RESUMEN

AIM: to investigate the myocardial expression of some structural proteins and markers of cellular proliferation and innate immunity for assessing their possible diagnostic and prognostic role in patients with chronic myocarditis. SUBJECTS AND METHODS: The investigation enrolled 23 patients (16 men; mean age, 52.0±12.4 years (range, 27 to 73) with various forms of noncoronarogenic myocardial injury who underwent right ventricular endomyocardial biopsy (n=4), intraoperative left ventricular biopsy (n=17) or autopsy (n=2). Prior to their morphological examination, the patients were divided into two groups: 1) 10 patients with dilated cardiomyopathy and presumptive myocarditis; 2) 13 patients with valvular heart disease, hypertrophic cardiomyopathy, myxoma, and chronic pulmonary thromboembolism, presumptively without myocarditis. Along with myocardial histological and immunohistochemical (IHC) examinations, the expression of vimentin, desmin, c-kit, Ki-67, and Toll-like receptors (TLR) 2 and 9 was determined. Polymerase chain reaction was used to identify whether herpes viruses of and parvovirus B19 genomes were present in the blood and myocardial samples; indirect ELISA was applied to estimate the blood level of antibodies against various cardiac antigens. RESULTS: According to the histological findings, active/borderline lymphocytic myocarditis was diagnosed in all the patients (Group 1) and in 6 patients (Group 2) in conjunction with the underlying disease (only in 9 and 7 patients, respectively), viral genome was detected in the myocardium of 15 patients, including in 5 without morphological signs of myocarditis (parvovirus B19 (n=11), herpesvirus 6 (n=4), herpes simplex virus types 1 and 2 (n=1), Epstein-Barr virus (n=2), and cytomegalovirus (n=1)), and in the blood (n=4). A marked correlation was found between TLR2 and TLR9 expressions and the morphological pattern of active myocarditis in the absence of this correlation with the expression level of other studied markers. The expression level of TLR2 in patients with and without borderline myocarditis was 0 [0; 0,75] and in those with active myocarditis was 1.5 [1; 1,5] points; that of TLR9 was 2 [2; 2] and 4 [3; 4] points, respectively (p<0.001). The expression of TLR2 and TLR9 in patients with borderline myocarditis was lower than in those without myocarditis (0 [0; 0] versus 0 [0; 1] and 2 [1,5; 2] versus 2 [2; 3] points), which can reflect cardiomyocyte destruction/depletion at later stages of the disease. There was also a close correlation between the expression level of TLR2 and that of TLR9 (r=0.824; p<0.001) and with Ki-67 levels (r=-0.531 and r=-0.702; p<0.01). There was also a correlation of the expression of the studied markers with viral persistence (desmin), the degree of myocardial dysfunction and cardiosclerosis (c-kit), which calls for further investigations. CONCLUSION: Determination of the myocardial expression level of TLR2 and TLR9 may serve as an immunohistochemical marker for myocarditis and preservation of its activity, which is especially valuable in patients with borderline forms. The marked expression of these markers for innate immunity may reflect both one of the mechanisms of genetic predisposition to myocarditis and its severe course and their secondary activation in the pathogenesis of the disease and is a potential target of therapy.

Asunto(s)

Cardiomiopatía Dilatada , Miocarditis , Receptor Toll-Like 1 , Receptor Toll-Like 2 , Adulto , Anciano , Biomarcadores/metabolismo , Biopsia , Corazón , Humanos , Masculino , Persona de Mediana Edad , Miocarditis/metabolismo , Miocarditis/terapia , Miocardio , Receptor Toll-Like 1/metabolismo , Receptor Toll-Like 2/metabolismo , Receptores Toll-Like

RESUMEN

A comparative immunohistochemical study for the expression of O6-methylguanine-DNA methyltransferase (MGMT) was performed in tissues of the eutopic endometrium and ovarian endometriosis. The highest level of MGMT expression in eutopic endometrial tissue was observed in epitheliocyte nuclei during the proliferative phase. In regions of endometriosis the expression of MGMT in epitheliocyte nuclei was shown to increase during stages I and II, but decreased in stages III and IV. The progression of endometriosis was accompanied by a gradual increase of study parameters in the nuclei and cytoplasm of stromal cells. These changes reflect the impairment of DNA reparation, which probably serves as a stage in the development and progression of endometriosis.

Asunto(s)

Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Reparación del ADN , Endometriosis/genética , Ovario/enzimología , Células del Estroma/enzimología , Proteínas Supresoras de Tumor/genética , Adolescente , Adulto , ADN/genética , ADN/metabolismo , Metilasas de Modificación del ADN/metabolismo , Enzimas Reparadoras del ADN/metabolismo , Progresión de la Enfermedad , Endometriosis/enzimología , Endometriosis/patología , Células Epiteliales/enzimología , Células Epiteliales/patología , Femenino , Regulación de la Expresión Génica , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Ovario/patología , Células del Estroma/patología , Proteínas Supresoras de Tumor/metabolismo , Útero/enzimología , Útero/patología

RESUMEN

Stratified mucin-producing intraepithelial lesion (SMILE) is a rare premalignant cervical lesion that combines the structural features of cervical intraepithelial neoplasia (CIN) and endocervical adenocarcinoma in situ (AIS). AIM: to analyze archival materials for the detection of SMILE and its subsequent morphological and immunohistochemical characterization. MATERIAL AND METHODS: Cervical cone specimens from 53 women with histologically verified CIN3 were examined. The diagnosis of SMILE was based on the positive mucicarmine staining and weak focal expression of p63. The samples containing SMILE were further immunohistochemically examined using the biomarkers P16, Ki-67, Oct4, CD117, CD34, p53, EMA, and CK15. SMILE was detected in 2 of the 53 patients and concurrent with CIN3 in both cases. SMILE was characterized by the stratified arrangement of atypical cells containing mucin, the positive mucicarmine staining of the entire layer of the atypical epithelium, weak focal p63 expression, high Ki-67 expression, and diffuse р16Іnk4а staining. Both SMILE samples showed weak diffuse p53 expression in the presence of single cells with the pronounced nuclear staining pattern for p53 in one female patient. Weak focal CK15 expression was visualized in SMILE. The expression of the stem cell markers Oct4 and CD117 and the angiogenic marker CD34 was absent in the examined cervical epithelial preparations. The diffuse and intense expression of the marker EMA, which was not different from that in the endocervical and stratified squamous epithelium, and CIN3 was established in SMILE. RESULTS: The findings suggest that SMILE is morphologically and immunohistochemically similar to CIN3. In this investigation, these abnormalities differed only in the mucicarmine staining and expression of p63. This may be indicative of the underdiagnosis of SMILE, attendant СIN3 in the routine practice of a clinical pathologist, as the diagnosis of CIN3 is primarily based on the results of assessment of only the preparations stained with hematoxylin and eosin; the expression of p16 and Ki-67 is evaluated in some cases, which fails to differentiate SMILE and CIN3 in a number of preparations. CONCLUSION: The diagnosis of SMILE can be made only by immunohistochemical examination.

Asunto(s)

Adenocarcinoma in Situ/patología , Biomarcadores de Tumor/genética , Proteínas de Neoplasias/genética , Displasia del Cuello del Útero/patología , Adenocarcinoma in Situ/diagnóstico , Adenocarcinoma in Situ/genética , Adulto , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Mucinas/genética , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/genética

RESUMEN

Comparative immunohistochemical analysis of the expression of somatic stem cells marker Musashi-1 in the endometrium was performed during various phases of menstrual cycle and in patients with nodular and diffuse adenomyosis. The expression of Musashi-1 reflecting proliferative potential of epithelial and stromal cells was quantitatively analyzed by the optical density in the nuclei and cytoplasm of epithelial and stromal cells of the eutopic endometrium and adenomyosis foci. In the eutopic endometrium, the immunohistochemical reaction was more intensive during proliferation phase in comparison with secretion phase. Enhanced expression of Musashi-1 was observed in adenomyosis foci in comparison with endometrial cells. The most intensive staining was found in nodular adenomyosis, especially in epithelial cells during the secretion phase. These data attest to the role of somatic stem cells in the development and progression of various forms of adenomyosis.

Asunto(s)

Adenomiosis/metabolismo , Inmunohistoquímica/métodos , Proteínas del Tejido Nervioso/metabolismo , Proteínas de Unión al ARN/metabolismo , Adulto , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Endometrio/metabolismo , Femenino , Humanos , Ciclo Menstrual/metabolismo , Persona de Mediana Edad , Células del Estroma/metabolismo , Adulto Joven

RESUMEN

AIM: to investigate the frequency of the types of fallopian tubal secretory cell expansion (SCE) in diseases of the reproductive organs and to determine the immunophenotype and biological role of the cells in the early stages of the pathogenesis of high-grade ovarian serous carcinomas (HGOSC). SUBJECTS AND METHODS: The investigation enrolled 287 patients with extraovarian diseases and ovarian serous tumors varying in grade, whose fallopian tubes were morphologically and immunohistochemically examined using p53, Ki-67, PAX2, Bcl-2, beta-catenin, and ALDH1 markers. The material was statistically processed applying the Mann-Whitney test and χ2 test. RESULTS: The rate of secretory cell proliferation (SCP) (more than 10 consecutive secretory cells) and that of secretory cell overgrowth (SCO) (more than 30 consecutive secretory cells) increase with age in all investigated reproductive system diseases. The rate of SCP in the corpus fimbriatum of the patients with HGOSC was 5.9 times higher than that in those with extraovarian disease (p<0.01); when comparing the same patient groups, that of SCO was 3.4 times higher (p<0.05). The immunohistochemical characteristics of the investigated lesions (in scores) were as follows: PAX2 was expressed in the intact epithelium (2.8), in SCP (1.3), in SCO (1.2), in serous tubal intraepithelial carcinoma (STIC) (1.0), and in HGOSC (0.9); Bcl-2 was in the intact epithelium (2.2), in SCP (2.1), STIC (0.9), and in HGOSC (0.6), ß-catenin was in the intact epithelium (0.5), in SCP (2.85), in SCO (2.95), in STIC (0.6), and in HGOSC (0.5); ALDH1 was in the intact epithelium (0.5), in SCP (2.91), in SCO (2.92), in STIC (1.2), and in HGOSC (0.6). There were statistically significant differences with a 95% confidence interval (p<0.05) for: 1) PAX2 between the intact epithelium and pathology (fallopian tube lesions and HGOSC); 2) Bcl-2 between the intact epithelium and SCE (SCP and SCO) and between SCE and HGOSC; 3) beta-catenin between the intact epithelium and SCE (SCP and SCO) and between SCE and HGOSC; 4) ALDH1 between the intact epithelium and SCE, between and SCE and STIC, and between STIC and HGOSC. CONCLUSION: SCE was shown to be an independent intraepithelial lesion. The incidence of this abnormality increased with age and significantly differed in the patients with fallopian tubal lesions in extraovarian diseases from that in those with malignant ovarian serous tumors (by 5.3 times), while these groups showed a three-fold difference in SCO. Thus, SCP may serve as a more sensitive marker for the early stages of the pathogenesis of ovarian serous carcinoma. The studied types of SCE demonstrated multiple molecular events (loss of PAX2 expression and increased Bcl-2, beta-catenin, and ALDH1 expressions), some of which underwent considerable changes, by increasing the severity of a pathological process (loss of ALDH1, and beta-catenin, and bcl-2 expressions). Thus, therapeutic exposure in the early stages of pathogenesis may have a few points of application and just several molecules can serve as independent markers for early pathological changes in the fallopian tubal epithelium.

Asunto(s)

Proliferación Celular , Cistadenocarcinoma Seroso/patología , Epitelio/patología , Trompas Uterinas/patología , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Ováricas/patología , Adulto , Anciano , Biomarcadores/metabolismo , Carcinoma Epitelial de Ovario , Epitelio/metabolismo , Trompas Uterinas/metabolismo , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad

RESUMEN

UNLABELLED: Endometriosis (EM) is morphologically characterized by the development of extrauterine endometrioid heterotopies, the major clinical symptoms of which is chronic pelvic pain, which is a serious problem not only in modern gynecology, but also in public health as a whole. AIM: to investigate neurogenic markers in the foci of EM of various sites and histological structure in women with and without pain syndrome. MATERIAL AND METHODS: The investigation was performed using the operative material (resected segments of the intestine, bladder, rectovaginal septum, and small pelvic peritoneum) obtained from 52 women with an intraoperative and morphologically verified diagnosis of EM and (Group 1) and without (Group 2) pain syndrome. Immunohistochemical examination was made on paraffin-embedded tissue sections in accordance with the standard protocols, by using the antibodies: 1) anti-PGP 9.5 polyclonal rabbit antibodies; 2) mouse anti-human neurofilament (NF) protein monoclonal antibodies (Clone 2F1); 3) mouse anti-nerve growth factor (NGF) monoclonal antibodies; 4) monoclonal mouse anti-human NGF receptor p75 (NGFRp75) antibodies (Dako, Denmark). RESULTS: Our findings demonstrate differences in the expression of PGP 9.5, NFs, NGF, and NGFRp75 in the foci and adjacent tissue in painful and painless EM irrespective of the locations of heterotopies. CONCLUSION: The found molecular features are a manifestation of the remodeling of nerve fibers and nerve endings in the foci of EM and PGP9.5, NGF, and NGFRp75 give rise to nerve fiber neoformation and pain syndrome in EM. At the same time, the immunohistochemical phenotype of EM foci does not depend on their site and reflects the presence or absence of pain syndrome.

Asunto(s)

Endometriosis/metabolismo , Dolor Pélvico/metabolismo , Nervios Periféricos/patología , Estudios de Casos y Controles , Endometriosis/complicaciones , Endometriosis/patología , Femenino , Humanos , Factor de Crecimiento Nervioso/metabolismo , Dolor Pélvico/etiología , Dolor Pélvico/patología , Nervios Periféricos/metabolismo , Receptor de Factor de Crecimiento Nervioso/metabolismo , Síndrome , Ubiquitina Tiolesterasa/metabolismo

RESUMEN

AIM: to study the incidence of fallopian tube lesions (secretory cell proliferations (SCP), p53 signature, serous tubal intraepithelial lesions (STIL), and serous tubal intraepithelial carcinomas (STIC) in ovarian epithelial tumors and to propose their pathogenetic association with a certain histotype of the ovarian tumor. MATERIAL AND METHODS: The investigation enrolled 136 patients with ovarian epithelial tumors, whose fallopian tubes were morphologically and immunohistochemically (IHC) examined using p53, Ki-67, and PAX2. Statistical analysis was carried out applying the Mann-Whitney test and χ(2) test. RESULTS: Lesions meeting the STIC criteria were found in 14.7% of cases (only in ovarian serous carcinoma (OSC)), those suspecting STICs were in 25.7%, and those without signs of STICs were in 59.6%. IFC examination diagnosed STIC in 10% of cases (only in OSC), STIL in 13.3%, p53 signature in 11.7% (only in serous tumors), and the normal/reactively changed tubal epithelium in 65%. The incidence of STILs correlated with the malignant potential of serous tumors significantly (p<0.05). There were significant differences in the incidence of STILs in patients with different histotypes of ovarian carcinomas (p<0.05). PAX2-negative SCP was detected in 75% of OSC, 60% of serous borderline tumors, and 40% of serous cystadenomas. The differences in the incidence of SCP between serous tumors of varying grade, between serous tumors and non-serous carcinomas, between OSC and non-serous carcinomas were significant (p<0.05). CONCLUSION: The investigation has shown that IHC examination should be used for the accurate diagnosis of STILs. It has also provided evidence for the pathogenetic association between STIC and high-grade OSC and revealed significant differences in the incidence of other fallopian tubal intraepithelial lesions in serous cystadenomas, borderline tumors, and OSC, in different ovarian carcinomas. The findings may suggest that the earliest stage in the pathogenesis of OSC is the development of SCP, followed by the formation of p53 signatures that may further give rise to STIL, and finally STC (due to the acquisition of additional mutations).

Asunto(s)

Proliferación Celular , Trompas Uterinas , Membrana Mucosa , Neoplasias Glandulares y Epiteliales , Neoplasias Ováricas , Proteína p53 Supresora de Tumor/metabolismo , Adulto , Anciano , Carcinoma Epitelial de Ovario , Trompas Uterinas/metabolismo , Trompas Uterinas/patología , Femenino , Humanos , Persona de Mediana Edad , Membrana Mucosa/metabolismo , Membrana Mucosa/patología , Neoplasias Glandulares y Epiteliales/metabolismo , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología

RESUMEN

The concurrence of undifferentiated connective tissue dysplasia (uCTD) and hereditary thrombophilia (HT) often accompanies female infertility, in the pathogenesis of which impaired endometrial receptivity plays an important role. AIM: to investigate endometrial morphological and immunophenotypic features in patients with primary infertility in the presence of uCTD and HT. MATERIAL AND METHODS: The pipelle endometrial biopsy specimens taken in the implantation window were examined in 81 patients, including 13 women with a clinical diagnosis of uCTD, 40 with HT, 19 with uCTD concurrent with HT, and in a control group of 9 heathy surrogate mothers. Morphological, immunohistochemical, and morphometric examinations were done to study the paraffin-embedded endometrial biopsy sections stained with hematoxylin and eosin, pikrofuksin by van Gieson, and with toluidine blue. Immunohistochemical tests were carried out using primary antibodies against ER, PgR, LIF, PAI-1, VEGF, Collagen I, Collagen III, fibronectin, laminin, MMP-2, and MMP-9. RESULTS: The uCTD, HT, and uCTD + HT groups were found to have signs of decreased endometrial receptivity as dramatically lower counts of mature pinopodes, slower endometrial maturation, reduced expression of the receptivity marker LIF, and deviations of the stromal progesterone-estrogen index from the normal value. Sclerotic foci with type III collagen accumulation were detected in the endometrial stroma. CONCLUSION: uCTD and HT and especially their concurrence are commonly a concomitant disease and risk factors for infertility in women due to impaired endometrial receptivity. In uCTD, connective tissue remodeling processes are substantially retarded, which ultimately leads to increased processes of endometrial stromal sclerosis, reduced endometrial receptivity, and infertility. The most pronounced morphological and immunophenotypical changes have been ascertained to develop in the uCTD + NT group. The findings may be used to predict and devise new infertility treatments in patients with uCTD + NT.

Asunto(s)

Enfermedades del Tejido Conjuntivo/patología , Endometrio/patología , Infertilidad/patología , Trombofilia/patología , Adulto , Biomarcadores/metabolismo , Estudios de Casos y Controles , Colágeno/metabolismo , Enfermedades del Tejido Conjuntivo/complicaciones , Endometrio/metabolismo , Femenino , Fibronectinas/metabolismo , Humanos , Infertilidad/complicaciones , Infertilidad/etiología , Laminina/metabolismo , Factor Inhibidor de Leucemia/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Inhibidor 1 de Activador Plasminogénico/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Trombofilia/complicaciones , Factor A de Crecimiento Endotelial Vascular/metabolismo

RESUMEN

UNLABELLED: Impaired endometrial receptivity is a major cause of reproductive losses in in vitro fertilization (IVF) cycles given a normal embryo. Its causes may be associated with many diseases, including inherited thrombophilia (IT) and undifferentiated connective tissue dysplasia syndrome (uCTDS). However, endometrial receptivity remains little studied. OBJECTIVE: to investigate the morphological and immunohistochemical substrates of impaired endometrial receptivity in women with uCTDS, IT, and their concurrence. SUBJECTS AND METHODS: Antibodies against ER, PgR, LIF, VEGF, and PAI-1 were used to morphologically and immunohistochemically examine pipelle endometrial biopsy specimens taken from 141 women in the implantation window (on days 6-7 after ovulation). In accordance with their clinical diagnoses, the patients were divided into 4 groups: 1) 13 patients with uCTDS; 2) 100 with IT; 3) 19 with uCTDS and IT; 4) 9 healthy surrogate mothers (a control group). In the examined groups, a total of 145 (90.1%) out of all the IVF protocols were unsuccessful. In the remaining 16 (9.9%) patients without exception, miscarriage started at less than 10 weeks' gestation. RESULTS: In the implantation window, the endometrium was immature in 101 (83.1%) women and corresponded to late proliferation or early secretion phases; 102 (84.3%) women were also found to have no mature pinopodes, pointing to the fact that the endometrial receptivity was very low. Immunohistochemical examination revealed the lower expression of the receptivity marker LIF in the endometrial surface epithelium and its higher expression in the stroma in the study groups (p < 0.05 for the uCTDS and uCTDS+IT groups) and the higher expression of PAI-1 and VEGF in the epithelium, stroma, and endothelium in the study groups than in the control group (p < 0.05), suggesting the intensity of neoangiogenetic processes and impaired fibrinolysis in these patients. CONCLUSION: uCTDS and IT are risk factors of impaired endometrial receptivity in the pathogenesis of infertility. The manifestations of impaired endometrial receptivity in this case are a decrease in mature pinopodes in the surface epithelium; focal stromal sclerosis; and redistribution of the receptivity marker LIF from the surface epithelium to the stroma, which may be used for diagnosis, prediction, and the development of targeted therapy.

Asunto(s)

Enfermedades del Tejido Conjuntivo/complicaciones , Endometrio/patología , Infertilidad Femenina/etiología , Trombofilia/complicaciones , Adulto , Estudios de Casos y Controles , Enfermedades del Tejido Conjuntivo/metabolismo , Enfermedades del Tejido Conjuntivo/patología , Implantación del Embrión , Endometrio/metabolismo , Endometrio/fisiopatología , Femenino , Humanos , Inmunohistoquímica , Infertilidad Femenina/metabolismo , Infertilidad Femenina/patología , Inhibidor 1 de Activador Plasminogénico/metabolismo , Síndrome , Trombofilia/metabolismo , Trombofilia/patología , Factor A de Crecimiento Endotelial Vascular/metabolismo

RESUMEN

We propose a new surgical approach to the treatment of familial colorectal adenomatous polyposis implying preservation of a portion of the rectum with removed mucosa. For reconstruction of the rectum, allotransplantation of the mixed culture of fetal allogenic somatic cells of the intestinal epithelium and mesenchymal cells of various origin is used. The mechanisms of mucosa reparation were studied in 34 patients. Endoscopic, morphological, and immunohistochemical studies showed that cell transplantation considerably accelerated reparation of the mucosa in mucosectomized rectum. The proposed treatment of familial colorectal adenomatous polyposis allows delaying the development of rectal polyps and cancer for many years.

Asunto(s)

Poliposis Adenomatosa del Colon/patología , Mucosa Intestinal/patología , Recto/patología , Humanos , Inmunohistoquímica

RESUMEN

Lipoleiomyoma is a benign tumor that consists of smooth muscle and fat components, which occurs in less than 0.5% of cases among all benign intestine tumors. The paper describes a case of acute ileum obstruction with the development of lipoleiomyoma invagination in a 23-year-old woman and presents the endoscopic verification and microscopic and immunohistochemical examination of the removed tumor.

Asunto(s)

Ileus/patología , Leiomioma/patología , Lipoma/patología , Adulto , Femenino , Humanos , Leiomioma/diagnóstico , Lipoma/diagnóstico

RESUMEN

OBJECTION: To study the origin and morphological substrate of pain syndrome in deep infiltrating endometriosis involving the bowel. SUBJECTS AND METHODS: The investigation was conducted using the intraoperative material (resected portions of the large and small bowels, appendix) obtained from 40 women diagnosed as having deep infiltrating endometriosis involving the bowel, which was accompanied by pain syndrome. Paraffin sections were immunohistochemically examined using the standard protocol. Antibodies to Ki-67, PTEN, ER, PR, ("Dako"), CD34 ("Cell Marque", USA), VEGF, EGF, EGFR, COX-2 ("Abcam"), and MMP 1 and 2 ("Abbiotec") were applied. Dako REAL EnVision Detection System kits ("Dako", Denmark) were used as secondary antibodies. RESULTS: The morphological substrate of pelvic pain syndrome in deep infiltrating endometriosis was established to be factors that acted in situ at the location of endometriotic foci and those caused by the infiltrative perivascular, intravascular, and perineural growth of endometrioid heterotopies. CONCLUSION: Inflammation and fibrosis in the endometriotic foci contribute to the accumulation of algogenes, which gives rise to somatogenic pain syndrome, and chronic nerve fiber injury as a source of nociceptive stimulation leads to neuropathic pain syndrome.

Asunto(s)

Endometriosis/genética , Endometriosis/patología , Dolor Pélvico/genética , Dolor Pélvico/patología , Adulto , Proliferación Celular , Endometriosis/complicaciones , Femenino , Regulación de la Expresión Génica , Humanos , Inflamación/genética , Inflamación/patología , Persona de Mediana Edad , Dolor Pélvico/etiología , Biosíntesis de Proteínas

RESUMEN

Spheroid cell structures in the cell cultures have been described and are used for studying cell-cell and cell- matrix interactions. At the same time, spheroid cell structure participation in the repair and development of cancer in vivo remains unexplored. The aim of this study was to investigate the cellular composition of spherical structures and their functional significance in the repair of squamous epithelium in human papilloma virus-associated cervical pathology--chronic cervicitis and cervical intraepithelial neoplasia 1-3 degree, and also construct a mathematical model to explain the development and behavior of such spheroid cell structure.

Asunto(s)

Alphapapillomavirus , Modelos Biológicos , Infecciones por Papillomavirus , Esferoides Celulares , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Adulto , Células Epiteliales/metabolismo , Células Epiteliales/patología , Femenino , Humanos , Infecciones por Papillomavirus/metabolismo , Infecciones por Papillomavirus/patología , Esferoides Celulares/metabolismo , Esferoides Celulares/patología , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patología , Displasia del Cuello del Útero/metabolismo , Displasia del Cuello del Útero/patología

Asunto(s)

Neoplasias Intestinales , Obstrucción Intestinal , Leiomioma , Enfermedad Aguda , Adulto , Femenino , Humanos , Neoplasias Intestinales/patología , Neoplasias Intestinales/fisiopatología , Neoplasias Intestinales/cirugía , Obstrucción Intestinal/patología , Obstrucción Intestinal/fisiopatología , Obstrucción Intestinal/cirugía , Leiomioma/patología , Leiomioma/fisiopatología , Leiomioma/cirugía

RESUMEN

We studied the expression and intracellular localization of ACA and TRA-1-81 in smooth muscle cell tumors. The study was performed on tissue specimens obtained during surgery from patients with uterine leiomyoma and leiomyosarcoma (mean age 34 and 51 years, respectively). ACA was present in leiomyoma, leiomyosarcoma, and control myometrium. Intracellular expression of ACA varied in different types of tumors and was minimum in normal myometrium and maximum in leiomyosarcoma. Membrane localization of the protein is typical of common and cellular leiomyoma, while in the growth zones of mitotically active leiomyoma and leiomyosarcoma the reaction product was primarily located in tumor cell cytoplasm. TRA was detected in some leiomyosarcoma cells. Thus, ACA dysregulation was revealed in the growth zones of leiomyomas and in leiomyosarcomas, which manifested in enhanced expression of this protein and its detachment from the plasma membrane, which leads ACA translocation into the cytoplasm and nucleus of tumor cells and potentiates their proliferative activity.

Asunto(s)

Antígenos de Superficie/metabolismo , Proteínas Sanguíneas/metabolismo , Leiomioma/metabolismo , Leiomiosarcoma/metabolismo , Glicoproteínas de Membrana/metabolismo , Neoplasias Uterinas/metabolismo , Adulto , Femenino , Humanos , Leiomioma/patología , Leiomiosarcoma/patología , Persona de Mediana Edad , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Transporte de Proteínas , Neoplasias Uterinas/patología , Útero/metabolismo , Útero/patología

RESUMEN

The study was organized to assess the sensitivity of combined technique of diagnostics of pre-cancer and cervix cancer consisted of liquid cytology and detection of clinically significant amount of Human Papillomavirus DNA in cervical samples of cervix. The cervical samples of 62 women were collected to into medium for liquid cytology and Papanikolau's stained in the system B&D TriPath. The results were evaluated according the Bethesda classification. Concurrently with the same material, the polymerase chain reaction technique in real time was applied using the Cobas 4800 device. To specify the cytological diagnosis ASC-US and under L-SIL and H-SIL the immunocitochemical detection of oncomarkers p16INK4a and Ki-67 was implemented using additionally prepared glass of the same material obtained by the liquid cytology technique. The study detected Human Papillomavirus DNA of oncogenic types in 12 cases out of 13 H-SIL (92.3%) < and in 3 cases out of 4 L-SIL (75%). In 31 female patients with ASC-US no clinically significant amount of Human Papillomavirus DNA was detected. This result correlated with the results of immunocitochemical analyses where expression of marker p16INK4a was not present. In 5 out of 9 female patients (55.6%.) aged 21-24 years with cytological diagnosis NILM Human Papillomavirus DNA was detected. The cytological analysis detected in 53 out of 63 female patients the atypical cells of cervix pavement epithelium (85.5%). The combined technique detected pathology in 58 female patients (93.5%). The cytological analysis of Human Papillomavirus was complemented by testing with Cobas 4800 device because this system permits to detect 14 highly oncogenic types of Human Papillomavirus with separate genetic typing of Human Papillomavirus of 16 and 18 types.

Asunto(s)

Papillomaviridae , Infecciones por Papillomavirus/diagnóstico , Estándares de Referencia , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Inhibidor p16 de la Quinasa Dependiente de Ciclina/análisis , Citodiagnóstico , Femenino , Humanos , Antígeno Ki-67/análisis , Papillomaviridae/clasificación , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Reacción en Cadena de la Polimerasa , Embarazo , Sensibilidad y Especificidad , Frotis Vaginal

RESUMEN

The key stage of the infection of the Escherichia coli cell with bacteriophage T4, the binding to the surface of the host cell, is determined by the specificity of the long tail fiber proteins of the phage, in particular, gp37. The assembly and oligomerization of this protein under natural conditions requires the participation of at least two additional protein factors, gp57A and gp38, which strongly hinders the production of the recombinant form of gp37. To overcome this problem, a modern protein engineering strategy was used, which involves the construction of a chimeric protein containing a carrier protein that drives the correct folding of the target protein. For this purpose, the trimeric beta-helical domain of another protein of phage T4, gp5, was used. It was shown that this domain, represented as a rigid trimeric polypeptide prism, has properties favorable for use as a protein carrier. A fragment of protein gp37 containing five pentapeptides repeats, Gly-X-His-X-His, which determine the binding to the receptors on the bacterial cell surface, was fused in a continuous reading frame to the C-terminus of the domain of gp5. The resulting chimeric protein forms a trimer that has the native conformation of gp37 and exhibits biological activity.

Asunto(s)

Bacteriófago T4/genética , Escherichia coli/metabolismo , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Virales/genética , Bacteriófago T4/fisiología , Escherichia coli/genética , Escherichia coli/virología , Modelos Moleculares , Ingeniería de Proteínas , Pliegue de Proteína , Multimerización de Proteína , Estructura Terciaria de Proteína , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/aislamiento & purificación , Proteínas de la Cola de los Virus/biosíntesis , Proteínas de la Cola de los Virus/genética , Proteínas de la Cola de los Virus/aislamiento & purificación

RESUMEN

Bacteriophage endolysins degrading bacterial cell walls are prospective enzymes for therapy of bacterial infections. The genome of the giant bacteriophage phiKZ of Pseudomonas aeruginosa encodes two endolysins, gene products (g.p.) 144 and 181, which are homologous to lytic transglycosylases. Gene 144 encoding a 260 amino acid residue protein was cloned into the plasmid expression vector. Recombinant g.p. 144 purified from Escherichia coli effectively degrades chloroform-treated P. aeruginosa cell walls. The protein has predominantly alpha-helical conformation and exists in solution in stoichiometric monomer : dimer : trimer equilibrium. Antibodies against the protein bind the phage particle. This demonstrates that g.p. 144 is a structural component of the phiKZ particle, presumably, a phage tail.

Asunto(s)

Glicosiltransferasas/metabolismo , Fagos Pseudomonas/enzimología , Pseudomonas aeruginosa/enzimología , Secuencia de Aminoácidos , Animales , Endopeptidasas/genética , Endopeptidasas/metabolismo , Glicosiltransferasas/genética , Datos de Secuencia Molecular , Fagos Pseudomonas/genética , Pseudomonas aeruginosa/genética , Especificidad por Sustrato

RESUMEN

DNA hybridization for detecting HSV, CMV, C. trachomatis, and U. urealyticum by biotin-labeled DNA probe was used for investigating clinical specimens from patients with infertility and chronic urogenital inflammations. High sensitivity and specificity of the method was confirmed by the results of PCR, ELISA, and immunofluorescent methods in 80-90% cases. DNA hybridization technique is a simple method requiring no sophisticated equipment, which recommends it for the diagnosis of sexually-transmitted diseases at clinical laboratories.

Asunto(s)

Sondas de ADN , ADN Bacteriano/análisis , ADN Viral/análisis , Infecciones Urinarias/diagnóstico , Biotina , Enfermedad Crónica , Células Epiteliales/microbiología , Células Epiteliales/virología , Femenino , Humanos , Immunoblotting/instrumentación , Immunoblotting/métodos , Masculino , Hibridación de Ácido Nucleico/métodos , Reacción en Cadena de la Polimerasa , Sensibilidad y Especificidad , Infecciones Urinarias/microbiología , Infecciones Urinarias/virología