THE HISTOGENESIS OF BASEMENT MEMBRANES

A parietal yolk sac carcinoma of the mouse that secretes large quantities of basement membrane-like material has been used to study the formation of basement membranes. Suitably characterized fluorescein-labeled antibodies against this material stained basement membranes of epithelial structures and vessels, as well as reticulin. When absorbed with reticulin and vascular basement membranes of the spleen until these structures no longer fluoresced, the antibody still stained the basement membrane-like material of the tumor, its normal embryonic counterpart (Reichert's membrane), and the basement membranes at the bases of epithelial cells. The observation made previously that parietal yolk sac cells secreted, in the absence of connective tissue and reticulin, the basement membrane (Reichert's membrane) upon which they rested has been confirmed through the localization of ferritin-labeled antibody to the endoplasmic reticulin of the secreting cells. Since a basement membrane proven to be an epithelial secretion is antigenically similar to basement membranes at the bases of all epithelial cells studied but antigenically different from connective tissue elements, it is postulated that the basement membranes at the bases of epithelial cells in general are an epithelial secretion, and are not a condensation of ground substance as is commonly believed.     

Adipocyte-derived collagen VI affects early mammary tumor progression in vivo, demonstrating a critical interaction in the tumor/stroma microenvironment

The interactions of transformed cells with the surrounding stromal cells are of importance for tumor progression and metastasis. The relevance of adipocyte-derived factors to breast cancer cell survival and growth is well established. However, it remains unknown which specific adipocyte-derived factors are most critical in this process. Collagen VI is abundantly expressed in adipocytes. Collagen(-/-) mice in the background of the mouse mammary tumor virus/polyoma virus middle T oncogene (MMTV-PyMT) mammary cancer model demonstrate dramatically reduced rates of early hyperplasia and primary tumor growth. Collagen VI promotes its growth-stimulatory and pro-survival effects in part by signaling through the NG2/chondroitin sulfate proteoglycan receptor expressed on the surface of malignant ductal epithelial cells to sequentially activate Akt and beta-catenin and stabilize cyclin D1. Levels of the carboxyterminal domain of collagen VIalpha3, a proteolytic product of the full-length molecule, are dramatically upregulated in murine and human breast cancer lesions. The same fragment exerts potent growth-stimulatory effects on MCF-7 cells in vitro. Therefore, adipocytes play a vital role in defining the ECM environment for normal and tumor-derived ductal epithelial cells and contribute significantly to tumor growth at early stages through secretion and processing of collagen VI.     

Antiviral Action and Cellular Toxicity of Four Thymidine Analogues: 5-Ethyl-, 5-Vinyl-, 5-Propyl-, and 5-Allyl-2′-Deoxyuridine

5-Ethyl-, 5-vinyl-, 5-propyl-, and 5-allyl-2'-deoxyuridine (dUrd) had antiviral activity against herpes simplex type 1 and type 2 grown in HeLa TK(-) cells, in the order 5-vinyl-dUrd, 5-ethyl-dUrd, 5-propyl-dUrd, 5-allyl-dUrd, but they were inactive against a TK(-) mutant of herpes simplex type 1. The antiviral activity of these compounds could be partially reversed by thymidine. Except for 5-vinyl-dUrd, they were not toxic to WI-38 and HeLa TK(-) cells at a concentration of 25 muM. All four analogues inhibited the growth of herpes simplex type 1-transformed HeLa TK(-) cells at a concentration of 1 muM.     

Extracorporeal liver support: a continuing challenge

Given that liver failure continues to pose an enormous clinical challenge, the concept of hepatic dialysis has enjoyed significant interest. In particular, many investigations have examined the therapeutic mechanisms and efficacy of artificial albumin dialysis based systems in acute on chronic liver failure, the results of which have been conflicting. Albumin dialysis systems do not appear to significantly decrease serum concentrations of inflammatory cytokines in severe acute on chronic liver failure. Thus, if these treatments do result in clinical improvement, then other therapeutic mechanisms must be involved.     

Modulation of agonist binding to human dopamine receptor subtypes by L-prolyl-L-leucyl-glycinamide and a peptidomimetic analog

The present study was undertaken to investigate the role of the hypothalamic tripeptide L-prolyl-L-leucyl-glycinamide (PLG) and its conformationally constrained analog 3(R)-[(2(S)-pyrrolidinylcarbonyl)amino]-2-oxo-1-pyrrolidineacetamide (PAOPA) in modulating agonist binding to human dopamine (DA) receptor subtypes using human neuroblastoma SH-SY5Y cells stably transfected with respective cDNAs. Both PLG and PAOPA enhanced agonist [3H]N-propylnorapomorphine (NPA) and [3H]quinpirole binding in a dose-dependent manner to the DA D2L,D2S, and D4 receptors. However, agonist binding to the D1 and D3 receptors and antagonist binding to the D2L receptors by PLG were not significantly affected. Scatchard analysis of [3H]NPA binding to membranes in the presence of PLG revealed a significant increase in affinity of the agonist binding sites for the D2L, D2S, and D4 receptors. Analysis of agonist/antagonist competition curves revealed that PLG and PAOPA increased the population and affinity of the high-affinity form of the D2L receptor and attenuated guanosine 5'-(beta,gamma-imido)-triphosphate-induced inhibition of high-affinity agonist binding sites for the DA D2L receptor. Furthermore, direct NPA binding with D2L cell membranes pretreated with suramin, a compound that can uncouple receptor/G protein complexes, and incubated with and without DA showed that both PLG and PAOPA had only increased agonist binding in membranes pretreated with both suramin and DA, suggesting that PLG requires the D2L receptor/G protein complex to increase agonist binding. These results suggest that PLG possibly modulates DA D2S, D2L, and D4 receptors in an allosteric manner and that the coupling of D2 receptors to the G protein is essential for this modulation to occur.     

An advanced system for the simulation and planning of orthodontic treatment

This paper presents a new system for three-dimensional (3-D) orthodontic treatment planning and movement of teeth. We describe a computer vision technique for the acquisition and processing of 3-D images of the profile of hydrocolloid dental imprints. Profile measurement is based on the triangulation method which detects deformation of the projection of a laser line on the dental imprints. The system is computer-controlled and designed to achieve depth and lateral resolutions of 0.1 and 0.2 mm, respectively, within a depth range of 40 mm. The 3-D image of the imprint is segmented in order to identify different teeth. Two operators are presented: one for the detection of molars and premolars based on a directional gradient, and one for incisors and canines based on 3-D registration with dental models contained in a database. We apply these 3-D dental models to simulate the 3-D movement of teeth, including rotations, during orthodontic treatment. With this objective, we have developed an original simplified model of arch-wire behaviour and a viscoplastic behaviour law for the alveolar bone in order to simulate teeth displacements during orthodontic treatment. The contribution of the paper is part of a diagnosis system (called MAGALLANES) that is designed to replace manual measurement methods, which use costly plaster models, with computer measurement methods and teeth movement simulation using cheap hydrocolloid dental wafers. This procedure will reduce the cost and acquisition time of orthodontic data and facilitate the conduct of epidemiological studies.     

Efficacy of ampicillin combined with ceftriaxone and gentamicin in the treatment of experimental endocarditis due to Enterococcus faecalis with no high-level resistance to aminoglycosides

OBJECTIVE: This study tests the usefulness of ceftriaxone combined with ampicillin as an alternative to ampicillin plus gentamicin for the treatment of experimental endocarditis due to Enterococcus faecalis without high-level resistance to aminoglycosides. It also determines whether adding ceftriaxone to ampicillin and gentamicin increases the effectiveness against experimental enterococcal endocarditis resulting from E. faecalis. METHODS: Animals with catheter-induced endocarditis were infected intravenously with 108 cfu of the EF91 strain of E. faecalis and were treated for 3 days with ampicillin 2 g every 4 h administered as 'human-like' (H-L) pharmacokinetics, plus gentamicin 1 mg/kg every 8 h H-L, or ceftriaxone 2 g every 12 h H-L alone or combined with gentamicin 6 mg/kg every 24 h administered subcutaneously. RESULTS: The results of therapy for experimental endocarditis resulting from EF91 showed that the combination of ampicillin plus ceftriaxone was as effective as ampicillin plus gentamicin. The triple combination did not improve on the overall efficacies of the two-drug combinations. CONCLUSIONS: Because of its lower nephrotoxicity, ampicillin plus ceftriaxone may be a useful alternative therapy for E. faecalis endocarditis in selected patients.     

Aceleração da recuperação após protocolo cirúrgico versus cuidados perioperatórios convencionais em cirurgia colorretal. Um estudo de coorte em centro único

Background

Enhanced recovery after surgery (ERAS) protocols consist of a set of perioperative measures aimed at improving patient recovery and decreasing length of stay and postoperative complications. We assess the implementation and outcomes of an ERAS program for colorectal surgery.