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.     

Biocompatibility pattern of a bicarbonate/lactate-buffered peritoneal dialysis fluid in APD: a prospective, randomized study.

BACKGROUND: In chronic ambulatory peritoneal dialysis, bicarbonate-buffered fluids, with their neutral pH and less advanced glycosylation end-products (AGE) and glucose degradation products (GDP), have better biocompatibility than conventional peritoneal dialysis (PD) solutions. That difference may be more beneficial in automated peritoneal dialysis (APD), due to its more frequent exchanges and longer contact times with fresh dialysate. We performed a prospective, randomized study in APD patients to compare the biocompatibility of conventional and bicarbonate/lactate-buffered PD fluids. METHODS: We randomized 14 APD patients to have APD with either conventional or bicarbonate/lactate-based fluids. After 6 months, both groups changed to the other solution. The overall observation period was 12 months. After 1 and 5 months and again after 7 and 11 months, phagocytotic and respiratory burst capacities of effluent peritoneal macrophages were determined. Plasma interleukin (IL)-6 and C-reactive protein (CRP) as well as effluent IL-6, CRP, transforming growth factor (TGF)-beta 1, AGE and CA125 concentrations were measured. Inflow pain was quantified using a patient questionnaire. RESULTS: Respiratory burst capacity remained unchanged and phagocytotic activity increased significantly during APD (P<0.001) with the bicarbonate/lactate fluid. Effluent IL-6 release was significantly lower than with the lactate fluid (P<0.05). While in the effluent TGF-beta 1 was unaffected, AGE concentration was lower after bicarbonate/lactate treatment (P<0.05). Effluent CA125 concentration, an indicator of mesothelial cell integrity, was higher (P<0.05) in neutral effluents. Finally, patients' inflow pain diminished (P = 0.05) when using the neutral fluid. CONCLUSIONS: The use of a neutral PD fluid in APD improved patients' inflow pain as well as biocompatibility parameters reflecting enhanced phagocytotic activity of peritoneal macrophages, reduced constitutive inflammatory stimulation (IL-6), reduced AGE accumulation in the peritoneal cavity and better preservation of the mesothelial cell integrity. From the biocompatibility point of view, a neutral fluid with low GDP content can be recommended as the primary choice for APD.     

Different proliferative activity of the glandular and myoepithelial lineages in benign proliferative and early malignant breast diseases.

The aim of the present study was to explore cell biological characteristics of normal breast, benign proliferative breast diseases and noninvasive breast malignancies based on the recently published adult progenitor cell concept from our group. Here, we investigated the proliferative activity of CK5/14(+), CK8/18/19(+) and alpha-smooth muscle actin(+) cellular phenotypes encountered in normal mammary gland, in a series of usual ductal hyperplasias and early malignant breast diseases, such as atypical ductal and lobular hyperplasias, as well as ductal and lobular in situ carcinomas. Immunohistochemical double labeling was performed on frozen sections from diagnostic breast biopsies by using antibodies to basal cytokeratins (CK5/14), glandular cytokeratins (CK8/18/19), smooth muscle actin and the Ki-67 antigen (MIB1). Normal breast tissues and usual ductal hyperplasias were characterized by a heterogeneous cellular composition of the growth fraction. The proliferative cell compartment consisted of CK8/18/19(+) glandular and, in a variable proportion, CK5/14(+) progenitor phenotypes. In contrast, noninvasive breast malignancies were composed of a monotonous proliferation of CK 8/18/19(+) neoplastic glandular cells. These findings indicate a significant role of progenitor cells in the development of benign proliferative breast diseases and lend support to the view that malignant transformation in the human breast usually occurs in a cell committed to the glandular lineage. Our results provide cell kinetic support to the functional progenitor cell hypothesis, and we propose this concept as an operative model for understanding benign proliferative and malignant breast diseases.     

Assessment of basal insulin requirement using fasting tests in insulin-treated patients with type 2 diabetes mellitus.

AIMS: Characterizing the time course of the rise of blood glucose concentrations in the fasting state during the day and night in patients with type 2 diabetes. METHODS: 40 consecutive insulin-treated patients with type 2 diabetes underwent fasting tests on two different days with either no breakfast and lunch (fasting time of 20 hours) or no dinner (fasting time of 21 hours). Glucose-lowering medication was stopped prior to the test according to the half-life of the medication prescribed. At the start of the fasting tests, blood glucose concentrations were lowered to below 7 mmol/L using an insulin infusion. RESULTS: 26 men and 14 women were included in the study. Mean (+/-SD) age was 61+/-10 years, BMI 31+/-7 kg/m (2), and HbA1c 7.5+/-1%. Diabetes duration was 14+/-8 years and duration of insulin therapy had been prescribed for a mean of 6+/-6 years. During the daytime fast, plasma glucose concentrations rose by a mean of 0.8+/-1.6 mmol/L. During the nighttime fast, plasma glucose concentrations increased particularly after midnight, by 4.3+/-2.1 mmol/L, i.e. significantly more than during the daytime fast. CONCLUSIONS: Fasting blood glucose concentrations in the majority of insulin-treated patients with type 2 diabetes increase markedly after midnight. No similar increase is observed during the day. Thus, for most patients with type 2 diabetes, an intermediate- or long-acting insulin injected at bedtime with a peak action six to eight hours after injection should be appropriate.     

Long-term results with vagus nerve stimulation in children with pharmacoresistant epilepsy.

PURPOSE: To retrospectively review our experience with VNS in pediatric patients with pharmacoresistant epilepsy and examine the seizure-frequency outcome and rates of discontinuation in two age groups: adolescent and pre-adolescent children. RESULTS: Complete pre- and post-VNS data were available for 46/49 patients. Median age at implantation was 12.1 (range 2.3-17.9) and median duration of epilepsy 8.0 (1.9-16.9) years. Twenty-one patients (45.6%) were under 12 years at the time of surgery. Median follow-up was 2 years; follow-up exceeded 4 years in 9/46 patients. As compared to baseline, median seizure-frequency reduction in the setting of declining numbers was 56% at 3 months, 50% at 6, 63% at 12, 83% at 24 and 74% at 36 months. When a last observation carried forward analysis was employed median seizure-frequency reduction in the range of 60% was observed at 1, 2 and 3 years post-VNS. Twenty patients (43.5%) had >75% seizure-frequency reduction. No response (increase or <50% reduction) was observed in 19/46 (41.3%). Five patients (10.1%) were seizure-free for more than 6 months by their last follow-up. There was no difference in the number of AEDs used before and after VNS. The long-term discontinuation rate was 21.7% and reflected a lack of clinical response or infection. CONCLUSIONS: In this series VNS was well-tolerated and effective as add-on therapy for refractory seizures in children of all ages. Response was even more favorable in the younger group (<12 years at implantation). Infection and lack of efficacy were the most common reasons for discontinuation of long-term VNS therapy in this group.