Intracranial circulation: pulse-sequence considerations in three- dimensional (volume) MR angiography

The technique and feasibility of magnetic resonance (MR) angiography of intracranial vessels were studied in 35 healthy volunteers. Variations in image orientation, repetition time (TR), and flip angle were evaluated to determine their effects on flow-related enhancement. Gradient modifications--including echo time (TE), motion compensation, bandwidth, and field of view--were also studied in an effort to reduce motion-induced phase shifts. Results indicated that a FISP (fast imaging with steady precession) sequence with a TR of 50 msec, TE of 15 msec, velocity compensation in the read and section-select directions, acceleration compensation in the read direction, anisotropic volume, and a 1.25-mm partition thickness produced three-dimensional angiographic MR images that were accurate and reproducible in the depiction of the major intracranial vessels. Difficulties with field of view, persistent signal void secondary to higher-order motion, and spatial resolution remain major problems requiring additional study.     

AlphaV beta3 (αvβ3) integrin inhibition reduces leukocyte–endothelium interaction in a pressure-induced reperfusion model

The leukocyte-endothelium interaction is known to contribute to reperfusion injury, which is considered to participate in the pathophysiology of pressure ulcers, and integrin alphaV beta3 (alphavbeta3) has been shown to mediate the processes of cellular adhesion in various types of cells. This study aims to clarify leukocyte behavior in our original microcirculatory pressure-induced reperfusion model, which can visualize the microcirculation in vivo. We also estimated the effect of alphavbeta3 integrin inhibition on the reduction of the leukocyte-endothelium interaction. Mice with dorsal skinfold chambers were divided into three groups: the baseline group (n=6), in which animals received no compression; the compression-reperfusion group (n=6), in which animals underwent 2-hour compression of the dorsal skin, followed by release, and the inhibitor-treated group (n=7), in which an alphavbeta3 inhibitor, CP4715, was administered in addition to the compression-release procedure. Staining with rhodamine 6G quantitatively visualized leukocyte behavior under the intravital fluorescent microscope. Compression-reperfusion induced a significant increase in rolling, sticking, and extravasation of the leukocytes. Treatment with the inhibitor strikingly reduced leukocyte sticking and extravasation. The present experiment has provided evidence that alphavbeta3 inhibition reduces leukocyte-endothelium interaction in our original pressure-induced reperfusion model.     

Raf-1 kinase,epidermal growth factor receptors,and mutant ras proteins in colonic carcinomas

Epidermal growth factor receptors (EGFR) andras mutations are known to play a significant role in controlling cell growth and tumor promotion. Both of them transmit mitogenic signals to the nucleus by activation of Raf-1 kinase. In this study, the expression of EGFR and mutant Ras proteins, and, for the first time, the expression, phosphorylation and kinase activity of Raf-1 kinase have been determined in paired samples of colorectal cancer and mucosa. The tumor and mucosa samples did not differ significantly with regard to Raf-1 kinase content and activity. A major difference between tumors and mucosa was found, however, in the phosphorylation of Raf-1. Most of the mucosa samples (13/20), but only 1/20 of the cancer samples, contained hyperphosphorylated Raf-1. EGFR were significantly (p=0.0025) decreased in the tumors. The decreased phosphorylation of Raf-1 in colonic carcinomas could be the result of activation of Raf-1 phosphatases or inactivation of kinases phosphorylating Raf-1. New forms of treatment based on EGFR overexpression do not seem to be suitable for the majority of colonic cancers.This work was supported by the state of Baden-Württemberg (Verbundforschungsprojekt: Aufklärung von Mechanismen der Tumorentstehung und Tumorabwehr).     

Analysis of ischemia-reperfusion injury in a microcirculatory model of pressure ulcers

The aim of this study was to establish a pressure ulcer model that visualizes the microcirculation, and to examine the participation of ischemia-reperfusion injury in the pathophysiology of pressure ulcers. An original system composed of a new skin fold chamber and compression device allowed loading quantitative vertical stress to the skin. An intravital microscopic technique enabled direct visualization of the microcirculation in the physiological condition and in response to pressure application. To estimate the effect of ischemia-reperfusion injury, animals were divided into two groups: the compression-release group (n = 8), in which the animals received four cycles of compression-release which consisted of 2 hours of compression followed by 1 hour of pressure release; and the compression alone group (n = 8) in which the animals underwent continuous compression for 8 hours. Functional capillary density was quantified before the compression procedure and on day 1 (35 hours) after the first evaluation. The cyclic compression-release procedure significantly decreased functional capillary density as compared to continuous compression, indicating that in our experimental setting repetition of ischemia-reperfusion cycle more severely damaged the microcirculation than single prolonged ischemic insult. This finding supports the significant contribution of ischemia-reperfusion injury to the pathophysiology of pressure ulcers at the level of dynamic in vivo microcirculation.     

Intercellular adhesion molecule-1 (ICAM-1, CD 54) is associated with actin-filaments.

Intercellular adhesion molecule 1 (ICAM-1, CD 54) is a membrane associated glycoprotein involved in cell-cell interactions of the immune system. Detergent extraction of cultured human fibroblasts--stimulated with Interferon-gamma (IFN-gamma) for ICAM-1-expression--under conditions that stabilize actin in the filamentous (actin-F) form (NaF-buffer, phalloidine) resulted in greater retention of ICAM-1 in the detergent insoluble phase, containing the cytoskeletal matrix, compared to actin-F-destabilizing conditions (KCl-buffer). We further examined the in vitro ICAM-1 association with actin using immunoaffinity purified ICAM-1, prepared from either normal human tonsils or a spleen derived from a patient with Non-Hodgkin's lymphoma. ICAM-1 from both sources demonstrated binding to actin coated polystyrene surfaces. Our findings suggest that ICAM-1 interacts with actin-F and may use similar mechanisms described with other adhesion molecules for membrane-cytosol communication.     

Reversal of the decline in the incidence of tuberculosis in the Austrian Tyrol and Vorarlberg in 1989.

The incidence of tuberculosis in the Austrian Tyrol and Vorarlberg has been declining over decades. In 1989 a reversal in this trend was observed. The number of initial isolates of Mycobacterium tuberculosis at the Federal Public Health Laboratory in Innsbruck increased by 2.2% in 1990 (137 strains), as compared with 1989 (134 strains). The number of cases reported to the health authorities increased by 7.6%. This increase has continued in 1991, with 162 initial isolates registered. It seems that the increase is connected with the presence of greater numbers of ethnic groups from countries with a high incidence of tuberculosis. It is unlikely that the increase is due to additional cases of tuberculosis resulting from the HIV epidemic. Nevertheless, it is recommended that patients with tuberculosis undergo HIV antibody testing. A comparison of the results of animal tests and cultures for demonstrating the presence of mycobacteria showed that the culture procedure is at least equally efficient.     

Complement-opsonized HIV: the free rider on its way to infection

The complement system (C) is one of the main humoral components of innate immunity. Three major tasks of C against invading pathogens are: (i) lysis of pathogens by the formation of the membrane attack complex (MAC); (ii) opsonization of pathogens with complement fragments to favor phagocytosis; and (iii) attraction of inflammatory cells by chemotaxis. Like other particles, HIV activates C and becomes opsonized. To escape complement-mediated lysis, HIV has adopted various properties, which include the acquisition of HIV-associated molecules (HAMs) belonging to the family of complement regulators, such as CD46, CD55, CD59, and the interaction with humoral regulatory factors like factor H (fH). Opsonized virus may bind to complement receptor positive cells to infect them more efficiently or to remain bound on the surface of such cells. In the latter case HIV can be transmitted to cells susceptible for infection. This review discusses several aspects of C-HIV interactions and provides a model for the dynamics of this process.     

Immunotopographic assessment of lymphoid and plasma cell malignancies in the bone marrow

To determine the utility of tissue section immunochemistry in the evaluation of bone marrow involved by lymphoid and plasma cell malignancies, snap-frozen, undecalcified bone marrow core and aspirate samples from 23 patients with these disorders were studied with a battery of monoclonal antibodies. With techniques that preserve architecture, difficult diagnostic cases characterized by core but not aspirate involvement, or the reverse, were resolved. By means of an extensive battery of monoclonal antibodies applied to serial sections, complex tumor cell phenotypes were established in all 23 cases. In addition to the identification of straightforward monoclonal surface immunoglobulin expression in small cleaved cell lymphomas (four cases), the battery approach added immunologic certainty in malignancies with unusual or difficult phenotypes: peripheral T-cell lymphomas with idiosyncratic antigen expression, and chronic lymphocytic leukemias and small cell lymphomas with faint surface immunoglobulin expression (four cases). For the chronic lymphocytic leukemias and the small cell lymphomas, the combined IgD+, B2+, B1+, Ia+, Leu-1+ phenotype taken as a whole had greater utility than any isolated marker. The acute lymphocytic leukemias and the myelomas studied demonstrate the wide range of B-cell antigens that must be detected to account for the variety of B-cell neoplasms encountered. Additionally, the previously undescribed phenotypic subset of CALLA+ myelomas, which is of prognostic relevance, was identified. Marrow frozen section immunotyping is a major asset in the evaluation of patients with lymphoma, leukemia, and myeloma when special care is accorded to tissue handling and to treatment of endogenous peroxidase/pseudoperoxidase and interstitial immunoglobulin.