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T Maruo

Publications and source records attributed to T Maruo.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effects of the levonorgestrel-releasing intrauterine system on proliferation and apoptosis in the endometrium.

BACKGROUND: The levonorgestrel-releasing intrauterine system (LNg-IUS) has been shown to be effective in the management of menorrhagia. In order to evaluate the effects of LNg-IUS on endometrial proliferation and apoptosis, proliferating cell nuclear antigen (PCNA) expression, apoptosis, Fas and Bcl-2 protein expression in the endometrium were determined at the early proliferative phase of the menstrual cycle before and 3 months after LNg-IUS insertion. METHODS: PCNA, Fas and Bcl-2 protein expression were analysed using an avidin-biotin immunoperoxidase method. Apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick-end labelling (TUNEL) method. RESULTS: PCNA, immunolocalized both in the nuclei of endometrial glands and stroma was less abundant 3 months after insertion (P < 0.05). Bcl-2 protein, immunolocalized in the cytoplasm of endometrial glands but not in the stroma, became scanty 3 months after insertion. Fas antigen, immunolocalized only in endometrial glands before insertion, became prominent in both endometrial glands and stroma 3 months after insertion. The apoptosis-positive rate of the nuclei in both endometrial glands and stroma was significantly higher 3 months after insertion relative to that before insertion (P < 0.05). CONCLUSIONS: LNg-IUS resulted in a decrease in endometrial proliferation and an increase in apoptosis in endometrial glands and stroma. The increase in apoptosis associated with increased Fas antigen expression and decreased Bcl-2 protein expression in the endometrium may be one of the underlying molecular mechanisms by which LNg-IUS insertion causes the atrophic change of the endometrium.

Adult↗
PubMed2001

Super high-dose intraarterial cisplatin infusion under percutaneous pelvic perfusion with extracorporeal chemofiltration for advanced uterine cervical carcinoma: I. Analysis for pharmacokinetics, tumor response, and toxicity of platinum.

The present study was designed to elucidate the clinical feasibility of a new intraarterial infusion system with an extracorporeal charcoal chemofiltration circuit, which is expected to achieve a super high-dose cisplatin pelvic perfusion with a limited systemic exposure to platinum. After inferior vena cava isolation was percutaneously achieved by balloon catheter technique, cisplatin (140-240 mg/m2) was administered by selective intrauterine arterial infusion, with inferior and superior gluteal arterial embolization. The platinum-containing blood was pumped through an extracorporeal charcoal chemofiltration circuit. Pharmacokinetics, tumor response, and toxicity of platinum under this system were studied in 14 patients with locally advanced uterine cervical carcinoma. Extracorporeal charcoal filters significantly (p < 0.05) reduced the prefilter area under concentration-time curve of plasma-free platinum by 86.7 +/- 5.2% at postfilter site and 76.3 +/- 6.6% at peripheral circulation, respectively. Although all adverse effects were mild under this system, tumor response and tissue platinum concentrations were augmented dose dependently with the administration of cisplatin. The extracorporeal chemofiltration system achieved a super high-dose cisplatin pelvic perfusion with the minimal adverse effects, allowing further cisplatin dose escalation with further augmented tumor response. This will contribute to the reduction in the extent of disease of locally advanced uterine cervical carcinoma.

Adenocarcinoma↗
PubMed2001

Super high-dose intraarterial cisplatin infusion under percutaneous pelvic perfusion with extracorporeal chemofiltration for advanced uterine cervical carcinoma: II. Its impact on clinical response and subsequent surgery.

The present pilot study was conducted to investigate the clinical efficacy of super high-dose intraarterial cisplatin infusion with percutaneous pelvic perfusion under extracorporeal chemofiltration (PPPEC) for locally advanced uterine cervical carcinoma. Cisplatin (140-240 mg/m2) was infused in uterine arteries in a neoadjuvant setting in 20 patients under the PPPEC system twice during a 2-week interval. Fourteen of 17 patients in whom reduction of the disease (tumor downstaging) was confirmed underwent radical surgery. Despite the tumor downstaging, the remaining three patients had poor PS and the other three showed insufficient stage regression. Clinical responses, histologic responses, and surgical review were studied. The rate of overall tumor response (complete response plus partial response), tumor downstaging, overall histologic response, and radical surgery performance after the second course of PPPEC were 95.0%, 85.0%, 95.0%, and 70.0%, respectively. Curative surgery, defined as negative carcinoma cells in surgical margins, was achieved in 85.7% of the cases, whereas the rate of complete surgery defined as negative carcinoma cells both in surgical margins and regional lymph nodes was 42.9%. With 42 months of median follow-up time, 3 of the 14 surgical patients died of the original disease, and the remaining 9 patients are in recurrence-free survival, whereas 2 patients are alive with disease. PPPEC achieved a high frequency of rapid tumor downstaging of locally advanced uterine cervical carcinoma without severe adverse effects and resulted in the favorable performance of the subsequent radical surgery and prognosis.

Adenocarcinoma↗
PubMed2001

Up-regulation by IGF-I of proliferating cell nuclear antigen and Bcl-2 protein expression in human uterine leiomyoma cells.

IGF-I has been reported to play a role in regulating proliferation of human leiomyoma cells. There is, however, little evidence to suggest that IGF-I inhibits apoptosis in the leiomyoma cells. The present study was conducted to elucidate whether IGF-I affects apoptosis and Bcl-2 protein expression, an apoptosis-inhibiting gene product, in cultured leiomyoma cells. In addition, we examined the effect of IGF-I on proliferating cell nuclear antigen (PCNA) expression in cultured leiomyoma cells. Isolated human leiomyoma cells were subcultured in phenol red-free DMEM supplemented with 10% FBS for 120 h and then stepped down to serum-free conditions for an additional 72 h in the absence or presence of graded concentrations of IGF-I (1.0, 10, and 100 ng/ml). The effects of IGF-I on Bcl-2 protein and PCNA expression in cultured leiomyoma cells were assessed by Western immunoblot analysis and immunocytochemical staining, whereas the effects of IGF-I on the cell viability and apoptosis of the cultured cells were determined by 3-(4,5-dimethylatriazol-2-yl)-2,5diphenyltetrasodium bromide (MTT) assay and terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling assay, respectively. Immunocytochemical staining demonstrated that IGF-I treatment resulted in the increase in PCNA labeling index in cultured leiomyoma cells in a dose-dependent manner. Immunoblot analysis of proteins extracted from the cultured leiomyoma cells revealed that the addition of IGF-I (10 and 100 ng/ml) significantly increased the expression of 35-kDa immunoreactive PCNA and 26-kDa Bcl-2 protein, compared with those in control cultures. Cell survival and proliferation of cultured leiomyoma cells, assessed by MTT assay, was significantly augmented by IGF-I treatment, compared with those of control cultures. Terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling assay showed that the apoptosis-positive rate of leiomyoma cells treated with IGF-I was significantly decreased, compared with that in control cultures. The present results suggest that IGF-I plays crucial roles in leiomyoma cell growth, not only in promoting the proliferative potential by up-regulation of PCNA expression but also in down-regulating apoptosis by up-regulation of Bcl-2 protein expression in leiomyoma cells.

Adult↗
PubMed2001

Tumor necrosis factor-alpha expression in human uterine leiomyoma and its down-regulation by progesterone.

Although tumor necrosis factor-alpha (TNFalpha) has been shown mainly to inhibit proliferation and induce apoptosis in a variety of cells, no information is available regarding whether human leiomyoma cells express TNFalpha. In the present study, we examined the expression of TNFalpha in leiomyomas, in comparison with that in the adjacent normal myometrium, using immunohistochemical staining and Western immunoblot analysis with a polyclonal antibody to human TNFalpha. Furthermore, we investigated the effect of sex steroid hormones on TNFalpha expression in leiomyoma cells cultured under serum-free, phenol red-free conditions. Immunohistochemical staining showed that TNFalpha expression in leiomyoma cells was higher than that in the adjacent normal myometrial cells, being more abundant in the proliferative phase than in the secretory, progesterone (P4)-dominated, phase of the menstrual cycle. TNFalpha expression in leiomyoma cells in pregnant uterus was scarce. Western immunoblot analyses of leiomyoma and normal myometrial tissue extracts revealed that TNFalpha, with a molecular mass of 17.3 kDa, was abundantly present in leiomyoma tissue extracts, relative to normal myometrial tissue extracts, and that TNFalpha expression in leiomyoma cells was most abundant in the proliferative phase of the menstrual cycle, less abundant in the secretory phase, and least abundant in pregnant uterus; whereas no such changes in TNFalpha expression were noted in the normal myometrium. In monolayer cultures of uterine leiomyoma cells under serum-free conditions, addition of P4 (3.18 x 10(-7) mol/L) resulted in a decrease in TNFalpha expression in the cells, relative to that in control cultures, whereas treatment with 17beta-estradiol (3.67 x 10(-8) mol/L) did not affect the TNFalpha expression in the cells. The concentrations of sex steroids used were within the physiological tissue concentrations noted in leiomyoma and myometrium. The present results suggest that the abundant expression of TNFalpha may be a molecular basis characteristic of leiomyomas in the human uterus and that P4 may play a vital role in down-regulating the expression of TNFalpha in human uterine leiomyoma.

Adult↗
PubMed2001

Expression of adrenomedullin by human placental cytotrophoblasts and choriocarcinoma JAr cells.

Adrenomedullin is a multifunctional peptide expressed in a variety of tissues. This study was conducted to investigate the expression of adrenomedullin and its mRNA by human trophoblasts and the possible existence of adrenomedullin receptor in those cells. Human placentas in all three trimesters were obtained from patients undergoing therapeutic abortions and deliveries. Total RNA was extracted from placental trophoblastic tissues and JAr choriocarcinoma cells, and the expression of adrenomedullin mRNA was determined by RT-PCR. Immunohistochemical analysis was performed by the avidin/biotin immunoperoxidase method using a specific antibody to adrenomedullin. The secretion of adrenomedullin by JAr cells cultured in medium containing [35S]cysteine-[35S]methionine was determined by immunoprecipitation followed by PAGE. The presence of adrenomedullin receptor in JAr cells was examined using a binding assay with [125I]rat adrenomedullin. Adrenomedullin mRNA was expressed by human placental trophoblastic tissues in all three trimesters and by JAr cells. Immunohistochemical analysis revealed that adrenomedullin is expressed by cytotrophoblasts in placentas in all three trimesters, but not by syncytiotrophoblasts. The expression of adrenomedullin in the cytotrophoblast was most abundant in first trimester placenta and became less abundant during the course of pregnancy. JAr cells synthesized and secreted immunoreactive adrenomedullin. Binding assay with [125I]rat adrenomedullin demonstrated specific binding of adrenomedullin to JAr cells, indicating the existence of a specific receptor for adrenomedullin in trophoblastic cells. Adrenomedullin is transcribed and secreted by cytotrophoblastic cells that possess adrenomedullin receptor. Adrenomedullin may play a potential role as an autocrine/paracrine factor in the growth of cytotrophoblasts, especially in early gestation.

Adrenomedullin↗
PubMed2001

Abundant expression of platelet-derived growth factor in spiral arteries in decidua associated with pregnancy-induced hypertension and its relevance to atherosis.

OBJECTIVE: To elucidate the role of platelet-derived growth factor (PDGF) in the pathophysiology of pregnancy-induced hypertension (PIH) in which the spiral arteries of the decidua demonstrate the atherosclerotic change. DESIGN AND METHODS: We determined serum levels of PDGF and PDGF expression in the decidua as well as serum levels of 17 beta-estradiol (E2) and progesterone (P4) both in normotensive cases and in PIH cases. Furthermore, we investigated whether sex steroid hormones could interact with PDGF in cultured vascular smooth muscle cells (SMC) by immunohistochemical staining for proliferating cell nuclear antigen. RESULTS: Serum PDGF levels were higher (P<0.01) but serum E2 levels were lower (P<0.01) in PIH cases compared with normotensive cases. There was no statistically significant difference between serum P4 levels in PIH cases and those in normotensive cases. Immunohistochemical staining for PDGF in SMC of spiral arteries was more prominent in PIH cases than in normotensive cases. The proliferative potential of cultured SMC was stimulated by PDGF, but inhibited by concomitant treatment with PDGF and E2. CONCLUSIONS: PDGF is suggested to play an important role in the pathophysiology of PIH through its stimulatory effect on vascular SMC proliferation which may elicit the atherosclerotic change in the spiral arteries of the placenta.

Adult↗
PubMed2001

Outcome of surgery in 124 cases of Duane's Retraction Syndrome (DRS) treated by intraoperatively graduated recession of the medial rectus for esotropic DRS, and of the lateral rectus for exotropic DRS.

PURPOSE: To determine the outcome and effectiveness of simple horizontal muscle recession surgery in Duane's Retraction Syndrome (DRS). CASES & METHODS: A total of 194 cases of DRS were operated on by us during the past 25 years. Surgery was aimed at improving the binocular alignment and eye position at the primary position as well as any abnormal head posture. Sufficient data were available in 124 cases. Recession of the medial rectus muscle was performed on 76 cases with esotropia and of the lateral rectus on 48 cases with exotropia. Recession dosage was determined during surgery based on three factors: size of the preoperative strabismus in primary position; forced ductions/resistance to traction, and the appearance of the rectus muscle at surgery. RESULTS: Both the primary eye position and the abnormal head posture were satisfactorily improved in 119 cases (89%) after surgery with a result rated "excellent" or "good" by a residual deviation of 7 degrees or less and a definitely improved abnormal head posture, for all types of DRS deviations. CONCLUSION: Recession of the appropriate horizontal rectus muscle is a safe and effective primary procedure for both the primary deviation and abnormal head posture in all types of DRS.

Adolescent↗
PubMed2001

Outcome of surgery for congenital fibrosis of the inferior rectus muscle.

PURPOSE: To report clinical findings and surgical outcome in a large series of patients with fibrosis of the inferior rectus muscle. MATERIALS AND METHODS: Subject Cases: A total of 17 cases were diagnosed with unilateral fibrosis of the inferior rectus muscle during the past 27 years at our institution. They were aged from 5 months to 17 years, with 15 cases under 10 years of age. No differences were present regarding the laterality or gender. FINDINGS: All the cases showed hypotropia with restricted eye elevation. Forced duction test showed resistance to upward eye movement. A horizontal deviation in primary eye position was also present in 10 cases (59%). The affected eye was amblyopic in the majority of cases. Binocular vision was absent in 15 of the 17 cases. RESULTS: Surgical Outcome: All the cases received either recession or free tenotomy of the inferior rectus muscle. Resection of the ipsilateral superior rectus muscle was additionally performed to correct residual hypotropia. Fibrosis of the inferior rectus was present as intraoperative finding in all the 17 cases. Hypotropia disappeared in 10 cases and decreased in 7 cases. Restoration of satisfactory binocular alignment was obtained in all the 17 cases. CONCLUSION: Recession of the inferior rectus muscle was effective treatment for fibrosis of the inferior rectus. Additional resection of the ipsilateral superior rectus muscle was useful to correct residual hypotropia. Free tenotomy is not recommended.

Adolescent↗
PubMed2001

Rupture of the spleen as an unusual complication of laparoscopy. A case report.

BACKGROUND: Laparoscopic surgery has many advantages but is not without complications, such as viscus perforation and intraabdominal hemorrhage. CASE: A rare and severe complication, massive abdominal bleeding due to splenic rupture, became symptomatic after an uneventful laparoscopy. Tearing away of delicate peritoneal reflections or small adhesions on the splenic capsule due to induction of pneumoperitoneum can result in sudden rupture and hemorrhage. CONCLUSION: This possibility should be remembered when laparoscopy is necessary in patients with a history of blunt abdominal trauma.

Abdominal Injuries↗
PubMed2001

Intermittent exotropia surgery in children: long term outcome regarding changes in binocular alignment. A study of 666 cases.

PURPOSE: To review and determine the long term outcome of surgery for intermittent exotropia in children. CASES: A total of 666 cases were reviewed. They were 15 years old or younger and underwent surgery for intermittent exotropia during the preceding 22 years. Bilateral recession of the lateral rectus muscles was performed in 349 cases. Unilateral recession of the lateral rectus and resection of the medial rectus muscles was performed in 298 cases. One and four muscle procedures were performed in 19 cases. The outcome was evaluated at 1 month and 4 years after surgery. RESULTS: Orthotropia or mini-microtropia was achieved in 401 patients (60.2%) one month after surgery. Bilateral recession of the lateral rectus muscles was more effective than unilateral recession- resection. Out of these 401 patients, half, 199 patients (49.6%) showed orthotropia or mini-microtropia 4 years after surgery while the other half, 202 (50.4%), became exotropic. Bilateral recession of the lateral rectus muscles was also more effective in producing orthotropia or mini-microtropia on a long term basis than unilateral recession-resection. The rate of orthotropia or mini- microtropia was higher when the patients were operated before 3 years and after 11 years of age. CONCLUSIONS: There was a strong tendency for intermittent exotropia to recurr and drift into permanent exotropia during 4 or more years following surgery. It is advocated to aim at orthotropia during the immediate post- surgical period and to avoid overcorrection. Early surgery is not necessary when the patient is over 4 years of age. Bilateral lateral rectus recession is the preferred surgical procedure.

Adolescent↗
PubMed2001

Regulation of human trophoblast proliferation and apoptosis during pregnancy.

In order to elucidate the regulation of human placental growth during pregnancy, we have assessed PCNA expression, apoptosis and Bcl-2 protein expression in placental trophoblasts over the course of pregnancy. PCNA, Bcl-2 protein and Fas antigen expression were examined by the avidin/biotin immunoperoxidase method, while apoptosis was assessed by in situ DNA 3'-end labeling method. Both PCNA expression and apoptotic DNA fragmentation were noted in cytotrophoblasts (C-cells), being most abundant in very early placenta, less abundant in midterm placenta and least abundant in term placenta. In contrast, Bcl-2 protein expression was noted in syncytiotrophoblasts (S-cells), being least abundant in very early placenta, less abundant in midterm placenta and most abundant in term placenta. These results indicate that very early placenta is characterized by highly proliferative activity of C-cells associated with increased occurrence of apoptosis. Since Bcl-2 protein is an apoptosis-inhibiting gene product, the minimal occurrence of apoptosis in term placenta seems likely to be attributable to the increased expression of Bcl-2 protein in S-cell in term placenta. On the other hand, in extravillous trophoblasts on cell columns, both PCNA and Bcl-2 protein expression were pronounced only in the shallower part, while Fas/Fas ligand expression and apoptosis were prominent in the deeper part. Thus, it seems likely that Bcl-2 protein expression also participates in the regulation of extravillous trophoblast apoptosis.

Apoptosis↗
PubMed2000

Screening of BRCA1 mutation using immunohistochemical staining with C-terminal and N-terminal antibodies in familial ovarian cancers.

We examined the subcellular localization of BRCA1 proteins using immunohistochemical staining with C-terminal (GLK-2 antibody) and N-terminal (Ab-2 antibody) monoclonal antibodies in 44 familial ovarian cancers. Among these, 24 cases were associated with 13 independent germ-line mutations of BRCA1, and loss of heterozygosity (LOH) at one or more BRCA1 microsatellite markers was found in all 21 informative tumors tested. With GLK-2 antibody, cytoplasmic staining was observed in 15 of 16 tumors (93.8%) with mutation in exon 11, and BRCA1 staining was absent in 8 of 8 tumors (100%) with mutation in exons other than exon 11. When immunohistochemical staining was performed with Ab-2 antibody, both nuclear and cytoplasmic staining were observed in 14 of 16 tumors (87.5%) with mutation in exon 11. Interestingly, nuclear staining was observed in 3 of 3 tumors (100%) with mutation downstream of exon 11, even though no staining was detected in 5 of 5 tumors (100%) with mutation upstream of exon 11. On the other hand, in familial ovarian cancers without BRCA1 mutations, nuclear staining or both nuclear and cytoplasmic staining was observed in 18 of 20 specimens (90%) and 20 of 20 specimens (100%) with GLK-2 antibody and with Ab-2 antibody, respectively. These results suggest that an immunohistochemical assay in combination with employing the C-terminal and the N-terminal antibodies appears to have potential as a reliable and useful technique for the screening of BRCA1 mutations, at least to predict the status of mutation, upstream or downstream of exon 11.

BRCA1 Protein↗
PubMed2000

Antenatal use of ambroxol for the prevention of infant respiratory distress syndrome.

OBJECTIVE: Our purpose was to evaluate the efficacy and safety of ambroxol for the prenatal prophylaxis of infant respiratory distress syndrome (IRDS). STUDY DESIGN: This was a prospective study with 2 groups of pregnant patients with premature labor or with premature rupture of membranes at an estimated gestation between 27 to 34 completed weeks. Ambroxol treatment group consisted of 39 subjects in whom 1,000 mg of ambroxol diluted in 500 ml of 5% glucose solution was given intravenously for 4 hours once a day for 3 days, while the control group consisted of 41 subjects in whom ambroxol was not administered. Main measures included Apgar scores, clinical signs of one or more of the following: respiratory rate of > 60/min, intercostal retraction, alar flaring, expiratory grunting, cyanosis on room air and radiological evidence of IRDS. Chi-square test was used to determine the statistical significance of the results. RESULTS: Tolerable maternal side effects were noted. Profile of newborns delivered were similar in both groups. Incidence of IRDS was significantly less in the treatment group (p < 0.01). CONCLUSIONS: Antenatal administration of ambroxol resulted in a significant decrease in the incidence of IRDS as well as perinatal morbidity and mortality. Due to the efficacy and safety of this drug, it might be useful for the prevention of IRDS.

Adult↗
PubMed2000

Adrenomedullin expression in the human endometrium.

Immunohistochemical studies were performed using a specific antibody to human adrenomedullin (AM) to determine its presence and cellular localization in the human endometrium, in the different phases of the menstrual cycle, and in the postmenopausal period. Specimens were obtained from 21 patients who underwent abdominal hysterectomy for various reasons. The endometrium had no pathological lesion in all cases. In the early and mid proliferative phases of the menstrual cycle, no immunostaining for AM was noted in the endometrium. AM immunostaining in the endometrium became apparent in the late proliferative phase. The staining intensity of AM in the endometrium became more abundant in the secretory phase. No appreciable difference in the staining intensity of AM in the endometrium was noted among early, mid, and late secretory phases. Immunostaining for AM was evident in both the epithelial and stromal compartments of the endometrium. In the postmenopausal endometrium, there was intense immunostaining for AM only in the stromal compartment. This is the first study to demonstrate the expression of AM in the endometrium in relation to the menstrual cycle. The results obtained suggest the participation of AM in the growth and differentiation of the endometrium.

Adrenomedullin↗
PubMed2000

Comparative analysis of the effects of gonadotropin-releasing hormone agonist on the proliferative activity, apoptosis, and steroidogenesis in cultured porcine granulosa cells at varying stages of follicular growth.

This study was conducted to analyze comparative effects of gonadropin-releasing hormone (GnRH) agonist on the proliferation, apoptosis, and differentiated function of cultured porcine granulosa cells from varying follicle stages. Comparative analyses of porcine granulosa cells from varying follicle stages to respond to GnRH agonist were performed in terms of proliferating cell nuclear antigen (PCNA) expression, occurrence of apoptosis, and 17beta-estradiol (E2) and progesterone (P) secretion. PCNA expression was examined by the avidin/biotin immunoperoxidase method with a monoclonal antibody to PCNA, and apoptosis was assessed by in situ DNA 3'-end labeling method and DNA fragmentation analysis. E2 and P were measured by radioimmunoassays. The PCNA positive rate of granulosa cells cultured in the presence of GnRH agonist (10(-9) M) was lower compared with that of cells cultured in the absence of GnRH agonist. However, the apoptosis positive rate was higher, and E2 and P secretion by cultured granulosa cells was lower in the presence of GnRH agonist (10(-9) M) compared with that in the absence of GnRH agonist. The inhibitory effect of GnRH agonist on PCNA positive rate of cultured cells was prominent in granulosa cells from small and medium but not from large follicles. By contrast, the inhibitory effect of GnRH agonist on E2 and P secretion by cultured cells was prominent in granulosa cells from large but not small and medium follicles. The stimulatory effect of GnRH agonist on apoptosis positive rate of cultured cells was, however, uniform regardless of the stages of follicular growth. These results demonstrate that GnRH agonist exerts diverse actions on granulosa cells over the course of follicular growth. One downregulates granulosa proliferation in immature follicles as well as steroidogenesis in mature follicles, and the other upregulates apoptosis of granulosa cells regardless of the stages of follicular growth.

Animals↗
PubMed2000

Changes in proliferative potential, apoptosis and Bcl-2 protein expression in cytotrophoblasts and syncytiotrophoblast in human placenta over the course of pregnancy.

In order to evaluate placental trophoblast proliferation and apoptosis during pregnancy, we investigated proliferating cell nuclear antigen (PCNA) expression, apoptosis and Bcl-2 protein expression in the human placenta using avidin/biotin immunoperoxidase method to examine PCNA and Bcl-2 protein expression, and TUNEL method to assess apoptosis. The appearance of apoptotic cells in very early term placental trophoblasts was also examined by transmission electron microscopy. PCNA was immunolocalized in the nuclei of cytotrophoblasts (C-cells). Determination of the mean percentage of PCNA-positive nuclei of C-cells revealed that PCNA expression in C-cells was highest in very early term (4th to 5th wk) placentas and significantly decreased with the advance of pregnancy. Bcl-2 protein was immunolocalized in the cytoplasm of syncytiotrophoblast (S-cell), being least abundant in very early term placentas, less abundant in early term and midterm placentas, and most abundant in term placentas. On the basis of TUNEL method, apoptosis was apparent in the nuclei of both C-cells and S-cell. The apoptosis positive rate of C-cell nuclei was highest in very early term 4th to 5th wk placentas, and significantly decreased in early term 7th to 9th wk and midterm placentas, but somewhat increased in term placentas compared to that in midterm placentas. On the other hand, apoptosis positive rate of S-cell nuclei was remarkably higher only in very early term 4th to 5th wk placentas compared to that in early term, midterm and term placentas. Transmission electron microscopy revealed the appearance of apoptotic nucleus in very early term placental trophoblasts. These results demonstrate for the first time that apoptosis in the human normal placenta predominates in both C-cells and S-cell in very early term 4th to 5th wk pregnancy and drastically diminished after 7th wk of pregnancy. An apparent increase in apoptosis in C-cells in term placentas compared to that in midterm placentas may reflect aging of the placenta or parturition-associated biological change. The abundant expression of Bcl-2 protein in S-cell in term placentas may be responsible for the diminished occurrence of apoptosis in S-cell in term placentas.

Abortion, Induced↗