Extent and diversity of inflammatory cell infiltrates in squamous cell carcinomas and basal cell epitheliomas of the head and neck

Using monoclonal antibodies reactive with Langerhans' cells (LCs), macrophages, and T cell subpopulations, the density and proportions of cells of the immune system of the normal oral mucosa were determined immunohistochemically, and compared with findings in oral squamous cell carcinomas (SCC) and basal cell epitheliomas (BCE). In normal oral epithelia, the dominant cell type was the LC, positive for CD 1, and expressing HLA-DR antigens (DR⁺). Many intraepithelial cells were lymphocytes of the suppressor/cytotoxic phenotype (CD 8⁺), which was also the most prominent cell type in the normal mueosal slroma. Significant differences were observed for the content of CD 8-, OKM 1-, and CD 4-positive cells in the epithelium of normal oral mucosa, SCC, and BCE, and for the amount of CD 1-positive Langerhans cells in the connective tissue of the different groups of tissues. When CD 4/CD 8 ratios were calculated, differences between SCC and BCE became most evident. A CD 4/CD 8 ratio greater 0.5 was seen to be characteristic for BCE. Thus, in contrast to the striking preponderance of suppressor/cytotoxic lymphocytes (CD 8⁺) in SCC, BCE showed typically almost balanced numbers of suppressor/cytotoxic (CD 8⁺) and helper/induced (CD 4⁺) lymphocytes. This finding further underlines the biological differences recognized between these most common neoplasias of the head and neck.     

Effects of different perfusates on functional parameters of isolated perfused dog kidneys.

BACKGROUND: The isolated perfused canine kidney has been established as a valid model for conducting both renal physiology and transplantation research. This model is of particular importance for developing new strategies to improve graft function after renal transplantation. In the present study, a newly developed method using isolated haemoperfused porcine kidneys was adapted for use in canine kidneys. In contrast to haemoperfusion, synthetic perfusion media can be standardized and can prevent the initiation of blood-mediated reperfusion reactions. Thus, an additional aim was to determine whether blood could be replaced by synthetic cell-free perfusion solutions. METHODS: Canine kidneys (n = 30) were harvested from donors euthanized in veterinary practices for causes unrelated to the present study. The kidneys were isolated and perfused with autologous blood or cell-free synthetic electrolyte buffer (Tyrode solution). During perfusion, we monitored renal perfusate flow (RPF), glomerular filtration rate (GFR), electrolyte and glucose reabsorption, oxygen consumption and urine concentration. RESULTS: Changes in perfusion medium did not affect the RPF. In contrast, GFR, urine concentration and oxygen consumption were significantly higher, whereas fractional excretion of sodium and glucose were significantly lower in blood- than in Tyrode-perfused kidneys. CONCLUSIONS: This system offers a simple model for studying whole-organ functional alterations after acute renal ischaemia. Renal function indicators were below values reported during in vivo physiological conditions. These functions were better conserved when kidneys were perfused with autologous blood than with Tyrode.     

Incidence and Clinical Significance of Ventricular Late Potentials in Idiopathic Dilated Cardiomyopathy Compared to Coronary Artery Disease

Objective: This prospective study was designed to compare incidence and clinical significance of ventricular late potentials between patients with idiopathic dilated cardiomyopathy (IDC) and postinfarct patients (CAD) using exactly the same method of signal-averaged electrocardiography (SAECG) in both patient groups. Methods: Time-domain analysis of SAECG was performed in 120 consecutive patients with IDC, 120 patients with CAD, and 60 healthy controls. Ventricular late potentials were detected in 27 of 120 patients with IDC (23%) compared to 41 of 120 patients with CAD (34%; P < 0.05). Results: Ventricular late potentials were found in 2 of 60 controls (3%). During 15 ± 7 months follow-up, serious arrhythmic events occurred in 17 of 120 patients with IDC (14%) and in 13 of 120 patients with CAD (11%). The sensitivity of ventricular late potentials for future arrhythmic events was 35% for IDC compared to 77% for CAD (P < 0.05). The positive predictive value of late potentials detected by time-domain analysis was 22% for IDC versus 24% for CAD (P = ns). Conclusion: In this selected patient population with IDC and CAD, time-domain analysis of SAECG revealed a lower incidence of ventricular ate potentials in patients with IDC as compared to postinfarct patients. Whereas ventricular late potentials had a high sensitivity but a low positive predictive value for identification of postinfarct patients with serious arrhythmic events during follow-up, both sensitivity and positive predictive value of ventricular late potentials for future serious arrhythmic events were low in the setting of IDC.     

Akromioklavikulargelenkverletzungen

There is some controversy over the treatment of acromioclavicular injuries. The use of the Rockwood classification as the basis for decisions on whether operative or nonoperative treatment is indicated is discussed critically, and the authors' preferred operative technique is described and illustrated by examples. We treat injuries classified according to the Rockwood classification as types I and II with conservative methods. In type III injuries the patient's age, job and free time activities determine whether or not surgery is indicated. In the case of type IV or type VI injuries we always perform temporary internal fixation of the acromioclavicular joint, using transarticular K-wire fixation or hookplate osteosynthesis. Satisfactory results of both operative and nonoperative treatment are reported in the literature. The authors' own results are presented.     

Cerebrospinal fluidCHOLINESTERASES—MARKERS for loss ofcholinergic basal forebrain neurons?

The present study was conducted to test the hypothesis that cholinergic basalforebrain neurons are a major source of cerebrospinal fluid (CSF) cholinesterases. To address thisquestion enzyme activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inboth CSF and parietal cortex were assayed following selective lesion of basal forebrain cholinergicneurons by a single intracerebroventricular application of the cholinergic immunotoxin192IgG-saporin. Cholinergic immunolesions led to a dramatic decrease in total AChE activity inparietal cortex, which was due to the specific loss of the G4 molecular form while the activity ofthe G1 form was increased as compared to nonlesioned animals. In contrast, the total enzymeactivity of BChE and its molecular forms were not affected by cholinergic lesion in both parietalcortex and CSF. The data suggest, that cholinergic basal forebrain neurons are seemingly not amajor source of cholinesterases in the CSF, and do not provide any evidence for using CSFcholinesterases as a diagnostic marker of basal forebrain cholinergic cell loss in humans.     

Impact of Social Confrontation on Rat CD4 T Cells Bearing Different CD45R Isoforms

The impact of social defeat on lymphocyte subpopulations and T helper subsets was investigated in Long Evans rats. CD4 T helper cell subsets with distinct functional properties and different cytokine profiles can be distinguished by using the mAbs OX-22 (anti-CD45RC) and OX-7 (anti-CD90, Thy1.1). Male intruders were exposed for 2, 6, or 48 h to aggressive resident pairs. All intruders were attacked upon introduction and were defeated as indicated by frequent display of full submissive postures. After 2 and 48 h of confrontation, drastic but differential effects on blood leukocyte numbers, CD4 and CD8a cells, and CD4 subsets were evident. However, after 6 h of confrontation most lymphocyte subset numbers corresponded to baseline levels. Focusing on CD4 subsets after 2 h of confrontation, we demonstrated that only the number of the CD45RC⁻CD90⁻subset declines, whereas neither the number of the CD45RC⁺CD90⁻subset nor the number of the CD45RC⁻CD90⁺subset (recent thymic emigrants) was influenced. Con A stimulation of sorted subsets identified the CD45RC⁻CD90⁻as a poor producer of IFN-γ. The data clearly demonstrate that social factors might differentially influence not only T cell subsets but also T helper cell subsets with distinct cytokine profiles in a possibly time-dependent manner. Such a stress-induced shift toward a CD45RC⁺CD90⁻-dominated milieu may have important consequences in interpreting results obtained from mitogenic stimulation of blood lymphocytes and cytokine production profiles measured after such a stimulation. In addition, a shift toward a CD45RC⁺CD90⁻dominance may modify the type and magnitude of immune response, at least temporarily.     

Role of mast cells in experimental anti-glomerular basement membrane glomerulonephritis

Recently, divergent reports on the role of mast cells (MC) in different glomerular diseases have brought our attention to their role in an accelerated model of anti-glomerular basement membrane (GBM) glomerulonephritis (GN). Genetically MC-deficient Kit(W)/Kit(W-v) mice, MC-reconstituted Kit(W)/Kit(W-v) mice and Kit+/+ control mice were subjected to anti-GBM GN. Kit(+/+) mice developed moderate proteinuria and glomerular damage following the induction of anti-GBM nephritis. In contrast, proteinuria and glomerular damage were dramatically increased in MC-deficient Kit(W)/Kit(W-v) mice. MC-reconstituted Kit(W)/Kit(W-v) mice showed proteinuria and glomerular damage comparable to Kit+/+ mice. A significant increase in infiltrating T cells and macrophages was detected in MC-deficient Kit(W)/Kit(W-v) mice as compared to Kit+/+ control mice and MC-reconstituted Kit(W)/Kit(W-v) mice. Accordingly, we observed an increase of TGF-beta1 mRNA in kidneys from Kit(W)/Kit(W-v) mice. Interestingly, we did not detect MC in the kidney using either Giemsa staining or RT-real-time PCR, but MC were found in the regional lymph nodes. Finally, mortality of Kit(W)/Kit(W-v) mice was significantly increased after the induction of anti-GBM GN due to uremia. Our report provides the first direct evidence that MC are protective in anti-GBM GN, possibly by modulating the influx of effector T cells and macrophages to inflammatory sites in the kidney.     

Neutralization assay using a modified vaccinia virus Ankara vector expressing the green fluorescent protein is a high-throughput method to monitor the humoral immune response against vaccinia virus

Vaccination against smallpox is again considered in order to face a possible bioterrorist threat, but the nature and the level of the immune response needed to protect a person from smallpox after vaccination are not totally understood. Therefore, simple, rapid, and accurate assays to evaluate the immune response to vaccinia virus need to be developed. Neutralization assays are usually considered good predictors of vaccine efficacy and more informative with regard to protection than binding assays. Currently, the presence of neutralizing antibodies to vaccinia virus is measured using a plaque reduction neutralization test, but this method is time-consuming and labor-intensive and has a subjective readout. Here, we describe an innovative neutralization assay based on a modified vaccinia virus Ankara (MVA) vector expressing the green fluorescent protein (MVA-gfp). This MVA-gfp neutralization assay is rapid and sensitive and has a high-throughput potential. Thus, it is suitable to monitor the immune response and eventually the efficacy of a large campaign of vaccination against smallpox and to study the vector-specific immune response in clinical trials that use genetically engineered vaccinia viruses. Most importantly, application of the highly attenuated MVA eliminates the safety concern in using the replication-competent vaccinia virus in the standard clinical laboratory.