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1.
Ultrasound Obstet Gynecol ; 62(5): 739-746, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-36920431

RESUMO

OBJECTIVE: Two-dimensional (2D) transvaginal ultrasound (TVS) is an accessible and cost-effective diagnostic tool for the detection of adenomyosis. Different ultrasound features related to adenomyosis have been described, but the predictive value of each ultrasound sign and their combinations requires further investigation. We aimed to analyze the accuracy of 2D-TVS and describe possible combinations of ultrasound signs with a high predictive value in the diagnosis of adenomyosis. METHODS: This was a prospective multicenter study of patients scheduled for laparoscopic hysterectomy who had been examined using standardized 2D-TVS at nine expert centers specializing in the diagnosis and treatment of endometriosis. 2D-TVS examination included nine typical adenomyosis ultrasound features, comprising heterogeneous myometrium, myometrial linear striations, myometrial cysts, subendometrial microcysts, asymmetrical myometrial thickening, uterine enlargement, the 'question mark sign', thickening of the junctional zone and hyperechoic myometrial spots, in order to predict or exclude the presence of adenomyosis. Ultrasound examination results were compared with histology after hysterectomy. The diagnostic reliability of the nine ultrasound signs and their combinations, and the influence of concurrent fibroids on the accuracy of the results, were analyzed. RESULTS: A total of 202 patients were enrolled into the study. Histopathological examination revealed adenomyosis in 130 patients (64.4%). The accuracy of prediction of adenomyosis by 2D-TVS examination using all signs was 63.4% (positive predictive value, 71.5%; negative predictive value, 48.6%; sensitivity, 71.5%; specificity, 48.6%). Heterogeneous myometrium, myometrial cysts, subendometrial microcysts and hyperechoic myometrial spots showed the highest accuracy (55.7-62.1%) as individual ultrasound signs for the prediction of adenomyosis. The combination of the most accurate ultrasound signs (subendometrial microcysts, myometrial cysts and heterogeneous myometrium) improved the specificity of prediction (86.1%) when compared with that of these three single markers (35.2-81.7%). Uterine enlargement and asymmetry showed both low sensitivity (60.8% and 52.3%, respectively) and specificity (41.7% and 49.3%, respectively) as individual sonographic signs. CONCLUSIONS: Heterogeneous myometrium, myometrial cysts, subendometrial microcysts and hyperechoic myometrial spots showed the highest accuracy for the detection of adenomyosis in this study, while uterine enlargement and asymmetry led to high false-positive and false-negative results. A combination of ultrasound features including the most accurate signs increases specificity. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.


Assuntos
Adenomiose , Cistos , Endometriose , Feminino , Humanos , Adenomiose/diagnóstico por imagem , Endometriose/diagnóstico por imagem , Endometriose/patologia , Miométrio/diagnóstico por imagem , Miométrio/patologia , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Ultrassonografia/métodos
2.
Rhinology ; 56(1): 1-30, 2016 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-28623665

RESUMO

BACKGROUND: Olfactory dysfunction is an increasingly recognised condition, associated with reduced quality of life and major health outcomes such as neurodegeneration and death. However, translational research in this field is limited by heterogeneity in methodological approach, including definitions of impairment, improvement and appropriate assessment techniques. Accordingly, effective treatments for smell loss are limited. In an effort to encourage high quality and comparable work in this field, among others, we propose the following ideas and recommendations. Whilst the full set of recommendations are outlined in the main document, points include the following: - Patients with suspected olfactory loss should undergo a full examination of the head and neck, including rigid nasal endoscopy with small diameter endoscopes. - Subjective olfactory assessment should not be undertaken in isolation, given its poor reliability. - Psychophysical assessment tools used in clinical and research settings should include reliable and validated tests of odour threshold, and/or one of odour identification or discrimination. - Comprehensive chemosensory assessment should include gustatory screening. - Smell training can be helpful in patients with olfactory loss of several aetiologies. CONCLUSIONS: We hope the current manuscript will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency and generalisability of work in this field.

3.
Hum Reprod ; 27(1): 173-82, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22095791

RESUMO

BACKGROUND: The Y-box-binding protein (YB-1) is described as a potential oncogene highly expressed in tumors and associated with increased cell survival, proliferation, migration and anti-apoptotic signaling. The aim of our study was to examine the expression and role of YB-1 in human endometriosis (Eo) and its association with cell survival, proliferation and invasion. METHODS: We analyzed the gene and protein expression levels of YB-1 by quantitative real-time RT-PCR and immunoassays, respectively, in peritoneal macrophages, ovarian endometrioma and eutopic endometrial tissues/cells derived from women with (n= 120) and without (n= 91) Eo. We also evaluated the functional consequences of YB-1 knockdown in the Z12 Eo cell line by measuring cell proliferation [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid cell proliferation assay], invasion (Matrigel invasion assay) and spontaneous and tumour necrosis factor (TNFα)-induced RANTES (regulated upon activation, normal T-cell expressed and secreted chemokine) expression and apoptosis (ELISA-based assay). RESULTS: YB-1 gene and protein expression was statistically significantly higher in ovarian lesions, eutopic endometrium and peritoneal macrophages of patients with Eo in comparison with the control group. Interestingly, the strongest YB-1 expression was observed in the epithelial compartment of endometrial tissues. In the Z12 cell line, YB-1 knockdown resulted in significant cell growth inhibitory effects including reduced cell proliferation and increased rates of spontaneous and TNFα-induced apoptosis. Significantly, higher RANTES expression and decreased cell invasion in vitro were also associated with YB-1 inactivation. CONCLUSION: High YB-1 expression could have an impact on the development and progression of Eo. This study suggests the role of YB-1 as a potential therapeutic target for Eo patients.


Assuntos
Endometriose/metabolismo , Endométrio/metabolismo , Regulação da Expressão Gênica , Proteína 1 de Ligação a Y-Box/biossíntese , Adulto , Apoptose , Proliferação de Células , Sobrevivência Celular , Quimiocina CCL5/metabolismo , Colágeno/química , Combinação de Medicamentos , Feminino , Humanos , Inflamação , Laminina/química , Macrófagos Peritoneais/citologia , Macrófagos Peritoneais/metabolismo , Modelos Biológicos , Ovário/patologia , Proteoglicanas/química , Linfócitos T/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
4.
Eur J Gynaecol Oncol ; 33(6): 574-8, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23327048

RESUMO

UNLABELLED: In gynecologic oncology lymphadenectomy is of prognostic and therapeutic importance because recurrence-free time and survival depend on the metastatic involvement of lymph nodes. Lymphadenectomies are not performed to such an extent as they are indicated. This might be due to a laborious or problematic preparation. The authors therefore report their experience in a seldom taught preparation of the left para-aortic compartment in the form of a learning curve. MATERIALS AND METHODS: To access the left para-aortic area, the descending colon is lifted to open the retroperitoneum along the line of Toldt. The mesentery of the descending colon was separated from the kidney along the fascia of Gerota by blunt preparation. Time was measured from the incision of the peritoneum until the renal vein was clearly visible. RESULTS: The authors collected the data from the first 25 preparations. Mean duration for the left para-aortic preparation was 7.8 minutes compared to 5.9 minutes for the right side. Duration of preparation of the left area dropped from 11.0 minutes within the first patients (#1 to #5) to 3.8 minutes in the last patients (#20 to #25). No complications were observed in the study group linked to the retromesenteric approach described. CONCLUSION: Retromesenteric para-aortic lymphadenectomy is quick to learn. The authors needed 20 preparations to observe a significant drop in the time needed for preparation. Retromesenteric para-aortic lymphadenectomy offers an excellent overview that lightens lymphadenectomy and therefore reduces the risks for patients.


Assuntos
Neoplasias dos Genitais Femininos/cirurgia , Excisão de Linfonodo/métodos , Adulto , Idoso , Aorta , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Espaço Retroperitoneal/cirurgia
5.
Minerva Ginecol ; 63(3): 247-59, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21654610

RESUMO

Endometriosis is a common, benign and chronic gynecological disorder. It is also an estrogen-dependent disorder that can result in intractable dysmenorrhea, heavy and/or irregular periods, painful bowel movements and urination during menstruation and infertility and ultimatively in repeated surgeries. Although surgery to remove endometriotic lesions is effective in relieving endometriosis-associated pain, recurrence rates are high and many women require continuous medical therapy to control symptoms. Symptom relief with palliation of pain and optimization of the quality of life should be the main aim of the medical therapy. Different pharmacologic treatment options are currently available. The most widely exerted medical therapy for endometriosis involves gonadotropin-releasing hormone (GnRH) agonists and oral contraceptives. Also progestogens and androgen derivates are used. New treatment options that are currently under investigation are selective progestogen receptor modulators (SPRMs), aromatase inhibitors (AI), GnRH- antagonists, cyclooxygenase (COX)-2 inhibitors, angiogenesis disruptor's und immune modulators. Although these new agents are promising, further confirmation in randomized clinical trials is required.


Assuntos
Endometriose/tratamento farmacológico , Endometriose/cirurgia , Feminino , Previsões , Hormônios/uso terapêutico , Humanos
6.
Hum Reprod ; 23(5): 1053-62, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18332088

RESUMO

BACKGROUND: Endometriosis is a benign and progressive disease with a high prevalence. Women with endometriosis, especially with atypical endometriosis, have a higher probability for developing ovarian cancer compared with women without endometriosis. The L1 cell adhesion molecule (L1CAM) is over expressed in ovarian and endometrial carcinomas and is associated with a bad prognosis. Here, we have analysed L1CAM expression in endometriosis. METHODS AND RESULTS: In our study with the samples from 79 patients with, and 37 patients without, endometriosis, we found that endometriosis cell lines and short-term cultures of endometrium from women with endometriosis expressed L1CAM at the mRNA and protein level. Quantitative RT-PCR analysis showed that L1CAM was expressed at significantly higher level in the epithelial compartment from patients with endometriosis compared with healthy controls (P = 0.0126). By immunohistochemical staining, 15 of 31 ovarian endometriotic lesions (48%) were shown to have L1CAM-positive staining. Of these 15 L1CAM-positive samples, 13 were atypical endometriotic lesions. Soluble L1 present in the conditioned medium of epithelial endometrium cultures from women with endometriosis was able to stimulate neurite outgrowth as measured in a chicken ganglion assay. CONCLUSIONS: We propose that L1CAM could promote endometriosis development by increasing enervation and aggravation. L1CAM expression is higher in atypical endometriosis compared with normal endometriosis.


Assuntos
Endometriose/fisiopatologia , Molécula L1 de Adesão de Célula Nervosa/metabolismo , Proteínas ADAM/biossíntese , Proteína ADAM10 , Adulto , Secretases da Proteína Precursora do Amiloide/biossíntese , Animais , Células Cultivadas , Embrião de Galinha , Meios de Cultura/farmacologia , Feminino , Humanos , Imuno-Histoquímica , Proteínas de Membrana/biossíntese , Neuritos/efeitos dos fármacos , Neuritos/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa
7.
R Soc Open Sci ; 4(3): 170024, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28405398

RESUMO

We propose a solution to a long-standing problem: how to terminate multiple vortices in the heart, when the locations of their cores and their critical time windows are unknown. We scan the phases of all pinned vortices in parallel with electric field pulses (E-pulses). We specify a condition on pacing parameters that guarantees termination of one vortex. For more than one vortex with significantly different frequencies, the success of scanning depends on chance, and all vortices are terminated with a success rate of less than one. We found that a similar mechanism terminates also a free (not pinned) vortex. A series of about 500 experiments with termination of ventricular fibrillation by E-pulses in pig isolated hearts is evidence that pinned vortices, hidden from direct observation, are significant in fibrillation. These results form a physical basis needed for the creation of new effective low energy defibrillation methods based on the termination of vortices underlying fibrillation.

8.
Rhinol Suppl ; 54(26): 1-30, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-29528615

RESUMO

Background: Olfactory dysfunction is an increasingly recognised condition, associated with reduced quality of life and major health outcomes such as neurodegeneration and death. However, translational research in this field is limited by heterogeneity in methodological approach, including definitions of impairment, improvement and appropriate assessment techniques. Accordingly, effective treatments for smell loss are limited. In an effort to encourage high quality and comparable work in this field, among others, we propose the following ideas and recommendations. Whilst the full set of recommendations are outlined in the main document, points include the following: • Patients with suspected olfactory loss should undergo a full examination of the head and neck, including rigid nasal endoscopy with small diameter endoscopes. • Subjective olfactory assessment should not be undertaken in isolation, given its poor reliability. • Psychophysical assessment tools used in clinical and research settings should include reliable and validated tests of odour threshold, and/or one of odour identification or discrimination. • Comprehensive chemosensory assessment should include gustatory screening. • Smell training can be helpful in patients with olfactory loss of several aetiologies. Conclusions: We hope the current manuscript will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency and generalisability of work in this field.


Assuntos
Transtornos do Olfato/diagnóstico , Transtornos do Olfato/terapia , Humanos , Testes Neuropsicológicos , Olfatometria , Percepção Olfatória , Qualidade de Vida
9.
J Int Med Res ; 34(3): 284-90, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16866022

RESUMO

Monocyte chemotactic protein-1 (MCP-1) is an important determinant of macrophage infiltration in tumours. This study investigated the effect of tamoxifen and the gonadotrophin-releasing hormone agonist buserelin on MCP-1 in the human endometrial cancer cell line EFE-184. Reverse transcription polymerase chain reaction and Western blot analysis were used to determine MCP-1 mRNA and protein expression, respectively. Immunoreactive MCP-1 in the cell culture media was quantified by enzyme-linked immunosorbent assay. Tamoxifen inhibited MCP-1 mRNA and protein expression in endometrial cancer cells and inhibited MCP-1 secretion in a time- and dose-dependent manner at concentrations of 10(-7) to 10(-5) M. Buserelin had no significant effect on MCP-1 mRNA and protein expression. These results suggest that tamoxifen directly inhibits the expression of MCP-1 in this cell line by blocking the MCP-1 signalling pathways. These findings may contribute to the understanding of the mechanisms underlying the different effects of tamoxifen and gonadotrophin-releasing hormone agonists in the treatment of endometrial cancer.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Busserrelina/uso terapêutico , Quimiocina CCL2/metabolismo , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/metabolismo , Tamoxifeno/uso terapêutico , Linhagem Celular Tumoral , Quimiocina CCL2/genética , Feminino , Humanos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico
10.
J Gen Physiol ; 69(3): 343 -61, 1977 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-300427

RESUMO

By use of a flow dilution olfactometer, tritium-labeled odorants were presented through the external naris to the bullfrog's intact olfactory sac. After stimulation the animal was frozen in liquid nitrogen. The dorsal surface and eminentia of the olfactory sac were then removed and sawed into sections perpendicular to the long axis of the mucosal surface. Each section was dissolved in a tissue solubilizer and counted in a liquid scintillation system. The amount of radioactivity in each section was used to estimate the number of odorant molecules it sorbed. For tritiated butanol there was a significant decrease in radioactivity from the section containing the external naris to that overhanging the internal naris. The steepness of the gradient was unaffected by a rather large range of stimulus flow rates, volumes, and partial pressures. Only when these parameters were pushed to extreme physical limits did this gradient change significantly. When the stimulus was presented through the internal rather than the external naris, the butanol gradient reversed its direction, decreasing from the internal to external. Unlike butanol, tritiated octane presented through the external naris was rather evenly distributed among the mucosal sections. That is, octane showed no distribution gradient across the mucosa. These results complement previous electrophysiological data that suggested a "chromatographic-like" differential sorption of odorant molecules across the mucosa.


Assuntos
Butanóis/metabolismo , Hidrocarbonetos/metabolismo , Mucosa Olfatória/metabolismo , Adsorção , Animais , Anuros , Pressão , Rana catesbeiana , Estatística como Assunto
11.
J Gen Physiol ; 83(2): 233-67, 1984 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-6609222

RESUMO

The magnitude of olfactory responses can be related to three primary variables [number of odorant molecules (N), sniff volume (V), and sniff duration (T)] and three derived variables [concentration (C = N/V), flow rate (F = V/T), and delivery rate (D = N/T)]. To evaluate the effects of these interdependent variables upon the olfactory response, the summated multiunit discharges were recorded from the olfactory nerves of nine frogs in response to octane presented at two levels (in 2:1 ratio) of each primary variable. This presentation defined eight "sniff" combinations representing three levels of each derived variable. In an ANOVA of the logs of the responses, the effect of each primary variable was highly significant, with no significant interactions. A multiplicative regression model incorporating the effects of the three primary variables represented responses exceedingly well, with positive effects of N and T and a negative effect of V. When, with this model, the effect of each of the derived variables was isolated from the effects of all other variables, the analysis showed a positive effect for C, a near-zero positive effect for D, and a negative effect for F. Placing certain constraints upon the model parameters generates 13 distinct one- and two-variable models (e.g., the [C, T] model requires N and V to have equal but opposite effects). In ranking these reduced models in terms of their ability to predict the neural response, the predictive ability of [F, N] and [C, T] was at least as good as that of the three-variable model.


Assuntos
Sistema Nervoso Central/fisiologia , Modelos Biológicos , Nervo Olfatório/fisiologia , Condutos Olfatórios/fisiologia , Olfato/fisiologia , Análise de Variância , Animais , Humanos , Matemática , Odorantes , Mucosa Olfatória/fisiologia , Rana catesbeiana
12.
J Gen Physiol ; 90(5): 625-50, 1987 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-3500998

RESUMO

Both regional differences in mucosal sensitivity and a gas chromatography-like process along the mucosal sheet have been separately proposed in two sets of earlier studies to produce different odorant-dependent activity patterns across the olfactory mucosa. This investigation evaluated, in one study, whether and to what degree these two mechanisms contribute to the generation of these activity patterns. Summated multiunit discharges were simultaneously recorded from lateral (LN) and medial (MN) sites on the bullfrog's olfactory nerve to sample the mucosal activity occurring near the internal and external nares, respectively. Precisely controlled sniffs of four odorants (benzaldehyde, butanol, geraniol, and octane) were drawn through the frog's olfactory sac in both the forward (H1) and reverse (H2) hale directions. By combining the four resulting measurements, LNH1, LNH2, MNH1, and MNH2, in different mathematical expressions, indexes reflecting the relative effects of the chromatographic process, regional sensitivity, and hale direction could be calculated. Most importantly, the chromatographic process and the regional sensitivity differences both contributed significantly to the mucosal activity patterns. However, their relative roles varied markedly among the four odorants, ranging from complete dominance by either one to substantial contributions from each. In general, the more strongly an odorant was sorbed by the mucosa, the greater was the relative effect of the chromatographic process; the weaker the sorption, the greater the relative effect of regional sensitivity. Similarly, the greater an odorant's sorption, the greater was the effect of hale direction. Other stimulus variables (sniff volume, sniff duration, and the number of molecules within the sniff) had marked effects upon the overall size of the response. For strongly sorbed odorants, the effect of increasing volume was positive; for a weakly sorbed odorant, it was negative. The reverse may be true for duration. In contrast, the effect of increasing the number of molecules was uniformly positive for all four odorants. However, there was little evidence that these other stimulus variables had a major influence upon the effects of the chromatographic process and regional sensitivity differences in their generation of mucosal activity patterns.


Assuntos
Odorantes , Mucosa Olfatória/fisiologia , Nervo Olfatório/fisiologia , Monoterpenos Acíclicos , Animais , Benzaldeídos , Butanóis , Octanos , Rana catesbeiana , Terpenos
14.
J Clin Endocrinol Metab ; 86(7): 3108-14, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11443174

RESUMO

The peroxisome proliferator-activated receptors (PPARs) alpha and gamma are nuclear receptors that play important roles in inflammatory diseases like ulcerative colitis and arthritis. In this study, we examined the possible role of PPARs in macrophage attraction into the peritoneal cavity of patients with endometriosis. We identified PPAR-alpha and -gamma messenger RNA by RT-PCR and protein by immunoblotting of lysates of peritoneal macrophages and monocytic U937 cells. Using immunocytochemistry, we localized PPAR-alpha and -gamma within the nuclei of both cell types. Monocyte chemotactic activity of peritoneal fluid from patients with endometriosis was quantified in Boyden chambers. Migration of U937 cells was increased by WY 14643 and reduced by rosiglitazone. Peritoneal fluid from patients with endometriosis activated U937 cells transiently transfected with a PPAR-alpha/GAL4 luciferase reporter. By contrast, peritoneal fluid did not cause significant activation of PPAR-gamma/GAL4 constructs. The U937 cells transiently transfected with a PPAR response element luciferase reporter showed disease stage-dependent up-regulation when treated with peritoneal fluid from patients with endometriosis. Treatment with peritoneal fluid from healthy controls down-regulated PPAR response element transactivation. We conclude that peritoneal fluid of endometriosis patients contains activators of PPAR-alpha that stimulate macrophage chemotaxis. Inhibitors of PPAR-alpha or activators of PPAR-gamma could be developed for the treatment of inflammation associated with endometriosis.


Assuntos
Quimiotaxia , Endometriose/patologia , Monócitos/fisiologia , Receptores Citoplasmáticos e Nucleares/fisiologia , Proteínas de Saccharomyces cerevisiae , Fatores de Transcrição/fisiologia , Apoptose , Líquido Ascítico/química , Linhagem Celular , Núcleo Celular/química , Proteínas de Ligação a DNA , Feminino , Proteínas Fúngicas/genética , Humanos , Immunoblotting , Imuno-Histoquímica , Macrófagos Peritoneais/química , Macrófagos Peritoneais/fisiologia , Monócitos/química , Cavidade Peritoneal/patologia , RNA Mensageiro/análise , Receptores Citoplasmáticos e Nucleares/análise , Receptores Citoplasmáticos e Nucleares/genética , Proteínas Recombinantes de Fusão , Fatores de Transcrição/análise , Fatores de Transcrição/genética , Transfecção
15.
J Clin Endocrinol Metab ; 85(7): 2604-8, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10902814

RESUMO

Our laboratories have focused recently on the production and localization of eotaxin, a C-C-chemokine of 8.4 kDa, whose major biological activity is the chemoattraction of eosinophils. Given evidence of autoimmune activity in the endometriosis syndrome, we hypothesized that eosinophil chemoattractants might be expressed in endometriosis. In histological sections, we observed eotaxin protein localized mainly in epithelial cells, with only very faint immunostaining in the surrounding stromal cells. Prominent eotaxin accumulation was noted in the luminal epithelium of secretory endometrium. Eotaxin distribution in endometriosis was similar to that seen in eutopic endometrium but with higher levels of eotaxin staining in the glandular epithelium. Peritoneal fluid concentrations of eotaxin were significantly higher in women with moderate or severe endometriosis than in women with minimal or mild endometriosis or no disease. The treatment of isolated human endometriosis epithelial cells with estradiol, medroxyprogesterone acetate, tumor necrosis factor-alpha, and interferon-gamma stimulated measurable eotaxin secretion into the conditioned media. The results indicate that eotaxin is produced in epithelial cells of normal endometrium and endometriosis tissues, varies across the menstrual cycle, and is elevated in women with endometriosis. We postulate that eotaxin, interacting with other known cytokines and immune cells, contributes to an inflammatory reproductive tract environment, leading to endometrial or blastocyst dysfunction.


Assuntos
Quimiocinas CC , Fatores Quimiotáticos de Eosinófilos/metabolismo , Citocinas/metabolismo , Endometriose/metabolismo , Endométrio/metabolismo , Adulto , Líquido Ascítico/química , Líquido Ascítico/metabolismo , Estudos de Casos e Controles , Células Cultivadas , Quimiocina CCL11 , Fatores Quimiotáticos de Eosinófilos/química , Citocinas/química , Citocinas/farmacologia , Endometriose/patologia , Endométrio/citologia , Ensaio de Imunoadsorção Enzimática , Estradiol/farmacologia , Feminino , Humanos , Imuno-Histoquímica , Interferon gama/farmacologia , Medroxiprogesterona/farmacologia , Congêneres da Progesterona/farmacologia , Fator de Necrose Tumoral alfa/farmacologia
16.
J Clin Endocrinol Metab ; 82(5): 1621-8, 1997 May.
Artigo em Inglês | MEDLINE | ID: mdl-9141560

RESUMO

Retrograde menstruation is postulated as the initiating event in the histogenesis of endometriosis; however, subsequent steps in the pathogenesis of this common disorder remain poorly characterized. The ip accumulation of activated leukocytes and the infiltration of endometriosis lesions by macrophages and T cells are cytological markers of the inflammatory nature of this syndrome. The apparent recruitment of these leukocytes prompted us to search for chemokine expression by endometriosis cells. We reported previously that pelvic fluid RANTES (regulated upon activation, normal T cell expressed and secreted) concentrations correlated with the stage of endometriosis. In the current study, RANTES messenger ribonucleic acid (mRNA) was identified in normal endometrium and endometriosis lesions, and techniques were developed to localize RANTES protein within these tissues. Using isolated endometrial and endometriosis cell cultures, we demonstrated that RANTES mRNA and protein can be induced by the proinflammatory cytokines tumor necrosis factor-alpha and interferon-gamma in endometrial stromal, but not in epithelial or adenocarcinoma cells. Immunocytochemical studies confirmed the biochemical findings. Metabolic labeling experiments verified that nascent RANTES secreted by cytokine-stimulated endometriosis stromal cells was the mature, 8-kDa protein predicted by the mRNA encoding this chemokine. The results indicate that RANTES is a normal constituent of the eutopic endometrium. We propose that secretion of RANTES by ectopic endometriosis implants provides a mechanism for peritoneal leukocyte recruitment.


Assuntos
Quimiocina CCL5/análise , Quimiocina CCL5/genética , Endometriose/metabolismo , Endométrio/química , Endométrio/metabolismo , Regulação da Expressão Gênica , Adulto , Células Cultivadas , Epitélio/química , Feminino , Humanos , Imuno-Histoquímica , Técnicas de Imunoadsorção , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , Células Estromais/química
17.
J Clin Endocrinol Metab ; 83(11): 4006-12, 1998 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9814484

RESUMO

One of the most abundant protein products of human secretory endometrium is glycodelin, a glycoprotein previously referred to as PP14. Although the precise function of this protein is unknown, its unique glycosylation pattern is believed to affect immunomodulatory activity during human embryonic implantation and inhibition of sperm-egg binding after ovulation. Having confirmed the expression of glycodelin in secretory endometrial glands, we used purified endometrial epithelial cell cultures to demonstrate the hormonal regulation of glycodelin synthesis and secretion. The findings were corroborated by transiently transfecting glycodelin gene promoter-reporter constructs into human epithelioid HeLa and Ishikawa cells. Our results indicate that glycodelin protein production by endometrial epithelial cells is directly up-regulated 4- to 9-fold by progestins and antiprogestins in vitro. Transcriptional regulation of the glycodelin gene promoter expressed in HeLa cells is progesterone receptor-dependent. As observed in the primary endometrial cells, progestins and antiprogestins both act as agonists on the in vitro expression of this endometrial gene. Our findings provide insight into the regulation of this abundant endometrial protein and raise interesting questions about the physical nature of the interaction of agonist- and antagonist-bound progesterone receptors with the glycodelin gene promoter.


Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Glicoproteínas/genética , Mifepristona/farmacologia , Proteínas da Gravidez/genética , Congêneres da Progesterona/farmacologia , Promegestona/farmacologia , Avaliação Pré-Clínica de Medicamentos , Endométrio/citologia , Endométrio/efeitos dos fármacos , Endométrio/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Feminino , Glicodelina , Células HeLa , Humanos , Regiões Promotoras Genéticas , Receptores de Progesterona/antagonistas & inibidores , Transfecção
18.
Ann N Y Acad Sci ; 510: 86-90, 1987.
Artigo em Inglês | MEDLINE | ID: mdl-3324882

RESUMO

A solution with both an odor and a taste may be considered to be a mixture that involves two sensory modalities. Estimates of the intensity of such mixtures appear to be additive. If the overall intensity of each of the unmixed components is compared with the overall intensity of the mixture, the additivity approaches 100%. If the intensities of the smell and taste of the unmixed components are compared with the overall intensity of the mixture, the additivity is less than 100%. Thus, the specific question that is given to the subjects influences the magnitude of the estimations. This suggests that the additive process involves a central (cognitive) mechanism. Considering that the perception of complex flavors also involves sensory information of touch, temperature, and possibly vision and hearing, a central interpretation seems appropriate. The influences of smell on the perception of taste also appear to involve a cognitive mechanism. These smell-taste confusions appear to be stimulus specific and are usually resolved in favor of taste. This may be true because the sensations of pressure, movement, and resistance are usually localized in the mouth. These accompanying sensations then suggest that the taste organs are active in determining the result even when no true taste is present. The influences of taste on the perception of smell are most pronounced when the tastant contains an odor. This suggests that the effect may be peripheral. That is, odorant molecules may be moving from the pharynx, through the posterior nares, to the olfactory receptors. If this interpretation is correct, the influences of taste on smell may be an odor-odor mixture involving "retronasal" and "nasal" olfaction.


Assuntos
Olfato/fisiologia , Paladar/fisiologia , Animais , Humanos , Percepção/fisiologia
19.
Ann N Y Acad Sci ; 943: 109-21, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11594532

RESUMO

The human endometrium is a complex tissue comprised of different cell types, including epithelial, stromal, inflammatory, perivascular, and blood vessel cells. The hormonal receptivity and distribution of these cell populations change during the menstrual cycle. Cyclical endometrial growth is dependent on its ability to regenerate a vascular capillary network, which grows in parallel with the proliferation and differentiation of the endometrial lining. Natural hormonal effects on the endometrium and endocrine manipulation of this tissue, in response to the use of exogenous steroid therapies, can affect endometrial capillary proliferation and function, leading to clinical abnormalities of uterine bleeding. We propose that the regulation of endometrial angiogenesis is mediated indirectly via complex interactions among cell types. Our laboratory has focused on a prototypical member of the angiogenic proteins, vascular endothelial growth factor (VEGF)-A. In this paper we present data demonstrating that VEGF-A expression in normal endometrial epithelial and stromal cells and in Ishikawa adenocarcinoma cells is increased by an ovarian steroid, estradiol. Infiltrating immune cells, particularly polymorphonuclear granulocytes, also are sources of VEGF-A. In inflammatory conditions involving the endometrium (e.g., endometriosis), a proinflammatory cytokine, IL-1beta, can mediate neoangiogenesis by inducing VEGF-A gene transcription. Thus, endometrial vascularization is effected by both endocrine and paracrine pathways.


Assuntos
Sistema Endócrino/fisiologia , Endométrio/irrigação sanguínea , Neovascularização Fisiológica/fisiologia , Comunicação Parácrina/fisiologia , Células Cultivadas , Citocinas/farmacologia , Endométrio/citologia , Fatores de Crescimento Endotelial/metabolismo , Feminino , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Humanos , Imuno-Histoquímica , Linfocinas/metabolismo , Gravidez , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Esteroides/farmacologia , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular
20.
Ann N Y Acad Sci ; 855: 635-7, 1998 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-9929662

RESUMO

Just as a written word can be encoded and retained in memory either verbally or in a visual form, so it might seem that an odor might be retained as either a verbal description/name or as a perceptual (olfactory) code. However, one view has it that olfactory memory in the short term does not exist as a separate perceptual code. This was examined in an experimental paradigm in which errors in memory could be recognized as deriving from the substitution of similar verbal codes or of similar olfactory codes. The set of odorants presented for recall was divided into three groups: (i) base odorants (odorants that might be replaced in memory either by similar verbal or similar olfactory representations); (ii) verbal foils (stimuli dissimilar to the base stimuli in odor but which is similar in name); and (iii) odor foils (the reverse). The substitution errors made when attempting to recall test odorants were classified as verbal errors or olfactory errors. A substantial proportion of the errors were olfactory, but verbal errors also occurred. These results support the presence of short-term perceptual olfactory memory, rather than simply verbal encoding of olfactory perceptions.


Assuntos
Memória de Curto Prazo/fisiologia , Olfato/fisiologia , Humanos , Odorantes , Aprendizagem Verbal
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