Factor Xa releases matrix metalloproteinase-2 (MMP-2) from human vascular smooth muscle cells and stimulates the conversion of pro-MMP-2 to MMP-2: role of MMP-2 in factor Xa-induced DNA synthesis and matrix invasion

Pro-matrix metalloproteinase-2 (pro-MMP-2) is expressed in vascular smooth muscle cells (SMCs). We report that activated coagulation factor X (FXa) induces the release of MMP-2 (65 kDa) from human SMCs. In addition, FXa cleaves pro-MMP-2 (72 kDa) into MMP-2. Pro-MMP-2 and MMP-2 were determined by gelatin zymography. MMP-2 was generated in conditioned medium containing pro-MMP-2 in a concentration-dependent fashion by FXa (3 to 100 nmol/L). FX at concentrations up to 300 nmol/L was ineffective. The conversion of pro-MMP-2 to MMP-2 was inhibited by a selective FXa inhibitor (DX-9065a) at 3 to 10 micromol/L. There was a concentration-dependent induction of an intermediate MMP-2 form (68 kDa) in lysates of FXa-treated cells. This indicates that cellular mechanisms are involved in FXa-induced conversion of pro-MMP-2. As a possible biological consequence of MMP-2 activation by FXa, DNA synthesis and matrix invasion of SMCs were determined. Both were stimulated by FXa and inhibited by the selective FXa inhibitor DX-9065a and the MMP inhibitor GM 6001 but not by hirudin or aprotinin. It is concluded that stimulation of SMCs by FXa increases the levels of MMP-2 in the extracellular space and that two different mechanisms are involved: release of active MMP-2 and cleavage of secreted pro-MMP-2. Both might contribute to the mitogenic potency of FXa and FXa-stimulated matrix invasion of SMCs.     

Stressful life events precede exacerbations of multiple sclerosis

OBJECTIVE: We longitudinally monitored life events and health changes in patients with multiple sclerosis (MS) to determine whether stressful events may trigger exacerbation of MS. METHODS: Twenty-three women with MS were followed for 1 year. Each subject completed the Psychiatric Epidemiologic Research Interview on a weekly basis. Further information on potentially stressful events was acquired using the Life Events and Difficulties Schedule. Neurologic symptoms were also monitored on a weekly basis throughout the year. Potential MS exacerbations were confirmed by a neurologist who was blind to the presence and timing of stressors. RESULTS: Eighty-five percent of MS exacerbations were associated with stressful life events in the preceding 6 weeks. Stressful life events occurred an average of 14 days before MS exacerbations, compared with 33 days before a randomly selected control date (p < .0001). Survival analysis confirmed that an increase in frequency of life events was associated with greater likelihood of MS exacerbations (hazard ratio = 13.18, p < .05). CONCLUSIONS: These results are consistent with the hypothesis that stress is a potential trigger of disease activity in patients with relapsing-remitting MS.     

Nursing exploration summer camp: improving the image of nursing

Improving the image of nursing and finding ways to encourage young people to enter the nursing field are two areas that need attention from nurse executives. That concept was turned into reality with Inova Nursing Exploration Summer Camp 2001, a camp for seventh and eighth graders who are exploring their interest in nursing careers. The camp was a unique partnership among a county public school system, a local university, and an integrated healthcare system. The program, developed by the system nurses in consultation with middle school educators, introduced students to the nursing profession via demonstrations, site visits at multiple hospitals, role-playing, discussions, and a trip to the local nursing school to experience life as a nursing student. The authors discuss the planning, implementation, and outcome of this unique summer camp.     

Teenagers with familial adenomatous polyposis: what is their risk for colorectal cancer?

PURPOSE: Familial adenomatous polyposis is a general growth disorder caused by highly penetrant germline mutations in the tumor suppressor gene APC. The major manifestation of these mutations is colorectal adenomatous polyposis, which, if untreated, leads to early development of colorectal cancer. To prevent this from happening, endoscopic screening of at-risk family members begins early in the second decade of life. Patients with adenomas are offered surgery sometime in that decade. There is a concern about the risk of cancer in teenagers if such surgery is deferred. We conducted this study to investigate that risk. METHODS: A brief survey was sent by facsimile or mail to all familial adenomatous polyposis registries affiliated with the Leeds Castle Polyposis Group. This questionnaire asked for the number of teenage or younger patients in the registry diagnosed with invasive colorectal carcinoma. Other questions addressed the stages and treatment of the tumors and the outcome of their treatment. Patients with carcinoma-in-situ or intramucosal carcinoma were excluded. RESULTS: Replies were received from 26 of 52 registries, but not all questions were answered by all registries. There were 14 patients identified as having invasive colorectal cancer younger than 20 years, the youngest of whom was 9 and the oldest 19. Two patients had two cancers each. Three patients were diagnosed at surgery, and seven were diagnosed when they presented with symptoms. Of the 13 cancers that had staging information, 8 were T1N0M0; 1 was T2N0M0; 2 were TxN1M0; 1 was T3N0M0; and 1 was TxNxM1. Only one patient died of their colorectal cancer. CONCLUSION: Cancer occurs rarely in familial adenomatous polyposis patients younger than 20 years, and only 1 case was reported younger than 15 years. Surgery for colorectal polyposis usually can be deferred safely until at least the age of 15, unless suspicious lesions are found.     

Palatal surface area measurement: comparisons among different cleft types

The purpose of this study was to use three-dimensional imaging methods to measure the palatal surface of unrepaired cleft patients. The surface area of the palate was defined and measured on three-dimensional computed tomography images of dental plaster models in four different groups of cleft patients at 3 months of age. There were 30 unilateral complete cleft lips and palates (UCLP), 27 bilateral complete cleft lips and palates (BCLP), 23 isolated cleft palates of incomplete form (CP), and 19 unilateral cleft lips without cleft palates (UCL). These patients were nonsyndromic, unoperated, and without other major deformities. The dental casts were scanned, and the computed tomography data were transferred to an imaging laboratory for processing and reconstruction of three-dimensional images. Surface area of the palate was delineated, which was defined as within the alveolar crest and the line connecting both tuberosities. In UCLP and BCLP, the edge of cleft formed the medial boundary of the area for each palatal shelf, and the palatal surface area was the combination of both palatal shelves and the premaxillary area in BCLP group. The surface area was measured. Repeated definition and measurement tasks were performed for calculation of errors. The imaging data management and measurement were performed using the Analyze program (Biomedical Imaging Resource, Mayo Foundation, MN). In addition, linear distances were measured between the canine points on the alveolar crest (line C) and the tuberosity points (line T). The measurements were compared among the different groups. Analysis of variance and multiple comparisons were used for statistical analyses. The results showed that the mean error between repeated area definitions and measurements in this study was 1.86%. The bilateral complete cleft lip and palate (BCLP) and unilateral complete cleft lip and palate (UCLP) groups had significantly smaller palatal surface area than the unilateral cleft lip without cleft palate (UCL) and isolated cleft palate of incomplete form (CP) groups. There was no significant difference between the BCLP and UCLP groups. Line C and line T distances were significantly longer in BCLP and UCLP groups than in UCL and CP groups. The findings suggest that compared with UCL and CP patients, there is an intrinsic tissue deficiency in the palate/maxilla of BCLP and UCLP patients.     

Application of proteomics technology to the field of neurotrauma

Near-completion of the Human Genome Project has stimulated scientists to begin looking for the next step in unraveling normal and abnormal functions within biological systems. Consequently, there is new focus on the role of proteins in these processes. Proteomics is a burgeoning field that may provide a valuable approach to evaluate the post-traumatic central nervous system (CNS). Although we cannot provide a comprehensive assessment of all methods for protein analysis, this report summarizes some of the newer proteomic technologies that have propelled this field into the limelight and that are available to most researchers in neurotrauma. Three technical approaches (two-dimensional gel electrophoresis, direct analysis by mass spectrometry, including two-dimensional chromatography coupled to mass spectrometry and isotope coded affinity tags, and antibody technologies) are reviewed, and their advantages and disadvantages presented. A discussion of proteomic technology in the context of brain and spinal cord trauma follows, addressing current and future challenges. Proteomics will likely be very useful for developing diagnostic predictors after CNS injury and for mapping changes in proteins after injury in order to identify new therapeutic targets. Neurotrauma results in complex alterations to the biological systems within the nervous system, and these changes evolve over time. Exploration of the "new nervous system" that follows injury will require methods that can both fully assess and simplify this complexity.