Reduction of IL-12 p40 production in activated monocytes after exposure to diesel exhaust particles

BACKGROUND: A reduction of IL-12 production by lung macrophages may partly explain the presumed adjuvant effect of diesel exhaust particles (DEP) in allergy and asthma. IL-12 stimulates T helper type 1 (Th1) lymphocytes, which inhibit Th2 cells via Th1-specific cytokines. The aim of this study was to investigate the influence of DEP on the production of IL-12 p40 in lipopolysaccharide (LPS)-activated monocytes. METHODS: The human monocytic cell line Mono-Mac-6 was stimulated with LPS (200 ng/ml) and grown with DEP (0-200 microg/ml) for 0, 6 or 24 h. IL-12 p40 and the pro-inflammatory cytokine TNF were analysed in the cell supernatants by ELISA and a cell assay, respectively. RESULTS: Levels of IL-12 p40 correlated inversely with the DEP exposure concentrations, whereas TNF increased in parallel to the DEP concentrations. At a DEP concentration of 200 microg/ml, the amount of IL-12 p40 was 35% of that observed without DEP. The corresponding TNF value was 230% of the control. Reduced viability, binding of cytokines to DEP or endotoxin in the DEP samples cannot fully explain the changes in the concentrations of these two cytokines. CONCLUSION: DEP seem to inhibit the production of IL-12 p40 and stimulate that of TNF in activated monocytes. This may partly explain the presumed adjuvant effect of DEP in atopy; by altering the Th1/Th2 balance via down-regulation of IL-12, the Th2 response characteristic of allergy and asthma may be favoured.     

Das kritische Intervall peripherer Nerven bei Reizung am gleichen und an verschiedenen Orten

Summary The critical interval of the ulnar nerve was studied in two different ways in 15 normal subjects. Needle electrodes were used for application of stimuli giving the adventage to obtain a supramaximal excitation of the nerve by impulses of rather short duration and low intensity. Recording of nerve action potentials was done by needle electrodes as well, and amplitudes seen with this method were considerably higher than those recorded by surface electrodes.After a single supramaximal stimulation of the nerve a second shock applied at the same site does not evoke a propagated nerve action potential until a certain interval (critical interval) of 0.55–0.70 msec has elapsed. This interval is markedly shortened to values between 0.35 and 0.55 msec if the first and the second stimulus are delivered to different points of the nerve, about 5 cm apart from each other.Furthermore it was observed that at high stimulus intensities the critical interval is not altered by varying the duration of the stimulating impulses between 0.05 and 1.0 msec.A possible explanation for these results is discussed.

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Increased Incidence of Missed Seizures During ECT in the Elderly Male

Monitoring seizure length is an important addition to the clinical practice of ECT. Without monitoring, undetected missed seizures may occur. In a retrospective study of ECT treatments for a sample of 58 patients with a DSM-III diagnosis of major depression, significantly more missed seizures (p < 0.05) occurred in the elderly males.     

Initial Impression of Two New Brief-Pulse Electroconvulsive Therapy Machines

Until last year only two U.S. manufacturers were producing ECT machines for purchase. These machines differed in waveforms: a sine-wave device (Medcraft Corp.) and a brief-pulse bidirectional square-wave machine (MECTA Corp.). Early in 1985 a new brief-pulse bidirectional square-wave machine called the Thymatron was marketed (Somatics Inc.). For the first time this created a choice in brief-pulse equipment available in the U.S. This paper summarizes our initial impressions to this new brief-pulse device and one of MECTA's most recent brief-pulse models (SR-1) in terms of features, safety, practicality, and cost.     

Flattening the quality of life curve? A prospective person-centred study from Norway amid COVID-19

Quality of Life Research - We examined multidimensional, heterogeneous reactions to the COVID-19 pandemic and associated measures to provide further insights into the developmental processes of...     

Circulating magnesium status is associated with type 2 diabetes remission after Roux-en-Y gastric bypass surgery: a long-term cohort study

BackgroundLow serum magnesium levels predict cardiovascular and all-cause mortality in patients with typ 2 diabetes.SettingOutpatient clinic of obesity and central hospital.ObjectivesTo assess long-term alterations in circulating magnesium status after Roux-en-Y gastric bypass (RYGB) surgery and associations with remission of type 2 diabetes (T2D).MethodsRetrospective analysis of 5-year outcomes of plasma magnesium (p-Mg) and glucometabolic statuses in patients who underwent primary RYGB and who completed the annual follow-up program. Data were investigated from 84 patients without diabetes and 62 with T2D before RYGB, who showed either prolonged remission (n = 30), temporary remission (n = 16), or no remission (n = 16) after surgery.ResultsBody mass indexes before RYGB were similar in patients with and without T2D, irrespective of remission. The patients not achieving remission showed longer diabetes durations; higher circulating glucose levels; more intensive antidiabetic drug treatment, including insulin; and significantly lower p-Mg concentrations (.73 [±.08] mmol/L compared with .80–.82 [±.07] mmol/L, respectively; P < .01) than the groups showing remission or without diabetes before surgery. After RYGB, the p-Mg increased similarly, by 10–12% in the groups with T2D before surgery, irrespective of remission; however, the nonremission group did not reach the p-Mg levels registered in the other groups after follow-up. The nonremission group reached .82 (.09) mmol/L, compared with .87 (.06) and .88 (.08) mmol/L (P < .05), respectively, in patients with remission or without a history of diabetes.ConclusionThe p-Mg concentrations increased after RYGB, with similar increments irrespective of T2D remission; however, the nonremission group started from an inferior level and did not reach the p-Mg concentrations seen in the groups achieving remission or without a history of diabetes before surgery.     

Binding of lipopeptide to CD14 induces physical proximity of CD14, TLR2 and TLR1

Lipoproteins or lipopeptides (LP) are bacterial cell wall components detected by the innate immune system. For LP, it has been shown that TLR2 is the essential receptor in cellular activation. However, molecular mechanisms of LP recognition are not yet clear. We used a FLAG-labeled derivative of the synthetic lipopeptide N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2R,S)-propyl]-(R)-cysteinyl-seryl-(lysyl)(3)-lysine (Pam(3)CSK(4)) to study the roles of CD14, TLR2 and TLR1 in binding and signaling of LP and their molecular interactions in human cells. The activity of Pam(3)CSK(4)-FLAG was TLR2 dependent, whereas the binding was enabled by CD14, as evaluated by flow cytometry and confocal microscopy. Using FRET and FRAP imaging techniques to study molecular associations, we could show that after Pam(3)CSK(4)-FLAG binding, CD14 and Pam(3)CSK(4)-FLAG associate with TLR2 and TLR1, and TLR2 is targeted to a low-mobility complex. Thus, LP binding to CD14 is the first step in the LP recognition, inducing physical proximity of CD14 and LP with TLR2/TLR1 and formation of the TLR2 signaling complex.     

Cross-reactivity between pollen extracts from six artemisia species

Pollen extracts of six different ARTEMISIA species, A. VULGARIS, A. SCOPARIA, A. PRINCEPS, A. TRIDENTATA, A. ANNUA, and A. CAMPESTRIS were compared using SDS-PAGE, IEF, immunoblotting, and immunoelectrophoretic methods. The band patterns obtained after SDS-PAGE and IEF showed a large degree of similarity between the extracts. Immunoblotting of these gels using a pool of sera from patients allergic to A. VULGARIS gave essentially the same IgE-binding band pattern with all the extracts, demonstrating an extensive degree of cross-reactivity between A. VULGARIS and the other ARTEMISIA species. FRIE using a polyspecific antiserum against A. VULGARIS showed that all the extracts contained several antigens that were immunologically identical to antigens in A. VULGARIS extract. Antigens showing immunological identity to the important A. VULGARIS allergens Ag 12 and ART V II were present in all the extracts. The cross-reactivity between A. VULGARIS and A. PRINCEPS was further verified by screening of ten Korean and nine Norwegian individual patient sera against extracts of both species in SDS-PAGE or IEF immunoblotting. Both groups of patients had essentially the same pattern of reactivity towards both pollen extracts.     

Analysis of T-cell receptor expressing lymphocytes infiltrating squamous cell carcinomas of the upper aerodigestive tract

T-lymphocytes expressing T -cell receptors (TCRs) of the / type have been suggested to play an important role in mucosal defense against infection and neoplastic transformation. In this study, an immunohistochemical investigation was performed on the distribution of / and / TCRs among tumor-infiltrating lymphocytes. Thirteen patients with squamous cell carcinomas of the upper aerodigestive tract were studied, using monoclonal antibodies and an avidin-biotin-peroxidase technique. Most of the T-cells had an / TCR. Only 1.6% of the T-cells within the cancer tissue and 1.2% of the T-cells in the parenchyma adjacent to the cancer tissue expressed /gd TCRs. These results are consistent with the results of similar studies in bronchial and breast carcinomas. Biopsies from normal oral mucosa in nine healthy individuals showed that 1.3% of the T -cells within the epithelium and 1.0% of those in the lamina propria adjacent to the epithelium expressed / TCRs. Quantitatively the results do not support the theory that / T-cells play an important role in the immunological response against cancer tissue in the mucosa of the upper aerodigestive tract. The functional role of these cells in the mucosa and in response to carcinomas is, however, still uncertain.     

Endoscopic neurosurgery "around the corner" with a rigid endoscope. Technical note.

Endoscopically "working around the corner" is presently restricted to the use of flexible endoscopes or an endoscope-assisted microneurosurgical (EAM) technique. In order to overcome the limitations of these solutions, endoscopic equipment and techniques were developed for "working around the corner" with rigid endoscopes. A steering insert with a 5 French working channel is capable of steering instruments around the corner by actively bending the guiding track and consecutively the instrument. A special fixation device enables strict axial rotation of the endoscope in the operating field. Endoscopic procedures "around the corner", including aqueductal stenting, pellucidotomy, third ventriculostomy and biopsy were performed in human cadavers. Special features of the used pediatric neuroendoscope system, i.e., reliable fixation, axial rotation, and controlled steering of instruments, increase the safety and reduce the surgical traumatization in selected cases, such as obstructive hydrocephalus due to a mass lesion in the posterior third ventricle, since endoscopic third ventriculostomy and biopsy can be performed through the same burr hole trephination. Limitations of this technique are given by the size of the foramen of Monro and the height of the third ventricle as well as by the bending angle of the instruments (40-50 degrees).