IARA MORENO LINHARES
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/58 - Laboratório de Ginecologia Estrutural e Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/58 - Laboratório de Ginecologia Estrutural e Molecular, Hospital das Clínicas, Faculdade de Medicina
77 resultados
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- Inhibition of Autophagy by Sera From Pregnant Women(2013) KANNINEN, Tomi T.; RAMOS, Bruna Ribeiro de Andrade; JAFFE, Shirlee; BONGIOVANNI, Ann Marie; LINHARES, Iara Moreno; RENZO, Gian Carlo Di; WITKIN, Steven S.Autophagy is a process that maintains homeostasis by eliminating senescent or damaged intracellular organelles and proteins. Its role in pregnancy has been scarcely studied. We compared the influence of sera from pregnant and nonpregnant women on autophagy induction. Peripheral blood mononuclear cells (PBMCs) were incubated with sera from 35 pregnant or nonpregnant women in the presence or absence of the autophagy inducer, rapamycin. After 48 hours, the cells were assayed for p62, a cytoplasmic protein essential for autophagy induction. Its concentration in the cytoplasm is inversely proportional to the level of autophagy induction. Sera were tested for immune mediators by enzyme-linked immunosorbent assay. Median (range) p62 concentrations were 6.7 ng/mL (1.1-22.7) for PBMCs incubated with pregnancy sera versus 2.5 ng/mL (0.8-7.7) for nonpregnant sera (P < .0001). In the presence of rapamycin, median p62 levels were 1.3 ng/mL (<0.1-4.9) with pregnancy sera, when compared to 0.6 ng/mL (<0.1-3.3) with control sera (P = .0191). Among the pregnant patients, the p62 level was inversely proportional to the results of a 50-g glucose challenge test (r = -.5630, P = .0005). Sera from pregnant women had elevated levels of insulin-like growth factor 1 (IGF-1), interleukin 13 (IL-13), and transforming growth factor 1 (TGF-1). Autophagy during pregnancy may be inhibited by IGF-1, IL-13, and/or TGF-1 and may influence insulin resistance.
- Uterine cervical ectopy during reproductive age: Cytological and microbiological findings(2014) ELEUTERIO JUNIOR, Jose; GIRALDO, Paulo Cesar; GONCALVES, Ana Katherine Silveira; AMARAL, Rose Luce Gomes do; LINHARES, Iara MorenoCervical ectopy is common in adolescents, pregnant women, and those taking high doses of estrogen-containing contraceptives. The majority of cases have spontaneous reversion, but some cases can be persistent. Studies suggested that the adequacy of a Pap smear could be affected and there is an increased risk cervical infections. This study is a cross-sectional study conducted from December 2009 to February 2011 with 457 women with cervical ectopy and 736 without ectopy. Cervical samples were collected in vials for analysis by ThinPrep cytology (Hologic, Marlborough, MA). The Mann-Whitney test and Fisher's exact test (95% CI) were applied. The study was approved by the ethics committee of the Federal University of Ceara. The mean ages of the study group and control group were 28.7 (+/- 14.8) and 33.6 (+/- 7.5) years old, respectively (P < 0.0001). Negative diagnosis for malignancy and intraepithelial lesion was present in 399 (87%) cases and 705 (96%) in the study and control groups, respectively (P < 0.0001). Shift in the flora suggestive of bacterial vaginosis (BV) was observed more frequently in the study group: 74 (16.2%) than in the control group: 86(11.7%) (P = 0.017). The differences among the other morphotypes showed no significance. The smears were atypical in 12.7% (58/457) of the patients from the study group and in 4.2% (31/736) in the control group (P < 0.001; RR = 3 [2.033-4.712]). The association between ectopy and inflammatory cytology, the presence of the shift in the flora suggestive of BV and cytological atypia is evident. Diagn. Cytopathol 2014;42:401-404. (c) 2013 Wiley Periodicals, Inc.
- Interferon-gamma gene polymorphism influences the frequency of a Chlamydia trachomatis cervical infection in young women(2015) ELEUTERIO JR., Jose; TELES, Rosiane A.; LINHARES, Iara M.; NORMAND, Neil; WITKIN, Steven S.Cervicitis associated with Chlamydia trachomatis is frequent worldwide, but the factors determining susceptibility to infection remain incompletely determined. We evaluated whether a functional single nucleotide polymorphism at position +874 in the gene coding for interferon gamma (rs2430561) influenced the likelihood of having a cervical C. trachomatis infection. This was a cross-sectional study of 142 sexually-active women attending a general gynaecology service on the outskirts of the city of Fortaleza in northeastern Brazil between August 2011 and August 2012. Endocervical swabs were evaluated for C. trachomatis DNA using hybrid capture. DNA from buccal swabs was utilised for detection of the interferon gamma 874 T/A single nucleotide polymorphism by gene amplification, endonuclease digestion and gel electrophoresis. Nineteen women (13.4%) were positive for C. trachomatis in their cervix. Positivity was 21.7% in women with the A,A genotype versus 7.0% in women with one or two T alleles (p=0.0227). The variant T allele frequency, associated with elevated interferon gamma production, was 36.2% in women who were negative for C. trachomatis as opposed to 18.4% in women who were positive for a cervical infection with this organism (p=0.0415). Possession of the T allele at position +874 in the gene coding for interferon gamma is associated with a reduced likelihood of a C. trachomatis cervical infection.
- The circulating 70 kDa heat shock protein (HSPA1A) level is a potential biomarker for breast carcinoma and its progression(2022) FREITAS, Gabriela Boufelli de; PENTEADO, Laura; MIRANDA, Mila Meneguelli; FILASSI, Jose Roberto; BARACAT, Edmund Chada; LINHARES, Iara MorenoThe early diagnosis of breast cancer can improve treatment and prognosis. We sought to evaluate whether the serum concentration of the 70 kDa heat shock protein (HSPA1A) was elevated in Brazilian women with breast cancer, and if levels correlated with tumor characteristics. This was a cross-sectional, analytical, case-control exploratory study performed at The University of Sao Paulo School of Medicine. From September 2017 to December 2018, 68 women with breast cancer and 59 controls were recruited. The HSPA1A concentration in serum samples was determined by ELISA by individuals blinded to the clinical data. The mean ages in the study and control groups were 54.9 and 52.0 years, respectively. The median serum levels of HSPA1A were elevated in women with breast cancer (1037 pg/ml) compared with controls (300 pg/ml) (p < 0.001). Elevated HSPA1A levels were associated with advanced histological tumor grade (p < 0.001) and with the cell proliferation index (KI67) (p = 0.0418). The HSPA1A concentration was similar in women with different histological subtypes, nuclear grade, hormone receptor expression, HER2 status and the presence or absence of angiolymphatic invasion. Elevated serum HSPA1A in Brazilian women with advanced histological grade and proliferation index breast cancer supports the potential value of additional investigation on larger and more varied populations to verify the value of HSPA1A detection as a component of breast cancer diagnosis and progression.
- The Vaginal Microbiome: New Findings Bring New Opportunities(2013) LINHARES, Iara M.; KANNINEN, Tomi T.; ORFANELLI, Theofano; JAYARAM, Aswathi; DOULAVERIS, Georgios; WITKIN, Steven S.Abstract As a result of exposure to the external environment, the human vagina is home to many diverse bacterial species. The composition of the latter varies according to the life stage of the individual female due to differences in hormone production and lifestyle. Advances in bacterial detection using culture-independent methods have greatly altered our knowledge of the composition of the vaginal microbiome especially in nonpregnant reproductive age women. The vaginae of approximately 80% of healthy women are dominated by one of four species of Lactobacillus: L. crispatus, L. iners, L. gasseri, and L. jensenii. The remaining 20% are dominated by a diverse group of anaerobic and facultative bacteria. A predominant characteristic of all bacterial populations in healthy women is the production of lactic acid. The resulting acidification of the vagina retards or prevents the growth of other potentially pathogenic bacteria. Lactic acid also has specific effects on vaginal epithelial cells and immune cells to further protect against pathogen establishment. The interactions between bacterial species as well as their ability to produce various metabolites also influences the composition of the host vaginal immune and biochemical milieu and influences susceptibility to various lower genital tract infections as well as the capability of bacteria to transcend the cervical barrier and invade the upper genital tract. In pregnant women migration of bacteria from the vagina to the uterus is a major cause of preterm birth. A more complete understanding of the composition of the vaginal microbiome and its influence on host processes will lead to development of new protocols utilizing novel reagents to improve the health of pregnant as well as nonpregnant women.
- The vaginal microbiome in pregnant women: knowledge gaps in relation to clinical relevance(2021) WITKIN, S. S.; MORON, A. F.; LINHARES, I. M.; SKUPSKI, D. W.
- Amylase in Vaginal Fluid: Association With Conditions Favorable to Dominance of Lactobacillus(2015) NASIOUDIS, Dimitrios; BEGHINI, Joziani; BONGIOVANNI, Ann Marie; GIRALDO, Paulo C.; LINHARES, Iara M.; WITKIN, Steven S.Vaginal glycogen is degraded by host -amylase and then converted to lactic acid by Lactobacilli. This maintains the vaginal pH at 4.5 and prevents growth of other bacteria. Therefore, host -amylase activity may promote dominance of Lactobacilli. We evaluated whether the -amylase level in vaginal fluid is altered in women with bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) and whether its concentration was associated with levels of lactic acid isomers and host mediators. Vaginal fluid was obtained from 43 women with BV, 50 women with VVC, and 62 women with no vulvovaginal disorders. Vaginal fluid concentrations of -amylase, secretory leukocyte protease inhibitor (SLPI), hyaluronan, hyaluronidase-1, -defensin, and elafin were measured by enzyme-linked immunosorbent assay (ELISA). Vaginal concentrations of neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase (MMP) 8, and d- and l-lactic acid levels in these patients were previously reported. The median vaginal fluid -amylase level was 1.83 mU/mL in control women, 1.45 mU/mL in women with VVC, and 1.07 mU/mL in women with BV. Vaginal levels of -amylase were correlated with d-lactic acid (P = .003) but not with l-lactic acid (P > .05) and with SLPI (P < .001), hyaluronidase-1 (P < .001), NGAL (P = .001), and MMP-8 (P = .005). The exfoliation of glycogen-rich epithelial cells into the vaginal lumen by hyaluronidase-1 and MMP-8 may increase glycogen availability and promote -amylase activity. The subsequent enhanced availability of glycogen breakdown products would favor proliferation of Lactobacilli, the primary producers of d-lactic acid in the vagina. Concomitant production of NGAL and SLPI would retard growth of BV-related bacteria.
- The Torque Teno Virus Titer in Saliva Reflects the Level of Circulating CD4(+) T Lymphocytes and HIV in Individuals Undergoing Antiretroviral Maintenance Therapy(2022) HONORATO, Layla; WITKIN, Steven S.; MENDES-CORREA, Maria Cassia; TOSCANO, Ana Luiza Castro Conde; LINHARES, Iara Moreno; PAULA, Anderson Vicente de; PAIAO, Heuder Gustavo Oliveira; PAULA, Vanessa Salete de; LOPES, Amanda de Oliveira; LIMA, Silvia Helena; RAYMUNDI, Vanessa de Cassia; FERREIRA, Noely Evangelista; SILVA JUNIOR, Almir Ribeiro da; ABRAHIM, Karim Yaqub; BRAZ-SILVA, Paulo Henrique; TOZETTO-MENDOZA, Tania ReginaIntroductionTorque teno virus (TTV) is a non-pathogenic virus present in body fluids. Its titer in the circulation increases in association with immune suppression, such as in HIV-infected individuals. We evaluated if the TTV titer in saliva from HIV-positive individuals undergoing antiretroviral therapy (ART) was related to the circulating CD4+ T lymphocyte concentration and the HIV titer. MethodsSaliva was collected from 276 asymptomatic individuals undergoing ART, and an additional 48 individuals positive for AIDS-associated Kaposi's Sarcoma (AIDS-KS). The salivary TTV titer was measured by gene amplification analysis. The circulating CD4+ T lymphocyte and HIV levels were obtained by chart review. ResultsTTV was detectable in saliva from 80% of the asymptomatic subjects and 87% of those with AIDS-KS. In the asymptomatic group the median log(10) TTV titer/ml was 3.3 in 200 males vs. 2.4 in 76 females (p < 0.0001). TTV titer/ml was 3.7 when HIV was acquired by intravenous drug usage, 3.2 when by sexual acquisition and 2.4 when blood transfusion acquired. The salivary TTV titer was inversely correlated with the circulating CD4+ T lymphocyte level (p < 0.0001) and positively correlated with the circulating HIV concentration (p = 0.0005). The median salivary TTV titer and circulating HIV titer were higher, and the CD4+ count was lower, in individuals positive for AIDS-KS than in the asymptomatic subjects (p < 0.0001). ConclusionThe TTV titer in saliva is a potential biomarker for monitoring immune status in individuals undergoing ART.
- Heat shock protein production and immunity and altered fetal development in diabetic pregnant rats(2013) SAITO, Felipe Hiroshi; DAMASCENO, Debora Cristina; DALLAQUA, Bruna; LINHARES, Iara Moreno; RUDGE, Marilza Vieira Cunha; CALDERON, Iracema De Mattos Paranhos; WITKIN, Steven S.We evaluated associations between the concentrations of heat shock proteins (hsp60 and hsp70) and their respective antibodies, alterations in maternal reproductive performance, and fetal malformations in pregnant rats with hyperglycemia. Mild diabetes (MD) or severe diabetes (SD) was induced in Sprague-Dawley rats prior to mating; non-treated non-diabetic rats (ND) served as controls. On day 21 of pregnancy, maternal blood was analyzed for hsp60 and hsp70 and their antibodies; and fetuses were weighed and analyzed for congenital malformations. Hsp and anti-hsp levels were correlated with blood glucose levels during gestation. There was a positive correlation between hsp60 and hsp70 levels and the total number of malformations (R = 0.5908, P = 0.0024; R = 0.4877, P = 0.0134, respectively) and the number of malformations per fetus (R = 0.6103, P = 0.0015; R = 0.4875, P = 0.0134, respectively). The anti-hsp60 IgG concentration was correlated with the number of malformations per fetus (R = 0.3887, P = 0.0451) and the anti-hsp70 IgG level correlated with the total number of malformations (R = 0.3999, P = 0.0387). Moreover, both hsp and anti-hsp antibodies showed negative correlations with fetal weight. The results suggest that there is a relationship between hsp60 and hsp70 levels and their respective antibodies and alterations in maternal reproductive performance and impaired fetal development and growth in pregnancies associated with diabetes.
- Influence of Mid-Trimester Amniotic Fluid on Endogenous and Lipopolysaccharide-Mediated Responses of Mononuclear Lymphoid Cells(2012) WITKIN, Steven S.; CHERVENAK, Joseph; BONGIOVANNI, Ann Marie; HERWAY, Catherine; LINHARES, Iara M.; SKUPSKI, DanielProblem We evaluated the influence of amniotic fluid (AF) on immune mediator production by mononuclear leukocytes. Method of study Thirty mid-gestation AFs were incubated with peripheral blood mononuclear cells (PBMCs) in the presence or absence of lipopolysaccharide (LPS). Supernatants were tested for interleukin (IL) -6, 10, 12, 23, tumor necrosis factor-alpha (TNF-alpha) and monocyte chemotactic protein (MCP)-1. Results Endogenous mediator production was minimal or non-detectable. AF stimulated endogenous MCP-1, IL-6 and TNF-alpha release. In the presence of LPS, production of MCP-1 and IL-10 by PBMCs was enhanced eightto ninefold by AF. Release of IL-6 and IL-23 was enhanced less than twofold by the addition of AF while TNF-alpha production was unchanged. AF-stimulated mediator production was similar irrespective of pregnancy outcome. Conclusion Selective AF stimulation of LPS-mediated MCP-1 and IL-10 release may be a mechanism to promote antibody production and the influx of phagocytic cells to engulf pathogens while downregulating the production of pro-inflammatory cytokines.