... O conhecimento dos médicos pediatras e odontopediatras, das cidades de Bauru e de Marília, a ... more ... O conhecimento dos médicos pediatras e odontopediatras, das cidades de Bauru e de Marília, a respeito da presença de flúor em ... Buzalaf MAR, Granjeiro JM, Damante CA, Ornelas F. Fluoride content of infant formulas prepared with deionized, bottled mineral and fluoridated ...
Few data are available about the prevalence of hepatitis B and C infections in early breast cance... more Few data are available about the prevalence of hepatitis B and C infections in early breast cancer patients and its impact on systemic treatments. The objectives of this study were to determine the incidence of positive serology for hepatitis B and C in women with early breast cancer and to assess the clinical course and its impact on liver function during adjuvant treatments. we retrospectively reviewed hepatitis B and C serology [HBs antigen (HBsAg), HBc antibodies (HBcAb), HBs antibodies (HBsAb) and HC (HCV) antibodies] in 746 consecutive patients with early breast cancer treated at our Institution between 2009 and 2011. Among 375 evaluable patients, we identified 312 controls (83.2%) and 63 patients (16.8%) with positive serology (cases): 15 patients (4%) with HCV, 8 (2.1%) with resolved HBV without anti-HBs (HBsAg-negative, HBsAgAb-negative, HBcAgAb-positive), 36 (9.6%) with resolved HBV with anti-HBs (HBsAg-negative, HBsAgAb-positive, HBcAgAb-positive) and 4 (1%) with chronic ...
Streptococcus Pneumoniae pathologies represent a health problem of primary importance worldwide, ... more Streptococcus Pneumoniae pathologies represent a health problem of primary importance worldwide, in terms of morbidity, mortality, and costs.
Proceedings of the National Academy of Sciences, 1997
Human T lymphocytes have been shown to express inhibitory natural killer cell receptors (NKR), wh... more Human T lymphocytes have been shown to express inhibitory natural killer cell receptors (NKR), which can down-regulate T cell antigen receptor-mediated T cell function, including cytolytic activity. In the present study, we demonstrate that CD3 ؉ NKR ؉ cells can be identified in HIVinfected patients. HIV-specific cytolytic activity was analyzed in five patients in whom autologous lymphoblastoid B cell lines could be derived as a source of autologous target cells. Phytohemagglutinin-activated T cell populations that had been cultured in interleukin 2 displayed HIV-specific cytotoxic T lymphocyte (CTL) activity against HIV env, gag, pol, and nef in 3 of 5 patients. Addition of anti-NKR mAb of IgM isotype could increase the specific CTL activity. Moreover, in one additional patient, HIV-specific CTL activity was undetectable; however, after addition of anti-NKR mAb such CTL activity appeared de novo. Similar results were obtained by analysis of CD3 ؉ NKR ؉ clones derived from two patients. These data provide direct evidence that CD3 ؉ NKR ؉ cells may include antigen (HIV)-specific CTLs and that mAb-mediated masking of inhibitory NKR may revert the down-regulation of CTL function.
Proceedings of the National Academy of Sciences, 1990
In this study, we have investigated the potential mechanisms responsible for the loss of human im... more In this study, we have investigated the potential mechanisms responsible for the loss of human immunodeficiency virus type 1 (HIV-1)-specific cytolytic activity in the advanced stages of HIV-1 infection. We have demonstrated that HIV-1-specific cytotoxic T lymphocytes are predominantly
Treatment of symptomatic neurosyphilis is an increasingly common clinical problem because of its ... more Treatment of symptomatic neurosyphilis is an increasingly common clinical problem because of its rising incidence, particularly in patients coinfected with the human immunodeficiency virus type 1 (HIV-1). 1 The mainstay of treatment remains intravenous ...
HIV-infected mothers can transmit their infection to their children in utero or at delivery (vert... more HIV-infected mothers can transmit their infection to their children in utero or at delivery (vertical transmission). There have been cases of children who were reported as acquiring infection vertically and later clearing the infection. We report the frequency of this phenomenon in a European cohort study. In four centres of the European Collaborative Study of children born to HIV-infected mothers, 299 children became HIV-antibody-negative and 264 of these had been followed up with virus culture and PCR for viral DNA at least once. Nine of the 264 children were positive by virus culture or PCR, and subsequently seroreverted. Two of the nine tested virus-positive after they became antibody-negative. Six cases were virus-positive early in life and became negative thereafter, which is consistent with clearance of infection. The pattern was less clear in the other three. The nine cases had had their last virus test at age 16-101 months. All nine children had been bottlefed only. Eight had been delivered vaginally. The children had no HIV-related symptoms and received no anti-HIV treatments. Based on only those children who had two or more positive virological tests, we estimate that 2.7% (6/219) cleared or "tolerated" the virus. The detection of virus or viral DNA in "uninfected" children born to HIV-infected mothers was rare and was not associated with clinical disease or immunological abnormalities. The timing of samples will affect the documentation of clearance since, in uninfected children of HIV-positive mothers who cleared the virus, viraemia was intermittent. Current paediatric opinion is to inform parents of children who serorevert that the child is not HIV-infected.
The Aspergillus galactomannan test was performed on cerebrospinal fluid and serum samples from 5 ... more The Aspergillus galactomannan test was performed on cerebrospinal fluid and serum samples from 5 patients with probable cerebral aspergillosis and from 16 control patients. Cerebrospinal fluid galactomannan levels were significantly higher in aspergillosis patients, and most galactomannan was produced intrathecally. Comparison of serum galactomannan values in pulmonary and cerebral aspergillosis patients showed significant overlapping. Detection of Aspergillus galactomannan in cerebrospinal fluid may be diagnostic of cerebral aspergillosis.
Correlates for the initiation of Mycobacterium tuberculosis hominis (Mth) replication from latenc... more Correlates for the initiation of Mycobacterium tuberculosis hominis (Mth) replication from latency are needed in order to improve Mth control. In order to analyze if perturbations of peripheral NK cells may be associated with exit from Mth latency, sequential patients with newly diagnosed lung tuberculosis (TB) were studied. Peripheral NK cells were analyzed by cytofluorometry, in vitro culture and functional assays. At the onset of lung TB, imbalances in NK cell subsets were evident. Decreased CD56(bright)CD16(+/-) subsets with significantly compromised NKp30 and NKp46 expression and with specifically decreased gamma-IFN production upon triggering were evident. These features were not completely restored when purified NK cells were cultured in vitro. Culture supplementation with alpha-IFN increased only NKp30 expression in TB and healthy donors. Extensive peripheral NK cell triggering was evident in these patients, as shown by the expression of NK cell activation markers and of the lymph node-homing chemokine receptor CCR7 on CD16(+) CD56(dull) cells. Significant persistence of decreased NKp30 and NKp46 after successful treatment with a standard four-drug regimen was detected after full recovery. NK cell function is deeply affected in patients at the onset of pulmonary TB. The involvement of multiple activatory receptors may provide a relevant contribution to the spread of mycobacteria exiting from latency.
Molecular and functional characterization of the natural cytotoxicity receptor (NCR) NKp44 in spe... more Molecular and functional characterization of the natural cytotoxicity receptor (NCR) NKp44 in species other than Homo sapiens has been elusive, so far. Here, we provide complete phenotypic, molecular and functional characterization for NKp44 triggering receptor on Pan troglodytes NK cells, the closest human relative, and the analysis of NKp44-genomic locus and transcription in Macaca fascicularis. Similar to H. sapiens, NKp44 expression is detectable on chimpanzee NK cells only upon activation. However, basal NKp44 transcription is 5-fold higher in chimpanzees with lower differential increases upon cell activation compared with humans. Upon activation, an overall 12-fold lower NKp44 gene expression is observed in P. troglodytes compared with H. sapiens NK cells with only a slight reduction in NKp44 surface expression. Functional analysis of 'in vitro' activated purified NK cells confirms the NKp44 triggering potential compared with other major NCRs. These findings suggest the presence of a post-transcriptional regulation that evolved differently in H. sapiens. Analysis of cynomolgus NKp44-genomic sequence and transcription pattern showed very low levels of transcription with occurrence of out-of-frame transcripts and no surface expression. The present comparative analysis suggests that NKp44-genomic organization appears during macaque speciation, with considerable evolution of its transcriptional and post-transcriptional tuning. Thus, NKp44 may represent an NCR being only recently emerged during speciation, acquiring functional relevance only in non-human primates closest to H. sapiens.
Several mechanisms may contribute to the decline in HIV-1 specific CD8+ cytotoxic T-lymphocyte (C... more Several mechanisms may contribute to the decline in HIV-1 specific CD8+ cytotoxic T-lymphocyte (CTL) activity that is observed in infected patients, including loss of CD4+ cell help, antigenic shift, impaired clonogenicity and functional impairment due to expression of inhibitory NK receptors (iNKRs). In addition to a decrease in HIV-1-specific cytolytic activity, an increased proportion of CD8+ T-cells producing IL-4 and IL-5 has been recently observed in advanced HIV-1 infection. Remarkably, an impaired HIV-1-specific CTL activity was primarily detected among the TC0/Tc2 CD8+ CTLs. A series of CD3+CD8+ T-cell clones expressing inhibitory NK receptors (iNKRs) isolated from HIV-1 infected patients was analyzed in order to determine their cytokine production pattern and to assess the extent of iNKR expression at the single cell level. Our data indicate that iNKR+CD3+CD8+ clones isolated from infected patients frequently express multiple iNKR and may produce IL-4 and IL-5 to a relevant extent.
... O conhecimento dos médicos pediatras e odontopediatras, das cidades de Bauru e de Marília, a ... more ... O conhecimento dos médicos pediatras e odontopediatras, das cidades de Bauru e de Marília, a respeito da presença de flúor em ... Buzalaf MAR, Granjeiro JM, Damante CA, Ornelas F. Fluoride content of infant formulas prepared with deionized, bottled mineral and fluoridated ...
Few data are available about the prevalence of hepatitis B and C infections in early breast cance... more Few data are available about the prevalence of hepatitis B and C infections in early breast cancer patients and its impact on systemic treatments. The objectives of this study were to determine the incidence of positive serology for hepatitis B and C in women with early breast cancer and to assess the clinical course and its impact on liver function during adjuvant treatments. we retrospectively reviewed hepatitis B and C serology [HBs antigen (HBsAg), HBc antibodies (HBcAb), HBs antibodies (HBsAb) and HC (HCV) antibodies] in 746 consecutive patients with early breast cancer treated at our Institution between 2009 and 2011. Among 375 evaluable patients, we identified 312 controls (83.2%) and 63 patients (16.8%) with positive serology (cases): 15 patients (4%) with HCV, 8 (2.1%) with resolved HBV without anti-HBs (HBsAg-negative, HBsAgAb-negative, HBcAgAb-positive), 36 (9.6%) with resolved HBV with anti-HBs (HBsAg-negative, HBsAgAb-positive, HBcAgAb-positive) and 4 (1%) with chronic ...
Streptococcus Pneumoniae pathologies represent a health problem of primary importance worldwide, ... more Streptococcus Pneumoniae pathologies represent a health problem of primary importance worldwide, in terms of morbidity, mortality, and costs.
Proceedings of the National Academy of Sciences, 1997
Human T lymphocytes have been shown to express inhibitory natural killer cell receptors (NKR), wh... more Human T lymphocytes have been shown to express inhibitory natural killer cell receptors (NKR), which can down-regulate T cell antigen receptor-mediated T cell function, including cytolytic activity. In the present study, we demonstrate that CD3 ؉ NKR ؉ cells can be identified in HIVinfected patients. HIV-specific cytolytic activity was analyzed in five patients in whom autologous lymphoblastoid B cell lines could be derived as a source of autologous target cells. Phytohemagglutinin-activated T cell populations that had been cultured in interleukin 2 displayed HIV-specific cytotoxic T lymphocyte (CTL) activity against HIV env, gag, pol, and nef in 3 of 5 patients. Addition of anti-NKR mAb of IgM isotype could increase the specific CTL activity. Moreover, in one additional patient, HIV-specific CTL activity was undetectable; however, after addition of anti-NKR mAb such CTL activity appeared de novo. Similar results were obtained by analysis of CD3 ؉ NKR ؉ clones derived from two patients. These data provide direct evidence that CD3 ؉ NKR ؉ cells may include antigen (HIV)-specific CTLs and that mAb-mediated masking of inhibitory NKR may revert the down-regulation of CTL function.
Proceedings of the National Academy of Sciences, 1990
In this study, we have investigated the potential mechanisms responsible for the loss of human im... more In this study, we have investigated the potential mechanisms responsible for the loss of human immunodeficiency virus type 1 (HIV-1)-specific cytolytic activity in the advanced stages of HIV-1 infection. We have demonstrated that HIV-1-specific cytotoxic T lymphocytes are predominantly
Treatment of symptomatic neurosyphilis is an increasingly common clinical problem because of its ... more Treatment of symptomatic neurosyphilis is an increasingly common clinical problem because of its rising incidence, particularly in patients coinfected with the human immunodeficiency virus type 1 (HIV-1). 1 The mainstay of treatment remains intravenous ...
HIV-infected mothers can transmit their infection to their children in utero or at delivery (vert... more HIV-infected mothers can transmit their infection to their children in utero or at delivery (vertical transmission). There have been cases of children who were reported as acquiring infection vertically and later clearing the infection. We report the frequency of this phenomenon in a European cohort study. In four centres of the European Collaborative Study of children born to HIV-infected mothers, 299 children became HIV-antibody-negative and 264 of these had been followed up with virus culture and PCR for viral DNA at least once. Nine of the 264 children were positive by virus culture or PCR, and subsequently seroreverted. Two of the nine tested virus-positive after they became antibody-negative. Six cases were virus-positive early in life and became negative thereafter, which is consistent with clearance of infection. The pattern was less clear in the other three. The nine cases had had their last virus test at age 16-101 months. All nine children had been bottlefed only. Eight had been delivered vaginally. The children had no HIV-related symptoms and received no anti-HIV treatments. Based on only those children who had two or more positive virological tests, we estimate that 2.7% (6/219) cleared or "tolerated" the virus. The detection of virus or viral DNA in "uninfected" children born to HIV-infected mothers was rare and was not associated with clinical disease or immunological abnormalities. The timing of samples will affect the documentation of clearance since, in uninfected children of HIV-positive mothers who cleared the virus, viraemia was intermittent. Current paediatric opinion is to inform parents of children who serorevert that the child is not HIV-infected.
The Aspergillus galactomannan test was performed on cerebrospinal fluid and serum samples from 5 ... more The Aspergillus galactomannan test was performed on cerebrospinal fluid and serum samples from 5 patients with probable cerebral aspergillosis and from 16 control patients. Cerebrospinal fluid galactomannan levels were significantly higher in aspergillosis patients, and most galactomannan was produced intrathecally. Comparison of serum galactomannan values in pulmonary and cerebral aspergillosis patients showed significant overlapping. Detection of Aspergillus galactomannan in cerebrospinal fluid may be diagnostic of cerebral aspergillosis.
Correlates for the initiation of Mycobacterium tuberculosis hominis (Mth) replication from latenc... more Correlates for the initiation of Mycobacterium tuberculosis hominis (Mth) replication from latency are needed in order to improve Mth control. In order to analyze if perturbations of peripheral NK cells may be associated with exit from Mth latency, sequential patients with newly diagnosed lung tuberculosis (TB) were studied. Peripheral NK cells were analyzed by cytofluorometry, in vitro culture and functional assays. At the onset of lung TB, imbalances in NK cell subsets were evident. Decreased CD56(bright)CD16(+/-) subsets with significantly compromised NKp30 and NKp46 expression and with specifically decreased gamma-IFN production upon triggering were evident. These features were not completely restored when purified NK cells were cultured in vitro. Culture supplementation with alpha-IFN increased only NKp30 expression in TB and healthy donors. Extensive peripheral NK cell triggering was evident in these patients, as shown by the expression of NK cell activation markers and of the lymph node-homing chemokine receptor CCR7 on CD16(+) CD56(dull) cells. Significant persistence of decreased NKp30 and NKp46 after successful treatment with a standard four-drug regimen was detected after full recovery. NK cell function is deeply affected in patients at the onset of pulmonary TB. The involvement of multiple activatory receptors may provide a relevant contribution to the spread of mycobacteria exiting from latency.
Molecular and functional characterization of the natural cytotoxicity receptor (NCR) NKp44 in spe... more Molecular and functional characterization of the natural cytotoxicity receptor (NCR) NKp44 in species other than Homo sapiens has been elusive, so far. Here, we provide complete phenotypic, molecular and functional characterization for NKp44 triggering receptor on Pan troglodytes NK cells, the closest human relative, and the analysis of NKp44-genomic locus and transcription in Macaca fascicularis. Similar to H. sapiens, NKp44 expression is detectable on chimpanzee NK cells only upon activation. However, basal NKp44 transcription is 5-fold higher in chimpanzees with lower differential increases upon cell activation compared with humans. Upon activation, an overall 12-fold lower NKp44 gene expression is observed in P. troglodytes compared with H. sapiens NK cells with only a slight reduction in NKp44 surface expression. Functional analysis of 'in vitro' activated purified NK cells confirms the NKp44 triggering potential compared with other major NCRs. These findings suggest the presence of a post-transcriptional regulation that evolved differently in H. sapiens. Analysis of cynomolgus NKp44-genomic sequence and transcription pattern showed very low levels of transcription with occurrence of out-of-frame transcripts and no surface expression. The present comparative analysis suggests that NKp44-genomic organization appears during macaque speciation, with considerable evolution of its transcriptional and post-transcriptional tuning. Thus, NKp44 may represent an NCR being only recently emerged during speciation, acquiring functional relevance only in non-human primates closest to H. sapiens.
Several mechanisms may contribute to the decline in HIV-1 specific CD8+ cytotoxic T-lymphocyte (C... more Several mechanisms may contribute to the decline in HIV-1 specific CD8+ cytotoxic T-lymphocyte (CTL) activity that is observed in infected patients, including loss of CD4+ cell help, antigenic shift, impaired clonogenicity and functional impairment due to expression of inhibitory NK receptors (iNKRs). In addition to a decrease in HIV-1-specific cytolytic activity, an increased proportion of CD8+ T-cells producing IL-4 and IL-5 has been recently observed in advanced HIV-1 infection. Remarkably, an impaired HIV-1-specific CTL activity was primarily detected among the TC0/Tc2 CD8+ CTLs. A series of CD3+CD8+ T-cell clones expressing inhibitory NK receptors (iNKRs) isolated from HIV-1 infected patients was analyzed in order to determine their cytokine production pattern and to assess the extent of iNKR expression at the single cell level. Our data indicate that iNKR+CD3+CD8+ clones isolated from infected patients frequently express multiple iNKR and may produce IL-4 and IL-5 to a relevant extent.
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