Rat myometrial smooth muscle cells express endothelial nitric oxide synthase

We examined if rat myometrial cells in culture generate nitric oxide (NO) and express various isoforms of NO synthase (NOS). Myometrial cells isolated from rats on day 18 of gestation were incubated with various stimulators and inhibitors of NOS for 24 and 48 h, and NO production was evaluated by measuring nitrites in the media and NOS proteins in the cell lysates. NO was produced by myometrial cells and its production inhibited by N(G)-methyl-L-arginine (L-NMMA). This inhibition was reversed by L-arginine (3 mM). Interleukin-1beta (IL- 1beta) significantly stimulated NO production, in a dose-dependent manner. The IL-1beta-stimulated NO production was inhibited by the NOS inhibitor, L-NMMA, whose effects were reversed by L-arginine. Abundant NOS III protein was detectable in freshly isolated myometrial cells, and this was maintained in culture in the presence of fetal bovine serum (FBS; 10%). In the absence of FBS, NOS III levels decreased significantly (by 90%) within 24 h. In contrast, NOS I and NOS II proteins were undetectable in freshly isolated muscle cells and in cells cultured without IL-1beta. However, NOS II protein in these cells was induced by IL-1beta. Thus, NO is produced by myometrial cells through the NOS III isoform, and the myometrial NO may be important in maintaining uterine quiescence during pregnancy.      

医学生心理健康状况与人格特征的相关分析

目的 :了解在校医学生的心理健康状况 ,为今后开展心理健教育提供有益的依据。方法 :采用 SCL-90和 EPQ量表对在校 5 88名医学生调查并作相关分析。结果 :医学生出现各类心理问题的比例为 6.80 %～ 3 2 .11% ,以强迫、人际敏感、抑郁和偏执为主。临医和护理专业学生心理问题的侧重点不同。女生在人际敏感、抑郁和恐怖等方面均高于男性。情绪稳定性 N和精神质 P与各因子及总均分呈正相关关系 (P<0 .0 1) ,掩饰度 L 与各因子呈显著负相关 (P<0 .0 1)。多因素回归分析表明 ,情绪稳定性 N和掩饰度 L对心理健康的影响起着重要作用。结论 :搞好学生的心理健康 ,加强健全人格教育是关键 ,同时要根据不同性别和专业区别地对待     

Changes in gap junctional intercellular communication in mouse skin carcinogenesis

Gap junction intercellular communication (GJIC) has been measured in cell lines that represent different stages of chemically induced mouse skin carcinogenesis. No significant difference in GJIC, as measured by dye spread, was found in cultures of normal keratinocyte, papilloma or squamous carcinoma cell lines. There was no correlation, in this system, between the presence of a mutant Ha-ras gene and down- regulation of communication. There was, however, a marked decrease in GJIC (80-90%) on progression from squamous to spindle carcinoma cells. Measurement of GJIC in somatic cell hybrids shows that the genetic defect responsible for this down-regulation is recessive and is common to two independently isolated spindle cell lines. No abnormalities were found in the spindle cells in expression of connexin 43, a cell component involved in gap junction formation and permeability. However, expression of E-cadherin, a cell-cell adhesion molecule implicated in the process of gap junction formation, was missing in the spindle carcinoma cells. Introduction of an E-cadherin cDNA into the spindle cells partially restored junctional communication without causing any noticeable alterations in cell morphology. During the study a non- tumourigenic keratinocyte line, a sub-clone of a normal keratinocyte line, was also found to have a low level of GJIC. However, the defect in this line was shown, by genetic complementation in somatic cell hybrids, to be different from that in the spindle carcinoma cell lines. Consistent with these data, analysis by immunofluorescence shows an abnormal distribution of connexin 43 in these cells.      

Percutaneous cecostomy: controlled transperitoneal approach

The authors present two cases of percutaneous cecostomy performed with a modified approach previously described for percutaneous gastrostomy and cholecystostomy. T-fastener devices were used to affix the cecum to the anterior abdominal wall; thus, the potential problem of fecal spillage was prevented. In both cases, adequate fecal drainage was provided without complication.     

Molecular imaging of bone marrow mononuclear cell homing and engraftment in ischemic myocardium

Bone marrow mononuclear cell (BMMC) therapy shows promise as a treatment for ischemic heart disease. However, the ability to monitor long-term cell fate remains limited. We hypothesized that molecular imaging could be used to track stem cell homing and survival after myocardial ischemia-reperfusion (I/R) injury. We first harvested donor BMMCs from adult male L2G85 transgenic mice constitutively expressing both firefly luciferase (Fluc) and enhanced green fluorescence protein reporter gene. Fluorescence-activated cell sorting analysis revealed approximately 0.07% of the population to consist of classic hematopoietic stem cells (lin-, thy-int, c-kit+, Sca-1+). Afterward, adult female FVB recipients (n = 38) were randomized to sham surgery or acute I/R injury. Animals in the sham (n = 16) and I/R (n = 22) groups received 5 x 10(6) of the L2G85-derived BMMCs via tail vein injection. Bioluminescence imaging (BLI) was used to track cell migration and survival in vivo for 4 weeks. BLI showed preferential homing of BMMCs to hearts with I/R injury compared with sham hearts within the first week following cell injection. Ex vivo analysis of explanted hearts by histology confirmed BLI imaging results, and quantitative real-time polymerase chain reaction (for the male Sry gene) further demonstrated a greater number of BMMCs in hearts with I/R injury compared with the sham group. Functional evaluation by echocardiography demonstrated a trend toward improved left ventricular fractional shortening in animals receiving BMMCs. Taken together, these data demonstrate that molecular imaging can be used to successfully track BMMC therapy in murine models of heart disease. Specifically, we have demonstrated that systemically delivered BMMCs preferentially home to and are retained by injured myocardium. Disclosure of potential conflicts of interest is found at the end of this article.     

Hemin-activated macrophages home to the pancreas and protect from acute pancreatitis via heme oxygenase-1 induction

Hemin upregulates heme oxygenase-1 (HO-1), a stress-induced enzyme implicated in protection from a variety of injuries while its related isoform HO-2 is constitutively expressed. The role of hemin or HO-1 in the pancreas and their potential modulation of pancreatic injury are unknown. We show that HO-1 is induced in pancreatitis caused by caerulein and more prominently in severe pancreatitis caused by feeding a choline-deficient diet (CDD). Intraperitoneal hemin administration dramatically increases peritoneal and pancreas macrophages that overexpress HO-1 in association with pancreatic induction of the chemoattractants monocyte chemotactic protein-1 and macrophage inflammatory protein-1alpha but not RANTES or macrophage inflammatory protein-2. Hemin administration before CDD feeding protected 8 of 8 mice from lethality while 7 of 16 controls died. Protection is mediated by HO-1-overexpressing macrophages since hemin-primed macrophages home to the pancreas after transfer to naive mice and protect from CDD-induced pancreatitis. Suppression of hemin-primed peritoneal cell HO-1 using HO-1-specific small interfering RNA prior to cell transfer abolishes protection from CDD-induced pancreatitis. Similarly, hemin pretreatment in caerulein-induced pancreatitis reduces serum amylase and lipase, decreases pancreatic trypsin generation, and protects from lung injury. Therefore, hemin-like compounds or hemin-activated macrophages may offer novel therapeutic approaches for preventing acute pancreatitis and its pulmonary complication via upregulation of HO-1.     

THE CHANGING INDICATIONS FOR CAROTID ENDARTERECTOMY IN THE UK

In early series the majority of carotid endarterectomies were performed in patients with amaurosis fugax (AFx) or transient ischaemic attacks (TIAs) who were thought to have atheromatous ulcers of the carotid bifurcation or the internal carotid artery (ICA). The degree of stenosis was considered to be of secondary importance. We compared our own data with two British series undertaken in the early and late 80s/early 90s. This reflects the broadening of indications and the change of practice for carotid endarterectomy over the years, on the one hand towards including patients who are at greater risk of perioperative stroke (previous CVAs vs TIAs, crescendo TIAs and stroke in evolution), and on the other towards patients who have had no symptoms attributable to the carotid lesion (asymptomatic cases, combined carotid and cardiac procedures).     

Autologous and allogeneic bone marrow transplantation for poor prognosis patients with B-cell chronic lymphocytic leukemia

Twenty patients with poor prognosis B-cell chronic lymphocytic leukemia (B-CLL) underwent uniform high-dose chemoradiotherapy followed by rescue with multiple monoclonal antibody-purged autologous bone marrow (BM) (12 patients) or T-cell-depleted allogeneic BM from HLA-identical siblings (8 patients) in a pilot study to assess the feasibility of BM transplantation (BMT) in this disease. All had poor prognosis disease by either staging, BM pattern, tumor doubling time criteria, or cytogenetics. All patients achieved remission criteria (defined as < or = 2 adenopathy, absence of splenomegaly, < or = 20% of the intertrabecular space involved on BM biopsy) before BMT. Despite the use of fludarabine, a median of three treatment regimens were required to achieve BMT eligibility. After BMT, all patients achieved complete hematologic engraftment. Toxicities were not significantly different between autologous versus allogeneic BMT. Two toxic deaths were observed. Of 19 evaluable patients, 17 clinical complete clinical remissions (89%) were observed, with 2 patients (1 allogeneic and 1 autologous) exhibiting persistent BM disease. Complete clinical remissions were documented at the phenotypic and molecular level for the majority of patients in whom dual fluorescence for CD5 and CD20 (15 of 15; 100%) and Ig gene rearrangements (11 of 14; 79%) were performed. Although long-term follow-up is needed to assess any potential impact on the disease-free and overall survival of these patients, this study shows the feasibility of using high-dose chemoradiotherapy and BMT in patients with poor prognosis B-CLL.