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BACKGROUND: In the phase II multicohort CheckMate 142 study, nivolumab plus low-dose (1 mg/kg) ipilimumab provided robust and durable clinical benefit with a manageable safety profile in previously treated patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) at 13.4- and 25.4-month median follow-up (Overman MJ, Lonardi S, Wong KYM et al. Durable clinical benefit with nivolumab plus ipilimumab in DNA mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer. J Clin Oncol. 2018;36:773-779. Overman MJ, Lonardi S, Wong KYM, et al. Nivolumab plus low-dose ipilimumab in previously treated patients with microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer: long-term follow-up. J Clin Oncol. 2019;37:635). Here, we present results from the 4-year follow-up of these patients. PATIENTS AND METHODS: Patients received nivolumab (3 mg/kg) plus low-dose (1 mg/kg) ipilimumab every 3 weeks (four doses) followed by nivolumab (3 mg/kg) every 2 weeks until disease progression. Primary endpoint was investigator-assessed objective response rate (ORR; as per RECIST version 1.1). RESULTS: A total of 119 patients were treated; 76% had ≥2 prior lines of therapy. Median follow-up was 50.9 months (range 46.9-62.7 months). Median duration of therapy was 24.9 months [95% confidence interval (CI) 15.8-33.2 months]. Investigator-assessed ORR increased from 55% (95% CI 45% to 64%) at 13.4 months to 65% (95% CI 55% to 73%) at 50.9 months with a disease control rate of 81% (95% CI 72% to 87%). The complete response rate increased from 3% at 13.4 months to 13% at 50.9 months. Partial responses were observed in 52% of patients; 21% had stable disease, and 12% had progressive disease. Median time to response was 2.8 months (range 1.1-37.1 months), and median duration of response was not reached (range 1.4+ to 58.0+ months). At data cut-off, 37 (48%) patients had ongoing responses. Median progression-free survival was not reached [95% CI 38.4 months-not estimable (NE)], and median overall survival was not reached (95% CI NE). Grade 3-4 treatment-related adverse events (TRAEs) were observed in 32% of patients; 13% of patients had any-grade TRAEs leading to discontinuation. CONCLUSIONS: The results confirm long-term benefit of nivolumab plus low-dose ipilimumab for previously treated patients with MSI-H/dMMR mCRC. The safety profile was manageable with no new safety signals. ispartof: ANNALS OF ONCOLOGY vol:33 issue:10 pages:1052-1060 ispartof: location:England status: published

Plenty of studies have examined the long term effect of weight loss on bone mineral density. This study aimed to explore the effects of 10% weight loss on early changes in bone metabolism as well as the possible influencing factors.Overweight and obese outpatients (BMI 24.0 kg/mA total of 75 participants were enrolled and 37 participants achieved a weight loss of at least 10%. It was found that PINP decreased (p = 0.000) and the β-Crosslaps increased (p = 0.035) in female participants. Decreases in PTH (p = 0.001), serum IL-2 (p = 0.013), leptin (p = 0.001) and increases in 25(OH) VitD (p = 0.001), serum ghrelin (p = 0.033) were found in 37 participants after 10% of their weight had been lost. Change in PINP was detected to be significantly associated with change in lean body mass (r = 0.418, p = 0.012) and change in serum ghrelin(r = - 0.374, p = 0.023).Bone formation was suppressed and bone absorption was increased in female subjects after a 10% weight loss. Bone turnover was found to be associated with lean body mass and affected by the circulating ghrelin level.

计算流体力学（computational fluid dynamics，CFD）是利用计算机模拟技术对流体流动进行数值计算分析的交叉学科，已被广泛应用于上气道气流动力学的研究中。CFD作为一种新工具，可为鼻腔气流运动提供可视化及量化的研究方法，特别是在分析正常及各种病理状态下的鼻腔气流特性、模拟与指导鼻腔鼻窦手术以及量化评估手术疗效等方面，有很好的应用前景。然而，目前CFD各变量与鼻腔疾病患者临床症状之间的相关性研究仍然较少。本文基于CFD在鼻腔疾病临床应用中的研究进展进行综述。.

Objectives To evaluate the ability of post-chemo-radiotherapy (CRT) diffusion-weighted-MRI apparent diffusion coefficient (ADCmean) and 18F-FDG PET maximum standardized uptake value (SUVmax) to predict disease-free survival (DFS) in head and neck squamous cell carcinoma (HNSCC), and to determine whether this ability is influenced by human papillomavirus oropharyngeal cancer (HPV-OPC) status. Methods This prospective cohort observational study included 65 participants (53 male, mean ± SD age 59.9 ± 7.9 years, 46 HPV-OPC) with stage III or IV HNSCC. Primary tumour and nodal ADCmean (pre-treatment, 6- and 12-weeks post-CRT) and SUVmax (12-weeks post-CRT) were measured. Variables were compared with 2-year DFS (independent t-test/Mann–Whitney test) and overall DFS (Cox regression), before and after accounting for HPV-OPC status. Variables were also compared between HPV-OPC and other HNSCC subgroups after stratifying for DFS. Results Absolute post-CRT ADCmean values predicted 2-year DFS and overall DFS for all participants (p = 0.03/0.03, 6-week node; p = 0.02/0.03 12-week primary tumour) but not in the HPV-OPC subgroup. In participants with DFS, percentage interval changes in primary tumour ADCmean at 6- and 12-weeks were higher in HPV-OPC than other HNSCC (p = 0.01, 6 weeks; p = 0.005, 12 weeks). The 12-week post-CRT SUVmax did not predict DFS. Conclusion Absolute post-CRT ADCmean values predicted DFS in HNSCC but not in the HPV-OPC subgroup. Amongst participants with DFS, post-CRT percentage interval changes in primary tumour ADCmean were significantly higher in HPV-OPC than in other HNSCC. Knowledge of HPV-OPC status is crucial to the clinical utilisation of post-CRT DWI-MRI for the prediction of outcomes. Supplementary Information The online version contains supplementary material available at 10.1007/s00432-021-03662-y.

Background This study investigated the psychometric properties of a Chinese version of the short form of Metacognitions Questionnaire (MCQ-30), which is an effective tool to assess metacognitive beliefs that have been linked to mental disturbance/disorder. We also tested whether metacognition factors would correlate with Internet gaming disorder (IGD) tendency. Methods Six hundred and eighty Chinese university students (Mean age=19.72, SD=1.38; 31.9% male) voluntarily completed an anonymous online questionnaire. Using standard translation procedures, the MCQ-30 items were translated from English into Chinese language and then back-translated. Depression, anxiety, and IGD tendency were assessed by validated scales. Results Confirmatory factor analysis (CFA) results supported the five-factor structure of the MCQ-30, with satisfactory model fit and good reliability. Criterion-related validity was also supported by significant positive correlations between the five factors and depression/anxiety symptoms. All of the five metacognition factors were also significantly correlated with IGD tendency, with positive beliefs about worry and cognitive confidence being the most salient factor after controlling for gender and age. Limitations This study did not examine the test–retest reliability of this scale, and the generalizability of the findings to other age groups remains unclear. Conclusions This study showed satisfactory psychometric properties of a Chinese version of the MCQ-30 and is the first to demonstrate a positive association between specific metacognition factors and IGD tendency among Chinese people. The latter finding supports an application of metacognitive therapy to the treatment of behavioral addictions, including IGD.

To investigate whether ERK/MNK/eIF4E contributes chemoresistance in ovarian cancer. The phosphorylated levels of Erk, Mnk, and eIF4E were systematically analyzed in ovarian cancer patients before and after chemotherapy, and ovarian cancer cells exposed to short- and long-term chemo-agent treatment. The roles of Erk/Mnk/eIF4E were investigated using pharmacological and genetic approaches. Increased phosphorylation levels of ERK, Mnk1, and eIF4E were observed in ovarian cancer cell exposed to chemotherapeutic agents, and paclitaxel-resistant SK-OV-3-r cells, and is a common response of ovarian cancer patients undergoing chemotherapy. MEK inhibitor U0126 inhibits basal and chemodrug-induced phosphorylation of ERK as well as Mnk1 and eIF4E, suggesting that Mnk1/eIF4E are the downstream signaling of ERK pathway and chemotherapy agents activate ERK/MNK/eIF4E in a MEK-dependent manner. eIF4E overexpression promotes ovarian cancer cell growth without affecting migration. In addition, ovarian cancer cells with eIF4E overexpression are more resistant to chemotherapeutic agents in aspect of growth inhibition and apoptosis induction compared to control cells. In contrast, eIF4E depletion augments chemotherapeutic agents’ effect in ovarian cancer cells. These demonstrate that eIF4E play roles in growth and chemoresistance in ovarian cancer. MEK inhibitor U0126 also significantly enhances chemotherapeutic agents’ inhibitory effects. Our work shows that ERK/Mnk/eIF4E activation is critically involved in ovarian cancer chemoresistance and inhibiting ERK/Mnk/eIF4E broadly sensitizes ovarian cancer response to chemotherapy.

To examine how tobacco use and depression/anxiety disorders are related to disturbed sleep in college students.85,138 undergraduate respondents (66.3% female, 74.5% white, non-Hispanic, ages 18-25) from the Spring 2011 American College Health Association-National College Health Assessment II database.Multivariate analyses of tobacco use (none, intermediate, daily) and mental health (diagnosed and/or symptomatic depression or anxiety) were used to predict sleep disturbance.Daily tobacco use was associated with more sleep problems than binge drinking, illegal drug use, obesity, gender, and working20 hours/week. Students with depression or anxiety reported more sleep disturbances than individuals without either disorder, and tobacco use in this population was associated with the most sleep problems.Tobacco use and depression/anxiety disorders are both independently associated with more sleep problems in college students. Students with depression and/or anxiety are more likely to be daily tobacco users, which likely exacerbates their sleep problems.

Summary The aim of this study was to investigate the association between the single-nucleotide polymorphisms (SNPs) of the interleukin 22 (IL-22) gene and systemic lupus erythematosus (SLE) in a Chinese population. Three IL-22 SNPs (rs2227485, rs2227513 and rs2227491) were genotyped using SNaPshot SNP genotyping assays and identified by sequencing in 314 SLE patients and 411 healthy controls. The IL-22 level of serum was assessed by enzyme-linked immunosorbent assay (ELISA) kits. Data were analysed by spss version 17.0 software. We found that rs2227513 was associated with an increased risk of SLE [AG versus AA: adjusted odds ratio (aOR) = 2·24, 95% confidence interval (CI) = 1·22–4·12, P = 0·010; G versus· A: adjusted OR = 2·18, 95% CI = 1·20-3·97, P = 0·011]. Further analysis in patients with SLE showed that the AG genotype and G allele were associated with an increased risk of renal disorder in SLE (G versus A: aOR = 3·09, 95% CI = 1·30–7·33, P = 0·011; AG versus· AA: aOR = 3·25, 95% CI = 1·35–7·85, P = 0·009). In addition, the concentration of IL-22 was significantly lower in the rs2227513 AG genotype compared with AA genotype (P = 0·028). These results suggest that rs2227513 polymorphism might contribute to SLE susceptibility, probably by decreasing the expression of IL-22.

Acute heart failure (AHF) is one of the most commonly seen clinical cases, with a high rate of re-hospitalization and mortality. AHF can be divided into two categories based on the systolic function of the left ventricle, which are heart failure with reduced ejection fraction (HFREF) and heart failure with preserved ejection fraction (HFPEF). Pathogenesis and treatment of the two are quite different. In this article we attempted to explore the value of combined use of clinical and laboratory indicators in the differential diagnosis of AHFREF and AHFPEF.AHF patients ≥18 years old without valvular heart disease, acute myocardial infarction, renal dysfunction, ongoing hemodialysis or acute pulmonary embolism were chosen. Patients with left ventricular ejection fraction (LVEF)0.5 fell into AHFREF group, and the remaining were placed in the AHFPEF group. Binary logistic regression analysis of age, gender, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), NT-proBNP, blood glucose, LVEF and cardiothoracic ratio (CTR) as covariates and AHF types as dependent variables.166 patients were enrolled and, among them, 66 cases (39.8%) were in the AHFREF group and 100 cases (60.2%) in the AHFPEF group. We chose age, SBP, DBP, HR and NT-pro BNP as covariates in the binary logistic regression analysis, and obtained the regression equation and the results were statistically significant (χ2=32.177, p0.001). Hosmer-Lemeshow model test was (χ2=8.654, p=0.372). Samples were tested with the remaining approximately 30% of the subjects.Combined application of clinical and laboratory indicators, such as age, blood pressure, HR and NT-proBNP play an important role in the differential diagnosis of AHFREF and AHFPEF.

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. Although much commoner in the eastern hemisphere, with an age-standardised incidence rate of 0.39 per 100 000 population, cancers of the nasopharynx form one of the rarer subsites in the head and neck.1 This paper provides recommendations on the work up and management of nasopharyngeal cancer based on the existing evidence base for this condition.Recommendations• Patients with nasopharyngeal carcinoma (NPC) should be assessed with rigid and fibre-optic nasendoscopy. (R)• Nasopharyngeal biopsies should be preferably carried out endoscopically. (R)• Multislice computed tomographic (CT) scan of head, neck and chest should be carried out in all patients and magnetic resonance imaging (MRI) where appropriate to optimise staging. (R)• Radiotherapy (RT) is the mainstay for the radical treatment for NPC. (R)• Concurrent chemoradiotherapy offers significant improvement in overall survival in stage III and IV diseases. (R)• Surgery should only be used to obtain tissue for diagnosis and to deal with otitis media with effusion. (R)• Radiation therapy is the treatment of choice for stage I and II disease. (R)• Intensity modulated radiation therapy techniques should be employed. (R)• Concurrent chemotherapy with radiation therapy is the treatment of choice for stage III and IV disease. (R)• Patients with NPC should be followed-up and assessed with rigid and/or fibre-optic nasendoscopy. (G)• Positron emission tomography–computed tomography (PET–CT), CT or MRI scan should be carried out at three months from completion of treatment to assess response. (R)• Multislice CT scan of head, neck and chest should be carried out in all patients and MRI scan whenever possible and specially in advanced cases with suspected recurrence. (R)• Surgery in form of nasopharyngectomy should be considered as a first line treatment of residual or recurrent disease at the primary site. (R)• Neck dissection remains the treatment of choice for residual or metastatic neck disease whenever possible. (R)• Re-irradiation should be considered as a second line of treatment in recurrent disease. (R)

Cell-cleavable protecting groups often enhance cellular delivery of species that are charged at physiological pH. Although several phosphonate protecting groups have achieved clinical success, it remains difficult to use these prodrugs in live cells to clarify biological mechanisms. Here, we present a strategy that uses a 7-methoxycoumarin-3-carboxylic acid ester as a fluorescent protecting group. This strategy was applied to synthesis of an (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate (HMBPP) analogue to assess cellular uptake and human Vγ9Vδ2 T cell activation. The fluorescent ester displayed low cellular toxicity (IC50 >100 μm) and strong T cell activation (EC50 =0.018 μm) relative to the unprotected anion (EC50 =23 μm). The coumarin-derived analogue allowed no-wash analysis of biological deprotection, which revealed rapid internalization of the prodrug. These results demonstrate that fluorescent groups can be applied both as functional drug delivery tools and useful biological probes of drug uptake.

Background Stenting of airway stenosis is a common procedure in specialized centers. The aim of this study was to summarize our clinical experience in ventilation strategy and anesthesia management of patients undergoing urgent tracheal stenting. Methods Clinical data of 22 patients with severe tracheal stenosis who underwent urgent endoscopic placement of a tracheal stent during a 2-year period were retrospectively reviewed. The efficacy and safety of different ventilation strategies and veno-arterial extracorporeal membrane oxygenation (ECMO), individualized based on the cause and location of tracheal narrowing, were evaluated. Results Sufficient ventilation was successfully established in all patients; ECMO was used in five patients with stenosis in the mid-trachea who were unable to tolerate conventional intubation; a laryngeal mask airway (LMA) was used in five patients with post-intubation tracheal stenosis; a cuffed tracheal tube was used in eight patients with lower tracheal stenosis; and low-frequency jet ventilation in rigid bronchoscopy was used in four patients with mid- or lower tracheal stenosis. Tracheal stents were successfully placed and there were significant improvements in dyspnea. There were significant increases in the partial pressure of carbon dioxide in patients ventilated with the LMA and cuffed tracheal tube. There was no hypoxia during the operative period. Conclusion Establishment of effective airway ventilation in patients with severe tracheal stenosis should be based on the cause, location, and severity of tracheal narrowing. Veno- arterial ECMO may be considered in patients with severe stenosis, if they are judged unable to tolerate conventional ventilation or jet ventilation.

Loss of function of mutated solute carrier family 12 member 3 (SLC12A3) gene is the most frequent etiology for Gitelman syndrome (GS), which is mainly manifested by hypokalemia, hypomagnesemia and hypocalciuria. We report the genetic characteristics of one suspicious Chinese GS pedigree by gene sequencing. Complete sequencing analysis of the SLC12A3 gene revealed that both the proband and his elder sister had a novel homozygous SLC12A3 mutation: c.2099T>C and p.Leu700Pro. Moreover, the SLC12A3 genes of his mother and daughter encoded the same mutated heterozygote. It was noted that in this pedigree, only the proband complained about recurrent episodes of bilateral lower limb weakness over 8 years, while his elder sister, mother and daughter did not present symptoms. The inconsistent clinical features of this pedigree implied that besides diverse phenotypes possibly originated from the same genotype, gender difference may also dominate the variant GS phenotypes. Further genetic and proteomic research are needed to investigate the precise mechanisms of GS, including the study of specific ethnicities.

Chromosomal aberrations are a hallmark of human cancers, with complex cytogenetic rearrangements leading to genetic changes permissive for cancer initiation and progression. Protection of Telomere 1 (POT1) is an essential component of the shelterin complex and functions to maintain chromosome stability by repressing the activation of aberrant DNA damage and repair responses at telomeres. Sporadic and familial mutations in the oligosaccharide-oligonucleotide (OB) folds of POT1 have been identified in many human cancers, but the mechanism underlying how hPOT1 mutations initiate tumorigenesis has remained unclear. Here we show that the human POT1's OB-folds are essential for the protection of newly replicated telomeres. Oncogenic mutations in hPOT1 OB-fold fail to bind to single-stranded telomeric DNA, eliciting a DNA damage response at telomeres that promote inappropriate chromosome fusions via the mutagenic alternative non-homologous end joining (A-NHEJ) pathway. hPOT1 mutations also result in telomere elongation and the formation of transplantable hematopoietic malignancies. Strikingly, conditional deletion of both mPot1a and p53 in mouse mammary epithelium resulted in development of highly invasive breast carcinomas and the formation of whole chromosomes containing massive arrays of telomeric fusions indicative of multiple breakage-fusion-bridge cycles. Our results reveal that hPOT1 OB-folds are required to protect and prevent newly replicated telomeres from engaging in A-NHEJ mediated fusions that would otherwise promote genome instability to fuel tumorigenesis.

To investigate the impact of novel P2Y(12) receptor inhibitors including prasugrel or ticagrelor on platelet reactivity in patients with acute coronary syndrome (ACS) receiving percutaneous coronary intervention (PCI), and provide clinical data for novel oral P2Y(12) receptor inhibitors use among Chinese patients.Between October 2011 to February 2014, 174 consecutive patients (135 males; (67.8±11.8) years old) with ACS undergoing PCI in Kiang Wu Hospital, Macau were prospectively enrolled in this study. Oral aspirin and one P2Y(12) receptor inhibitor were administered for 5 days or above after PCI, patients were divided into clopidogrel, prasugrel and ticagrelor groups in accordance with the agent administered. Platelet reactivity of the patients was detected by VerifyNow P2Y(12) reaction unit (PRU); and the high on-treatment platelet reactivity (HPR) and non-HPR were defined as PRU≥208 and PRU208 respectively. Patients with HPR during clopidogrel therapy were switched either to prasugrel or ticagrelor, or continued the same treatment; and then the platelet reactivity was monitored again.There were 113 clopidogrel cases (64.9%), 20 prasugrel cases (11.5%) and 41 ticagrelor cases (23.6%). Fifty-seven cases (32.8%) were defined as HPR post P2Y(12) receptor inhibitor use, in which 55 cases (55/113, 48.7%) were treated with clopidogrel. The degree of inhibition of platelet reactivity was significantly different in patients on clopidogrel, prasugrel and ticagrelor therapy, percent inhibition assayed by the VerifyNow P2Y(12) system was 28.2%±23.5%, 61.4%±26.7% and 81.3%±19.8% respectively (P0.05). Different degree of platelet reactivity was achieved by the 3 P2Y(12) receptor inhibitors at multiple time points. The among-group differences in platelet reactivity became apparent at the early treatment stage (P0.05). Platelet aggregation decreased significantly in patients switched from clopidogrel to prasugrel or ticagrelor (P0.05).Novel oral P2Y(12) receptor inhibitors are more effective in inhibiting platelet reactivity in ACS patients, and our results show that novel oral P2Y(12) receptor inhibitors provide a new option for ACS patients with HPR post clopidogrel or high-risk features of ischemic complications, including stent thrombosis and post-PCI ischemic events.

This paper proposed a relative value method for measuring the indicators of cardiac reserve and investigated the application on monitoring and evaluating cardiac function for pregnant women. A heart sound sensor is placed at the precordial region to detect phonocardiogram. In order to access the cardiac reserve mobilization level during pregnancy, the cardiac reserve indicators of 1,683 normal pregnant women, 96 abnormal cases with different obstetric complications and 624 non-pregnant women were measured, analyzed and compared. The result shows that the differences between the indicators of pregnant and non-pregnant women were significant (p < 0.05). The ratio of diastolic to systolic duration (D/S) was obviously declined with the increase of gestational weeks and the occurrence of obstetric complication. This very encouraging result indicates that the D/S can be used as an indicator for evaluating the cardiac safety of parturition, which provides a reference for cardiac safety assessment of pregnant women.

We previously reported that polo-like kinase 1 (Plk1) depletion by lentivirus-based RNA interference led to mitotic arrest and apoptosis in cancer cells, whereas normal diploid cell lines, hTERT-RPE1 and MCF10A, survived a similar level of depletion. To study homogeneous cell lines, we generated several Plk1-depleted hTERT-RPE1 and MCF10A clones that were derived from single cells depleted of Plk1. We found that in the long term, Plk1 depletion slowed proliferation of hTERT-RPE1 cells, apparently due to attenuated progression through S phase. These cells had altered morphology and were elongated compared with control. In contrast, MCF10A clones with mild levels of depletion showed no obvious phenotype. They appeared to have normal proliferation rates with no cell-cycle arrest. However, one MCF10A clone, which was severely depleted of Plk1, although viable, showed sporadic G2/M arrest and apoptosis. This MCF10A clone and all the hTERT-RPE1 clones displayed evidence of DNA-damage checkpoint activation. These data further support the interpretation that cancer cell lines have a much greater requirement for Plk1 than normal nontransformed diploid cells.

Background The pathogenesis of endometriosis remains poorly defined. The aberrant angiogenesis that occurs in eutopic endometrium may play a role in the lesion formation and survival. The difference in gene expression profile between human endometrial endothelial cells (HEECs) from eutopic endometria of patients with and without endometriosis would be a factor that affects the occurrence of endometriosis. Methods To explore the difference, we performed in vitro culture and identified the endothelial origin, as well as observed growth features, of HEECs from the two different sources. We also identified their differences in gene expression profiles by combined suppression subtractive hybridization (SSH) with Genechip, and confirmed the results by quantitative reverse transcription-polymerase chain reaction. Results The HEECs derived from endometriosis patients exhibited a potent survival ability in vitro compared with those from non-endometriosis patients. In the HEECs from EM patients, an altered secretion pattern of extracellular matrix (ECM) components and up-regulation of GREM1 were found. These findings may be used to interpret the remarkable change of phenotype in HEECs from endometriosis patients. The synergistic action of these differentially expressed genes is to promote cell proliferation and concomitantly to inhibit apoptosis. Among the up-regulated ECM genes, TSP2 was the only one which exhibits the capacity to suppress angiogenesis; it may therefore function as an antagonist to the aberrant angiogenesis and may confine its extent and severity. Conclusion It may be postulated that differential regulation of some of these genes in eutopic HEECs plays a facilitating role during the peritoneal vascularization of ectopic endometrial lesions by enhancing angiogenic activity via a paracrine effect.

TM7SF4 (transmembrane 7 superfamily member 4) gene encodes a seven-pass transmembrane protein that is primarily expressed in dendritic cells called as dendritic cell-specific expressed seven transmembrane protein (DC-STAMP). This protein regulates immunological functions, osteoclastogenesis and myeloid differentiation. Although the roles of TM7SF4 have been currently studied on Paget's disease of bone and papillary thyroid cancers, it is unclear whether TM7SF4 plays a role in breast cancer. In current study, we investigated the expression of TM7SF4 in human breast cancer cell lines.In this study, five breast cancer lines were cultured. Small hairpin RNA against TM7SF4 using a lentiviral vector was generated and transfected into MCF-7 breast cancer cells. Effects of down-regulating TM7SF4 in transfected cells were examined by Western blot, RT-PCR, apoptotic rate, colony formation, and cell cycle analyses.The results demonstrated that down-regulation of TM7SF4 led to a decrease in colony formation in MCF-7 cells compared to the control group. This is likely due to a decrease in proliferation and cell cycle and an increase in apoptosis.To our knowledge, our data demonstrate for the first time that TM7SF4 plays an essential role in regulating cell cycle progression in breast cancer.

M2A antigen is an oncofetal antigen associated with germ cell neoplasia, present in testis on fetal gonocytes and re-expressed on carcinoma in situ (CIS) and germ cell tumours. We developed a panel of monoclonal antibodies (mAb), M2A (IgG2a), D1-26 (IgG2b) and D2-40 (IgG1), to this antigen in order to characterize its structure and study its distribution among germ cell tumours. M2A antigen was purified by sequential lectin and antibody affinity chromatography and characterized as a monomeric Mr 40 000 surface sialoglycoprotein, extensively glycosylated with O-linked carbohydrate structures, but devoid of N-linked sugars. Terminal sialic acid residues were required for reactivity with mAb M2A and D1-26, but not D2-40. Sections of 69 testicular germ cell tumours, fixed in formalin and embedded in paraffin, were stained with mAb D2-40 to examine the distribution of M2A antigen. Uniform membrane staining was observed in seminomas, and focal staining in 69% of embryonal carcinomas, 29% of teratomas and 25% of yolk sac tumours. CIS in the vicinity of all germ cell tumours also displayed uniform membrane staining. The characterization of M2A antigen, and the development of mAb which react with it in conventionally preserved archival specimens, provide important initiatives to study the origin and progression of germ cell neoplasia. © 1999 Cancer Research Campaign

S100 protein is a 20 kDA calcium-binding protein that accumulates during CNS maturation in mammals. The human gene coding for the beta subunit of S100 protein (S100 beta) is located on chromosome 21, in a subtelomeric position in 21q22.3. In order to investigate the effect of trisomy 21 on S100 beta gene expression, we performed Southern, Northern and Western blot analysis on DNA, RNA and protein, respectively, extracted from the cerebellum of control and Down syndrome (DS) subjects aged 1-18 months. Southern blot analysis revealed a novel EcoRI polymorphism in the S100 beta gene in two of 15 DNA samples examined, and a 1.5 gene dosage for S100 beta in DS. Northern and Western blot analysis showed an approximately 10-fold increase in S100 beta mRNA and protein levels between 1 and 18 months. No differences in the rates of accumulation of S100 beta mRNA and protein were observed between DS and normal subjects. These results demonstrate an increase in S100 beta mRNA and protein levels during infancy indicative of postnatal astrocytic maturation and show that there is no gross deregulation in the expression of the S100 beta gene in DS as a consequence of trisomy 21.

Kornyei JL, Li X, Lei ZM, Rao ChV. Restoration of human chorionic gondadotropin response in human myometrial smooth muscle cells by treatment with follicle-stimulating hormone (FSH): evidence for the presence of FSH receptors in human myometrium. Eur J Endocrinol 1996;134:225–31. ISSN 0804–4643 Human myometrial smooth muscle cells contain receptors for human chorionic gonadotropin (hCG)/ luteinizing hormone (LH). Exogenous hCG and LH can cause a modest hyperplasia in myometrial smooth muscle cells in culture. This response is lost after about the third subculture of the cells. The present study investigated whether the loss of hCG response could be restored by co-culturing with human follicle stimulating hormone (FSH). The results showed that co-culturing with FSH can indeed restore a modest mitogenic response of hCG. However, FSH alone was not mitogenic. The FSH restoration of hCG response can be blocked by antibodies to FSH or hCG but not by non-specific rabbit IgG. The FSH treatment resulted in an increase of steady state levels of hCG/LH receptor mRNA and protein in myometrial smooth muscle cells. Since the FSH actions could be receptor mediated, we investigated the presence of FSH receptor mRNA transcripts and protein in freshly dispersed myometrial smooth muscle cells. Northern blotting demonstrated that myometrial smooth muscle cells, just as rat ovary, a classical target of FSH action, contain multiple FSH receptor mRNA transcripts. Western immunoblotting demonstrated that myometrial smooth muscle cells also contain a 60 kDa FSH receptor protein just as rat ovary and human granulosa cells used as positive control tissues. The immunocytochemistry also demonstrated that myometrial smooth muscle cells, as rat ovary and human granulosa cells, contain FSH receptor immunostaining. In summary, it is novel that FSH could restore the mitogenic response of hCG in human myometrial smooth muscle cells and these cells contain FSH receptors. These findings may have functional implications for direct regulation of human myometrium not only by hCG/LH but also by FSH. ChV Rao, Department of Obstetrics and Gynecology, 438 MDR Building, University of Louisville, School of Medicine, Louisville, Kentucky 40292, USA

This paper represents a reconstruction algorithm using a direct sensitivity matrix (DSM) approach for fast 3D image reconstruction in electrical impedance imaging. The boundary element method (BEM) is used in the construction of this matrix. The first images of a conductivity perturbation inside a sphere are reconstructed, using theoretical data.

The negative impacts of excessive and problematic video game playing on both children and adults are attracting increasing concern. Based on self-determination theory (SDT; Ryan & Deci, 2000), this study hypothesized that the three basic psychological needs of autonomy, competence, and relatedness are positively associated with purpose in life, which in turn acts as a protective factor against problem video game playing among Chinese young adult players. Through a questionnaire survey with a sample of 165 Chinese adults aged between 18 and 30 years (mean age ¼ 22.7 years), we found that perceived autonomy, competence, relatedness, and purpose in life were all negatively correlated with problem game playing. The demographic and psychological factors explained 38% of the variances of problem game playing. Specifically, gender, perceived relatedness, and purpose in life emerged as the three most salient predictors of problem game playing among the Chinese young adults. The mediating role of purpose in life was evidenced and it was found that purpose in life mediated the influences of the psychological needs proposed by SDT on problem game playing. Moreover, young men were significantly more susceptible to problem game playing than their female counterparts. To conclude, psychological needs and purpose in life influenced Chinese young adults’ vulnerability to problem game playing directly or indirectly. Intervention programs that encourage social involvement and voluntary work, as well as counseling service that helps clients to search for life purpose, are suggested for intervening in problem game playing among Chinese young adults.

Differential normalized fluorescence (DNF) is an efficient and effective method for the differentiation of normal and cancerous tissue fluorescence spectra. The diagnostic features are extracted from the difference between the averaged cancerous and averaged normal tissue spectra and used as indices in tissue classification. In this paper, a new method, probability-based DNF bivariate analysis, is introduced based on the univariate DNF method. Two differentiation features are used concurrently in the new method to achieve better classification accuracy. The probability of each sample belonging to a disease state is determined with Bayes decision theory. This probability approach classifies the tissue spectra according to disease states and provides uncertainty information on classification. With a data set of 57 colonic tissue sites, probability-based DNF bivariate analysis is demonstrated to improve the accuracy of cancer diagnosis. The bivariate DNF analysis only requires the collection of a few data points across the entire emission spectrum and has the potential of improving data acquisition speed in tissue imaging.

The sinoatrial node (SAN) and the atrioventricular node (AVN) are specialized tissues in the heart: the SAN is specialized for pacemaking (it is the pacemaker of the heart), whereas the AVN is specialized for slow conduction of the action potential (to introduce a delay between atrial and ventricular activation during the cardiac cycle). These functions have special requirements regarding electrical coupling and, therefore, expression of connexin isoforms. Electrical coupling in the center of the SAN should be weak to protect it from the inhibitory electrotonic influence of the more hyperpolarized non-pacemaking atrial muscle surrounding the SAN. However, for the SAN to be able to drive the atrial muscle, electrical coupling should be strong in the periphery of the SAN. Consistent with this, in the center of the SAN there is no expression of Cx43 (the principal connexin of the working myocardium) and little expression of Cx40, but there is expression of Cx45 and Cx30.2, whereas in the periphery of the SAN Cx43 as well Cx45 is expressed. In the AVN, there is a similar pattern of expression of connexins as in the center of the SAN and this is likely to be in large part responsible for the slow conduction of the action potential.

We performed a linkage analysis on 25 extended multiplex Portuguese families segregating for bipolar disorder, by use of a high-density single-nucleotide-polymorphism (SNP) genotyping assay, the GeneChip Human Mapping 10K Array (HMA10K). Of these families, 12 were used for a direct comparison of the HMA10K with the traditional 10-cM microsatellite marker set and the more dense 4-cM marker set. This comparative analysis indicated the presence of significant linkage peaks in the SNP assay in chromosomal regions characterized by poor coverage and low information content on the microsatellite assays. The HMA10K provided consistently high information and enhanced coverage throughout these regions. Across the entire genome, the HMA10K had an average information content of 0.842 with 0.21-Mb intermarker spacing. In the 12-family set, the HMA10K-based analysis detected two chromosomal regions with genomewide significant linkage on chromosomes 6q22 and 11p11; both regions had failed to meet this strict threshold with the microsatellite assays. The full 25-family collection further strengthened the findings on chromosome 6q22, achieving genomewide significance with a maximum nonparametric linkage (NPL) score of 4.20 and a maximum LOD score of 3.56 at position 125.8 Mb. In addition to this highly significant finding, several other regions of suggestive linkage have also been identified in the 25-family data set, including two regions on chromosome 2 (57 Mb, NPL = 2.98; 145 Mb, NPL = 3.09), as well as regions on chromosomes 4 (91 Mb, NPL = 2.97), 16 (20 Mb, NPL = 2.89), and 20 (60 Mb, NPL = 2.99). We conclude that at least some of the linkage peaks we have identified may have been largely undetected in previous whole-genome scans for bipolar disorder because of insufficient coverage or information content, particularly on chromosomes 6q22 and 11p11. info:eu-repo/semantics/publishedVersion

Schizophrenia is a common psychiatric disorder with a complex genetic etiology. To understand the genetic basis of this syndrome in Portuguese Island populations, we performed a genome-wide scan of 29 families with schizophrenia, which identified a single region on 5q31-5q35 with strong linkage (NPL=3.09, P=0.0012 at D5S820). Empirical simulations set a genome-wide threshold of NPL=3.10 for significant linkage. Additional support for this locus in schizophrenia comes from higher-density mapping and mapping of 11 additional families. The combined set of 40 families had a peak NPL=3.28 (P=0.00066) at markers D5S2112-D5S820. These data and previous linkage findings from other investigators provide strong and consistent evidence for this genomic region as a susceptibility locus for schizophrenia. Exploratory analyses of a novel phenotype, psychosis, in families with schizophrenia and bipolar disorder detected evidence for linkage to the same markers as found in schizophrenia (peak NPL=3.03, P=0.0012 at D5S820), suggesting that this locus may be responsible for the psychotic symptoms observed in both diseases. Molecular Psychiatry (2004) 9, 213-218. doi:10.1038/sj.mp.4001418 Published online 30 December 2003

Cushing's syndrome occurring during pregnancy is frequently due to an adrenal neoplasm. Adrenal gland tumors occasionally respond to luteinizing hormone (LH) or human chorionic gonadotropin (hCG). We report a case of Cushing's syndrome during and following pregnancy due to an adrenal carcinoma which expressed the LH/hCG receptor. The presence of these receptors may have led to the growth and function of the tumor during pregnancy.

In this study, a segment LS method was used to determine the AR parameters for multi-channel upper limb EMG. Different sampling frequencies, time-windows and attenuation factors were tested and an optimum selection was obtained. According to the experiment result, the segment LS algorithm should be the best method compared with others.

The presence of luteinizing hormone receptors in human pineal glands from five females and three males, ranging in age from 61-89 yr, was examined by in situ hybridization and immunocytochemistry. The results demonstrated the presence of these receptors at the mRNA and protein levels in all the pineal glands examined. Pineal gland luteinizing hormone receptors could potentially be involved in the regulation of melatonin synthesis.

Leptin, protein product of the ob gene, not only regulates food intake and energy expenditure but also has a number of other actions in the body. Leptin actions are mediated by its receptors that have either a long or a truncated intracellular domain, which is coupled to signal transduction pathways. Previous studies have demonstrated that human placenta expresses both leptin and its receptors. However, it is not known whether human umbilical cord and fetal membranes are also sites of expression of these molecules. Therefore, the present study investigated leptin and its receptor expression in these tissues from term pregnancy. Reverse-transcription polymerase chain reaction (RT-PCR) amplified expected size fragments of leptin and also its short and long receptor isoforms from umbilical cord and fetal membranes. The authenticity of PCR-amplified fragments was confirmed by Southern blot hybridization with corresponding cDNA probes. Western blotting revealed that the transcripts were translated into 16-kDa leptin, and 125-kDa (long) and 100-kDa (short) leptin receptor isoforms. However, the long form is present in umbilical cord and the short form in the fetal membranes. Immunocytochemistry revealed that leptin and its receptor isoforms were present in endothelial cells and smooth muscle of umbilical veins and artery, myofibroblasts in Wharton's jelly, amnion covering the cord, amnion and chorion in reflected fetal membranes and decidua from membranes. Amnion, however, contained the highest levels of leptin and its receptor immunostaining. In summary, term pregnancy human umbilical cord and fetal membranes co-express leptin and its receptor genes, which supports the hypothesis that leptin is an autocrine and paracrine regulator in these tissues.

To clarify the relationship between serum angiotensin I-converting enzyme (ACE) activity and Type II diabetic patients with or without diabetic nephropathy. We examined 36 healthy controls, 58 Type II diabetic patients without diabetic nephropathy, and 50 Type II diabetic with diabetic nephropathy. The diabetic duration of all of Type II diabetic patients was more than 5 years. All patients matched well in age and BMI. An insertion/deletion polymorphism of ACE gene was identified by polymerase chain reaction(PCR). Serum ACE activity was determined using spectrophotometry. Although the distribution of DD, ID, and II genotypes of the ACE gene did not differ among the three groups, serum ACE activity was significantly higher in Type II diabetic patients with diabetic nephropathy than in that without diabetic nephropathy(P0.05), especially in the groups with D allele of ACE gene. Serum ACE activity had no difference between healthy controls and Type II diabetic patients without diabetic nephropathy. There is no association between serum ACE activity and Type II diabetic patients without diabetic nephropathy in any genotype of ACE gene. The increasing serum ACE activity plays a role in the initiation of diabetic nephropathy or may serve as a risk marker for later development of overt diabetic nephropathy in Type II diabetic patients.

To clarify the relationship among angiotensin 1-converting enzyme(ACE) gene insertion/deletion(I/D) polymorphism, serum ACE activity, and diabetic retinopathy in Type II diabetic patients, we examined 36 healthy controls, 40 Type II diabetic patients without diabetic retinopathy, and 68 Type II diabetic patients with diabetic retinopathy. All of patients suffered from Type II diabetes beyond 5 years and matched in age and body mass index. An insertion/deletion polymorphism of ACE gene was identified by polymerase chain reaction(PCR). Serum ACE activity was determined using spectrophotometry. The distribution of DD, ID, and II genotypes of the ACE gene did not differ among the three groups (16.7%, 33.3%, and 50.0% in the healthy controls; 22.5%, 35.0%, and 42.5% in Type II diabetic patients patients without diabetic retinopathy; and 20.6%, 30.9%, and 48.5% in Type II diabetic patients with diabetic retinopathy; respectively). The frequency of ACE I/D genotypes was not significantly different between non-proliferative retinopathy and proliferative retinopathy of Type II diabetic patients with diabetic retinopathy (P0.05). Serum ACE activity of three groups was similar (P0.05). These results do not support the hypothesis that the DD genotype of the ACE gene would be a clinically useful genetic marker for predicting the development of diabetic retinopathy in Type II diabetic patients. There is no association between ACE gene I/D polymorphism and the prognosis of diabetic retinopathy in Type II diabetic patients. ACE may not involve in forming diabetic retinopathy in Type II diabetic patients.

The recent results of the studies on corrosion of biomedical metallic materials are reviewed. The investigations on in vitro and in vivo corrosion and the correspondent local tissue responses, remote and systematic effects are discussed in order to explore the corrosion mechanism and to estimate the biocompatibility. The further research and development of bio-medical metallic materials are addressed.

To analyze the genotype of the measles virus epidemic strains in Dongguan according to the patients suffered measles in 2000.The saliva of 55 patients with acute measles symptoms were collected and detected with RT-PCR. The PCR products of the 5 samples were sequenced and analyzed with the software DNASTAR.The positive detection rate was 87.3%, whereas the positive rate of anti MV-IgM in serum was only 70.9%. 68.8% of the saliva samples of patients with anti MV-IgM negative results showing MV RNA positive. The 293 bp fragment of N gene and 194 bp fragment of M gene were amplified from the vaccine virus and the specimens. The sequences of the epidemic strains were identical in both M gene and N gene.These results suggested that the outbreak came from a single MV strain. The epidemic strain was obviously different from the standard strains discovered in other countries of the world (the deviation were 1.4%-11.7%) that might belong to H genotype.

To study the prevalence of hypertension and population blood pressure levels in Macao area.According to requirements set in "Manual for National Sampling Survey on Hypertension in 1991", 5,171 permanent residents aged more than 15 years in Macao area were investigated and their blood pressure measured with standardized methods and under strict quality control.The survey showed that crude prevalence rate of hypertension was 29.46 percent in Macao, 20.45 percent after standardization, and it should be categorized into a hypertension prevalent area based on the domestic criteria for hypertension categorization. Systolic and diastolic blood pressure averaged 17.18 kPa (128.82 mmHg) and 10.86 kPa (81.47 mmHg), respectively, for males and 16.32 kPa (122.38 mmHg) and 10.15 kPa (76.15 mmHg), respectively, for females, higher than those in Guangdong Province and Beijing. Prevalence in males was higher than that in females and it increased more quickly in those more than 35 years old, similar to that in the other areas at home. Prevalence in new immigrants was lower than that in the original residents.Hypertension was severely prevalent in Macao area and an important issue in public health not to be ignorant. Health education and health promotion should be strengthened to reach the primary and secondary prevention for it.

Lei, M., H. Ghezzo, M. F. Chen, and D. H. Eidelman.Airway smooth muscle orientation in intraparenchymal airways. J. Appl. Physiol. 82(1): 70–77, 1997.—Airway smooth muscle (ASM) shortening is the central event leading to bronchoconstriction. The degree to which airway narrowing occurs as a consequence of shortening is a function of both the mechanical properties of the airway wall as well as the orientation of the muscle fibers. Although the latter is theoretically important, it has not been systematically measured to date. The purpose of this study was to determine the angle of orientation of ASM (θ) in normal lungs by using a morphometric approach. We analyzed the airway tree of the left lower lobes of four cats and one human. All material was fixed with 10% buffered Formalin at a pressure of 25 cmH2O for 48 h. The fixed material was dissected along the airway tree to permit isolation of generations 4–18 in the cats and generations 5–22 in the human specimen. Each airway generation was individually embedded in paraffin. Five-micrometer-thick serial sections were cut parallel to the airway long axis and stained with hematoxylin-phloxine-saffron. Each block yielded three to five sections containing ASM. To determine θ, we measured the orientation of ASM nuclei relative to the transverse axis of the airway by using a digitizing tablet and a light microscope (×250) equipped with a drawing tube attachment. Inspection of the sections revealed extensive ASM crisscrossing without a homogeneous orientation. The θ was clustered between −20° and 20° in all airway generations and did not vary much between generations in any of the cats or in the human specimen. When θ was expressed without regard to sign, the mean values were 13.2° in the cats and 13.1° in the human. This magnitude of obliquity is not likely to result in physiologically important changes in airway length during bronchoconstriction.

Human myometrium contains functional hCG/LH receptors. The purpose of this study was to determine whether or not leiomyomas that arise from myometrium also contain these receptors. Northern blotting demonstrated that leiomyomas and normal adjacent myometria contained hCG/LH receptor mRNA transcripts. Western immunoblotting showed that leiomyomas and corresponding normal myometria also contained 60- and 50-kDa receptor proteins. Ligand blotting revealed that only the 50-kDa receptor protein in leiomyomas and corresponding normal myometria could bind 125I-hCG and that this binding inhibited by excess unlabeled hCG. In situ hybridization and immunocytochemistry revealed that smooth muscle cells in leiomyomas and corresponding normal myometria contained the hCG/LH receptor mRNA transcripts and receptor proteins. The receptor levels were lower in leiomyomas than in corresponding normal myometria. However, the receptors were functional, as treatment with hCG resulted in a decrease of connexin-43 protein levels in leiomyomas as in normal myometria. In summary, human uterine leiomyomas express a functional hCG/LH receptor gene at a reduced level compared with that for normal corresponding myometria. This finding could be relevant to an understanding of the growth control mechanisms in leiomyomas and the manner in which medical therapy for leiomyomas might work.

Human myometrium contains receptors for hCG/human LH (hLH). This suggested the possibility that hCG and hLH might regulate human myometrium, which has not previously been considered a direct target of gonadotropin regulation. To investigate such a possibility, highly pure and viable smooth muscle cells were isolated from nonpregnant human myometrium and cultured as monolayers. The cells contained hCG/LH receptor mRNA transcripts and a 50-kDa immunoreactive protein that can bind 125I-hCG in a ligand-specific manner. The presence of hCG during culture resulted in a significant increase of myometrial smooth muscle cell density. The hCG effect was time- and concentration-dependent and was mimicked by hLH but not by human FSH or human FSH or human thyroid-stimulating hormone. Human CG also greatly increased the size of a subpopulation of myometrial smooth muscle cells without affecting their chromosomal ploidy. Antibodies to hCG/LH receptors and hCG blocked hCG effects. Human prolactin and growth hormone, which do not bind to hCG/LH receptors, also increased the myometrial smooth muscle cell density. A protein kinase A inhibitor (H-89) blocked hCG response whereas calphostin (a protein kinase C inhibitor) and lavendustin A (a tyrosine kinase inhibitor) had no effect on hCG response, suggesting that a cAMP/protein kinase A signaling mechanism is involved in hCG action. Eicosanoids from cyclooxygenase and 5-lipoxygenase pathways of arachidonic acid metabolism are probably not involved, because the inhibitors of these enzymes had no effect on hCG response. While progesterone and estradiol could not mimic or modify hCG action, epidermal growth factor did mimic hCG in increasing myometrial smooth muscle cell density.(ABSTRACT TRUNCATED AT 250 WORDS)

L-tetrahydropalmatine (Rotundium) is an alkaloid of Corydalis turtschaninovii. Some animal experiments had demonstrated that Rotundium had a good antiarrhythmic effect in blocking the calcium channel and that it was a class IV antiarrhythmic agent, similar to that of Bepridil in literatures. This is a clinical report of Rotundium (oral given) on an atrial fibrillation (AF) patients. The therapeutical results were evaluated by 24 hours ambulatory electrocardiographic monitoring and ECG. The results showed that the effective rate of Rotundium on paroxysmal atrial fibrillation and sustained atrial fibrillation of 45 mm (left atrium diameter) or more was 30%, while LAD of less than 45 mm was 80% (P0.01). Among 8 cases' duration of AF were 6 months or more, 3 cases were effective, the effective rate 37.5%, while among 10 cases' duration of AF were less than 3 weeks, 3 cases were converted to sinus rhythm, 5 cases were effective. There was a significant difference between two groups. Age and sex exerted no effect on efficacy. During taking Rotundium, blood pressure had no apparent changes and no severe side effects were found. The results showed that Rotundium is an effective, safe new drug to treat AF, especially in paroxysmal atrial fibrillation. The antiarrhythmic mechanism of Rotundium might be related to its prolonging of the effective refractory period of atrial and atrioventricular node.

The surroundings of a coking plant were contaminated with benzo(a)pyrene [B(a)P] in various degrees. B(a)P in urine and blood of the coking workers was detected, and levels of B(a)P in urine and blood showed correlated. Also, the relationship between the contents of B(a)P in urine and the surroundings of the plant was found. The levels of immunoglobulin (IgG, IgA, IgM) and complement C3 in serum of the coking workers decreased. The levels of IgG and C3 in the workers were significantly different from those in controls. And, the serum contents of B(a)P in the workers also correlated with their immune function.

The expression of thromboxane (TX) A2 synthase and thromboxane A2 receptor gene in human uterus was investigated by immunoblotting, immunocytochemistry, Northern blot, in situ hybridization, and autoradiographic analyses. Human uterus contains a single immunoreactive protein of 55 kDa that corresponds to the molecular size of human TXA2 synthase. Human uterus also contains a single 2.8-kb TXA2 receptor mRNA transcript and a receptor protein that can bind TXA2 antagonist, 125I-PTA-OH. The immunoreactive TXA2 synthase, TXA2 receptor mRNA, and protein are present in endometrial glands, stromal cells, myometrial smooth muscle, and uterine blood vessels. The TXA2 synthase and TXA2 receptors in different uterine cells varied within as well as between various reproductive states. There were differences in the binding site numbers even between elongated and circular myometrial smooth muscle in all reproductive states except postmenopause. In summary, the data presented demonstrate for the first time that different human endometrial and myometrial cells and uterine blood vessels express TXA2 synthase as well as TXA2 receptor gene. The expression, as well as changes during various reproductive states, suggests that TXA2 could be an autocrine/paracrine regulator of human myometrial contractions, endometrial secretory functions, and intrauterine blood flow and could play a role in the initiation and/or progression of labor in women.

In order to evaluate the clinical effects of maprotiline (home made), the authors made a clinical comparison with Ludimil (Cida-Geigy) 96 cases (66 endogenous depression and 30 neurotic depression) meet the CMA diagnostic criteria (1984) were analysed. The patients' symptoms were assessed with HAMD, side effects with TESS. The study group included 72 patients treated with chinese product, the rest cases as control group treated with Ludimil. No significant differences of efficacy in terms of age, sex and duration of symptoms were found in both groups. After the six-week course of Maprotiline treatment, the authors found the dosage, therapeutic effect and adverse reaction in both groups are very similar. It is concluded that the chinese product is safe and effective.

The cell composition of human and bovine corpora lutea (CL) from various reproductive states was investigated by computerized video-based interactive Bioquant image analysis system IV and by light microscope immunocytochemistry. Human and bovine CL contained more nonluteal cells than luteal cells. Human CL contained a lower number of luteal and a greater number of nonluteal cells than bovine CL. Regardless of the reproductive state, human CL contained more small luteal cells than large luteal cells. In all reproductive states except in the late luteal phase, the bovine CL also contained more small luteal cells than large luteal cells. The average sizes of all the cells in human CL were smaller than in bovine CL. Human CL contained more vascular space than bovine CL during mid and late luteal phases. The number of luteal cells increased and nonluteal cells decreased from early to mid luteal phase, and then luteal cells decreased and nonluteal cells increased in late luteal phase and in degenerating human and bovine CL. While the change of number of small and large luteal cells first occurred from early to mid luteal phase in human CL, it did not take place until the late luteal phase in bovine CL. The average size of large luteal cells in humans and of small luteal cells in cattle did not change, whereas size of the other cells changed in different reproductive states in both human and bovine CL. The cell composition of term pregnancy human CL was similar to mid or late luteal phase, whereas the cell composition of early pregnancy bovine CL was similar to mid luteal phase.(ABSTRACT TRUNCATED AT 250 WORDS)