Loss of PTEN expression is an independent predictor of favourable survival in endometrial carcinomas.

BACKGROUND: We and others previously reported the prognostic significance of PTEN mutational status on favourable survival in endometrial carcinomas. Here, we demonstrate that loss of PTEN expression in immunohistochemistry is an independent prognostic marker for favourable survival in endometrial carcinomas. METHODS: We conducted immunohistochemical analyses of PTEN, PIK3CA, phosphorylated Akt (p-Akt), and p27 in primary endometrial carcinomas from 221 patients. Mutation of PTEN was analysed further. RESULTS: Expression of PTEN was lost in 56 patients (25%), and PIK3CA was overexpressed in 159 patients (72%). Overexpression of PIK3CA was associated with p-Akt overexpression (P<0.001), which was in turn associated with loss of nuclear p27 expression (P=0.028). Loss of PTEN expression was found to be associated with endometrioid histology (P=0.03), and was inversely associated with the presence of lymphovascular space invasion (P=0.03). Univariate and multivariate survival analyses revealed that factors of PTEN loss, age <70, histological grade 1, early International Federation of Gynecology and Obstetrics (FIGO) stage, and absence of lymphovascular invasion were independent prognostic indicators for better overall survival (P=0.03, 0.04, 0.01, <0.001, and 0.03, respectively). The subset analysis showed a stronger tendency of PTEN loss towards favourable survival in advanced-stage (III and IV) disease than in early-stage (I and II) disease (P=0.05 vs 0.14). Moreover, our mutational analysis demonstrated that PTEN expression loss was associated with PTEN-truncating mutations (P=0.03). CONCLUSION: The current observations further support the prognostic significance of PTEN aberration on favourable outcome in endometrial carcinomas, providing useful implications for the individualised management of the disease.

Limit on neutrinoless ßß decay of 136Xe from the first phase of KamLAND-Zen and comparison with the positive claim in 76Ge.

We present results from the first phase of the KamLAND-Zen double-beta decay experiment, corresponding to an exposure of 89.5 kg yr of (136)Xe. We obtain a lower limit for the neutrinoless double-beta decay half-life of T(1/2)(0ν)>1.9×10(25) yr at 90% C.L. The combined results from KamLAND-Zen and EXO-200 give T(1/2)(0ν)>3.4×10(25) yr at 90% C.L., which corresponds to a Majorana neutrino mass limit of <(120-250) meV based on a representative range of available matrix element calculations. Using those calculations, this result excludes the Majorana neutrino mass range expected from the neutrinoless double-beta decay detection claim in (76)Ge, reported by a part of the Heidelberg-Moscow Collaboration, at more than 97.5% C.L.

Exploiting multimedia in reproductive science education: research findings.

Education in reproductive science is operating from an outdated paradigm of teaching and learning. Traditionally, reproductive education follows the pattern where students read a textbook, listen to instructor presentations, re-read the textbook and class notes and then complete a test. This paradigm is inefficient, costly and has not incorporated the potential that technology can offer with respect to increases in student learning. Further, teachers of reproductive science (and all of science for that matter) have little training in the use of documented methods of instructional design and cognitive psychology. Thus, most of us have learned to teach by repeating the approaches our mentors used (both good and bad). The technology now exists to explain complex topics using multimedia presentations in which digital animation and three-dimensional anatomical reconstructions greatly reduce time required for delivery while at the same time improving student understanding. With funding from the Small Business Innovation Research program through the U.S. Department of Education, we have developed and tested a multimedia approach to teaching complex concepts in reproductive physiology. The results of five separate experiments involving 1058 university students and 122 patients in an OB/GYN clinic indicate that students and patients learned as much or more in less time when viewing the multimedia presentations when compared to traditional teaching methodologies.

Alleles and intron polymorphism of KIR3DL1 shown by combination of allele group-specific primers and sequencing.

Allelic polymorphism of killer immunoglobulin-like receptor (KIR) genes may affect receptor expression as well as function. We used a combination of allele group-specific primers and DNA sequencing techniques to verify our KIR genotyping primers in polymerase chain reaction and identified three KIR3DL1 alleles. By sequencing some introns of 3DL1 in 18 genomic DNA samples, we found that a 4-bp insert in intron 1 of 3DL1*002 exists in multiple alleles, but that a 2-bp deletion in intron 7 is unique to 3DL1*01501 and that a 19-bp insert in intron 1 seems specific to the CEPH family 1416. Our data suggest that extensive KIR gene polymorphisms are ubiquitous as well as quite complex.

Silent venous thromboembolism before treatment in endometrial cancer and the risk factors.

Venous thromboembolism (VTE) often occurs after surgery and can even occur before surgery in patients with gynaecological malignancies. We investigated the incidence of VTE before treatment of endometrial cancer and associated risk factors. Plasma D-dimer (DD) levels before initial treatment were examined in 171 consecutive patients with endometrial cancer. Venous ultrasound imaging (VUI) of the lower extremities was performed in patients with DD >or=1.5 microg ml(-1), as the negative predictive value of DD for VTE is extremely high. For patients with deep vein thrombosis (DVT), pulmonary scintigraphy was performed to ascertain the presence of pulmonary thromboembolism (PTE). Risk factors for VTE were analysed using univariate and multivariate analyses for 171 patients. Of these, 37 patients (21.6%) showed DD >or=1.5 microg ml(-1), 17 (9.9%) displayed DVT by VUI and 8 (4.7%) showed PTE on pulmonary scintigraphy. All patients with VTE were asymptomatic. Univariate analysis for various risk factors revealed older age, non-endometrioid histology and several variables of advanced disease as significantly associated with VTE before treatment. Obesity, smoking and diabetes mellitus were not risk factors. Multivariate analysis confirmed extrauterine spread and non-endometrioid histology as independently and significantly associated with risk of VTE. These data suggest that silent or subclinical VTE occurs before treatment in at least around 10% of patients with endometrial cancer. Risk factors for VTE before treatment might not be identical to those after starting treatment.

High incidence of silent venous thromboembolism before treatment in ovarian cancer.

Venous thromboembolism (VTE) such as deep-vein thrombosis (DVT) and pulmonary thromboembolism (PTE) often occurs after surgery and rarely occurs even before surgery in patients with ovarian cancer. It is well known that levels of plasma D-dimer (DD) before treatment in most ovarian cancer patients are increased. This study therefore examined whether increased levels of DD are associated with presence of VTE before treatment of ovarian cancer. Between November 2004 and March 2007, DD levels prior to initial treatment were measured in 72 consecutive patients with presumed epithelial ovarian cancer (final diagnosis: epithelial ovarian cancer, n=60; and epithelial ovarian borderline malignancy, n=12). Venous ultrasound imaging (VUI) of the lower extremity was conducted for all patients except for two patients in whom DVT was detected by pelvic computed tomography (CT). When DVT was found, pulmonary scintigraphy was subsequently performed to ascertain presence of PTE. D-dimer levels were above the cut-off value (0.5 microg ml(-1)) in 65 of 72 patients (90.2%). Venous ultrasound imaging or CT revealed DVT in 18 of 72 patients (25.0%) and pulmonary scintigraphy found PTE in 8 patients (11.1%). All patients with VTE were asymptomatic when VTE was found. D-dimer levels were associated with incidence of VTE (0-1.4 microg ml(-1); 0 of 26 (0%), 1.5-7.4 microg ml(-1); 9 of 30 (30%) and > or =7.5 microg ml(-1); 9 of 16 (56.3%), P for trend=0.0003). However, even if 1.5 microg ml(-1) was used as a cut-off value, this had low specificity and positive predictive value (47.2, 38.3%), though it had high sensitivity and negative predictive value (100, 100%). Therefore, ovarian cancer patients with DD level > or =1.5 microg ml(-1) should be examined using VUI to detect silent DVT. Patients with VTE underwent preventive managements including anticoagulant therapy before initial treatment, chemotherapy or surgery, and after surgery. There was no clinical onset of postoperative VTE in all 72 patients. Measurement of DD levels and subsequent ultrasonography revealed that silent or subclinical VTE frequently occurs before surgery in ovarian cancer. The usefulness of preoperative assessment of VTE needs further confirmation in randomised controlled trials.

Tissue factor expression as a possible determinant of thromboembolism in ovarian cancer.

Ovarian cancer, and clear cell carcinoma in particular, reportedly increases the risk of venous thromboembolism (VTE). However, the mechanisms remain unclear. Tissue factor (TF) supposedly represents a major factor in the procoagulant activities of cancer cells. The present study examined the involvement of TF expression in VTE for patients with ovarian cancer. Subjects comprised 32 consecutive patients (mean age 49.8 years) with histologically confirmed ovarian cancer. Presence of VTE was examined using a combination of clinical features, D-dimer levels and venous ultrasonography. Immunohistochemical analysis was used to evaluate TF expression into 4 degrees. Venous thromboembolism was identified in 10 of the 32 patients (31%), including five of the 11 patients with clear cell carcinoma. Tissue factor expression was detected in cancer tissues from 24 patients and displayed significant correlations with VTE development (P=0.0003), D-dimer concentration (P=0.003) and clear cell carcinoma (P<0.05). Multivariate analysis identified TF expression as an independent predictive factor of VTE development (P<0.05). Tissue factor (TF) expression is a possible determinant of VTE development in ovarian cancer. In particular, clear cell carcinoma may produce excessive levels of TF and is more likely to develop VTE.

Are smoking and chlamydial infection risk factors for CIN? Different results after adjustment for HPV DNA and antibodies.

To identify the risk factors for cervical intraepithelial neoplasia (CIN), we reanalysed the data from our previous case-control study by adjusting for human papillomavirus (HPV) antibodies. Unlike our previous study based only on HPV DNA, smoking and Chlamydia trachomatis infection were revealed as significant risk factors for CIN after adjustment for HPV antibodies.

Ultrasound diagnosis of uterine arteriovenous fistula associated with placental site trophoblastic tumor.

We report a case of a woman with abnormal vaginal bleeding who had a placental site trophoblastic tumor (PSTT) detected following hysterectomy. Surgery was performed because of a large uterine arteriovenous fistula detected by transvaginal color and pulsed Doppler sonography. Color Doppler sonography revealed a lacunar-type lesion with a marked increase in uterine vascularity, and pulsed Doppler sonography demonstrated a low resistance index. This vascular pattern indicated the formation of blood lacunae and arteriovenous shunts caused by PSTT within the uterine myometrium. This is the first report to describe the ultrasound findings in a case of PSTT complicated by a uterine arteriovenous fistula.

[Surgically treated pancoast tumor].

A 40-year-old male was detected his right apical lung tumor by roentgenographic screening on January 1997, but he did not refer to a hospital since he had no symptom. He went a orthopedics because of his right chest, back, and arm pain on October 1997, and he received traction and physical therapy. He went roentgenographic screening again on January 1998 and he was pointed out that the tumor increased. He admitted our hospital. Biopsy using bronchofiberscopy revealed adenocarcinoma and induction radiotherapy (40 Gy) was performed. Right upper lobectomy with chest wall resection and lymph node dissection was performed under hook approach. This approach was useful to dissect the tumor from the invaded plexus brachialis. Postoperative radio-chemotherapy was added but the patient died 7-postoperative months because of multiple metastases. Early detection should be led to early starting of the therapy.

Electroosmosis injection of blood serum into biocompatible microcapillary chip fabricated on quartz plate.

A chip which allows the detection of various human health markers from a trace amount of blood has been studied. As a goal, a microcapillary with a 30 x 30 microm cross-section was fabricated using all-dry etching technologies on a 2 x 2 cm SiO2 chip. The coating of the biocompatible 2-methacryloyloxyethylphosphorylcholine (MPC) polymer on the inner quartz wall of the microcapillary demonstrated a sufficiently long adsorption suppression of proteins in the serum on the quartz surface, while rapid stopping occurred for serum injected into the microcapillary with a bare quartz surface. The latter rapid stopping corresponded well to fast electroosmosis flow due to the negatively increasing zeta-potential by the adsorption of proteins on the quartz surface. The electroosmosis pump arranged a downstream of the microcapillary was also developed to inject serum into it. As a preliminary application, a given concentration-standard solution was injected into the ion-sensitive field-effect transistor (ISFET) embedded in the chip, employing the electroosmosis pump arranged downstream of the sensor position. Hence, the pH and Na+ and K+ cation concentrations were measured.

Recycled addition of CD4+ T cell-rich population for induction of human autologous cytotoxic T lymphocytes: A practically efficient method.

When CD4(+) T cell-rich population appears in theinitial trial in induction cultures of humanautologous cytotoxic T lymphocytes (CTL), the cultureresults frequently in no or weak killing activity andtherefore usually be discarded as an ;unsuccessful'CTL induction culture. However, addition of theinitial CD4(+) T cell-rich population enabledefficient induction of the autologous CTL in theensuing trials. The CTL thus generated exhibitedstronger killing activities against autologous braintumor cells and ovarian tumor cells than previouslyobserved. This simple recycling of the primed butinert CD4(+) T cell-rich population for CTLinduction will promote clinical practice of adoptiveimmunotherapy of human tumors with autologous CTL.

[Risk assessment in urgent or emergent coronary artery bypass grafting for acute coronary syndrome].

Emergent coronary artery bypass grafting (CABG) for the treatment of acute coronary syndrome has increased the operative mortality. Forty-nine patients underwent urgent or emergent CABG for the treatment of medically refractory unstable angina in 10 patients, and for acute myocardial infarction (AMI) in 39 patients. Ten operative deaths were occurred in the AMI patients, and the mortality was 20 percent. The preoperative risk factors were evaluated in 10 patients who died in the operative period. Cardiopulmonary resuscitation before operation, intra aortic balloon pumping, the use of catecholamine, and intubation with or without percutaneous cardiopulmonary support revealed operative risk factor. Because the patients who have preoperatively shock, it seemed to be needed that the rescue of the patients should improve the clinical results for urgent or emergent CABG.

Five cases of asymptomatic spontaneous pneumothorax.

Asymptomatic spontaneous pneumothorax (ASPT) is an uncommon condition. Between January 1, 1989 and December 31, 1997, 269 patients were admitted to our department with spontaneous pneumothorax. Of the 269 patients, 5 had no symptoms at the time of discovery. Their ages ranged from 15 to 61 years (mean, 37.8 years), and all of them were male. Of the 5 patients with no complaints, 2 had bilateral metachronous pneumothoraces and 3 had hemilateral pneumothorax. All of these ASPTs were revealed by chest roentgenographs taken during medical examinations or follow-up studies relating to other diseases. The mean value of body mass index (BMI) was 19.96 +/- 1.4 (range 18.7 - 22.1). Two of the 5 patients underwent bilateral partial lung resection. Histopathological examination of the resected specimens showed elastofibrosis, scar formation, and an interruption of the elastic fiber of the pleura. In these 5 cases, clinical courses were uneventful, and relapse of the pneumothorax did not occur. Clinical physicians should be aware of the possibility of asymptomatic pneumothorax, as well as the optimal radiographic techniques for revealing small pneumothoraces.

A novel human glassy-cell carcinoma cell line producing IL-6 and IL-8 from uterine cervix.

A novel human cell line, TOM-2, was established from a rare uterine cervical cancer, glassy cell carcinoma (GCC). TOM-2 is the second established GCC cell line so far reported. The cells were intermediately or poorly differentiated with dysplastic nuclei and polygonal shape and secreted two tumor markers and cytokines, i.e., CA-125 and SCC, interleukin (1L)-1alpha, -6, and -8, and TNF-alpha. Growth of TOM-2 was so strongly dependent on population density that it was not possible to determine the plating efficiency. In mass culture, the following characteristics were observed: doubling time, 83 h; mode of chromosome number, 79; human papillomavirus type 18 DNA, detectable; tumorigenicity, easily transplantable into subcutis of nude mice; chemosensitivity in vitro, considerably sensitive to Cisplatin and 5-FU but not to 9 other antineoplastic agents. This novel cell line will be useful for developing new therapeutic strategies for the rare cancer, GCC.

Diagnosis of fetal anomalies by three-dimensional imaging using helical computed tomography.

We present the first report on the use of helical computed tomography (CT), a new, non-invasive diagnostic technique that produces three-dimensional (3-D) images, in prenatal diagnosis. This technique was used to construct 3-D images in the prenatal diagnosis of two anomalous fetuses. The 3-D images provided clear information about the anomalies: trisomy 18 in one case and cystic hygroma in the other. In one case, rapid intervention after a planned Caesarean section prevented respiratory distress. Surgery to correct the anomaly was performed 2 days postnatally; the infant recovered uneventfully.

Decreased T cell response to anti-CD2 in systemic lupus erythematosus and reversal by anti-CD28: evidence for impaired T cell-accessory cell interaction.

OBJECTIVE: To assess the ability of T cells from patients with systemic lupus erythematosus (SLE) to respond to a mitogenic combination of anti-CD2 monoclonal antibodies (MAb), and to learn the molecular basis of the documented defect. METHODS: Peripheral blood mononuclear cell (PBMC) populations from individuals with SLE and paired controls were stimulated in vitro with anti-CD2, and the proliferative response was compared with that evoked by stimulation with phytohemagglutinin (PHA) and anti-CD3. Surface markers on lymphocyte populations were assessed by flow cytometry after staining with specific MAb. RESULTS: The proliferative response to anti-CD2 was decreased to a greater extent than was the response to anti-CD3 or PHA in SLE patients. This defect was found in approximately one-half of the patients examined, was not associated with disease activity, and was maintained upon repeated testing. Since either monocytes or resting B cells can serve as accessory cells for T cells following activation by anti-CD2, we examined the T cell response after depletion of adherent cells. In approximately two-thirds of the individuals with a decreased response, depletion of monocytes or substitution of monocytes with allogeneic, resting B cells from normal donors corrected the defect. The addition to PBMC of anti-CD28, but not of a neutralizing antibody to interleukin-10, largely reversed the anti-CD2 proliferative defect. Significantly fewer CD8+ T cells expressed CD28 in SLE, and this defect was also documented, to a lesser extent, in CD4+ cells. CONCLUSION: This study provides evidence that some functional T cell defects in SLE may be due, at least in part, to decreased CD28-mediated costimulatory activity following the interaction of T cells with conventional accessory cells.

Direct extraction of A and B blood group antigens from human red cells by liposomes.

BACKGROUND: Some of the major blood group antigens are on lipids and proteins of the red cell membrane. Incubation of intact red cells with liposomes containing specially designed artificial lipids has been shown to result in the extraction of membrane proteins by the liposomes. The extraction of blood group structures and the retention of their antigenicity have not been reported. STUDY DESIGN AND METHODS: After the incubation of red cells with liposomes, the extraction of the antigens from human red cells by liposomes was examined by evaluation of the agglutination of the liposomes by respective antisera. RESULTS: Agglutination specific to the A and B blood group antigens was seen, which indicated that the antigenicity of the blood group antigens was retained even after the extraction by the liposomes. The presence of an artificial boundary lipid, 1,2-dimyristamido-1,2-deoxyphosphatidylcholine, in the liposome was crucial to the efficient extraction of the A and B antigens. On the other hand, the extraction of D, M, N, and P1 was not always detectable by agglutination. CONCLUSION: The A and B blood group antigens were directly extracted from red cells by liposomes without loss of antigenicity.