Transfer of the HIV-1 cyclophilin-binding site to simian immunodeficiency virus from Macaca mulatta can confer both cyclosporin sensitivity and cyclosporin dependence

HIV-1 specifically incorporates the peptidyl prolyl isomerase cyclophilin A (CyPA), the cytosolic receptor for the immunosuppressant cyclosporin A (CsA). HIV-1 replication is inhibited by CsA as well as by nonimmunosuppressive CsA analogues that bind to CyPA and interfere with its virion association. In contrast, the related simian immunodeficiency virus SIV_mac, which does not interact with CyPA, is resistant to these compounds. The incorporation of CyPA into HIV-1 virions is mediated by a specific interaction between the active site of the enzyme and the capsid (CA) domain of the HIV-1 Gag polyprotein. We report here that the transfer of HIV-1 CA residues 86–93, which form part of an exposed loop, to the corresponding position in SIV_mac resulted in the efficient incorporation of CyPA and conferred an HIV-1-like sensitivity to a nonimmunosuppressive cyclosporin. HIV-1 CA residues 86–90 were also sufficient to transfer the ability to efficiently incorporate CyPA, provided that the length of the CyPA-binding loop was preserved. However, the resulting SIV_mac mutant required the presence of cyclosporin for efficient virus replication. The results indicate that the presence or absence of a type II tight turn adjacent to the primary CyPA-binding site determines whether CyPA incorporation enhances or inhibits viral replication. By demonstrating that CyPA-binding-site residues can induce cyclosporin sensitivity in a heterologous context, this study provides direct in vivo evidence that the exposed loop between helices IV and V of HIV-1 CA not merely constitutes a docking site for CyPA but is a functional target of this cellular protein.     

Can we predict the outcome of a partial rupture of the anterior cruciate ligament? A prospective study of 43 cases

The concept of partial rupture of the anterior cruciate ligament (ACL) has been confirmed by arthroscopic examination and palpation. We present a prospective study of 43 patients who were diagnosed arthroscopically as suffering from a partial rupture of the ACL by the same surgeon. The patients followed a rehabilitation protocol and were examined by an independant observer after 5 years. Twenty-five patients had a stable knee, whereas 18 eventually suffered a complete ACL rupture. ACL partial rupture is easily recognizable with arthroscopy, but the quantity and state of the still intact fibres is difficult to assess. Received: 20 April 1996 Accepted: 17 December 1996     

Gd-DTPA-cascade-polymer: Potential blood pool contrast agent for MR imaging

Gadolinium-DTPA (diethylenetriaminepentaacetic acid)-cascade-polymer, a potential new blood pool contrast agent for magnetic resonance (MR) imaging, was compared with a known blood pool agent, Gd-DTPA-polylysine, in an animal model. The relative signal intensities of liver, renal cortex, pancreas, and trunk muscle were assessed in 12 pigs between 4 seconds and 120 minutes after injection of a 20 μmol/kg dose of each contrast agent, by using a FLASH (fast low-angle shot) sequence. Except for muscle, all tissues showed visible enhancement after injection of either contrast agent. After injection of Gd-DTPA-polymer, enhancement patterns in the liver, renal cortex, and pancreas were similar to those seen after injection of Gd-DTPA-polylysine. No statistically significant differences in enhancement between the two contrast agents were found at any time point. The authors conclude that the contrast kinetics of Gd-DTPA-cascade-polymer are similar to those of Gd-DTPA-polylysine and that this agent may also be used as a blood pool contrast agent for MR imaging.     

Initial experience with dynamic MR imaging in evaluation of normal bone marrow versus malignant bone marrow infiltrations in humans

The purpose of this study was (a) evaluation of dynamic contrast-enhanced MR imaging of normal bone marrow versus malignant bone marrow infiltrations in patients with proven B-cell-type chronic lymphocytic leukemia (B-CLL) and (b) correlation with the clinical stage according to Binet (stages A, B, C) and response to therapy. Bone marrow imaging of the lumbar spine, pelvis, and proximal femurs was performed at 1.5 T in 45 patients without known malignancy and in 30 patients with B-CLL. The differences between opposed-phase and in-phase dynamic gradient-echo sequences before and up to 10 minutes after intravenous application of .1 mmol/kg body weight of gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) were evaluated in normal bone marrow. The contrast-enhancement patterns of normal and malignant bone marrow were compared using the opposed-phase dynamic gradient-echo sequence. Ten of the patients with bone marrow infiltrations (Binet stage C) additionally underwent MR imaging follow-up during therapy. Opposed-phase gradient echo sequences demonstrated a signal decrease of normal bone marrow, and in-phase gradient echo sequences demonstrated a signal increase of normal bone marrow after administration of Gd-DTPA. The dynamic signal intensity time courses differed significantly (P < .05) between Binet stages B and C and controls as well as among the three Binet stages of B-CLL. In the 10 patients followed during therapy, MR imaging sensitively demonstrated response (n = 6), nonresponse (n = 2), or relapse after initial response (n = 2). In out-of-phase imaging, both normal bone marrow and initial bone marrow infiltration in CLL stage Binet A show signal decrease after administration of contrast agent, whereas there is increase in signal intensity in higher-grade bone marrow infiltration in Binet stage B or C disease. The signal loss of normal bone marrow in out-of-phase imaging is a phase effect rather than a T2* effect. The differentiation of initial from higher-grade bone marrow infiltration on out-of-phase images relies solely on a shift in the fat/water ratio.     

Inhibition of HSV-1-specific cytotoxic T lymphocytes by recombinant-derived gp120 of HIV-1.

The ability of human immunodeficiency virus type-1 (HIV-1) and recombinant HIV-1 gp120 to prevent target cell lysis by herpes simplex virus type 1 (HSV-1)-specific cytotoxic T lymphocytes (CTL) was assessed by limiting dilution analysis. Live and inactivated HIV-1 as well as recombinant-derived gp120 all substantially inhibited HSV-1-specific CTL. Soluble CD4 antigen reversed the inhibition by gp120 when simultaneously added with gp120 to the assay. In addition, the monoclonal anti-CD4 antibody a-Leu3a mimicked the effects of gp120 in these experiments. These data suggest that the observed decrease in measurable CTL activity is caused by direct or steric hindrance of the CD4-class II major histocompatibility complex interaction between the effector and target cells.     

Osteitis Unterschenkel

Osteomyelitis patients feel their social and professional existence is threatened. Health insurances are faced with total treatment costs for each patient with osteomyelitis, which can reach 500.000,00 EUR. We must therefore make every effort, from the first onset of infection, to prevent the condition from becoming chronic and thus keep the potential problems to patients and insurance companies to a minimum: once the condition has become chronic there is absolutely no guarantee that treatment will be successful. Treatment must start with the removal of absolutely all necrotic tissue – soft tissue and bone – and of all implants. As in tumor surgery, en bloc resection is best. Up to now there is still no means of determining the exact limits of the infection. The surgeons's personal experience with osteomyelitis is the most important factor both in the treatment of these cases and therefore in the containment of treatment costs. Bone reconstruction is attempted after the soft tissue defects have been treated, either by bone grafting (defect < 3 cm) or by segment transfer. Modern techniques of reconstruction surgery can yield quite good results even in chronic oxteomyelitis, providing management has been optimum throughout. Patients with osteomyelitis should therefore be treated in specialist hospitals.     

The Frictional Behavior of Coated Guiding Archwires

Background: The vast range of orthodontic wires made of different alloys makes it increasingly difficult for orthodontists to judge them. Coated orthodontic wires form a group of innovative guiding archwires. Material and Methods: In the present in vitro study the frictional behavior of eight coated wires of different dimensions was investigated in archwire-guided canine retraction in the upper jaw. For this purpose five superelastic nickel titanium alloy wires (Titanol^/reg; Low Force River Finish Gold and Gold 2: Forestadent^®, Pforzheim Germany; Titanol^® Superelastic tooth Sentalloy Ionguard™: GAC, Central Islip, NY, USA; NITI Imagination™: GAC, Central Islip, NY, USA), two #-titanium wires (TMA^® Low Friction Ionguard: Ormco, Glendora, CA, USA; TMA^® Low Friction Ionguard Purple: Ormco, Glendora, CA, USA) and one steel wire (Stainless steel Imagination™: GAC, Central Islip, NY, USA) were selected. The coatings were made of Teflon^® or polyethylene, and by ion implantation. Three uncoated archwires (Rematitan^® Lite Dimple; Dentaurum, Pforzheim, German; Titanol^® Low Force River Finish: Forestadent^®, Pforzheim, Germany; BioForce Sentalloy™: GAC, Central Islip, NY, USA) were used for comparison purposes. The force losses due to friction were measured using the Orthodontic Measurement and Simulation System (OMSS). Results: The results indicated that all coatings can reduce frictional losses compared with an uncoated reference wire by the same manufacturer. Measured frictional losses ranged from 48.3-6.1% with the Teflon^® coatings reducing the frictional losses to less than 10% in some cases. Conclusion: An unequivocal correlation between the surface roughness and frictional forces of the wires could not be verified by scanning electron microscopy. Zusammenfassung Hintergrund: Die Vielzahl an orthodontischen Drähten aus diversen Legierungen macht es die Kieferorthopäden immer schwerer, sie zu beurteilen. Eine Gruppe von neu angebotenen Führungsbögen stellen die beschichteten orthodontischen Drähte dar. Material und Methode: In der vorliegenden In-vitro-Studie wurde das Reibungsverhalten von acht beschichteten Drähten unterschiedlicher Dimension bei den bogengeführten Eckzahnretraktion im Oberkiefer untersucht. Neben fünf Nickel-Titan-Drähten (Titanol^® Low Force River Finish Gold und Gold 2: Fa. Forestadent^®; Titanol^® Superelastic zahnfarben: Fa. Forestadent^®; BioForce Sentalloy Ionguard™: Fa. GAC; NiTi Imagination™: Fa. GAC) wurden zwei #-Titan- (TMA Low Friction Iongard: Fa. Ormco; TMA Low Friction Ionguard Purple: Fa. Ormco) und ein Stahldraht (Stainless Steel Imagination™: Fa. GAC) ausgewählt. Die Beschichtungen bestanden aus Teflon^®, Polyethylen oder Ionenimplantation. Als Referenz wurden drei unbeschichtete Drähte (Rematitan^® Lite Dimple: Fa. Dentaurum; Titanol^® Low Force River Finish: Fa. Forestadent^®; BioForce Sentalloy™: Fa. GAC) in die Untersuchung einbezogen. Die Reibungsverluste wurden mit dem Orthodontischen Mess- und Simulations-System (OMSS) bestimmt. Ergebnisse: Die Ergebnisse zeigten, dass alle Beschichtungen, verglichen mit einem unbeschichteten Referenzdraht desselben Herstellers, eine Reduktion der Reibungsverluste bewirken. Die gemessenen Reibungsverluste lagen zwischen 48,3% und 6,1%, wobei bei Teflon^®-Beschichtungen der Reibungsverlust zum Teil auf unter 10% sank. Schlussfolgerung: Ein eindeutiger Zusammenhang zwischen der Oberflächenrauheit und den Friktionswerten der Drähte konnte anhand von rasterelektronenmikroskopischen Aufnahmen nicht bestätigt werden.     

Evidence for a human IgG1 class switch program

In activated murine B lymphocytes, immunoglobulin class switch recombination occurs as a highly regulated process which is targeted to distinct switch regions. Here we present first evidence that in human B lymphocytes, switch recombination is targeted to distinct switch regions as well. In a panel of clonally unrelated IgG1-expressing human B cells, immortalized by Epstein-Barr virus (EBV) transformation, seven out of nine cells show switch recombination between Sμ and Sγ1 on both alleles, the active and inactive one. The remaining cells show no switch recombination on the inactive IgH locus. The very strong correlation of switch recombination on both alleles of IgG1-expressing cells proves that class switch recombination to IgG1 is not random but directed in human B lymphocytes.