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Biomedical subjects

Lukasz Wicherek

Publications and source records attributed to Lukasz Wicherek.

At least 19 recordsLinked to original sources

The obstetrical history in patients with Pfannenstiel scar endometriomas--an analysis of 81 patients.

INTRODUCTION: The participation of immune tolerance during pregnancy was suggested to be an important factor predisposing to the implantation of decidual cells after cesarean section in Pfannenstiel scar. Delivery at term is related to the termination of immune tolerance to fetal antigens that is maintained throughout pregnancy. Substantial proportion of cesarean section deliveries is performed before the onset of true term labor. The aim of this study was to analyze the clinical symptoms of spontaneous beginning of labor in pregnant women in whom cesarean sections were performed and in whom Pfannenstiel scar endometriomas were observed during follow-up. MATERIALS AND METHODS: We have retrospectively analyzed 81 patients following the surgical removal of scar endometrioma after cesarean section. Obstetrical histories of cesarean sections in the number of 5,370 preceding the occurrence of the scar endometrioma were analyzed. These data were collected in six different Gynecological and Obstetrical wards in Malopolska Province in Poland. Analysis of data was started by the retrospective evaluation of regular uterine contractions, uterine cervix ripening before cesarean section and the indications for surgery. RESULTS: In 67 women from the group of 81 patients cesarean sections were performed with unripe uterine cervix and without the presence of regular uterine contractions. Elective indications for cesarean sections were predominant in this group of women. The relative risk of scar endometriomas occurrence following cesarean sections performed before onset of labor in comparison to cesarean sections following spontaneous onset of labor was statistically significantly higher [RR = 2.16, 95% CI = 1.21-3.83; OR = 2.18, 95% CI = 1.22-3.89]. CONCLUSIONS: Cesarean section performed before spontaneous onset of labor may increase substantially the risk of occurrence of scar endometriomas.

Adult↗

Comparison of RCAS1 and metallothionein expression and the presence and activity of immune cells in human ovarian and abdominal wall endometriomas.

BACKGROUND: The coexistence of endometrial and immune cells during decidualization is preserved by the ability of endometrial cells to regulate the cytotoxic immune activity and their capability to be resistant to immune-mediated apoptosis. These phenomena enable the survival of endometrial ectopic cells. RCAS1 is responsible for regulation of cytotoxic activity. Metallothionein expression seems to protect endometrial cells against apoptosis. The aim of the present study was to evaluate RCAS1 and metallothionein expression in human ovarian and scar endometriomas in relation to the presence of immune cells and their activity. METHODS: Metallothionein, RCAS1, CD25, CD69, CD56, CD16, CD68 antigen expression was assessed by immunohistochemistry in ovarian and scar endometriomas tissue samples which were obtained from 33 patients. The secretory endometrium was used as a control group (15 patients). RESULTS: The lowest metallothionein expression was revealed in ovarian endometriomas in comparison to scar endometriomas and to the control group. RCAS1 expression was at the highest level in the secretory endometrium and it was at comparable levels in ovarian and scar endometriomas. Similarly, the number of CD56-positive cells was lower in scar and ovarian endometriomas than in the secretory endometrium. The highest number of macrophages was found in ovarian endometriomas. RCAS1-positive macrophages were observed only in ovarian endometriomas. CD25 and CD69 antigen expression was higher in scar and ovarian endometriomas than in the control group. CONCLUSION: The expression of RCAS1 and metallothionein by endometrial cells may favor the persistence of these cells in ectopic localization both in scar following cesarean section and in ovarian endometriosis.

Abdominal Wall↗

The length of menstrual bleeding and the risk of urogenital infections in the context of the activity of hemoglobin-derived microbicidal peptides.

OBJECTIVE: Well-known natural unspecific antimicrobial factors acting in the vagina are additionally reinforced during menstrual bleeding by hemocidins--a recently discovered novel class of microbicidal peptides generated proteolytically from hemoglobin. The aim of the presented research was to investigate the relation between the average length of menstrual bleeding and the frequency of urogenital infections. We expected that the shorter menstrual bleeding might increase the risk of urogenital infections because is synonymous with the shorter period of exposition on bactericidal action of hemocidins. STUDY DESIGN: The study contains statistical analysis of an average declared length of menstrual bleeding in the group of 267 young, sexually active women with the symptoms of urogenital infections. The control group consisted of 300 young healthy women. RESULTS: The length of menstrual bleeding in the group of patients with urogenital infections (average 4.35 days) was statistically significantly shorter than in the control group (average 4.95 days). The average length of the menstrual cycle was equal and counted ca. 28 days in both groups. CONCLUSION: The length of menstrual bleeding seems to be a significant factor in the vaginal ecology maintenance.

Adolescent↗

The analysis of RCAS1 and DFF-45 expression in nasal polyps with respect to immune cells infiltration.

BACKGROUND: Nasal polyp constitutes a benign growth process in the nasal and sinus mucosa. RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is a protein expressed mainly by various human cancer cells. It is not only the marker of cancer process and its expression can also be observed in physiological processes. It is responsible for the regulation of immune cells activity. DFF45 (DNA fragmenting factor) has been described as a substrate for caspase-3. DFF45 seems to play an important role in the onset of apoptotic process by acting probably through the regulation of DNA fragmentation. The aim of the study was to evaluate the ability of nasal polyps to regulate the cytotoxic immune response and to determine their resistance to apoptosis. RESULTS: The higher RCAS1 level was identified in lymphocytic nasal polyps, the medium one in eosinophilic while the lowest was identified in neutrophilic. DFF-45 expression was higher in eosinophilic than in neutrophilic and lymphocytic nasal polyps. CONCLUSION: The changes in DFF-45 level in nasal polyps might indicate a different resistance to apoptosis mediated by immune cells. The alterations in RCAS1 expression indicate that nasal polyps have the ability to regulate the cytotoxic immune response. The breaking of resistance to immune mediated apoptosis in nasal polyps might have a new therapeutic impact.

Adult↗

Metallothionein expression and infiltration of cytotoxic lymphocytes in uterine and tubal implantation sites.

INTRODUCTION: In spite of increasing number of immune cells in the endometrium during the decidualization, the integrity of endometrial tissue in each menstrual cycle is maintained by adaptive changes in expression of several factors that regulate activity of immune cells and concomitant hormonal alterations during the menstrual cycle. This regulatory function of endometrium is also related to resistance to apoptosis, in which metallothionein (MT) may play a role. MATERIALS AND METHODS: Study group included 26 women with spontaneous abortion and 18 patients with tubal ectopic pregnancy. Control group included 17 women whose endometrial tissue samples were taken during the normal secretory cycle phase. Expression of metallothionein (MT), CD56 and CD69 were assessed in tissue samples by immunohistochemistry. RESULTS: The number of CD56-positive cells was significantly higher in women with ruptured than unruptured ectopics. MT expression was higher in tubal mucosa distant from the implantation site in ruptured compared to unruptured ectopics. It was found also to be significantly lower than in decidua taken from women with spontaneous abortion. CD69 expression was similar in women with spontaneous abortion as well as patients with ruptured ectopics compared to the control group. On the other hand, CD69 expression in unruptured ectopics was significantly lower than in women with spontaneous abortion and the control group. CONCLUSION: The concentration of immune cells and increase of their activity in tubal mucosa, with insufficient protection against immune-mediated apoptosis assessed by MT expression, might result in tubal rupture during ectopic pregnancy.

Abortion, Spontaneous↗

Analysis of free hemoglobin level and hemoglobin peptides from human puerperal uterine secretions.

OBJECTIVE: Hemocidins are a novel class of antibacterial peptides generated proteolytically from hemoglobin. These peptides play a particularly important role in maintaining vaginal homeostasis during menstrual bleeding. To investigate the hemoglobin fragmentation process during the last stages of pregnancy, we examined uterine secretion (lochia) samples from a group of 22 healthy women who underwent cesarean delivery at term. METHODS: Patients were divided into three groups: (1) the elective cesarean deliveries without symptoms of spontaneous labor, (2) the nonelective cesarean deliveries with spontaneous beginning of labor, and (3) the nonelective cesarean deliveries during advanced labor. The samples were subjected to chromatographic estimation of free hemoglobin and peptides. In three representative patients the identification of all lochial peptides was performed. RESULTS: All samples contained a significant amount of free hemoglobin and its level increased with labor progression. The presence of peptide fractions was also detected in most lochia samples. They were confirmed to be human hemoglobin fragments, almost identical to the recently described bactericidal hemocidins from menstrual discharge. The level of peptides also increased during labor. The subgroup with advanced labor demonstrated the highest amount of hemocidins. CONCLUSIONS: The presented results prove that proteolysis of free hemoglobin in the female upper reproductive tract begins together with the clinical symptoms of normal labor. We speculate that cesarean delivery affects molecular mechanisms involved in antibacterial hemocidins generation and, in effect, might be responsible for the increased risk of gynecologic infections in cesarean deliveries.

Anti-Bacterial Agents↗

[Comparative analysis of CD56 lymphocytes and CD69 antigen expression in endometrium during decidualization].

INTRODUCTION: The exceptionality of endometrium, differentiating it from other epithelial tissues is related with its ability to regulate the number and activity of infiltrating immunological cells according to menstrual cycle phases. The aim of this study was a comparative evaluation of the number of CD56 positive cells, as well the analysis of CD69 antigen expression during decidualization. MATERIALS AND METHODS: The expression of CD56 and CD69 antigens was analyzed using the immunohistochemistry method in 20 decidual tissue samples derived after curettage following spontaneous abortion and in 38 endometrial tissue samples obtained during hysterectomy performed because of benign myoma diagnosis. The endometrial tissue samples were divided regarding to the menstrual cycle phases. Following phases were distinguished: early proliferative, mid-proliferative, late proliferative, early secretory, mid secretory and late secretory. RESULTS: The higher CD56 positive cells were recognized in the endometrium during mid secretory cycle phase. The number of CD56 positive cells was significantly lower in endometrium, independent of menstrual cycle phase in comparison to endometrium following abortion. The expression of CD69 antigen was observed to increase beginning with early secretory cycle phase and remained at high level during the secretory cycle phase and the abortion. CONCLUSIONS: The observed differences in the number of CD56 positive cells during decidualization without the changes in immune cells activity evaluated using CD69 antigen expression may indicate the participation of activated mononuclear cells in the normal development of pregnancy beginning with implantation.

Abortion, Spontaneous↗

Cycle dependent RCAS1 expression with respect to the immune cells presence and activity.

INTRODUCTION: The number of cytotoxic immune cells grows in the endometrium during the secretory cycle phase. RCAS1 is a protein inhibiting the activated immune cytotoxic cells. The expression of RCAS1 has been confirmed in endometrium. The aim of the present study was to evaluate the RCAS1 expression alterations with respect to the menstrual cycle changes and the number and activity of cytotoxic immune cells. MATERIAL AND METHODS: RCAS1, CD25, CD69, CD56, CD16, CD68 antigens expression was assessed by immunohistochemistry in endometrial tissue samples which were obtained from 33 patients. Tissue samples were classified according to the menstrual cycle phases, with division of the cycle into three phases: proliferative (8 cases), periovulatory (10 cases), and secretory (15 cases) ones. RESULTS: A significantly higher RCAS1 expression was observed in the periovulatory and the secretory menstrual cycle phases than in the proliferative phase. The changes in RCAS1 expression were combined with significant differences in the number of immune cells and their activity. The highest level of CD69 antigen expression was observed during the periovulatory cycle phase, while the highest level of CD25 antigen expression was observed during proliferative phase, the number of CD56 positive cells was at the highest level during the secretory cycle phase. No significant differences in the number of macrophages and CD16 antigen expression were observed with respect to the menstrual cycle phases. CONCLUSION: RCAS1 endometrial expression may favor the coexistence of active lymphocytes and endometrial cells.

Adult↗

The metallothionein and RCAS1 expression analysis in breast cancer and adjacent tissue regarding the immune cells presence and their activity.

INTRODUCTION: The generation of proper immune response in the tumor environment seems to be essential in antitumor defense. RCAS1 expression has been shown to participate in the regulation of immune cytotoxic activity, metallothionein participates in the protection of cells against immune mediated apoptosis. Since MT and RCAS1 expression is observed within healthy tumor environment we aimed to focus on the proteins expression in tumor and its healthy adjacent tissue in invasive ductal breast cancer regarding the immune cells presence and activity. MATERIAL AND METHODS: RCAS1, metallothionein, CD3, CD56, CD4, CD25, CD69, CD68 and CD16 antigens expression was assessed by immunohistochemistry in invasive ductal breast cancer. Tissue samples were obtained from 45 patients and were grouped according to the presence of lymph nodes metastases. Two groups were obtained: with and without lymph nodes metastases. RESULTS: Significant differences were observed in RCAS1 and metallothionein expression in tumor and significant differences in metallothionein expression in healthy stroma regarding the presence of lymph nodes metastases. The significantly higher RCAS1 expression was noticed in tumor in comparison to stroma in patients with the presence of lymph nodes metastases. No such difference was observed in patients without the metastases. Significantly higher metallothionein expression was identified in tumor than in stroma in both groups of patients, with and without lymph nodes metastases. These changes in RCAS1 and metallothionein expression were significantly related with the changes in the number and activity of immune cells. CONCLUSION: RCAS1 and metallothionein expression in breast cancer healthy stroma seems to be essential for the coexistence of cytotoxic immune cells and normal epithelial cells. The loss of the ability to compensate the growing cytotoxic immune response in the environment might participate in the development of tumor spread.

Analysis of Variance↗

The characterization of the exposure to immune mediated apoptosis and the regulation of immune cytotoxic activity in the environment of a neoplasm and in decidua.

Acquiring the immune-mediated apoptosis and the ability to regulate the cytotoxic immune response are the main phenomena playing fundamental roles in such situations as neoplasm survival and creation of immune tolerance during pregnancy. The aim of this study was to investigate these phenomena through the evaluation of metallothionein and RCAS1 proteins in neoplasm and its healthy environment (clear surgical margin), physiological conditions in placenta and its environment (decidua) and the comparison to non-neoplasmatic lesions originating from the environment (nasal polyps, endometriosis). We have shown that the growth of RCAS1 expression was simultaneous to the infiltration of activated immunological cells of tumor environment as well as decidua. The activity of immunological cells was in our study selectively suppressed. Metallothionein expression growth was also observed in healthy tumors stroma and in decidua probably in response to the growing cytotoxic activity and tumor spread. Alterations in RCAS1 and Metallothionein expression seem to be associated with local immune dysfunction in nasal polyps and endometriosis. In conclusion, the ability to compensate the growing cytotoxic immune response is physiologically observed in decidua, the lost of this ability in tumor environment might participate in the development of tumor spread.

Antigens, Neoplasm↗

Metallothionein and RCAS1 expression in comparison to immunological cells activity in endometriosis, endometrial adenocarcinoma and endometrium according to menstrual cycle changes.

OBJECTIVE: Endometrium is a specialized organ in which phenomena controlling the level of cell proliferation and apoptosis are marked. The aim of our study was to determine the presence of proteins involved in apoptosis and proliferation: RCAS1, MT and the number of CD56-positive cells and their activity to elucidate their possible role in the development of adenocarcinoma and endometriosis. MATERIALS AND METHODS: MT, RCAS1, CD56-positivity and CD69 expression were assessed in 55 tissue samples by Western blot and immunohistochemistry methods. RESULTS: We found that endometrium during secretory menstrual cycle phase is characterized by significantly higher RCAS1 and higher MT expression than in proliferative phase. The number of CD56-positive cells and the CD69 antigen expression was significantly increased. Endometrial adenocarcinoma was characterized by significantly increased RCAS1 expression, while MT expression was comparable to the level found in the secretory phase. The number of CD56-positive cells was significantly decreased and their activity was comparable to the level found in the secretory phase. Endometriosis was accompanied by significantly lower RCAS1 and MT expressions, with lower number of CD-56 positive cells and lower expression of CD69 antigen in comparison to the secretory phase. CONCLUSIONS: The ability of endometrium to determine cytotoxic activity (RCAS1 expression changes) and high protection against DNA damage (MT expression) with concomitant changes in the number of immune cells and their activity, observed in normal endometrium during the menstrual cycle phases seems to be fundamental for pathological features of endometrial adenocarcinoma and endometriosis.

Adenocarcinoma↗

The molecular changes during placental detachment.

OBJECTIVES: RCAS1 is a membrane protein that plays a role in the maintenance of maternal immune tolerance during pregnancy. The work presented here demonstrates the results of RCAS1 expression in placenta in cases of placental abruption and patients with retained placental tissue during the third stage of labor. STUDY DESIGN: The placenta tissue samples were obtained during vaginal and cesarean delivery (derived from 117 pregnancies). Pregnant women were divided into four groups according to the onset of labor and the time of placental detachment in term labors. The samples were analyzed by the Western blot method. Statistical analysis was performed using the Shapiro-Wilk procedure. The Mann-Whitney test and Student's t-test were applied to compare the differences between parametric data. RESULTS: The average relative amount of RCAS1 observed in those patients with retained placental tissue was statistically significantly higher than in the patients with placental abruption. CONCLUSION: The differences observed in placental RCAS1 levels confirm the participation of this protein in the inhibition of maternal immune response during gestation. The present results also indicate that RCAS1 participates in the changes in the maternal immune system that take place during parturition and reinforce its potential involvement in the mechanism of placental abruption.

Abruptio Placentae↗

The placental RCAS1 expression during stillbirth.

BACKGROUND: Independently of the fetal death cause the beginning and course of stillbirth is closely related with the growing cytotoxic activity at the maternal-fetal interface. RCAS1 participates in the inhibition of maternal immune response during pregnancy. The alterations of RCAS1 protein expression in placental cells seem to determine the beginning of the labor and participate in the placental abruption. The aim of the present study was to investigate RCAS1 expression in placentas obtained following stillbirths or normal term births. METHODS: RCAS1 expression was evaluated by Western blot method with the use of monoclonal anti-RCAS1 antibody in 67 placental tissue samples. Pregnant women were divided into four groups according to the mode of labor onset--spontaneous or induced, and the type of labor, stillbirth or labor at term. Placental beta-Actin expression was chosen as a control protein. Relative amounts of placental RCAS1 were compared with the use of Student's t-test, whereas beta-Actin control data were compared with the use of Mann-Whitney U test. RESULTS: The average relative amount of RCAS1 was significantly lower in women with induced stillbirths than in women with induced labor at term. Similarly, significantly lower RCAS1 placental levels were observed in patients with spontaneous stillbirths than in women with spontaneous labor at term. Significant differences in RCAS1 expression were also observed with the respect to the beginning of the stillbirth: spontaneous and induced. Lowest RCAS1 placental levels were observed in women with spontaneous stillbirth. CONCLUSIONS: These preliminary results indicate that the alterations of RCAS1 expression in the human placenta may be involved in the changes of maternal immune system that take place during stillbirth.

Adult↗

The level of maternal immune tolerance and fetal maturity.

OBJECTIVES: Fetal maturity does not seem to be directly connected with the phenomenon of immune tolerance during pregnancy although the fetal maturation influences the process of initiation of the labor at term finishing the immune tolerance during pregnancy. CAP and RCAS1 are expressed by the trophoblast cells and afterwards by the placenta, these proteins are able to modulate the maternal immune response. MATERIALS AND METHODS: 160 patients were randomly selected to our study. The patients were divided into two groups using K score according to the newborn's maturity: maturated and not fully maturated. Within the groups of matured and not fully matured newborns the subgroups were selected according to the type of the labor: spontaneous or induced. The oxytocinase plasma activity was established in plasma samples obtained from pregnant women a few days before delivery. The placental RCAS1 relative amount was assessed by Western blot analysis. RESULTS: The differences in oxytocinase plasma level with respect to the fetal maturity were identified in our study however no RCAS1 expression changes were found regarding the fetal maturation. We determined the alterations in RCAS1 expression with respect to the occurrence of clinical symptoms of the spontaneous beginning of the labor in maturated and not-fully maturated groups of newborns. CONCLUSIONS: Oxytocinase seems to be a useful marker of normal fetal development. The assessment of RCAS1 in placenta directly after delivery appears to indicate the level of maternal immune tolerance during the labor initiation. The level of the immune tolerance at the moment of the delivery drops independently of the fetal maturity.

Actins↗

Cycle dependent expression of endometrial metallothionein.

OBJECTIVES: Molecular changes observed in endometrium with respect to menstrual cycle changes seem to be crucial for the reproductive function. Accumulation of cytotoxic cells increases the exposure of endometrial cells to apoptosis. Protection against apoptosis may be reached by endometrial cells by self molecular regulation. Metallothionein was suggested to participate in this process. The aim of our study was to evaluate endometrial MT immunoreactivity with respect to the menstrual cycle phases. MATERIALS AND METHODS: MT expression was assessed using immunohistochemistry method in 47 endometrial tissue samples derived from randomly selected patients with respect to the menstrual cycle phases--proliferative and secretory with distinguishing early, mid and late subphases in each. RESULTS: MT expression changes were observed respectively to hormonal fluctuations with the highest level during mid secretory phase and its respective decrease during the early, late secretory and mid proliferative menstrual cycle phases. The lowest MT immunoreactivity level was disclosed during early proliferative phase. CONCLUSION: Significant differences in MT expression observed in endometrium with respect to menstrual cycle changes might suggest MT participation in endometrial cells protection against apoptosis.

Adult↗

Antibacterial hemoglobin peptides in human menstrual blood.

This work documents that normal menstrual vaginal blood of healthy females is exceptionally rich in hemocidins--hemoglobin (Hb) fragments having bactericidal properties. The peptide fractions were isolated from the plasma of vaginal discharge of three healthy nulliparous women and subjected to identification by automatic sequencing as well as by mass spectrometry. All 44 identified peptides originate from Hb (mainly from the N-terminal part of alpha-globin) and all demonstrated differential killing activity toward Escherichia coli. The screening of antimicrobial activity was performed using two synthetic peptides identical to those found in menstrual blood. These peptides were active mainly toward Gram-negative bacteria and to a less degree toward Gram-positive bacteria. Our results confirm recent observations that Hb-derived fragments manifest pronounced antibacterial activity and suggest that these peptides help in maintaining human vaginal homeostasis during physiologic menstrual bleeding.

Adolescent↗

Comparative analysis of RCAS1 level in neoplasms and placenta.

The tumor associated antigen RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) expressed with high frequency in various cancer and trophoblast cells, inhibits growth of estrogen receptor-expressing cells and induces apoptosis. Because previous reports demonstrated RCAS1 presence only by non-quantitative immunocytochemistry methods, we decided to use a Western blotting with anti-RCAS1 monoclonal antibodies for estimation of the relative content of the tumor-associated antigen. One hundred tissue samples were assayed (neoplasms, chronic inflammatory diseases, healthy tissues, trophoblasts and placentas at term). RCAS1 was present in all neoplastic, placental and trophoblast tissue samples and its level in malignant samples was statistically significantly higher than in benign neoplasms. The amount of RCAS1 in chronic inflammations was also significantly increased in immune mediated diseases, like allergic nasal polyps and sarcoidosis. The RCAS1 protein was not revealed in healthy mucous membrane and in muscle tissues. The presented results suggest that RCAS1 might play an important role in tumor escape from host immunological surveillance and carry weight in the down regulation of the maternal immune response, thereby maintaining pregnancy.

Antigens, Neoplasm↗