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Biomedical subjects

Toshinobu Tanaka

Publications and source records attributed to Toshinobu Tanaka.

At least 19 recordsLinked to original sources

Arias-Stella reaction in an adenomyomatous polyp of the uterus.

We describe a rare case of an Arias-Stella reaction in an adenomyomatous polyp of the endometrium found in the first trimester of pregnancy. A 33-year-old Japanese woman, gravida 1, para 1, presented for an initial prenatal examination at 6-week gestation; ultrasound revealed a myoma-like solid mass in the cervical canal. An abnormal Papanicolaou's smear (highly suspicious of adenocarcinoma) prompted the resection of this pedunculated polyp. Histologically, the musculature located in the center of the polyp was covered by the endometrium; numerous glands within both the endometrium and the musculature exhibited an Arias-Stella reaction. This explains the result of Papanicolaou's smear, because subsequent smears - both intrapartum and postpartum - were negative. To our knowledge, this is the first reported incident of an Arias-Stella reaction in an adenomyomatous polyp. This could be one of the diagnostic pitfalls in Papanicolaou's smears taken during pregnancy.

Adenocarcinoma↗

Intestinal surgery in advanced ovarian cancer.

PURPOSE OF REVIEW: This review examines the current role of intestinal surgery in advanced ovarian cancer. Institutions differ considerably in surgical procedures and therapeutic outcomes for this disease. Moreover, therapeutic outcomes are influenced by the inclusion criteria for surgical procedures and the degree of surgical completion. We discuss the role of intestinal surgery and suggest surgical indications for intestinal surgery in advanced ovarian cancer. RECENT FINDINGS: Prognosis in advanced ovarian cancer is better when there is a smaller postoperative tumor mass. However, it is necessary to investigate the effects of intestinal surgery on residual tumor mass and its prognostic benefits. Here, recent reports were reviewed to ascertain the usefulness and safety of intestinal surgery for advanced ovarian cancer and examine surgical indications and institutional requirements. SUMMARY: By performing aggressive intestinal surgery such as combined bowel resection, optimal cytoreductive surgery can be performed in 70-98% of cases. The morbidity associated with intestinal surgery is acceptably low. Prognostic benefits for intestinal surgery are clear in patients with operable ovarian cancer with no residual disease. Women with suspected ovarian cancer should therefore be referred to centers with experienced tumor surgeons.

Colectomy↗

Tumor necrosis factor regulation of apoptosis in mouse preimplantation embryos and its antagonism by transforming growth factor alpha/phosphatidylionsitol 3-kinase signaling system.

Survival and apoptosis of cells in preimplantation embryos are fundamental for successful pregnancy. Relevant to these processes, tumor necrosis factor (TNF) and transforming growth factor alpha (TGFA) are produced by mammalian oviducts and uteri. In early embryos, TNF induces apoptosis, whereas TGFA could act as a survival factor. Here we investigated the TNF regulation of apoptosis in early mouse embryos and its antagonism by TGFA. TNF receptor superfamily, member 1a mRNA was detectable throughout early embryonic stages, with an increase after the early blastocyst stage, whereas the expression of TNF receptor superfamily, member 1b transcripts were detected only at the expanded blastocyst stage. Although pregnant uteri produced TNF, physiologic levels were low during the preimplantation period. Treatment with TNF inhibited the development of two-cell stage embryos to blastocysts showing decreased proliferation and increased apoptosis both in vitro and in vivo. These detrimental effects of TNF on early embryo development and survival were blocked by a neutralizing anti-TNF antibody. In addition to the death receptor-mediated pathway, TNF-induced apoptosis was further mediated by disruption of mitochondrial functions, characterized by release of cytochrome c and activation of caspase 9. The proapoptotic effects of TNF in blastocysts were counteracted by cotreatment with TGFA. The antagonistic effect of TGFA on TNF-induced apoptosis was blocked by phosphatidylionsitol 3-kinase (PI3K) inhibitors. The present findings demonstrate the stage-selective susceptibility to the apoptosis-inducing effect of TNF in mouse preimplantation embryos and that the TGFA/PI3K signaling system has an important role in the control of TNF-induced apoptosis in blastocysts.

Animals↗

Can we omit para-aorta lymph node dissection in endometrial cancer?

BACKGROUND: Patients with endometrial cancer can present with various complicating illnesses, including obesity, diabetes mellitus, hypertension and advanced aging. These patients are at high risk of severe post-operative complications. Thus, the question of whether or not to perform systemic pelvic and para-aortic lymphadenectomy remains controversial for all patients. It is reported that external iliac lymph nodes are the most commonly involved lymph nodes in endometrial cancer, and para-aortic lymph node (PAN) metastases spread via a route shared by the common iliac lymph nodes. The aim of this study was to evaluate the potential efficacy of omitting PAN dissection when metastasis of the common iliac and external iliac lymph nodes is negative. METHODS: Between January 1994 and June 2004, a total of 101 patients at Akita University Hospital who had undergone total hysterectomy and bilateral salpingo-oophorectomy, total pelvic lymphadenectomy and para-aortic lymphadenectomy to the level of the renal vein for endometrial cancer were enrolled in this study. RESULTS: Eleven patients in all were found to have metastasis for PANs. Among 13 patients with common and/or external iliac positive lymph nodes, 10 showed PAN metastasis. Of the 88 patients with negative lymph nodes, 87 showed no PAN metastasis. Based on these data, common and/or external iliac lymph nodes had 90.9% sensitivity (10/11) and 96.7% specificity (87/90) for detecting PAN metastasis. CONCLUSION: Para-aortic lymphadenectomy might be avoided by the negativity of such lymph nodes, thereby minimizing post-operative complications.

Adenocarcinoma, Clear Cell↗

Adenofibroma of the endometrium protruding into the vaginal cavity: findings on transvaginal ultrasonography, MRI and CT.

Adenofibroma is a rare benign biphasic neoplasm that is classified into the mixed epithelial and mesenchymal tumor group. We report the case of a 42-year-old woman with adenofibroma of the endometrium protruding into the vagina. Transvaginal ultrasonography revealed the tumor as an intravaginal mass containing multiple cystic components. Magnetic resonance imaging (MRI) showed a heterogeneous high-intensity mass filling the vaginal cavity on T2-weighted imaging, with a low-contrast enhanced septum identified within the mass on gadolinium-enhanced, T1-weighted imaging. Contrast-enhanced computed tomography (CT) showed a heterogeneous low-attenuating multicystic mass filling the vaginal cavity. Although preoperative diagnosis of this rare tumor is very difficult, the combination of MRI, CT, and ultrasonography offers a useful diagnostic tool.

Adenofibroma↗

Real-time quantitative RT-PCR detection of disseminated endometrial tumor cells in peripheral blood and lymph nodes using the LightCycler System.

OBJECTIVE: Some endometrial cancer patients without clinical evidence of extrauterine spread die as a result of recurrence even after curative operation. These recurrences may arise from occult tumor cells that are not detected by conventional methods. The goal of this study was to develop a quantitative method for the detection of disseminated tumor cells (DTCs) in the peripheral blood (PB) and lymph nodes (LNs) of patients with endometrial cancer. METHODS: Ninety-eight PB samples from 30 patients and 218 LNs from 14 patients were studied. Real-time quantitative analysis was performed using a LightCycler instrument and a TaqMan probe for cytokeratin 19 (CK19) as a marker gene. RESULTS: This method resulted in the reproducible quantitation of 10 to 10(6) MCF-7 cells (CK19-expressing breast cancer cell line) per 10(6) peripheral blood nucleated cells. CK19 mRNA expression was detected in 28 PB samples and in 62 LNs. Only three preoperative PB samples and one postoperative PB sample (from four patients) and 33 LNs (from six patients) were PCR-positive. The PCR-positive rate of LNs was higher in patients with pathologically metastatic (path-positive) LNs than in patients with path-negative but PCR-positive LNs. Furthermore, the CK19 mRNA background expression rate was higher in the LNs of path-negative but PCR-positive patients than in LNs of path-negative and PCR-negative patients. CONCLUSIONS: Real-time qRT-PCR with TaqMan probes is a sensitive, specific and rapid method for the detection of DTCs in PB and LNs. Additional studies with larger numbers of patients and adequate follow-up would be of benefit.

Aged↗

Expression of CD44 mRNA induced by interleukin-1beta in human cultured uterine cervical fibroblasts.

OBJECTIVE: Hyaluronic acid in the cervix plays an important role in the process of cervical ripening. CD44 is a receptor for hyaluronic acid. We investigated whether CD44 is related to cervical ripening by examining the expression of CD44 mRNA in human cultured cervical fibroblasts with or without inflammatory cytokines. STUDY DESIGN: CD44 mRNA expressions derived from cultured human uterine cervical fibroblasts in the presence or absence of interleukin-1beta (IL-1beta) (1-100 pg/ml) or interleukin-8 (IL-8) (1-100 ng/ml) were analyzed by the Northern blot analysis. The human CD44 cDNA probe was hybridized with three species of mRNA. Sizes of the mRNAs were 1.6, 2.2, and 5.0 kilobases (kb). RESULTS: Interleukin-1beta stimulated the expression of CD44 mRNA in a dose-dependent manner. Interleukin-8 did not stimulate the expression. CONCLUSIONS: It is concluded from the present study that human cervical CD44 mRNA expression is induced by interleukin-1beta. Accordingly, we deduce that the concentration of hyaluronic acid in the cervical tissue is increased because of the expression of CD44.

Cells, Cultured↗

Survivin contributes to the anti-apoptotic activities of transforming growth factor alpha in mouse blastocysts through phosphatidylinositol 3'-kinase pathway.

Transforming growth factor alpha (TGFA) is produced by epithelial cells in the oviducts and uteri and has the potential to act as an anti-apoptotic factor on preimplantation embryos expressing its receptor. Previously, we demonstrated that survivin (also known as BIRC5), an anti-apoptotic gene expressed in mouse preimplantation embryos, protects embryos from apoptosis. In this study, we investigated the role of survivin on TGFA-mediated inhibition of apoptosis in mouse blastocysts. Under the suboptimal conditions produced by single embryo culture, blastocysts showed an increase of apoptosis that correlated with a decrease of survivin expression. TGFA treatment significantly decreased apoptosis and increased the levels of survivin mRNA in a dose-dependent manner in blastocyst, and conversely, these activities were neutralized by an anti-TGFA antibody. Antibody treatment alone exerted little effect on either the occurrence of apoptosis or the levels of survivin mRNA. Upregulation of survivin expression by TGFA treatment was insignificant before the blastocyst stage. Using an antisense approach, we examined whether upregulation of survivin is responsible for the anti-apoptotic effect of TGFA in blastocysts. Apoptosis was inhibited by TGFA treatment in blastocysts, but the effect was abrogated by cotreatment with antisense oligonucleotides directed against survivin. These data suggest that survivin contributes to the anti-apoptotic activities of TGFA in blastocysts. We also found that the upregulation of survivin expression was mediated by activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Thus, TGFA inhibits apoptosis in mouse blastocysts through upregulation of survivin expression via the PI3K pathway.

Animals↗

Gonadotropin-releasing hormone I analog acts as an antiapoptotic factor in mouse blastocysts.

Both GnRH-I and its receptor (GnRHR)-I have been shown to be expressed in the mammalian preimplantation embryo. In this study, we investigated the molecular mechanisms of GnRH-I in the regulation of early embryonic development in mouse. We found that GnRH-I and GnRHR-I mRNAs were detectable throughout early embryonic stages and that expression levels of both increased significantly after the early blastocyst stage. In blastocysts, GnRH-I and GnRHR-I expression was detected in both inner cell mass and trophectoderm cells. The pregnant uterus also expressed both genes, suggesting that preimplantation embryos could be affected by GnRH through both paracrine and autocrine signaling. Treatment with GnRH-I agonist, buserelin, promoted development of two-cell-stage embryos to the expanded and hatched blastocyst stages and inhibited apoptosis in a dose-dependent manner. In contrast, treatment with GnRH-I antagonist, ganirelix acetate, inhibited development of preimplantation embryos beyond the expanded blastocyst stage and induced apoptosis; both effects could be reversed by cotreatment with GnRH-I agonist. GnRH-I antagonist-induced cell death was mediated by disruption of mitochondrial function, release of cytochrome c, and activation of caspase-3. Furthermore, treatment with GnRH-I antagonist decreased expression of two antiapoptotic growth factors, epidermal growth factor and IGF-II, in blastocysts. These results indicate that GnRH-I, acting as an antiapoptotic factor, is an important growth factor in development of mouse blastocysts.

Animals↗

Roles of forkhead transcription factor Foxc2 (MFH-1) and endothelin receptor A in cardiovascular morphogenesis.

OBJECTIVE: Foxc2/MFH-1 is a member of the forkhead family of transcription factors and Foxc2-deficient mice exhibit aortic arch anomalies (type B interruption of the aortic arch). Endothelin receptor type-A (ETA) is one of the two known endothelin receptors that belong to the G-protein-coupled receptor family. ETA-deficient mice show defects in the great arteries, primarily type B interruption of the aortic arch. Based on similar phenotypes in the cardiovascular system of Foxc2- and ETA-deficient mice, we investigated whether Foxc2 and ETA have a close relationship in aortic arch patterning. METHODS: The Foxc2 and ETA homozygotes were obtained by crossing the Foxc2 and ETA heterozygotes, respectively. The double Foxc2/ETA homozygotes were obtained by crossing the double Foxc2/ETA heterozygotes. RESULTS: We investigated the expression of ETA in Foxc2-null mice and the expression of Foxc2 in ETA-null mice and found that the absence of either Foxc2 or ETA had no effect on the expression of the other. Next, we analyzed mice lacking both Foxc2 and ETA to examine the relationship between Foxc2 and ETA on aortic arch patterning in vivo. We found that the majority of Foxc2/ETA double-mutant embryos died around 11.5 dpc and that all surviving mice had persistent truncus arteriosus. CONCLUSIONS: The results suggest that Foxc2- and ETA-expressing cells additively form the aorticopulmonary septum.

Animals↗

Expression of Smac/DIABLO in mouse preimplantation embryos and its correlation to apoptosis and fragmentation.

Regulation of early embryonal development during fertilization and implantation is crucial for mammalian reproduction. Several studies have described cell death during preimplantation embryogenesis in a range of mammalian species, both in vivo and in vitro. Therefore, apoptosis may be involved in early embryonic arrest and the characteristic cytoplasmic fragments are the equivalents of apoptotic bodies, the end-product of apoptosis. Although apoptosis is expected to associate with fragmentation in early preimplantation embryos, the mechanism through which this fragmentation occurs has not been elucidated. Recently, second mitochondria-derived activator of caspase/Direct IAP Binding Protein with Low pI (Smac/DIABLO) was identified as a mitochondrial protein that is released into the cytosol during apoptosis. Once released, the Smac/DIABLO blocks the anti-apoptotic activity of inhibitor of apoptosis proteins (IAPs). We hypothesized that the Smac/DIABLO may be involved in the fragmentation of mouse preimplantation embryos. Therefore, we investigated the expression of Smac/DIABLO mRNA and protein and its localization in mouse oocytes and preimplantation embryos. Smac/DIABLO mRNA was detected by RT-PCR in the oocytes and the preimplantation embryos. Immunohistochemistry studies showed that the Smac/DIABLO protein localized in mitochondria and was released into the cytosol in both fragmented embryos and embryos in which apoptosis was induced by staurosporine. These observations indicate that the Smac/DIABLO is involved in the fragmentation and apoptosis of preimplantation embryos.

Animals↗

HCG up-regulates survivin mRNA in human granulosa cells.

The apoptosis of granulosa cells is involved in follicular atresia and degeneration of the corpus luteum. The mechanisms that regulate follicular atresia and luteal degeneration remain obscure. Survivin is a member of the family of inhibitors of apoptosis protein that is expressed during fetal development and in cancer tissues. The present study investigates the expression of survivin, as well as its regulation and function in granulosa cells. We identified survivin at the protein level in granulosa cells and detected not only survivin but also splice-variant transcripts in human and mouse granulosa-luteal cells. One-step real-time PCR analysis revealed that HCG increases the amount of survivin mRNA expressed in cultured human granulosa cells. These results suggest that survivin is involved in supporting luteal function, and that HCG contributes to this role.

Alternative Splicing↗

Right ventricular pre-ejection myocardial velocity and myocardial acceleration in normal fetuses assessed by Doppler tissue imaging.

Myocardial acceleration during isovolumic contraction obtained from Doppler tissue imaging has been introduced as an index of right ventricular contractile function that is unaffected by the shape of the ventricle and loading conditions, but normal value of myocardial acceleration during isovolumic contraction and the effect of aging on the index are not known in normal fetuses. We studied 61 normal fetuses aged 20 to 39 weeks (29.8 +/- 5.1 weeks). Fetuses were divided into 4 age groups: 20 to 24 weeks (n = 11); 25 to 29 weeks (n = 20); 30 to 34 weeks (n = 20); and 35 to 39 weeks (n = 10). Using Doppler tissue imaging, peak pre-ejection myocardial velocity was measured at the base of right ventricular free wall from 4-chamber view. Myocardial acceleration was calculated by dividing pre-ejection velocity by the time interval from onset of the pre-ejection myocardial velocity to the time at peak velocity of this wave. The mean pre-ejection myocardial velocity was 5.0 +/- 1.1 cm/s. There was a stepwise increase in the pre-ejection myocardial velocity from the fetuses of 20 to 24 weeks to the fetuses of 35 to 39 weeks. The mean myocardial acceleration was 160 +/- 30 cm/s 2 . The mean myocardial acceleration did not differ between the fetuses aged 20 to 24 weeks (139 +/- 13 cm/s 2 ) and the fetuses aged 25 to 29 weeks (143 +/- 21 cm/s 2 ), but after 30 weeks increased with gestational age. For the total group combining the 4 different gestational age groups, the pre-ejection myocardial velocity and myocardial acceleration correlated with gestational age ( r = 0.85 and 0.75). This study demonstrated the gestational age-related changes in pre-ejection myocardial velocity and myocardial acceleration. The load-independent index of contractility, myocardial acceleration, increased mainly after 30 weeks' gestation.

Echocardiography, Doppler↗

Expression of tumor necrosis factor-alpha stimulated gene-6 mRNA in cultured human uterine cervical fibroblasts.

BACKGROUND: Uterine cervical ripening process is an active biochemical process similar in part to inflammatory reaction. In this process, hyaluronan plays important roles including facilitation of tissue hydration, release of matrix metalloproteinases and migration of inflammatory cells. The activities of hyaluronan are mediated by the hyaluronan binding proteins, hyaladherins. In the present study, we investigated the mRNA expression of tumor necrosis factor-alpha stimulated gene-6 (TSG-6), a member of the hyaladherin family, in cultured human uterine fibroblasts and uterine cervical tissues. METHODS: We developed one-step RT-PCR method for the quantification of TSG-6 mRNA and quantified the expression of TSG-6 mRNA in cultured human uterine fibroblasts, treated with or not proinflammatory cytokines, and TSG-6 mRNA in uterine cervical tissues. RESULTS: We clarified that [1] TSG-6 mRNA was expressed constitutively in cultured human uterine cervical fibroblasts, [2] expression of TSG-6 mRNA was upregulated in a dose dependent manner by proinflammatory cytokines, such as IL-1beta and TNF-alpha, which were key mediators in the cervical ripening process, [3] expression of TSG-6 mRNA in uterine cervices during parturition was significantly (P < 0.05) higher than that in a non-pregnant state. CONCLUSIONS: Our results suggest that TSG-6 might participate in the cervical ripening process.

Base Sequence↗

Endometrial adenocarcinoma after liver transplantation.

In June 1999, a 50-year-old Japanese woman underwent a liver transplant and was started on tacrolimus hydrate. A routine gynecologic examination at that time was unremarkable. In December 2001, the patient was found to suffer from endometrial adenocarcinoma and total abdominal hysterectomy with adnexa was carried out. No significant changes in liver function were observed. However, because fever in the patient of up to 38.5 degrees C continued, the volume of the tacrolimus hydrate was reduced, and then stopped completely. The patient's fever decreased to approximately 36.5 degrees C and she was discharged on the 18th postoperative day. The present case is the first report of endometrial adenocarcinoma in a patient after liver transplantation.

Adenocarcinoma↗

Surgical indications for combined partial rectosigmoidectomy in ovarian cancer.

AIM: To evaluate surgical indications for combined partial rectosigmoidectomy in ovarian cancer with direct invasion of the rectum and sigmoid colon or dissemination into the pouch of Douglas. METHODS: Subjects comprised 25 patients with ovarian cancer who underwent primary surgery and rectosigmoidectomy between 1990 and 2002 at our hospital. Federation of Obstetrics and Gynecology staging of tumors was II (n = 6), III (n = 17) or IV (n = 2). The histologic type was serous adenocarcinoma (n = 18), clear cell adenocarcinoma (n = 4), and others (n = 3). Bowel resection was performed during primary surgery in 18 patients, and after neoadjuvant chemotherapy (NAC) in seven patients. Cumulative survival rate was compared between NAC and non-NAC groups. Patients were divided into three groups based on extent of surgical resection to compare survival rates: no residual tumor (n = 19); maximum residual tumor diameter <1 cm (n = 5); and maximum residual tumor diameter > or =1 cm (n = 1). RESULTS: Cumulative 5-year survival was 41.3% for all patients. Cumulative 5-year survival in the 18 patients who underwent bowel resection during primary surgery was 62.2%, compared to 13.9% in the seven patients who underwent bowel resection after NAC. Cumulative 5-year survival based on extent of surgical resection was: no residual tumor, 60.8%; residual <1 cm, 0%; and residual > or =1 cm, 0%. Cumulative 5-year survival for patients with complete tumor resection (no residual tumor), excluding clear cell adenocarcinoma, was 79.5%. CONCLUSION: In ovarian cancer with direct invasion of the rectum or sigmoid colon or dissemination into the pouch of Douglas, complete tumor resection with rectosigmoidectomy during primary surgery is associated with good clinical outcomes.

Adult↗

Human papilloma virus type 16 infection and the early onset of cervical cancer.

Human papilloma viruses (HPV), particularly type 16, have been associated with cervical cancer. It has been noted that the average onset of cervical cancer is occurring in younger women coupled with a higher prevalence of cervical HPV infection. However, the correlation between HPV 16 infection and the early onset of cervical cancer is still unclear. We hypothesize that HPV infection is an indicator of early onset of cervical cancer. To test this hypothesis, cervical smears from 197 women were evaluated by the polymerase chain reaction for HPV 16. These data revealed that the HPV 16-positive women were significantly younger than the HPV 16-negative women. Moreover, the average age of HPV 16-positive women with CIN 3 or invasive cancer was significantly younger compared with the other groups. These data clearly suggest that HPV 16 infection is a significant risk factor for the progression for cervical cancer in a young population of women.

Adult↗