treatment with sulphasalazine. We describe five patients, all with inflammatory arthropathy who developed cutaneous vasculitis, lupus-like disease or atypical serology after exposure to sulphasalazine. Three of four cases investigated were found to have the slow acetylator phenotype. These reactions can complicate the diagnosis and delay discontinuation of the drug. Moreover, present guidelines for the diagnosis of drug-induced lupus do not apply to the majority of patients with sulphasalazine-induced lupus.

Monoclonal anti-TNF alpha antibody as a probe of pathogenesis and therapy of rheumatoid disease.

Rheumatoid arthritis is a common cause of chronic disability for which current therapies are of limited value in controlling the disease process and outcome. Our initial approach to understanding the pathogenesis of RA and defining a novel therapeutic target was to investigate the role of cytokines by blocking their action with antibodies on cultured synovial-derived mononuclear cells in vitro. These investigations suggested that neutralization of TNF alpha with antibodies significantly inhibited the generation of other pro-inflammatory cytokines also over-produced, such as, IL-1, GM-CSF, IL-6 and IL-8. The implication that blockade of a single cytokine, TNF alpha might have far-reaching effects on multiple cytokines and thereby exert significant anti-inflammatory and protective effects on cartilage and bone of joints, was tested in arthritic DBA/1 mice immunized with collagen II. Impressive amelioration of joint swelling and joint erosions in this model encouraged clinical trials with a monoclonal anti-TNF alpha antibody. The cA2 chimeric anti-TNF alpha high-affinity antibody was initially tested in an open-label study at a dose of 20 mg/kg on 20 patients, with substantial and universal benefit. Subsequently, a randomized placebo-controlled double-blind trial was performed on 73 patients comparing a single intravenous injection of placebo (0.1% human serum albumin) with two doses of cA2. Using a composite disease activity index, at 4 weeks post infusion, 8% of patients receiving placebo improved compared with 44% receiving 1 mg/kg cA/2 and 79% receiving 10 mg/kg. Between 2 to 4 repeated cycles of cA2 were administered to 7 patients and all patients showed improvement of a similar magnitude with each cycle. These data support our proposition that TNF alpha is implicated in the pathogenesis of RA, and is thus a key therapeutic target. Monoclonal anti-TNF alpha antibodies control disease flares and are candidate agents for longer-term control of RA, although repeated therapy with cA2 is associated with anti-idiotypic responses in 50% of patients and a trend toward shortening of the duration of response. In the DBA/1 arthritic mice, synergy of action of anti-TNF and anti-CD4 is observed together with suppression of an anti-globulin response, indicating one way in which benefit might be augmented in the future.

The clinical implications of autoantibody detection in rheumatology.

The laboratory plays an increasing role in the diagnosis and clinical management of patients with rheumatic diseases. It is therefore essential that the results of laboratory tests are both accurate and reliable, and give clinicians correct information. It is also important to keep clinicians informed of the changes occurring in the rapidly evolving field of investigation of autoantibodies.

Antiribosomal P protein antibodies in different populations of patients with systemic lupus erythematosus.

We report a significantly increased prevalence of antiribosomal P protein antibodies in Malaysian Chinese patients (38%) with SLE compared to white Caucasian (13%) and Afro-Caribbean (20%) patients. The increased prevalence was not due to a generalized increase in autoantibody production because anti-dsDNA and anti-SSA antibodies were present in comparable frequencies in the three ethnic groups while anti-Sm and anti-SSB antibodies were rarely found in the Malaysian Chinese patients.

Antiribosomal P protien antibodies in different populations of patients with systemic lupus erythematosus

We report a significantly increased prevalence of antribosomal P protein antibodies in Malaysian Chinese patients (38 percent) with SLE compared to white caucasian (13 percent) and Afro-Caribbean (20 percent) patients. The increase prevalence was not due to a generalized increase in autoantibody production because anti-dsDNA and anti-SSA antibodies were present in comparable frequencies in the three ethnic groups while anti-Sm and anti-SSB antibodies were rarely found in the Malaysian Chinese patients (AU)

Serological and immunogenetic markers of extraglandular primary Sjögren's syndrome.

The clinical course of 48 patients with primary Sjögren's syndrome (primary SS) was reviewed. Forty-three north European patients were typed for HLA class I and class II alloantigens. In this population with primary SS HLA B8, DR3 and DRw52 all occurred more frequently than in the control population (P < 0.009, P < 0.0035, P < 0.02 respectively). The subgroup of primary SS patients with antibodies to Ro and/or La antigen had the greatest prevalence of DR3 (relative risk 33.4). The primary SS patients fall into two distinct groups: those with extraglandular disease in whom lymphopaenia, hypergammaglobulinaemia, antibodies to Ro and/or La and HLA DR3 were all more frequent and those patients with either glandular disease alone or only one extraglandular feature. There was no difference in disease duration between the two groups, although on average the latter group were 10 years older.

Serological profile of rheumatoid arthritis in west Africa.

Rheumatoid arthritis (RA) in West Africa is atypical in a number of respects. In order to investigate this we evaluated the serological profile of a series of West African patients diagnosed as having RA. We found the presence of a wide range of autoantibodies including antinuclear antibodies (ANA), anticardiolipin antibodies and antineutrophil cytoplasmic antibodies but the pattern of these autoantibodies was similar to that reported in other studies. Our serological studies support the hypothesis that these patients do have RA and the presence of these autoantibodies is of interest with regards to implications for diagnosis.

Antibodies to neutrophil cytoplasmic antigens in rheumatoid arthritis.

In this study we examined the sera from 42 randomly selected patients with RA. ANCA was demonstrated by indirect immunofluorescence on human granulocytes in 10 patients with active disease and in none of the patients with inactive disease. ELISA's for the detection of specific antigens showed the presence of anti-myeloperoxidase in 3 patients, and anti-lactoferrin in 1 patient. The specificity of the remaining antibodies was unidentified. All 3 patients with antibodies to myeloperoxidase had vasculitis.

The Consensus Workshops for the Detection of Autoantibodies to Intracellular Antigens in Rheumatic Diseases: 1989-1992.

The European Consensus Study Group for Autoantibodies was formed in 1988 to examine test systems for the detection of autoantibodies found in patients with rheumatic and related conditions. In the last four years it has organised an annual exercise to examine the sensitivity and reproducibility of different methodologies for the detection of these antibodies, and the concordance obtained between leading laboratories in Europe. The results of these exercises show an improvement in detection rates. In addition, the group has produced a methodology handbook, containing recommended methods as used by expert laboratories, and has made recommendations on the performance of assays for the detection of autoantibodies.

Antibodies to protein P in systemic lupus erythematosus.

A synthetic peptide was used to develop an enzyme linked immunosorbent assay (ELISA) to detect antibodies to the ribosomal proteins P0, P1, and P2. Significantly increased levels of IgG antibodies to protein P were found in 16% (18/116) of patients with systemic lupus erythematosus but slightly increased levels were detected in 2% (2/98) of patients with rheumatoid arthritis and one normal control subject. No association was observed between the presence of IgG antibodies to protein P and either lupus psychosis or depression. Sequential studies in individual patients failed to show an association between antibody levels and the development of psychosis.