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Biomedical subjects

S A Sampaio

Publications and source records attributed to S A Sampaio.

At least 19 recordsLinked to original sources

Comparison of black fly species (Diptera: Simuliidae) on an Amerindian reservation with a high prevalence of fogo selvagem to neighboring disease-free sites in the State of Mato Grosso do Sul, Brazil. The Cooperative Group on Fogo Selvagem Research.

Fogo selvagem is an autoimmune blistering skin disease that principally occurs among rural Brazilians living in geographically clumped disease foci. Exposure to hematophagous black flies possibly is related to the cause of the disease. We compared the occurrence, proportions, and richness of simuliid species immatures and the biting activity of adult females within a recently discovered, high prevalence focus of fogo selvagem, the Limão Verde Terena Reservation, to that of neighboring regions with no reported cases of fogo selvagem. Nine black fly species were collected from 12 stream sites during 5 trips to the fogo selvagem focus. The species showed longitudinal (upstream-downstream) trends in occurrence, proportions, and richness, and the abundance of simuliid immatures was greater at downstream sites. The most prevalent species at the focus, Simulium nigrimanum (Macquart), dominated the stream sites with highly abundant simuliid assemblages, and was the most common black fly in human bait collections. This species was absent or in very low numbers in neighboring valleys and villages that did not have cases of fogo selvagem.

Animals↗

An active focus of high prevalence of fogo selvagem on an Amerindian reservation in Brazil. Cooperative Group on Fogo Selvagem Research.

Fogo Selvagem (FS) is an autoimmune disease characterized by subcorneal vesicles and antidesmoglein-1 autoantibodies. Previous epidemiologic data have linked the onset of FS to exposure to an environmental antigen(s). This investigation describes a unique human settlement with an extraordinarily high prevalence of FS. This community is made up of Amerindians belonging to the Terena tribe, which has settled on the Limao Verde reservation in the state of Mato Grosso do Sul in Brazil. Twenty-six well-characterized FS cases have been identified within a total population of 998, yielding a prevalence of 2.6%. Seventeen of the patients (65 %) were males, and over 50% were older than 30 y of age. The incidence of the disease shows temporal periodicity, i.e., years with several cases of FS alternating with years with no cases. Over one-half of the cases occurred in genetically related family members. Another Terena reservation, the Ipegue/Taunay, located 90 km west of the Limao Verde reservation, was also evaluated as a control group. This reservation, with a population of 2203, had no recorded cases of FS. Thus, the Limao Verde reservation represents a new focus of FS in which the disease exhibits temporal, geographic, and familial clustering. These results suggest that the environmental antigen or antigens precipitating FS are endemic to the Limao Verde reservation. This reservation appears to be an ideal population for carrying out sero-epidemiologic, genetic, and environmental studies aimed at disclosing the etiology of FS.

Adolescent↗

Pemphigus foliaceus autoantibodies bind both epidermis and squamous mucosal epithelium, but tissue injury is detected only in the epidermis. The Cooperative Group on Fogo Selvagem Research.

BACKGROUND: Fogo selvagem (FS) is an autoimmune intraepidermal blistering disease mediated by antidesmosomal autoantibodies. Patients with FS do not have mucosal lesions despite extensive skin involvement. OBJECTIVE: Our purpose was to evaluate the epidermis and the oral epithelium of patients with FS as targets of antidesmosomal autoantibodies. METHODS: Fifteen patients were studied clinically, histologically, and immunologically. Biopsy specimens from the skin and the oral mucosa were studied by light microscopy and direct immunofluorescence. The serum of each of these patients was also titrated by indirect immunofluorescence. RESULTS: All patients showed skin lesions and subcorneal acantholyis, but none exhibited oral blisters or erosions. Direct immunofluorescence analysis demonstrated the presence of tissue-bound autoantibodies in both the epidermis and the oral epithelium of all patients with FS. Antiepidermal autoantibodies were also found in the sera of the patients. CONCLUSION: Relevant epitopes on desmoglein 1 molecules of oral epithelium may not be available to react with pathogenic FS autoantibodies.

Adolescent↗

Brazilian pemphigus foliaceus, endemic pemphigus foliaceus, or fogo selvagem (wild fire).

Brazilian pemphigus foliaceus, also known as fogo selvagem, is the endemic form of pemphigus foliaceus occurring in certain regions of Brazil. Epidemiologic data strongly support the notion that this disease is caused by exposure to an environmental agent or agents. This form of pemphigus foliaceus is a true human autoimmune disease mediated by autoantibodies of the IgG class, IgG4 subclass. These autoantibodies are pathogenic and highly specific for the disease. The environment agent may sensitize the patient to produce autoantibodies. These autoantibodies may cross-react with the epidermis and induce disease in the patient.

Autoantibodies↗

Successful treatment of sporotrichosis with oral fluconazole: a report of three cases.

We report three cases of sporotrichosis successfully treated with oral fluconazole. A verrucous lesion on the toe was cured after 126 days, and a lesion on the left foot resolved after 91 days' treatment. A case of lymphangitic-type sporotrichosis required 174 days of treatment to achieve a cure, and a higher dose (400 mg daily) was necessary in this case. Any side-effects were insignificant. We conclude that this new bis-triazole compound can be successfully used as an alternative treatment for sporotrichosis when conventional drugs must be avoided.

Administration, Oral↗

A Pan-American 5-year study of fluconazole therapy for deep mycoses in the immunocompetent host. Pan-American Study Group.

Eighty-eight immunocompetent patients with deep mycoses from eight countries were evaluated with the same protocol for efficacy of fluconazole monotherapy. Entry doses were raised from 100 to 400 mg as safety was shown in initial cohorts, and dosages up to 2,400 mg daily and durations up to 44 months were studied. Results were very similar in different countries. Twenty-seven of 28 evaluable patients with paracoccidioidomycosis, 13 of 19 with sporotrichosis, 14 of 16 with coccidioidomycosis, and eight of eight with histoplasmosis demonstrated objective responses to therapy, as did one patient each with zygomycosis and alternariosis. For these patients, relapses have been unusual thus far. In contrast, one patient with chromoblastomycosis responded but relapsed, and six did not respond; one patient with mycetoma responded but relapsed, and two did not respond. The drug was well tolerated by patients, including six who received intravenous therapy. In vitro susceptibility tests suggested that clinical response was correlated with susceptibility but that resistance did not preclude clinical response. Fluconazole therapy appears efficacious for several deep mycoses; dosages of greater than 200 mg daily may be needed for some diseases. The further evaluation of fluconazole for these entities is warranted.

Adolescent↗

Environmental risk factors in endemic pemphigus foliaceus (Fogo selvagem). "The Cooperative Group on Fogo Selvagem Research".

Endemic pemphigus foliaceus or Fogo selvagem (FS) is an epidermal organ-specific autoimmune disease mediated by autoantibodies. Individuals at risk are peasants who live and work on farms located in the interior of certain endemic states of Brazil. This case-control study compares a group of 52 FS patients with 52 patients suffering from other dermatoses admitted and followed at the hospital for pemphigus (Hospital do Penfigo) in the city of Goiania, state of Goias. Patients and controls matched 1:1 by age, sex, and occupation were examined by two dermatologists at the time of admission and asked to respond to a prepared questionnaire. This questionnaire concerned current and past (1 and 5 years) exposure to environmental risk factors. The following risk factors were assessed: black fly bites, presence of rodents at home, exposure to cereal dust, exposure to fumes or dust released by tree and shrub removal, and exposure to insecticides. Relative risks were estimated from tabulated data by the odds ratio and tested for significance by the chi-square test. The 95% confidence interval for the odds ratio was also calculated for each of the risk factors. The only risk factor showing an odds ratio significantly different from one was exposure to simuliidae bites (odds ratio 4.7, p less than 0.001). This study reinforces the hypothesis that chronic exposure to black fly antigens may precipitate IgG4 antibody formation in predisposed individuals. These antibodies in turn may cross-react with epidermal antigens and cause acantholysis and the clinical expression of the disease known as FS.

Adolescent↗

Cutaneous lupus erythematosus: direct immunofluorescence and epidermal basal membrane study.

Biopsy specimens of cutaneous discoid lesions of 71 patients with cutaneous lupus erythematosus (CLE) were studied. The material was examined by direct immunofluorescence (DIF) to establish positivity and morphologic patterns of immunoglobulins and complement deposits in the basement membrane zone (BMZ). A correlation between DIF results and thickening of the epidermis basement membrane (BM) stained by periodic acid-Schiff (PAS), obtained from 31 matched biopsy specimens, also is presented. Direct immunofluorescence had positive results in 66.20% of the 71 examinations and 70.97% of the matched examinations, whereas PAS showed BM thickening in 100% of the specimens. This observation stresses the importance of such histopathologic findings in the diagnosis of discoid lesions in CLE. There was no correlation between DIF patterns and PAS-stained BMZ thickening. These findings merit additional study. In conclusion, an accordance between PAS-stained BM thickening and immunoglobulin deposits has occurred in 70.97% of cases. This phenomenon does not depend on the presence of immunocomplexes, for it occurs even in cases in which immunocomplex deposits were not detected.

Adolescent↗

HLA antigens and risk for development of pemphigus foliaceus (fogo selvagem) in endemic areas of Brazil.

Endemic pemphigus foliaceus (EPF), is an autoimmune disease associated with production of IgG antibodies against epidermal antigens. We have tested 38 patients and 50 control subjects living in endemic areas to investigate whether HLA genes are associated with host factors that determine whether or not exposed individuals will develop this disease. A variant of HLA-DR1, an antigen common in Blacks (DRB1*0102), was found to be the main susceptibility factor (relative risk = 7.3, P less than 0.0002). Two amino acids, in positions 85 and 86 of DRB1, distinguish DRB1*0102 from DRB1*0101. These residues appear to be involved in the formation of a functional epitope that causes T cell recognition and determines disease susceptibility. Moreover, subjects having DQw2 did not develop the disease, while the frequency of DQw2 in controls was 22% (RR = 0.04, P less than 0.006). Thus HLA genes appear to play a crucial role in the response to an environmental factor which in this setting frequently leads to the development of autoimmune disease. An HLA-DQ allele, DQw2, appears to be associated with factors that prevent the development of the disease in exposed individuals.

Autoimmune Diseases↗

Endemic pemphigus foliaceus in western Parana, Brazil (1976-1988). Cooperative Group for Fogo Selvagem Research.

Endemic pemphigus foliaceus or fogo selvagem (FS) is a blistering autoimmune disease indigenous to certain states of Brazil. In the state of Parana the disease has been reported in the north-central regions where a total of 632 cases were documented in the period of 1940-80. The present study describes a new focus of FS in the western region of the state of Parana. This focus includes a total of 213 new cases of FS and only 11 cases of pemphigus vulgaris seen in this region from February 1976 to July 1988. Over 90% of these patients were peasants working in agriculture or involved in other outdoor activities.

Adolescent↗

Endemic pemphigus foliaceus (fogo selvagem). I. Clinical features and immunopathology.

Endemic pemphigus foliaceus is an autoimmune disease that has remarkable features. Endemic foci are found in characteristic environments within the interior of Brazil. The epidemiologic data strongly suggest that an environmental factor initiates the autoantibody response in the host. As such it is an important disease for in-depth study. A group of interested investigators in both Brazil and the United States has been formed to attempt to do just that. As part of the overall effort, this Cooperative Research Group for the Study of Fogo Selvagem presents a definition of the disease, a proposed clinical classification for various forms of the disease, and an outline of what is currently known of its immunopathologic characteristics.

Adult↗

Endemic pemphigus foliaceus (Fogo Selvagem): II. Current and historic epidemiologic studies.

This paper details current and historic epidemiologic features of Fogo Selvagem (Endemic pemphigus foliaceus) in Brazil. The following features are described. a) The disease occurs in endemic fashion in regions of Brazil within the states of Goias, Mato Grosso do Sul, Parana, Sao Paulo, and Minas Gerais. It appears that the disease is spreading toward the northwest and west, involving the states of Mato Grosso, Para, Maranhao, Rondonia, Acre, and Amazonas. b) People at risk are young peasants or children of either sex or any race exposed to the local ecology in rural areas of endemic states. Although the disease has been described in urban centers, these occurrences are rare. c) Fogo Selvagem commonly appears in wild areas being colonized and disappears as these areas become urbanized. d) The majority of patients live in close proximity to rivers and within the 10-15 Km flying range of mosquitos or black flies (such as Simulium). It is hypothesized that a black fly, Simulium pruinosum may be the vector that precipitates the disease. f) There is a significant number of Fogo Selvagem in family units where multiple, genetically related individuals are affected. g) Finally, autoantibodies against lupus-associated antigens are not present in the sera of patients with Fogo Selvagem. Clinical examination of the skin, and serologic screening for pemphigus autoantibodies are specific parameters that can be used in the search for the etiologic agents that lead to autoimmune disease of the skin. To identify and prove an etiologic agent for this well-characterized autoimmune disease would be of tremendous importance to the understanding of autoimmune skin diseases, and potentially other organ-specific autoimmune disorders.

Age Factors↗

Treatment of chromomycosis by cryosurgery with liquid nitrogen: a report on eleven cases.

Cryosurgery with liquid nitrogen was used to treat 11 cases of chromomycosis, 5 with localized lesions and 6 with generalized ones. Freezing time varied from 30 seconds to 4 minutes and the number of cycles from 1 to more than 40. All 5 cases with localized lesions responded extremely well to treatment, with no relapse for up to 53 months. Three patients with generalized lesions attained clinical and mycologic remission for up to 26 months, while 3 had significant improvement without cure. Cryosurgery with liquid nitrogen is therefore an effective treatment for chromomycosis, especially for cases presenting with localized lesions.

Adult↗

Serologic abnormalities in patients with endemic pemphigus foliaceus (Fogo selvagem), their relatives, and normal donors from endemic and non-endemic areas of Brazil.

Based on epidemiologic data, a current hypothesis states that Fogo selvagem (FS) may be triggered by environmental factors present in endemic areas of Brazil. Because the appearance of new cases is limited to those areas, we wanted to ascertain if the presence of the pemphigus autoantibodies was restricted to the patients. To further delineate the restriction of the autoantibody response in these patients we also investigated the presence of lupus-associated autoantibodies. Using indirect immunofluorescence (IF) we tested the sera of patients with FS (n = 196), their relatives (n = 138), their cohabitants (n = 13), and normal donors from endemic (n = 38) and non-endemic areas (n = 44) for pemphigus autoantibodies. Antinuclear antibodies (ANA) and anti-nDNA antibodies were determined by indirect IF against Hep-2 cells and Crithidia lucilliae, respectively. Autoantibodies against nRNP, Ro/SSA, La/SSB, and Sm were assayed by double immune diffusion in agarose gels. FS autoantibodies were present in the sera of all patients with active disease (n = 196, 100%, titers greater than 40 to 2560), but were not found in any sera from normal individuals in endemic or non-endemic areas. The titer of the FS autoantibody showed a rough correlation with the extent and activity of the disease. Furthermore, lupus-associated autoantibodies were not present in any of the tested samples. We conclude the FS antiepidermal autoantibodies are specific serologic markers of the disease and are not present in unaffected individual from the endemic areas. As such, they provide an important marker that should be useful in ongoing epidemiologic studies aimed at identifying putative etiologic agent(s).

Antibodies, Antinuclear↗

[Immunopathogeny of pemphigus].

This article reviews recent concepts of pathogenetic mechanisms in pemphigus. We describe the pathogenic effect of the autoantibodies, the animal model for the disease and the ultrastructural alterations which follow the antibody-antigen interaction. The role of complement and protease systems in development of tissue injury are also discussed.

Animals↗

An autoantibody in pemphigus serum, specific for the 59 kD keratin, selectively binds the surface of keratinocytes: evidence for an extracellular keratin domain.

We have identified a novel IgG antikeratin autoantibody in the serum of a Brazilian pemphigus foliaceus patient (Cascas-42). This antibody is specific for the 59 kD acidic murine keratin and its 56.5 kD human counterpart (Moll's catalogue #10), and is distinct from the pemphigus antibody system. Antikeratin autoantibodies present in the Cascas-42 serum were purified by affinity chromatography with a 59 kD murine keratin-agarose column (IAP-Cascas-42 antibodies). The specificity of the IAP-Cascas-42 antibodies was tested by indirect immunofluorescence and immunoelectron microscopy against epidermal cryosections, trypsin-dissociated keratinocytes, and epidermal cell cultures. The serum was also tested with extracts from unlabeled and surface 125I-labeled keratinocytes (Iodo-Gen method) by immunoblot analysis of one- and two-dimensional polyacrylamide gel electrophoresis. The IAP-Cascas-42 antibodies bind the intercellular spaces of murine epidermis, and the cell surfaces of viable, dissociated murine keratinocytes, as well as murine epidermal cells in culture by immunofluorescence and immunoelectron microscopy. These autoantibodies did not stain cytoplasmic keratins and did not react with parallel human epidermal substrates. The Cascas-42 serum identified the 59 kD murine acidic keratin and its 56.5 kD human counterpart in epidermal extracts by two-dimensional polyacrylamide gel electrophoresis and immunoblot analysis. In addition, surface radioiodination of viable murine keratinocytes selectively labeled the 59 kD keratin suggesting that a domain of this molecule is exposed on the cell surface. The 125I-labeled 59 kD keratin was also recognized by the Cascas-42 serum by immunoblotting and autoradiography. These studies suggest that in murine epidermis, the 59 kD keratin is a transmembrane protein with an extracellular domain recognized by the IAP-Cascas-42 antibodies.

Animals↗

Antigenic specificity of fogo selvagem autoantibodies is similar to North American pemphigus foliaceus and distinct from pemphigus vulgaris autoantibodies.

Fogo selvagem (FS) is clinically, histologically, and immunopathologically similar to sporadic pemphigus foliaceus (PF, as seen in North America and Europe), although the epidemiology of these 2 diseases differs markedly. It has been proposed that FS is identical to PF but, for some reason, occurs in an endemic focus in central Brazil. If this hypothesis is correct, the autoantibodies in FS and PF should have similar antigenic specificities. We studied sera from 13 patients with FS from central Brazil, and compared them with 20 sera from patients with PF from the United States. All these sera had circulating antibodies that bound the cell surface of epithelial cells in identical patterns by indirect immunofluorescence on monkey esophagus or normal human skin. In immunoprecipitation studies none of the 13 FS sera precipitated the pemphigus vulgaris (PV) antigen from radiolabeled extracts of cultured human keratinocytes. This is similar to the findings with PF sera of which 19 of 20 sera did not react with PV antigen, but in sharp contrast to the results with PV sera which, as previously reported, all immunoprecipitate the PV antigen. Immunoblotting performed on extracts of normal human epidermis demonstrated that 7 of 20 PF sera specifically and intensely bound an approximately 160 kD polypeptide, previously identified as desmoglein I, a desmosomal glycoprotein. Similarly, 3 of 13 FS sera specifically bound a 160 kD polypeptide. Thirteen normal sera from North America, 8 normal and disease control sera from central Brazil, 11 PV sera, and 12 bullous pemphigoid sera did not specifically bind this polypeptide. Two-dimensional gel electrophoresis confirmed that the 160 kD polypeptides identified by the subgroup of PF and FS sera were identical. These studies demonstrate that, although the exact molecular specificities of the majority of PF and FS sera remain to be determined, FS autoantibodies do not bind the PV antigen and a subgroup of FS autoantibodies have molecular specificity identical to that of a subgroup of PF autoantibodies.

Antibody Specificity↗

Elevated thymosin alpha I levels in Brazilian pemphigus foliaceus.

Levels of thymosin alpha I in the sera of 37 patients with Brazilian pemphigus foliaceus (BPF) were measured using a competitive binding radioimmunoassay. The values were compared with 19 patients with other forms of pemphigus, 13 relatives of patients with BPF, 18 patients with other dermatological diseases, and 265 normal controls. We found that 27 (73%) of the patients with BPF had thymosin alpha I serum levels that were at least two standard deviations above the mean for normal individuals. The mean value for patients with BPF was significantly greater than any other groups studied. The thymosin elevation is similar to alterations seen in certain viral diseases and suggests that BPF is aetiopathogenically distinct from the forms of pemphigus.

Adult↗