Khaleque Newaz Khan

Nagasaki University, Nagasaki, Nagasaki, Japan

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Publications (37)95.14 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Is there any risk of intra-uterine bacterial colonization and concurrent occurrence of endometritis in women with endometriosis?
    Human reproduction (Oxford, England). 09/2014;
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    ABSTRACT: Human heat shock protein 70 (HSP70) has been reported to enhance Toll-like receptor 4-mediated pelvic inflammation and growth of endometriotic cells. However, information on tissue expression of HSP70 before and after treatment with estrogen suppressing agent is scanty. Here, we investigated tissue expression HSP70 in the eutopic/ectopic endometria of gonadotropin-releasing hormone agonist (GnRHa)-treated and -non-treated women with endometriosis.
    European journal of obstetrics, gynecology, and reproductive biology. 06/2014; 180C:16-23.
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    ABSTRACT: Is there any occurrence of hidden (occult) endometriotic lesions in normal peritoneum of women with and without visible endometriosis? We detected a slightly higher occurrence of occult microscopic endometriosis (OME) in normal peritoneum of women with visible endometriosis than in control women. Based on a small number of cases, the concept of invisible microscopic endometriosis in visually normal peritoneum has been reported for more than a decade but there is controversy regarding their tissue activity and clinical significance. This case-controlled research study was conducted with prospectively collected normal peritoneal samples from 151 women with and 62 women without visible endometriosis. Normal peritoneal biopsy specimens from different pelvic sites of were collected during laparoscopy. A histological search of all peritoneal biopsy specimens for the detection of invisible endometriosis was done by immunoreaction to Ber-EP4 (epithelial cell marker), CD10 (stromal cell marker) and Calretinin (mesothelial cell marker). Tissue expression of estrogen/progesterone receptors (ER/PR) and cell proliferation marker, Ki-67, was performed by immunohistochemistry to identify tissue activity. Three different patterns of OME were detected based on (I) the presence of typical gland/stroma, (II) reactive hyperplastic change of endometrioid epithelial cells with surrounding stroma and (III) single-layered epithelium-lined cystic lesions with surrounding stroma. A higher tendency toward the occurrence of OME was found in women with visible endometriosis (15.2%, 23/151) compared with control women (6.4%, 4/62) (P = 0.06, χ(2) test). The epithelial cells and/or stromal cells of OME lesions were immunoreactive to Ber-EP4 and CD10 but not reactive to Calretinin. ER and PR expression was observed in all patterns of OME lesions. Ki-67 index was significantly higher in pattern I/II OME lesions than in pattern III OME lesions (P< 0.05 for each). Bias in the incidence rate of OME lesions in this study cannot be ignored, because we could not analyze biopsy specimens from the Pouch of Douglas of women with revised classification of the American Society of Reproductive Medicine Stage III-IV endometriosis due to the presence of adhesions in the pelvis. We re-confirmed a decade long old concept of invisible (occult) endometriosis in visually normal peritoneum of women with visible endometriosis. The existence of a variable amount of tissue activity in these occult lesions may contribute to the recurrence/occurrence of endometriosis or persistence/recurrence of pain manifestation in women even after successful ablation or excision of visible lesions by laparoscopy. This work was supported in part by Grants-in-aid for Scientific Research from the Japan Society for the Promotion of Science. There is no conflict of interest related to this study. Not applicable.
    Human Reproduction 12/2013; · 4.67 Impact Factor
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    ABSTRACT: To evaluate factors related to the occurrence of Sheehan syndrome. The obstetrical disseminated intravascular coagulation score, total volume of hemorrhage, shock index, level of consciousness at the time of shock occurrence and pituitary magnetic resonance imaging findings were evaluated in nine women who showed massive hemorrhage during delivery. These clinical outcomes were analyzed in all these patients who were prospectively followed-up to identify any possible occurrence of Sheehan syndrome. Compared to six women with non-Sheehan syndrome, three women who were diagnosed with Sheehan syndrome showed significant elevation of the obstetrical disseminated intravascular coagulation score, decrease in the level of consciousness during shock and remarkable pituitary gland atrophic change with an empty sella turcica detected by pituitary magnetic resonance imaging. The volume of hemorrhage during delivery and shock index were not significantly different between these two groups of women. Careful attention and follow-up should be paid to women with post-partum massive hemorrhage for early detection and management of women with Sheehan syndrome.
    Journal of Obstetrics and Gynaecology Research 08/2013; · 0.84 Impact Factor
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    ABSTRACT: To examine clinical and surgical performances of cases with placental polyps in which uterine preservation surgery was conducted. During the period September 2002 to April 2009, we examined eight cases (hysteroscopic resection, six cases; laparotomy, one case; dilatation and curettage, one case) diagnosed with placental polyp that had been treated with polyp extraction surgery. Imaging evaluation was done using magnetic resonance imaging and 2-D ultrasound. Three of the eight cases (37.5%) had been first-time pregnancies. Most of our cases experienced minimal surgical manipulation after medical abortion. Among them, six cases (75%) were mid-term medical abortions, one case (12.5%) received no treatment after spontaneous abortion, and one case (12.5%) had postsurgical abortion (dilatation and curettage). All cases showed variable amount of blood flow in the internal mass and myometrium by color Doppler ultrasound. Magnetic resonance imaging angiography showed contrast effects in the intrauterine cavity and myometrium in selected cases. The average duration from diagnosis to surgery was 32 days (range, 11-105). Color Doppler revealed a reduction in blood flow in five cases during the waiting period until surgery with an average blood loss of 10 g (range, 0-20) during surgery. Use of color Doppler ultrasound may be useful in diagnosing placental polyp. Although hysteroscopic resection of placental polyp is effective in patients hoping for uterine preservation, delaying timing of surgery may reduce blood loss during operative procedure.
    Journal of Obstetrics and Gynaecology Research 08/2013; · 0.84 Impact Factor
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    ABSTRACT: Endometriosis is an estrogen-dependent chronic inflammatory condition associated with variable degrees of pelvic pain and infertility. Studies have showed that the growth and progression of endometriosis continue even in ovariectomized animals. This indicates that besides ovarian steroid hormones, the growth of endometriosis can be regulated by the innate immune system in the pelvic environment. As a component of innate immune system, increased infiltration of macrophages has been described in the intact tissue and peritoneal fluid of women with endometriosis. Different immune cells and dendritic cells express Toll-like receptors (TLR) and exhibit functional activity in response to microbial products. In this review article, we discuss the role of the TLR system in endometrium and endometriosis and outline the involvement of cytokines/endotoxin in causing adverse reproductive outcome. In the first part of this review article, the fundamentals of innate immune system, functional characteristics of TLR and signaling pathways of TLR4 are discussed for easy understanding by the readers.
    Journal of Obstetrics and Gynaecology Research 07/2013; · 0.84 Impact Factor
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    ABSTRACT: Is there any combined effect between inflammation and stress reaction on Toll-like receptor 4 (TLR4)-mediated growth of endometriotic cells? A combined effect of local inflammation and stress reaction in the pelvic environment may be involved in TLR4-mediated growth of endometriotic stromal cells. In endometriosis, higher endotoxin levels in the menstrual fluid (MF) and peritoneal fluid (PF) and higher tissue concentrations of human heat shock protein 70 (HSP70) in the eutopic and ectopic endometria promote TLR4-mediated growth of endometriotic cells. This is a case-controlled research study with prospective collection and retrospective evaluation of sera, MF, PF and endometrial tissues from 43 women with and 20 women without endometriosis. PF was collected from 43 women with endometriosis and 20 control women during laparoscopy. Sera and endometrial biopsy specimens were collected from a proportion of these women. MF was collected from a separate population of 20 women with endometriosis and 15 control women. HSP70 concentrations in sera, MF, PF and in culture media were measured by ELISA. Gene expression of HSP70 by endometrial cells in response to lipopolysaccharide (LPS) was examined by qRT-PCR. The individual and combined effects of LPS and HSP70 on the secretion of interleukin-6 (IL-6) and tumor necrosis factor α (TNFα) by PF-derived macrophages (Mϕ) were examined by ELISA, while their effects on endometrial cell proliferation were examined by bromodeoxyuridine and [(3)H]-thymidine incorporation assay. Concentrations of HSP70 were maximal in MF, intermediate in PF and the lowest in sera. In MF and PF, HSP70 levels were higher in women with endometriosis than in controls. LPS stimulated gene expression and secretion of HSP70 by eutopic endometrial stromal cells (ESCs) and this effect was abrogated after pretreatment of cells with an anti-TLR4 antibody. This effect was significantly higher for ESCs derived from women with endometriosis than for ESCs from control women. Exogenous treatment with either HSP70 or LPS significantly stimulated the production of IL-6 and TNFα by Mϕ and promoted the proliferation of ESCs, and a significant additive effect between LPS and HSP70 was observed. While individual treatment with either polymyxin B, an LPS antagonist, or anti-HSP70 antibody was unable to suppress the combined effects of LPS and HSP70 on cytokine secretion or ESC proliferation, pretreatment of cells with the anti-TLR4 antibody was able to significantly suppress their combined effects. Further studies are needed to examine the mutual role between other secondary inflammatory mediators and endogenous stress proteins in promoting pelvic inflammation and growth of endometriotic stromal cells. Our findings suggest that endotoxin and HSP70 are mutually involved in a stress reaction and in inflammation. A combined effect between local inflammation and a stress reaction in pelvic environment may be involved in TLR4-mediated growth of endometriotic cells.Since endometriosis is a multi-factorial disease, it is difficult to explain uniformly its growth regulation by a single factor. Our findings may provide some new insights in understanding the physiopathology or pathogenesis of endometriosis and may hold new therapeutic potential. This work was supported by Grants-in-Aid for Scientific Research (grant no. 16591671 and 18591837) from the Ministry of Education, Sports, Culture, Science and Technology of Japan (to K.N.K.). There is no conflict of interest related to this study. Not applicable.
    Human Reproduction 07/2013; · 4.67 Impact Factor
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    ABSTRACT: STUDY QUESTION: Is the occurrence of pelvic pain in women with ovarian endometrioma associated with coexisting peritoneal lesions (PLs)? SUMMARY ANSWER: Pelvic pain in women with ovarian endometrioma is usually associated with coexisting PLs. An increased tissue inflammatory reaction with elevated prostaglandin (PG) production may be responsible for the generation of pain. WHAT IS KNOWN ALREADY: Severe pelvic pain in women with ovarian endometrioma is reported to be associated with deeply infiltrating endometriosis. However, information on pelvic pain in women with ovarian endometriosis with and without coexistent peritoneal superficial lesions is limited. STUDY DESIGN, SIZE AND DURATION: Retrospective clinical study with case-controlled biological research using prospectively collected tissue samples derived from women with and without endometriosis and their retrospective evaluation. PARTICIPANTS/MATERIALS, SETTING, METHODS: We performed a retrospective cohort study conducted in 2988 cases who had laparoscopic surgery for indications of ectopic pregnancy, tubal infertility and other benign gynecologic diseases. We analyzed the occurrence of pelvic pain in the cases with ovarian endometrioma according to the distribution of coexisting PLs and pattern of intrapelvic adhesions. Inflammatory reaction of eutopic and ectopic endometria was measured by immunoreaction to macrophage marker, CD68. The tissue expression of cyclooxygenase (COX) 2 was examined by immunohistochemistry and tissue concentrations of PG F2α were measured by ELISA. MAIN RESULTS AND THE ROLE OF CHANCE: Among the 2988 surgical cases, 350 (11.7%) were found to have ovarian endometrioma at laparoscopy. Coexisting PLs were present in 269 of these women and in this group 85.4% of cases experienced pelvic pain and 14.6% had no pain. In contrast, among the 81 women with ovarian endometrioma only, 38.3% cases experienced pelvic pain and 61.7% cases had no pain and the difference between the groups was statistically significant (P < 0.01). The infiltration of CD68-immunoreactive macrophages was significantly higher in the eutopic and ectopic endometria of women with peritoneal endometriosis than in ovarian endometrioma. The tissue expression of COX2 and levels of PGF2α were significantly higher in both the eutopic and ectopic endometria derived from women with peritoneal endometriosis than in similar tissues derived from women with ovarian endometrioma. LIMITATIONS, REASONS FOR CAUTIONS: Lack of evaluation in the detection of general or disseminated deeply infiltrating endometriosis in the pelvic cavity could be a bias or limitation in this study. Further multicenter prospective studies are needed to strengthen our current findings. WIDER IMPLICATIONS OF THE FINDINGS: Our findings may provide some new insights to understand the physiopathology of pelvic pain in women with ovarian cystic endometriosis and may hint at proper surgical manipulation to prevent the recurrence of pelvic pain in these women. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Sports, Culture, Science and Technology of Japan. There is no conflict of interest related to this study. TRIAL REGISTRATION NUMBER: Not applicable.
    Human Reproduction 10/2012; · 4.67 Impact Factor
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    ABSTRACT: The purpose of this work was to investigate whether clinical cytology could be useful in the preoperative diagnosis of pelvic actinomycosis. This study involved the prospective collection of samples derived from the endometrium and the uterine cervix, and retrospective data analysis. Nine patients with clinically diagnosed pelvic actinomycosis were enrolled. The clinical and hematological characteristics of patients were recorded, and detection of actinomyces was performed by cytology, pathology, and bacteriological culture of samples and by imprint intrauterine contraceptive device (IUD) cytology. The detection rate of actinomyces was 77.7% by combined cervical and endometrial cytology, 50.0% by pathology, and 11.1% by bacterial culture. The higher detection rate of actinomyces by cytology than by pathology or bacteriology suggests that careful cytological examination may be clinically useful in the preoperative diagnosis of pelvic actinomycosis.
    International Journal of Women's Health 01/2012; 4:527-33.
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    ABSTRACT: We measured serum anti-Müllerian hormone levels before and after surgery in women undergoing unilateral and monolocular cystectomy for benign ovarian diseases. Comparing to control benign cysts, we found a significant decline in serum anti-Müllerian hormone levels with consequent depletion of follicles in tissue specimens after surgery for women with ovarian endometrioma.
    Fertility and sterility 02/2011; 95(8):2589-91.e1. · 3.97 Impact Factor
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    ABSTRACT: To test the hypothesis that bacterial contamination of menstrual blood could be a local biologic event in the development of endometriosis, menstrual blood was cultured and bacterial endotoxin was measured in menstrual blood and peritoneal fluid. Our results suggest that compared with control women, higher colony formation of Escherichia coli in menstrual blood and endotoxin levels in menstrual fluid and peritoneal fluid in women with endometriosis may promote Toll-like receptor 4-mediated growth of endometriosis.
    Fertility and sterility 12/2010; 94(7):2860-3.e1-3. · 3.97 Impact Factor
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    ABSTRACT: We recently demonstrated the effect of gonadotrophin-releasing hormone agonist (GnRHa) on tissue inflammation, angiogenesis and apoptosis in endometriosis, adenomyosis and uterine myoma. Here, we investigated expression of GnRH receptors (GnRHRs) and effect of GnRHa on the proliferation of cells derived from endometria and pathological lesions of women with these reproductive diseases. Biopsy specimens were collected from lesions and corresponding endometria of 35 women with pelvic endometriosis, 45 women with ovarian endometrioma, 35 women with adenomyosis and 56 women with uterine myoma during laparoscopy or laparotomy. The gene and protein expressions of GnRHR in eutopic/ectopic cells and tissues were examined by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. The immunoreactivity of GnRHR in tissue was analysed by quantitative-histogram (Q-H) scores. The exogenous effect of GnRHa on cell proliferation was examined by 5-bromo-2-deoxyuridine incorporation assay. The Ki-67-immunoreactive cell proliferation index was analysed in biopsy specimens derived from GnRHa-treated and -non-treated women. Types I and II GnRHRs mRNA and proteins were expressed in eutopic endometria and pathological lesions derived from women with endometriosis, adenomyosis and uterine myoma. GnRHR expression was the highest in the menstrual phase when compared with other phases of the menstrual cycle. Higher Q-H scores of GnRHR immunoreaction were found in blood-filled opaque red lesions than in other peritoneal lesions. Exogenous treatment with GnRHa significantly suppressed the proliferation of cells derived from respective endometria and pathological lesions when compared with GnRHa-non-treated cells. Local tissue expression of GnRHR was detected in endometriosis, adenomyosis and uterine myoma. In addition to a hypo-estrogenic effect, a direct anti-proliferative effect of GnRHa may be involved in the regression of these reproductive diseases with consequent remission of clinical symptoms.
    Human Reproduction 11/2010; 25(11):2878-90. · 4.67 Impact Factor
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    ABSTRACT: We investigated the effect of human seminal fluid on the growth of endometrial cells derived from women with and without endometriosis. Seminal plasma (SP) was collected from 18 healthy fertile men. Serum, peritoneal fluid (PF) and tissue specimens of eutopic and ectopic endometrium were collected from 45 women with endometriosis and 20 women without endometriosis during laparoscopic surgery. Prostaglandin (PG) E2, hepatocyte growth factor (HGF), and estradiol (E2) levels in each sample of SP, serum and PF were measured by enzyme-linked immunosorbent assay. The growth pattern of cells derived from eutopic and ectopic endometria in response to SP was examined by 5-bromo-2-deoxyuridine (BrdU) incorporation assay. Seminal plasma was able to significantly stimulate the growth of epithelial cells and stromal cells derived from the eutopic and ectopic endometria of women with endometriosis (2-3-fold) when compared with control media. The SP-promoted proliferation of both gland cells and stromal cells derived from eutopic endometria was also remarkably higher in women with endometriosis than that of women without endometriosis. Although levels of PGE2, HGF and E2 in SP were variable when compared with other body fluids, the levels of PGE2 and HGF in SP were significantly higher than those in either peritoneal fluid or serum of women with or without endometriosis. Pretreatment of cells with individual anti-PGE2 antibody, anti-HGF antibody and two selective estrogen receptor modulators, tamoxifen and raloxifene was unable to suppress SP-mediated growth of endometrial cells. However, pretreatment of cells with combined anti-PGE2 antibody plus anti-HGF antibody or combined anti-PGE2 antibody plus anti-HGF antibody plus tamoxifen or raloxifene was able to significantly suppress SP-promoted growth of eutopic and ectopic endometrial cells. Human seminal fluid enriched with different macromolecules may promote the growth of endometrial cells derived from women with endometriosis. Our findings may suggest some detrimental effect of unprotected sexual intercourse in women with endometriosis.
    European journal of obstetrics, gynecology, and reproductive biology 04/2010; 149(2):204-9. · 1.97 Impact Factor
  • Journal of Reproductive Immunology - J REPROD IMMUNOL. 01/2010; 86(1):29-29.
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    ABSTRACT: Information is limited regarding the multifunctional role of GnRH agonist (GnRHa) therapy in reproductive diseases. We investigated the pattern of changes in inflammatory reaction, micro-vessel density and apoptosis in the tissues collected from women with endometriosis, adenomyosis and uterine myoma who were treated with or without GnRHa therapy. Biopsy specimens were collected from lesions, myometria and corresponding endometria of 45 women with ovarian endometrioma, 35 women with adenomyosis and 56 women with uterine myoma. A fraction of these women were treated with GnRHa therapy for a variable period of 3-6 months before surgery. We performed immunohistochemical analysis of CD68, a macrophage (Mvarphi) marker and von Willebrand factor (VWF), a vessel marker, using respective antibodies. Changes in apoptosis were examined using TdT-mediated dUTP-biotin nick end-labeling assay and by the immunoexpression of activated caspase-3 in tissues after GnRHa therapy. The infiltration of CD68-positive Mvarphi and VWF-positive micro-vessel density were significantly decreased in the endometria of women with endometriosis, adenomyosis and uterine myoma in the GnRHa-treated group when compared with that in the non-treated group. Marked decreases in inflammatory and angiogenic responses were observed in lesions and myometria of these diseases. When compared with the non-treated group, a significant increase in apoptotic index (apoptotic cells per 10 mm(2) area) and quantitative-histogram scores of activated caspase-3 after GnRHa therapy were observed in the eutopic endometria, lesions and myometria of these diseases. GnRHa was able to markedly reduce the inflammatory reaction and angiogenesis and to significantly induce apoptosis in tissues derived from women with endometriosis, adenomyosis and uterine myoma. These multiple biological effects at the tissue level may be involved in the regression of these reproductive diseases.
    Human Reproduction 12/2009; 25(3):642-53. · 4.67 Impact Factor
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    ABSTRACT: Macrophages, dendritic cells, and Toll-like receptors (TLRs) are integral components of the innate immune system. This rapidly reactive system responds immediately to infectious or other non-self agents, thereby inducing an inflammatory response to protect the host until the activation of the slower adaptive immune system. The fundamentals of the innate immune system, functional characteristics of TLRs, and signaling pathways of TLR4 are discussed for the easy understanding by readers. Studies showed that the growth and progression of endometriosis continue even in ovariectomized animals. This indicates that besides ovarian steroid hormones, the growth of endometriosis can be regulated by the innate immune system in the pelvic environment. As a component of the innate immune system, increased infiltration of macrophages has been described in the intact tissue and peritoneal fluid of women with endometriosis. In this review article, we discuss the role of bacterial endotoxin and TLR4 in endometrium and endometriosis and outline the involvement of endotoxin in causing adverse reproductive outcome.
    Gynecologic and Obstetric Investigation 05/2009; 68(1):40-52. · 1.10 Impact Factor
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    ABSTRACT: Endometriosis, a chronic disease characterized by endometrial tissue located outside the uterine cavity is associated with chronic pelvic pain and infertility. However, an in-depth understanding of the pathophysiology of endometriosis is still elusive. It is generally believed that besides ovarian steroid hormones, the growth of endometriosis can be regulated by innate immune system in pelvic microenvironment by their interaction with endometrial cells and immune cells. We conducted a series of studies in perspectives of pelvic inflammation that is triggered primarily by bacterial endotoxin (lipopolysaccharide) and is mediated by toll-like receptor 4 and showed their involvement in the development of pelvic endometriosis. As a cellular component of innate immune system, macrophages were found to play a central role in inducing pelvic inflammatory reaction. We further report here that peritoneal macrophages retain receptors encoding for estrogen and progesterone and ovarian steroids also participate in producing an inflammatory response in pelvic cavity and are involved in the growth of endometriosis either alone or in combination with hepatocyte growth factor (HGF). As a pleiotropic growth factor, HGF retains multifunctional role ometriosis. We describe here the individual and step-wise role of HGF, macrophages and ovarian steroid hormones and their orchestrated involvement in the immunopathogenesis of pelvic endometriosis.
    American journal of reproductive immunology (New York, N.Y.: 1989) 12/2008; 60(5):383-404. · 3.32 Impact Factor
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    ABSTRACT: We investigated the role of human heat-shock protein 70 (Hsp70) in Toll-like receptor 4 (TLR4)-mediated growth of endometriosis. TLR4 expression was examined in macrophages (M) isolated in primary culture from the peritoneal fluid of women with and without endometriosis. The production of a number of macromolecules by non-treated M, Hsp70-treated M and after treatment with anti-TLR4 antibody was examined by enzyme linked immunosorbent assay (ELISA). The single and combined effects of Hsp70 and lipopolysaccharide (LPS) on the growth of endometrial stromal cells were analyzed by 5-bromo-2-deoxyuridine (BrdU) incorporation study. Hsp70 levels in eutopic and ectopic endometria were measured by ELISA. TLR4 was detected in isolated M at protein and gene level. Hsp70 (10 microg/ml) significantly stimulated the production of hepatocyte growth factor, vascular endothelial cell growth factor, interleukin-6 and tumor necrosis factor alpha by M derived from women with endometriosis compared with M derived from women with no endometriosis (P < 0.05 for each). This effect of Hsp70 was abrogated after pretreatment of M with anti-TLR4 antibody. BrdU incorporation indicated that Hsp70 significantly enhanced the growth of endometrial stromal cells ( approximately 50% increase) from women with endometriosis compared to non-treated cells. A synergistic effect on cell proliferation was observed between exogenous Hsp70 and LPS and this was significantly suppressed by pretreatment of cells with anti-TLR4 antibody (P < 0.05). Tissue levels of Hsp70 were significantly higher in the eutopic endometria (P < 0.05) and opaque red lesions (P < 0.01) derived from women with endometriosis than from other peritoneal lesions or from women with no endometriosis. A prominent stress reaction was observed in blood-filled opaque red peritoneal lesions. Human Hsp70 induces pelvic inflammation and may be involved in TLR4-mediated growth of endometrial cells derived from women with endometriosis.
    Human Reproduction 08/2008; 23(10):2210-9. · 4.67 Impact Factor
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    ABSTRACT: We investigated the outcome of laparoscopic salpingotomy for tubal pregnancy by follow-up hysterosalpingography (HSG) or second-look laparoscopy (SLL) and reexamined the indication for and limitation of this conservative surgery. From April 1991 to December 2003, we treated 181 cases of tubal pregnancy using laparoscopic salpingotomy. The tubal patency was assessed by either HSG or SLL performed at 3 months post-surgery. The patients with a successful initial operation and confirmed ipsilateral patent tubes at follow-up were classified as truly successful cases (group I). Even after successful operation, if the treated tubes were found to be occluded, they were considered as unsuccessful cases. Therefore, those cases that were unsuccessful at initial surgery as well as at follow-up were categorized as group II. One hundred and thirty-four cases (74%) were successfully treated by salpingotomy at initial laparoscopy and 85 of them (63.4%) were found to be truly successful at follow-up (group I). The remaining 47 cases (26.0%) were unsuccessful at initial surgery and 18 (13.4%) cases at follow-up (group II). Thirty-one other patients refused to accept a tubal patency test or were not examined for personal reasons or were lost to follow-up. No difference in surgical outcome was observed between these two groups of patients with regard to gestational age, intra-operative hemorrhage, size or anatomic location of the pregnancy mass, and pre-operative adhesions of the fallopian tube. However, pre-operative serum levels of hCG were significantly higher in group II than in group I. In addition, the unsuccessful cases were more frequently associated with positive fetal heart beat (FHB), tubal rupture, and pre-operative serum levels of hCG of more than 10,000 IU/l (p<0.05, chi2 test). The log-rank test indicated a higher pregnancy success rate in group I (p<0.05) than in group II in those who desired future pregnancy. Laparoscopic salpingotomy may be practised as conservative surgery for proximal ectopic pregnancy, and gestational mass size is not as important and is not a relative contraindication for conservative laparoscopic surgery, as previously reported. Low pre-operative HCG levels, absence of FHB, absence of tubal rupture initially or minimal rupture may be considered suitable parameters for successful surgery and for achieving future pregnancy.
    European Journal of Obstetrics & Gynecology and Reproductive Biology 04/2008; 137(2):210-6. · 1.84 Impact Factor
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    ABSTRACT: The association between uterine myoma and infertility is still controversial. The anatomical defect of endometrium by uterine fibroids could be a factor for reducing pregnancy rates and increasing miscarriage rates. However, pregnancy and implantation rates were found to be significantly lower in women with intramural myomas (IMMs), when there was no deformity of uterine cavity. This could be due to other biological factors such as increased accumulation of inflammatory cells within fibroid tissue and corresponding endometrium that might impair fertility. Therefore, we tried to investigate the pattern of macrophage (Mvarphi) accumulation in different uterine fibroids and the production of chemokine and prostaglandin (PG) by these tissues. The selection criteria of uterine fibroids were based on the classification of European Society of Hysteroscopy. Biopsy specimens were collected from respective nodules and autologous endometrium of 20 women with submucosal myoma (SMM), 29 women with IMM and 18 women with subserosal myoma (SSM). CD68 immunoreactive Mvarphis were identified in these tissues by immunohistochemistry. A fraction of corresponding tissues were homogenized, and levels of monocyte chemotactic protein-1 (MCP-1) and PGF(2alpha) were measured by enzyme-linked immunosorbent assay (ELISA). Mvarphi infiltration in the myoma nodule and corresponding endometrium of women with SMM and IMM was significantly higher than that of women with SSM or control women (P<0.01 and P<0.05, respectively). This tissue accumulation of inflammatory cells was independent of the sizes of the myoma nodules and phases of menstrual cycle. The tissue concentration of MCP-1 corresponded to increased Mvarphi infiltration and was significantly higher in women with SMM and IMM than that in women with SSM (P<0.05 for each). A positive correlation was observed between MCP-1 concentration and accumulated Mvarphi numbers in the endometrium of women with SMM and IMM but not in women with SSM. The tissue levels of PGF2alpha were also significantly higher in the nodule and corresponding endometrium of women with SMM and IMM than that in SSM or control women (P<0.05 for each). Higher production of MCP-1 could be responsible for the increased accumulation of Mvarphi in women with SMM and IMM. The augmented inflammatory reaction in endometrium and increased PGF2alpha levels might be detrimental to reproductive outcome in women with SMM or IMM.
    Human Reproduction 11/2006; 21(10):2545-54. · 4.67 Impact Factor