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Biomedical subjects

E A Donadi

Publications and source records attributed to E A Donadi.

At least 19 recordsLinked to original sources
PubMed2006

Molecular mechanisms associated with donor-specific microchimerism in peripheral blood of Brazilian patients after liver transplantation.

A large number of studies in liver transplantation have demonstrated allogeneic microchimerism. The clinical and immunologic implications of this finding remain inconclusive, just as the influence of HLA mismatch and donor alloreactivity also are controversial. The present study analyzed the presence of allogeneic microchimerism in liver transplant recipients in relation to donor leukocyte kinetics and rejection episodes. The study was extended to determining the influence of immunogenetic factors in patients after liver transplantation. The presence of allogeneic microchimerism was analyzed on peripheral blood of 50 recipients. DNA extracted from the samples was subjected to typing for HLA-DRB1 and -DQB1 alleles by polymerase chain reactions using sequence-specific primers (PCR/SSP). Microchimerism was identified by nested PCR/SSP. Microchimerism was detected in 72% of patients. There was significant effect of microchimerism on rejection episodes (P=.002), while HLA mismatches did not show significance for one or two mismatches (P=.98). Allogeneic microchimerism detected in the majority of liver transplant patients was observed to be significantly associated with rejection episodes.

Brazil↗
PubMed2006

Microchimerism evaluation in recipients of living-related or unrelated deceased allograft renal transplants.

The presence of microchimerism in the peripheral blood of solid organ graft recipients has been associated with long-term solid organ acceptance, immunologic tolerance, and less aggressive immunosuppressive therapy. Molecular biology assays are among the most sensitive methods to detect microchimerism, primarily to evaluate Y chromosome sequences in females as indirect evidence of circulating male nucleated donor cells. We screened for the presence of the SRY sequence region in peripheral blood of 13 female recipients of male kidney grafts: 5 living-related and 8 deceased grafts. Only patients who received grafts from related living donors exhibited microchimerism. Five of 13 patients studied exhibited better graft outcomes, including the 4 who were positive for the SRY sequences.

Adult↗
PubMed2006

Identification of a novel 120 bp allele at the TNFd microsatellite locus.

Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine mainly secreted by macrophages and T-cells that play a key role in the pathogenesis of many infectious and inflammatory diseases. The TNF gene cluster is located within the class-III region of the highly polymorphic major histocompatibility complex on human chromosome 6p21. A cluster of six multiallelic microsatellites has been identified in the TNF region, named TNF a-e. TNFb, TNFc, TNFd, and TNFe are (GA)n repeats, whereas TNFa and TNFf are (GT)n and (CA)n repeats, respectively. The TNFd microsatellite locus maps 8-10 kb centromeric to the TNF-alpha gene, downstream to the TNF-beta gene.

Alleles↗
PubMed2006

Quantitative cell-cycle protein expression in oral cancer assessed by computer-assisted system.

The knowledge of cell-cycle control has shown that the capacity of malignant growth is acquired by the stepwise accumulation of defects in specific genes regulating cell growth. Histologic diagnosis might be improved by a quantitative evaluation of more specific diagnosis biomarkers, which could help to precisely identify pre-malignant and malignant oral lesions. The aim of the present study is to evaluate whether computer-based quantitative assessment of p53, PCNA and Ki-67 immunohistochemical expression, could be used clinically to foresee the risk of oral malignant transformation. This retrospective study was carried out in ninety-five oral biopsies, 27 were classified as fibrous inflammatory hyperplasia, 40 as leukoplakia and 28 as oral squamous cell carcinoma. Sixteen out of the 40 leukoplakia were diagnosed as non-dysplastic leukoplakia, the other 24 being dysplastic leukoplakia, of which 50.0% were classified as moderate to severe dysplasia. Comparison of the four groups of oral tissues showed significant rises in p53 and Ki-67 positivity index, which increased steadily in the order benign, pre-malignant, and malignant. In contrast, it was not possible to relate higher PCNA levels with pre-malignant and malignant oral lesions. We therefore conclude that PCNA immunohistochemistry expression is probably an inappropriate marker to identify oral carcinogenesis, whereas joint quantitative evaluation of p53 and Ki-67, appears to be useful as a tumor marker, providing a pre-diagnostic estimate of the potential for cell-cycle deregulation of the oral proliferate status.

Biomarkers, Tumor↗
PubMed2005

Effects of arginine supplementation on the humoral and innate immune response of older people.

OBJECTIVE: To evaluate whether oral supplementation with arginine affects the humoral and innate immune response after vaccination against Streptococcus pneumoniae in a group of people aged 60 y and older, free-living in the community. DESIGN: A randomized controlled trial with one supplemented group and one control group. SETTING: Older persons living in the community. SUBJECTS: A total of 29 adults aged 60 y and older. INTERVENTIONS: The older people were randomized into two groups, one with arginine supplementation (15 g/day) for 4 weeks after pneumococcal vaccine. The control group received only the vaccine. Anthropometric measurements and immune system function parameters: neutrophil chemotaxis and phagocytosis, natural killer cell activity, determination of serum pneumococcal polysaccharide antibodies and serum C3 and C4. RESULTS: Neutrophil phagocytosis and the serum concentration of complement (C3 and C4) did not differ between groups. IgG antibodies against pneumococcal polysaccharide serotypes 1, 5 and 6B increased in both groups. The following parameters increased in the arginine-supplemented group compared to the nonsupplemented group: neutrophil chemotaxis (34 vs 19 units of migration, P = 0.002), natural killer cell cytotoxicity (23.3 vs 13.4 10 M/Ul 40%, P = 0.011) and IgG against antigen 5 (12.3 vs 6.2 mug/ml, P = 0.044). CONCLUSIONS: This study suggests that, after the pneumococcal vaccine, the intake of arginine increased neutrophil chemotaxis, natural killer cytotoxicity and serum concentration of IgG against antigen 5 in older people. These results suggest that arginine supplementation may enhance the immune response elicited by the pneumococcal vaccine in older people. SPONSORSHIP: Supported in part by CAPES and FAEPA.

Administration, Oral↗
PubMed2005

Increased activity of plasma and tissue kallikreins, plasma kininase II and salivary kallikrein in pemphigus foliaceus (fogo selvagem).

BACKGROUND: Pemphigus foliaceus (PF) is an autoimmune blistering disease of unknown aetiology, which is endemic in Brazil. Although the pathogenesis of PF is still unknown, proteins of the contact system have been implicated. OBJECTIVES: As the components of the kinin system may interact with those of the contact system, in this study we evaluated the plasma levels of high-molecular-weight kininogen (HK) and low-molecular-weight kininogen (LK), and the activity of plasma kallikrein, tissue kallikrein and kininase II in plasma of patients with PF presenting with Nikolsky's sign. As kidneys and salivary glands are relevant sources of tissue kallikrein for plasma, we also evaluated urinary/salivary kallikrein and urinary kininase II activities. METHODS: Fifteen patients and 15 age- and sex-matched controls were studied. Kininogen levels were determined by enzyme-linked immunosorbent assay, and the activities of kallikreins and kininase II were determined using selective chromogenic substrates. RESULTS: Compared with controls, plasma HK levels were decreased (P = 0.031), whereas the activities of plasma kallikrein, tissue kallikrein and kininase II in plasma, and the activity of salivary kallikrein, were increased in patients (P < 0.001 for each comparison). Plasma levels of LK and the activities of urinary kallikrein and urinary kininase II were not significantly different from controls. CONCLUSIONS: Diminished levels of HK associated with increased activities of plasma kallikrein and kininase II indicate that the kinin system is activated at the systemic level in PF. As active plasma kallikreins may act on some proteins of the contact system, it is possible that the enzyme may contribute to blister formation. The further observation of an increased tissue kallikrein activity at the systemic and saliva levels may be interpreted as a systemic reflex of skin inflammation. Whether the activation of the kinin system is a cause or a consequence of blister formation needs further clarification.

Adolescent↗
PubMed2005

Association of tumor necrosis factor a-2 and a-8 microsatellite alleles with human papillomavirus and squamous intraepithelial lesions among women in Brazil.

Infection with oncogenic human papillomavirus (HPV) is considered to be the major risk factor for cervical cancer. Tumor necrosis factor (TNF) is a pluripotent cytokine that plays an important role in inhibiting the action of microbial agents, and TNF microsatellite polymorphisms have been associated with several diseases, including cancer and viral infections. This study analyzed the associations between TNFa to -e microsatellite polymorphisms and the severity of squamous intraepithelial lesions (SIL), according to the presence of the oncogenic HPV16 and HPV18 types. Samples from 146 HPV-positive women with low-grade SIL (LSIL) and high-grade SIL (HSIL) and samples from 101 healthy women were studied. TNF microsatellite polymorphism typing and HPV detection and typing were performed using PCR-amplified DNA hybridized with sequence-specific primers. Data were analyzed by Fisher's exact test using the GENEPOP software. Significant associations were observed between LSIL and the TNFa-8 allele (4/166; P = 0.04), as well as between TNFa-2 with HPV18 only (16/44; P = 0.002) and TNFa-2 with HPV18 coinfection with HPV16 (16/44; P = 0.001). Patients exhibiting the TNFa-2 allele and harboring HPV18, in the presence or absence of coinfection with HPV16, had an increased risk of HSIL occurrence (13/38; P = 0.04; 5/10; P = 0.04) compared to patients with other HPV types. These results suggest that the TNFa-8 allele is associated with increased susceptibility to the occurrence of LSIL and that despite the presence of a high TNF-alpha production allele, the ability of HPV18 to resist the inhibitory effects of TNF-alpha may contribute to the occurrence of infection and consequently to HSIL in women with cervical HPV18 infection.

Adolescent↗
PubMed2004

Langerhans' cell count and HLA class II profile in cervical intraepithelial neoplasia in the presence or absence of HIV infection.

OBJECTIVES: The progression of immunosuppression in human immunodeficiency virus (HIV)+ women has been correlated with elevated incidence of squamous intraepithelial lesions (SIL), probably indicating the role of local immune milieu. In this study, we analysed S100, and HLA class II molecule expression in cervical biopsies according to HIV status, to the severity of SIL and to human papillomavirus (HPV) type. METHODS: Biopsies from 34 HIV+ and 44 HIV- patients with normal cervix or low- or high-grade SIL were studied. Langerhans' cells (LC) (S100), HLA class II and HLA-DQ molecules were evaluated by immunohistochemistry. HPV detection was performed using polymerase chain reaction (PCR). For statistical analysis Mann-Whitney (P< or =0.05) and Spearman test were used. RESULTS: Epithelial S100 and HLA class II density were significantly increased with the severity of lesion (P=0.032; P=0.005). Epithelial S100+ increased in HPV+ (P=0.038), and HLA class II density decreased in HPV 16+ (P=0.035) or 18+ (P<0.0001) samples. HIV infection was associated with increased stromal S100+ (P=0.0005) and decreased HLA class II densities (P=0.0001). Decreased stromal S100+ was observed in women with CD4<500 cells/microl (P=0.050). Among HIV+ patients with SIL, the lowest S100 and epithelial HLA class II densities were detected in women with CD4<200 cells/microl (P=0.045). CONCLUSIONS: After the establishment of AIDS, increased numbers of immature LCs and a reduction in HLA class II occurred, possibly turning the cervical milieu more favourable to HPV persistence. HPV 16 and 18 infections may interfere with the antigen presenting activity, possibly as an evasion mechanism.

Adult↗
PubMed2004

The kinin system in the envenomation caused by the Tityus serrulatus scorpion sting.

Several lines of evidence in experimental animals indicate that the kinin system may participate in the pathogenesis of envenomation by the Tityus serrulatus (Ts) scorpion sting, but there are no studies in humans with regard to this system. In this study, we evaluated the plasma levels of high-molecular (HKg) and low-molecular (LKg) weight kininogens (detected by ELISA), the activities of plasma or tissue kallikreins and kininase II (enzymatic action upon selective substrates), and the Ts plasma venom levels (ELISA). A total of 27 patients (12 males) aged 12-72 were evaluated immediately at hospital admittance. According to the severity of envenomation, patients were classified as mild (n = 15), moderate (n = 8), and severe cases (n = 4). Controls were paired for age and sex. Plasma venom levels were associated with the severity of envenomation. Severe cases presented lower levels of LKg in relation to mild and controls. Inverse correlations were seen between LKg levels and the venom concentration. The results of this study suggested that the kinin system may participate in the pathogenesis of human Ts envenomation and knowledge about this system may be useful to develop new strategies to reduce the damage caused by scorpion envenomation.

Adolescent↗
PubMed2004

Development of donor-specific microchimerism in liver transplant recipient with HLA-DRB1 and -DQB1 mismatch related to rejection episodes.

Migration of donor-derived cells to recipient tissues after liver transplantation has been suggested as a mechanism to induce and maintain allograft tolerance, although important issues remain including acute rejection posttransplantation mortality, and complications related to immunosuppressive therapy. We therefore examined the relation of rejection to chimerism based upon recipient and donor mismatch of HLA-DRB1 and -DQB1 alleles. Laboratory analysis of peripheral blood was performed before and 10 days to 16 months after liver transplantation in 32 recipients, using ganglion or spleen cell samples of respective donors. DNA was extracted for HLA-DRB1 and DQB1 allele typing using polymerase chain reactions with sequence-specific primers (PCR-SSP). Microchimerism was analyzed through nested PCR. Our results confirmed that patients with one or two mismatched HLA-DRB1 and-DQB1 alleles showed microchimerism and no rejection (P <.05). Microchimerism was present in 71.88% of the patients, and a significant association of rejection P <.05 was found when microchimerism was correlated to graft rejection. These results suggest that the presence of microchimerism may be associated with acceptance, tolerance and survival of the allograft.

Graft Rejection↗
PubMed2004

HLA-DQB1 alleles may influence the surface expression of DQ molecules in lymphomononuclear cells of type 1 diabetes mellitus patients.

To evaluate the expression of human leucocyte antigen (HLA) class II (DR and DQ) molecules on lymphomononuclear cells involved in the pathogenesis of type 1 diabetes, we studied 20 patients and 20 controls matched to patients for age, sex and HLA class II profile. The coexpression of HLA and CD3, CD4, CD8, CD19 and CD14 molecules was evaluated by flow cytometry. HLA-DRB1, -DQA1 and -DQB1 alleles were assigned using amplified DNA hybridized with sequence-specific primers. The fluorescence intensity of HLA-DR and -DQ molecules observed on the surface of the lymphomononuclear cells of patients did not differ significantly from controls. Patients presented decreased percentage of double-positive CD4(+)/DQ(+) cells and increased percentage of CD19(+)/DR(+) cells, irrespective of the HLA class II profile; however, the more dramatic alteration of the lymphomononuclear phenotype profile was observed for patients possessing the HLA-DQB1*0201 allele. These patients exhibited decreased percentage of CD3(+), CD4(+), CD8(+), CD19(+) and CD14(+) cells bearing HLA-DQ molecules and decreased fluorescence intensity for HLA-DQ molecules on CD19(+) cells compared to patients without the DQB1*0201 allele. Although type 1 diabetes patients shared CD4/DQ or CD19/DR phenotype abnormalities, patients typed as DQB1*0201 presented additional abnormalities in terms of DQ expression and cell phenotypes bearing DQ molecules.

Adolescent↗
PubMed2004

Polymorphism of HLA class I genes in the Brazilian population from the Northeastern State of Pernambuco corroborates anthropological evidence of its origin.

The allelic distribution of human leukocyte antigen (HLA) class I genes (HLA-A, HLA-B, and HLA-Cw) of the population from the State of Pernambuco in Northeastern Brazil was studied in a sample of 101 healthy unrelated individuals. Low to medium resolution HLA class I typing was performed using polymerase chain reaction-amplified DNA hybridized to sequence specific primers (PCR-SSPs). Twenty allele groups were detected for HLA-A, 28 for HLA-B, and 14 for HLA-Cw. The most frequent alleles were HLA-A*02(0.2871), HLA-B*15(0.1238), and HLA-Cw*04(0.2277), and the most frequent genotypes were A*02/A*02(0.0990), B*15/B*15(0.0594), and Cw*04/Cw*04 and Cw*07/Cw*07, both with a frequency of 0.0792. The observed heterozygosity for the studied loci was 79.21% for HLA-A, 87.13% for HLA-B, and 77.23% for HLA-Cw. The most frequent haplotype was A*02-Cw*04-B*35(0.0485), which is also present in Western European, Amerindian, and Brazilian Mulatto populations, but absent in African populations. Taken together, these data corroborate the historic anthropological evidences of the origin of the Northeastern Brazilian population from Pernambuco.

Biological Evolution↗
PubMed2004

Is HLA class II susceptibility to primary antiphospholipid syndrome different from susceptibility to secondary antiphospholipid syndrome?

To assess whether the major histocompatibility complex (MHC) profile of patients presenting with primary antiphospholipid syndrome (PAPS) is different from that of patients with secondary antiphospholipid syndrome (SAPS), we studied 123 patients, 34 of whom presented PAPS and 35 SAPS due to systemic lupus erythematosus (SLE), 54 SLE patients without antiphospholipid syndrome (APS), and 166 controls. HLA-DRB1 and DQB1 alleles were typed using amplified DNA hybridized with sequence-specific primers. Compared to controls, PAPS patients exhibited a nonsignificantly increased frequency of DR53-associated alleles, and SAPS patients presented an increased frequency of HLA-DRB1*03 alleles (corrected P = 0.05). In addition, HLA-DRB1*03 alleles were over-represented in SAPS patients presenting anticardiolipin antibody (aCL) (Pc = 0.02), in SLE patients as a whole (Pc < 0.0001), and in SLE patients without APS (Pc = 0.02). The frequency of aCL among SLE patients presenting or not HLA-DRB1*03 alleles was closely similar. A trend to an increase in the frequency of the DQB1*0604 allele (14.3 versus 4.2%, P = 0.03) and of the DQB1*0302 allele (31.4 versus 12.7%, P = 0.01) was observed in SAPS. Taken together, these results indicate that the association of SAPS with HLA-DRB1*03 is due to the association with SLE and is not due to aCL, and suggest that the HLA class II profile of PAPS is different from that of SAPS.

Adolescent↗
PubMed2003

Increased plasma levels of IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha in patients moderately or severely envenomed by Tityus serrulatus scorpion sting.

Scorpion envenomation is a common medical problem in many countries and an important cause of morbidity and mortality, especially among children. The plasma levels of pro-inflammatory (IL-1beta, IL-6, IL-8 and TNF-alpha) and anti-inflammatory (IL-10) cytokines were measured in individuals stung by Tityus serrulatus (Ts) scorpions. According to clinical manifestations patients were classified, as defined by the Brazilian Ministry of Health, as having mild (n=15, mean age=42.2 years), moderate (n=8, mean age=26 years) or severe (n=4, mean age=14 years) envenomation. Blood samples were taken immediately (T1) and 6h (T2) after admission to the hospital. Eighteen age-matched healthy volunteers were used as control. TNF-alpha, IL-1beta, IL-6 and IL-8 levels were significantly increased in moderate and severe cases and the levels of these cytokines were positively correlated with the severity of envenomation, as evaluated by clinical profile and plasma venom concentration. IL-10 levels were increased in severe and moderate cases and reduced in mild cases. The results reported in the present study suggest that the physiopathological manifestation of Ts envenomation may be mediated, at least in part, by cytokines, and that the early treatment after scorpion sting with drugs that inhibit cytokine production, such as glucocorticoids, may have a potential beneficial effect, ameliorating the severity of the clinical manifestations observed, particularly in severe and moderate cases.

Adolescent↗
PubMed2002

Kallikreins and kininogens in saliva and plasma of patients presenting with rheumatoid arthritis.

We evaluated the activities of salivary kallikrein and tissue/plasma kallikreins, and the plasma levels of high-molecular (HKg) and low-molecular (LKg) weight kininogens in patients with rheumatoid arthritis. The patients exhibited higher levels of the active salivary kallikrein compared to the controls. In contrast, the total salivary kallikrein activity of patients was not different from controls. In plasma from the patients, tissue kallikrein activity or plasma prekallikrein activity was not significantly different from the controls. Plasma HKg levels observed in patients were higher than in controls, whereas plasma LKg levels did not differ significantly from controls. Our results showed that most of the salivary kallikrein seen in patients is in its active form, suggesting the presence of systemic or local factors with the ability to activate salivary pro-kallikrein.

Arthritis, Rheumatoid↗
PubMed2002

HLA-DRB1, DQB1, and DQA1 allele profile in Brazilian patients with type 1 diabetes mellitus.

HLA class II profile was evaluated in 64 Brazilian patients presenting with type 1 diabetes mellitus. Although the Brazilian population is highly miscegenated, HLA-DRB1*301, DRB1*04, DQB1*0302, and DQB1*0201 alleles, which are associated with the development of type 1 diabetes in several Western populations, were also overrepresented in Brazilian patients. In addition to HLA-DRB1*15 and DQB1*0602 alleles, DRB1*11, DRB1*13, and DQA1*01 allele groups were associated with protection against the development of type 1 diabetes in Brazilian patients.

Adolescent↗
PubMed2001

Kinin system in lupus nephritis.

There are few studies regarding the evaluation of the kinin system in patients with systemic lupus erythematosus (SLE). In this study, we evaluated the plasma levels of high-molecular weight kininogen (HKg), low-molecular weight kininogen (LKg) and plasma kallikrein; the plasma activity of tissue kallikrein and kininase II, and urinary kallikrein and kininase II activities in patients presenting with active lupus nephritis. A total of 30 patients (29 women) aged 21-62 years (median = 39) and 30 controls matched to the patients for sex and age were studied. Patients presenting with other underlying diseases or using drugs, which could interfere with the kinin system, were excluded. HKg and LKg levels were indirectly evaluated by ELISA. Plasma kallikrein, tissue kallikrein, and kininase II were evaluated by their enzymatic activity on selective substrates. The Mann-Whitney test was used for statistical analysis. HKg, LKg and plasma kallikrein levels were significantly increased in patients (p < 0.001, for each comparison). Similarly, tissue kallikrein and kininase II activities were significantly increased in plasma and urine of patients (p <0.001, for each comparison). In urine, the activities of tissue kallikrein and kininase II were at least seven times higher than those seen in the plasma of patients. These results indicate that the kinin system is involved in the acute manifestations of lupus nephritis. Kinins may facilitate immunecomplex deposition and may induce the release of other pro-inflammatory mediators, including cytokines actively involved in the pathogenesis of lupus nephritis.

Adult↗