Acute dysvascular limb in a young adult. A case study

Acute dysvascular limb in young adults is a rare entity. Diagnosis is often difficult because symptoms are not recognized as ischemic. The most common causes of this condition are premature atherosclerosis, thromboangiitis obliterans, microemboli, popliteal entrapment syndrome, collagen vascular disease, Takaysu's arteritis, and coagulopathy. A case study is presented to illustrate the disease process. A systematic approach to diagnosis, consisting of history and physical examination, palpation and auscultation of peripheral pulses at rest and following exercise, and noninvasive vascular examination at rest and following exercise, is recommended. Suggestion of an ischemic condition following noninvasive studies should be followed up with an arteriogram. The prognosis is dependent on the underlying etiology of the ischemia, early detection, and appropriate treatment.     

Epidermal growth factor, transforming growth factor-alpha, and epidermal growth factor receptor localization in the baboon (Papio anubis) oviduct during steroid treatment and the menstrual cycle

OBJECTIVES: Polypeptide growth factors may modulate the actions of estrogen (E2) and progesterone (P) in reproductive tissues in an autocrine/paracrine manner. The objective of this study was to determine whether the baboon oviduct contains epidermal growth factor (EGF), transforming growth factor-alpha (TGF alpha), and EGF receptor (EGF-R) and whether changes in their expression are correlated with various hormonal states. METHODS: Oviductal tissue was obtained from adult female baboons (Papio anubis) after oophorectomy and steroid treatment, and during the menstrual cycle. Ampullary regions were fixed in Bouin's fixative and embedded in paraffin for immunocytochemistry using rabbit polyclonal antibodies against EGF and EGF-R, and mouse monoclonal antibody against TGF alpha. RESULTS: Both EGF and EGF-R were present in all tissue compartments (most strongly in the epithelium, followed by smooth muscle and stroma) at all reproductive stages and showed similar staining patterns. However, the most intense immunoreactive product was found in the tissue obtained from the E2-treated and late follicular phase animals. At this time, intense staining was present in the apical regions of the mature ciliated cells, whereas the stain was dispersed uniformly over the cytoplasm of all other cell types. Immunoreactive TGF alpha was limited primarily to the nonciliated epithelial cells, and staining was most intense in the E2-treated and late follicular phase tissues. Transforming growth factor-alpha formed intense perinuclear deposits in the mature secretory cells, an area that corresponds to the Golgi region. No immunoreactive product was observed for any of these proteins when preimmune serum was substituted for the primary antibody or when the primary antibody was preabsorbed with antigen. CONCLUSION: In summary, EGF, TGF alpha, and EGF-R are present in the ampulla of the baboon oviduct. Moreover, the localization and intensity of immunoreactive product are dependent on cell type and hormonal state. These data are consistent with the concept that EGF, TGF alpha, and EGF-R may be regulated by E2 and P and thus may play a role in cell differentiation and function. In addition, the specific localization of TGF alpha suggests that this growth factor may be synthesized for release from the secretory cells and thus may also function as a modulator of gamete/embryo viability and development.     

Prevention of vertebrate neuronal death by the crmA gene

Interleukin-1 beta converting enzyme (ICE) is a mammalian homolog of CED-3, a protein required for programmed cell death in the nematode Caenorhabditis elegans. The activity of ICE can be specifically inhibited by the product of crmA, a cytokine response modifier gene encoded by cowpox virus. Microinjection of the crmA gene into chicken dorsal root ganglion neurons was found to prevent cell death induced by deprivation of nerve growth factor. Thus, ICE is likely to participate in neuronal death in vertebrates.     

Inhibition of granulocyte-derived proteases reduces the increase in plasma endothelin associated with myocardial ischemia in the pig

Plasma endothelin (ET) is increased in association with myocardial infarction. The aim of the present study was to get insight into the mechanisms behind this ischemia-induced increase in plasma ET. Since granulocytes increase ET production in vitro, we examined to what extent inhibition of granulocyte-derived proteases could reduce the increase in plasma ET observed in association with myocardial ischemia. We infused Eglin C, a selective inhibitor of the granulocyte-derived proteases elastase, cathepsin G, and chymotrypsin, in pigs subjected to 90 min left anterior descending coronary artery occlusion followed by 210 min reperfusion (n = 7). Arterial plasma ET increased in an untreated control group (n = 7) from 5.0 +/- 0.6 (mean +/- SEM) fmol . ml-1 before myocardial ischemia to 6.1 +/- 0.6 fmol . ml. at 90 min ischemia and reached a maximum of 6.8 +/- 0.9 fmol . ml-1 at 90 min reperfusion. The increase in plasma ET associated with myocardial ischemia was almost completely abolished in the Eglin C treated group (p = 0.005). Plasma ET in the Eglin C treated animals was 4.7 +/- 0.4, 4.7 +/- 0.4, and 4.6 +/- 0.4 fmol . ml-1 before myocardial ischemia, at 90 min ischemia, and at 90 min reperfusion, respectively. Our study suggests a role for granulocyte-derived proteases in the increase in plasma ET associated with myocardial ischemia. We have shown that the increase in plasma ET associated with myocardial ischemia was reduced by inhibition of granulocyte-derived proteases using the selective protease inhibitor Eglin C.     

Epidemiological aspects of inflammatory bowel disease in a north Italian population: a 4-year prospective study

OBJECTIVE: To determine the incidence and clinical characteristics at presentation of inflammatory bowel disease (IBD) in a defined area of north Italy. DESIGN: A 4-year prospective population-based epidemiological study. SETTING: An area in Lombardia defined by the National Health Service scheme with about 294,000 inhabitants, two referral hospitals and 259 general practitioners (GPs). PATIENTS: Subjects presenting to a GP with symptoms compatible with IBD underwent a diagnostic work-up at one of the referral hospitals. Those with ulcerative colitis (UC), Crohn's disease (CD) or indeterminate colitis diagnosed according to a defined protocol were included, as were residents of the area with IBD diagnosed elsewhere. Rigid case ascertainment methods were used. Patients were followed for one year; 125 patients were identified. RESULTS: The patient ascertainment rate was constant over the 4 years; UC was diagnosed in 82 patients, CD in 40, and indeterminate colitis in three. The mean annual incidence of IBD for the whole period was 10.6/10(5) inhabitants (95% confidence limits, 7.2-15.1), 7.0/10(5) for UC (4.3-10.7) and 3.4/10(5) (1.6-6.3) for CD. The mean interval between onset of symptoms and diagnosis was under 6 months. The clinical characteristics of our patients were similar to those of north European and American series. CONCLUSION: The incidence of IBD was higher than previously observed in Italy but was still lower than in some north European countries and in the USA. Our data could be used as a basis for future longitudinal studies and in international comparative investigations.     

Membrane-type 1 matrix metalloprotease (MT1-MMP) enables invasive migration of glioma cells in central nervous system white matter

Invasive glioma cells migrate preferentially along central nervous system (CNS) white matter fiber tracts irrespective of the fact that CNS myelin contains proteins that inhibit cell migration and neurite outgrowth. Previous work has demonstrated that to migrate on a myelin substrate and to overcome its inhibitory effect, rat C6 and human glioblastoma cells require a membrane-bound metalloproteolytic activity (C6-MP) which shares several biochemical and pharmacological characteristics with MT1-MMP. We show now that MT1-MMP is expressed on the surface of rat C6 glioblastoma cells and is coenriched with C6-MP activity. Immunodepletion of C6-MP activity is achieved with an anti-MT1-MMP antibody. These data suggest that MT1-MMP and the C6-MP are closely related or identical. When mouse 3T3 fibroblasts were transfected with MT1-MMP they acquired the ability to spread and migrate on the nonpermissive myelin substrate and to infiltrate into adult rat optic nerve explants. MT1-MMP-transfected fibroblasts and C6 glioma cells were able to digest bNI-220, one of the most potent CNS myelin inhibitory proteins. Plasma membranes of both MT1-MMP-transfected fibroblasts and C6 glioma cells inactivated inhibitory myelin extracts, and this activity was sensitive to the same protease inhibitors. Interestingly, pretreatment of CNS myelin with gelatinase A/MMP-2 could not inactivate its inhibitory property. These data imply an important role of MT1-MMP in spreading and migration of glioma cells on white matter constituents in vitro and point to a function of MT1-MMP in the invasive behavior of malignant gliomas in the CNS in vivo.     

Effect of morphine on gastroesophageal reflux and transient lower esophageal sphincter relaxation

BACKGROUND: Results from animal studies and preliminary data from pilot studies in patients with primary biliary cirrhosis suggest that tauro-ursodeoxycholic acid has metabolic properties that may favour its long-term use as an alternative to ursodeoxycholic acid for patients with chronic cholestatic liver diseases. No direct comparison of tauro-ursodeoxycholic and ursodeoxycholic acids have yet been carried out in primary biliary cirrhosis. METHODS: The effects of ursodeoxycholic and tauro-ursodeoxycholic acids were compared in 23 patients with primary biliary cirrhosis according to a crossover design. Both drugs were administered at the daily dose of 500 mg. in a randomly assigned sequence for two 6-month periods separated by a 3-month wash-out period. RESULTS: Serum liver enzymes related to cholestasis and cytolysis consistently improved, as compared to baseline values, during the administration of both ursodeoxycholic and tauro-ursodeoxycholic acids, but no significant difference between these two bile acids was found. Both treatments were well tolerated and no patient complained of side effects. CONCLUSION: In the short-term, tauro-ursodeoxycholic acid appears to be safe and at least as effective as ursodeoxycholic acid for the treatment of primary biliary cirrhosis.