Interleukin-1beta polymorphisms in Colombian patients with autoimmune rheumatic diseases

Interleukin-1 beta (IL-1beta) exerts a range of inflammatory and immunomodulatory activities that are important in host defense and autoimmune response. The IL-1beta gene, located on chromosome 2 (2q13), is polymorphic. The influence of its polymorphism on 355 patients with autoimmune rheumatic diseases was examined. To this effect, 172 patients with rheumatoid arthritis (RA), 114 with systemic lupus erythematosus (SLE), and 69 with primary Sjogren's syndrome (pSS) were studied. The control group consisted of 392 matched healthy individuals. Genotyping of IL-1beta single-nucleotide polymorphisms (SNPs) at positions -511 (C/T) and + 3953 (C/T) was performed by the polymerase chain reaction-restriction fragment length polymorphism technique. In addition, levels of IL-1beta were measured by immunoassay in supernatants of lipopolysaccharide (LPS)-stimulated and nonstimulated peripheral blood monocytes (PBM) obtained from 19 homozygous individuals for the three most common IL-1beta likely haplotypes, all belonging to the control group. Allele + 3953T was protective for SLE (odds ratio (OR) = 0.57, 95% confidence intervals (CI) = 0.34-0.88, P = 0.01) as was the haplotype -511C + 3953T (OR = 0.43, 95%CI = 0.25-0.74, pc = 0.006). The latter was associated with a lower LPS-stimulated-PBM IL-1beta secretion. Results suggest that IL-1beta polymorphism influences the susceptibility to acquire SLE in our population. The protective association might be explained by the observed inhibitory effect of IL-1beta + 3953T allele on the secretion of IL-1beta under inflammatory circumstances.     

Monitoring gp43 antigenemia in Paracoccidioidomycosis patients during therapy

Paracoccidioidomycosis (PCM) is a systemic fungal disease that is particularly important among individuals living and working in rural areas of endemicity in Latin America. Detection of anti-Paracoccidioides brasiliensis antibodies is of limited value due to false-negative results. Detection of P. brasiliensis-gp43 circulating antigen is a practical approach for a specific diagnosis of the disease. In a previous study we described an inhibition enzyme-linked immunosorbent assay able to detect the 43-kDa P. brasiliensis antigen in sera of 100% of patients with the acute form of PCM and in 95.31 and 100% of patients with the chronic multifocal and unifocal forms of PCM. To investigate its potential application for the follow-up of PCM patients during treatment, antigen levels were monitored at regular intervals for up 8 to 12 months in serum samples from 23 patients. The results showed that treatment with itraconazole resulted in decreasing levels of circulating gp43 that were correlated with the reduction of anti-gp43 antibodies. It was also observed that by the end of 12 months of treatment gp43 levels were <5 microg/ml in all patients.     

DNA damage in cytologically normal urothelial cells of patients with a history of urothelial cell carcinoma

In order to determine if patients with a history of previous urothelial cell carcinoma (UCC) but with current normal urinary cytology have DNA damage in urothelial cells, the single-cell gel electrophoresis (comet) assay was conducted with cells obtained by urinary bladder washings from 44 patients (28 with a history of previous UCC). Increased DNA damage was observed in cytologically "normal" urothelial cells of patients with a history of UCC when compared with referents with no similar history and after correcting the data for smoking status and age (P < 0.018). Increased DNA damage also correlated with the highest tumor grade, irrespective of time or course of the disease after clinical intervention (Kendall tau correlation, 0.37, P = 0.016). Moreover, aneuploidy, as assessed by DNA content ratio (DCR; 75th/25th percentile of total DNA fluorescence of 50 comets/patient) was unaltered by smoking status, but increased with UCC grade: 1.39 +/- 0.12 (median +/- 95% confidence interval; referents); 1.43 +/- 0.11 (Grade I UCC; P = 0.264, against referents); 1.49 +/- 0.16 (Grade II UCC; P = 0.057); 1.57 +/- 0.16 (Grade III UCC; P = 0.003). Micronucleated urothelial cells (MNC) were also scored on Giemsa-stained routine cytological smears and were found not to correlate with DNA damage or DCR. MNC frequencies were higher for patients with a history of UCC and/or smoking than referents with neither history, but there was no statistical difference between groups. Taken together, these results suggest that the normal-appearing urothelium of patients resected for UCC still harbor genetically unstable cells.     

Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis

Supravalvular aortic stenosis (SVAS) is an inherited obstructive vascular disease that affects the aorta, carotid, coronary and pulmonary arteries. Previous molecular genetic data have led to the hypothesis that SVAS results from mutations in the elastin gene, ELN. In these studies, the disease phenotype was linked to gross DNA rearrangements (35 and 85 kb deletions and a translocation) in three SVAS families. However, gross rearrangements of ELN have not been identified in most cases of autosomal dominant SVAS. To define the spectrum of ELN mutations responsible for this disorder, we refined the genomic structure of human ELN and used this information in mutational analyses. ELN point mutations co-segregate with the disease in four familial cases and are associated with SVAS in three sporadic cases. Two of the mutations are nonsense, one is a single base pair deletion and four are splice site mutations. In one sporadic case, the mutation arose de novo. These data demonstrate that point mutations of ELN cause autosomal dominant SVAS.      

Localized lymphatic sporotrichosis after fish-induced injury (Tilapia sp.).

Localized lymphatic sporotrichosis generally develops after the fungus Sporothrix schenckii is traumatically introduced into skin or mucosa by contaminated plant material. An 18-year-old male fisherman was injured by spines of the dorsal fin of a fish on the left third finger. The lesion became ulcerated, edematous and suppurative and did not respond to tetracycline and cephalexin. Fifteen days after the accident, a nodular lymphangitic pattern of swelling was observed. Histopathological findings and an intradermal test were suggestive of sporotrichosis and mycological cultures confirmed the diagnosis. The lesions resolved after oral treatment with potassium iodide. Sporotrichosis is a common subcutaneous mycosis in Brazil, and there is a previous report in the literature of this disease being acquired via trauma involving fish spines.     

Inhibition of Paracoccidioides brasiliensis by pesticides: is this a partial explanation for the difficulty in isolating this fungus from the soil?

The aim of this study was to evaluate the effect of ten pesticides on Paracoccidioides brasiliensis, and thereby to investigate the possible association between these data and the difficulty in isolating P. brasiliensis from agricultural soil. Six fungicides (Alto 100, Benlate, Captan, Dithane, Plantacol, Rovral), two herbicides (Pivot, Roundup) and two insecticides (Azodrin and Curacron) were evaluated. Five P. brasiliensis isolates from the environment (labelled group 'N,' for 'nature') and five isolates from patients (group 'P'), were grown on Sabouraud's dextrose agar, at 35 degrees C, with ten different concentrations of each pesticide. The dose of pesticide that causes 50% growth inhibition (ED50) was calculated for each isolate. All pesticides assayed inhibited P. brasiliensis in a dose-dependent manner, and great variability among ED50 values was observed in isolates from both groups. No statistically significant difference was observed between averages of ED50 from groups N and P, except with Alto 100. The inhibitory effect of pesticides on P. brasiliensis suggests that they can interfere with attempts to isolate P. brasiliensis from soil, where tonnes of pesticides are applied over large areas planted with various crops.     

Notes on parasitism by Amblyomma humerale (Acari: Ixodidae) in the state of Rondônia,western Amazon,Brazil

The tick Amblyomma humerale Koch is endemic to South America. All host records refer to the adult stage parasitizing tortoises, mostly yellow-footed tortoise, Geochelone denticulata (L.), and red-footed tortoise, Geochelone carbonaria (Spix). The current study reports the presence of A. humerale in the state of Rond?nia, Brazil. A total of 215 adult ticks (201 males, 14 females) was collected from six G denticulata in an Indian reserve and nine Geochelone sp. in rural Monte Negro County, giving an overall mean infestation of 14.3 +/- 12.0 (range: 2-44) ticks per tortoise. Male ticks always outnumbered females on the host and nine tortoises had only male ticks. Male ticks were mostly attached in clusters on the ventral sides of the carapace near the anterior and posterior margins, and more rarely on the outer margin of the plastron. All females were found attached to the tortoise skin, at different sites such as head, neck, shoulders or legs. Male ticks were rarely observed attached to the body skin. Seven engorged nymphs collected on small vertebrates from Monte Negro County molted to adults of A. humerale. This included one nymph each on the seven-colored lizard, Plica plica (L), green tree climber, Plica umbra (L.), and wide-foraging lizard, Kentropyx calcarata Spix,three nymphs on the common opossum, Didelphis marsupialis L., and one nymph on the silky anteater, Cyclopes didactylus L. These constitute the first host records for the immature stages of the tick A. humerale.     

Contextual modulation of synchronization to random dots in the cat visual cortex

Synchronization of neuronal activity has been proposed as a binding mechanism for integration of image properties into one coherent percept. In the present study, we investigated the contextual modulation of synchronization to random dot patterns. Coherent motion of random dots evoked well synchronized responses in area 17 of anaesthetized cats when the stimulus was presented in the compound receptive field of recorded sites. Gradually changing the directional coherence of random dots in the surround while maintaining fully coherent motion of the stimulus in the receptive field significantly suppressed synchronization of neuronal activity for some stimulus conditions. However, usually one or two peaks of increased synchronization were found in the surround coherence tuning curves with low (8–12%) and/or moderate (25–50%) coherence in the surround. At the population level, synchronization was significantly depressed with incoherent motion in the receptive field and when both the surround and the receptive field were jointly stimulated with 0% coherence. The intriguing finding was the discovery of two distinct groups of cells with opposite synchronization changes dependent on the presence or absence of significant synchronization in their spontaneous activity. The latter group of neurons showed peaks of increased synchronization with lower surround coherence, thus probably being more sensitive to the direction of the surround motion. Overall, our findings support the notion that binding of stimulus properties can be achieved by synchronized activity of cortical cells. However, our findings go further than the original hypothesis of feature binding by synchrony to show that synchronization of cortical activity may be directly related to the decision making processes, which in turn are related to the threshold of perception of coherent motion.