Inhibitory Effect of Glucocorticosteroids on Anti-IgE-Induced Histamine Release from Human Basophilic Leukocytes: Evidence for a Dual Mechanism of Action

Anti-IgE-induced histamine release from human leukocytes is inhibited when the cells before challenge are cultured overnight in the presence of glucocorticoids (GCSs). The present report suggests that the GCSs might exert their effect by at least a dual mechanism of action. Histamine release was induced by a suboptimum concentration of anti-IgE. When the release recorded in the presence of the steroid is plotted against the release recorded in its absence, the data points of several experiments fit a regression line characterized by two parameters: its slope and its intercept with the abscissa. Structure-activity examination with selected GCSs indicates that the orders of potency for affecting these two parameters are not identical. Furthermore, pulse experiments suggest that the cells require different times of contact with the steroid to express inhibition according to the two parameters. The removal of adherent cells or platelets did not markedly affect the degree of leukocyte histamine release or its inhibition by a given GCS, suggesting that the steroid interacts directly with the basophil. Finally, steroid-induced inhibition was not affected by the putative phospholipase A2-inhibitor p-bromophenacylbromide (BPB) or the 5-lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA).     

Detection of large deletions in the LDL receptor gene with quantitative PCR methods

Background  

Familial Hypercholesterolemia (FH) is a common genetic disease and at the molecular level most often due to mutations in the LDL receptor gene. In genetically heterogeneous populations, major structural rearrangements account for about 5% of patients with LDL receptor gene mutations.     

Heterogeneous expression of CD59 on human Purkinje cells

The expression of CD59 and other complement regulators was studied in human cerebellum from 14 individuals with no cerebellar pathology, from one patient with multiple sclerosis (MS) and from two patients with paraneoplastic cerebellar degeneration (PCD). CD59 was present on the Purkinje cells at various levels in eight of the 14 cases with no cerebellar pathology. CD59 was also present on the Purkinje cells of the patient with MS, but not on the scarce remaining Purkinje cells of the two patients with PCD. Other complement regulators (CD35, CD46 and CD55) were not expressed on the Purkinje cells, whereas CD59, CD46 and CD55 were present on the molecular, granulosa and endothelial cells. The results suggest that Purkinje cells not expressing CD59 could be especially prone to complement-mediated damage.     

Role of group A streptococcal IgG-binding proteins in triggering experimental glomerulonephritis in the rabbit

Our previous studies have indicated that the IgG-binding M-family proteins (IgGBP) of group A streptococci may be involved in eliciting experimental acute poststreptococcal glomerulonephritis (APSGN) in the rabbit. These surface proteins were also found to trigger production of anti-IgG, which might conceivably act to enhance renal deposition of immune complexes (IC). In the present study, a clinical isolate of serotype M22 (strain AL168), an isogenic double mutant deficient for both the IgGBPs Mrp and Emm, as well as mutants deficient in only one of the proteins were tested for capacity to induce glomerulonephritis. Streptococci to be used for injecting rabbits were heat-killed. Surface-bound IgG was removed by 1 M KSCN and cells were then repeatedly washed in PBS before use. Rabbits were injected intravenously with 109 cells three times a week for 8 weeks and, following one month of rest, for another 6 weeks. Deposits of IgG and C3 as well as induced chemokines TNF-alpha, IL-1beta and IL-6 were traced in cryostat sections using specific antibodies and appropriate peroxidase-labelled anti-antibodies. In four rabbits immunized with the double mutant strain, no deposits were found, and as examined by TEM, only subtle and transient renal changes were observed. In contrast, the original strain AL168 induced pronounced inflammatory and degenerative glomerular changes in all four rabbits injected, and deposits of TNF-alpha, IL-1beta and IL-6 were found in mesangial and endothelial cells. Similar deposits and glomerular changes were seen in all eight rabbits injected with the mrp-emm+ mutant and in four out of seven animals receiving the mrp+emm- mutant. There was a highly significant correlation between high levels of circulating anti-IgG and development of APSGN. These results confirm an important role of streptococcal IgGBP in triggering experimental APSGN as earlier proposed by our group.     

Erratum zu: Durchimpfung von Kindern und Jugendlichen in Deutschland: Aktuelle Daten aus KiGGS Welle 2 und Trends aus der KiGGS-Studie

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Ein Erratum zu dieser Publikation wurde veröffentlicht: https://doi.org/10.1007/s00103-019-02901-5     

Significance and clinical impact of routinely tested urinary ethyl glucuronide after liver transplantation – development of a risk score

Alcohol abuse after liver transplantation can seriously impact graft and patient survival. However, to date, there is no defined standard procedure to identify patients consuming alcohol after liver transplantation. The aim of this study was to analyze the diagnostic value and clinical impact of routinely measured urinary ethyl glucuronide (uEtG) – a metabolite of ethanol – in patients after liver transplantation. Data of 362 consecutive patients after liver transplantation who visited the University Hospital of Tuebingen for outpatient follow-up were analyzed. Forty-eight patients (13%) displayed positive uEtG results. The uEtG positive group contained significantly more patients with pretransplant alcoholic liver disease. However, two thirds of the uEtG positive patients had no history of pretransplant alcoholic liver disease. Several clinical parameters were significantly associated with positive uEtG. In order to enable a more cost-effective application of uEtG in the future, a clinical risk score was developed (specificity 0.95). In conclusion, routine testing for uEtG reveals a considerable percentage of patients practicing alcohol intake after liver transplantation. Application of our proposed risk score could help focusing uEtG testing on patients at risk.     

Familial gastrointestinal stromal tumor syndrome: phenotypic and molecular features in a kindred.

PURPOSE: Members of a family with hereditary gastrointestinal stromal tumors (GISTs) and a germline KIT oncogene mutation were evaluated for other potential syndrome manifestations. A tumor from the proband was analyzed to compare features with sporadic GISTs. PATIENTS AND METHODS: Members of a kindred in which six relatives in four consecutive generations comprised an autosomal dominant pattern of documented GISTs and cutaneous lesions underwent physical examination, imaging studies, and germline KIT analysis. A recurrent GIST from the proband was studied using microarray, karyotypic, immunohistochemical, and immunoblotting techniques. RESULTS: In addition to evidence of multiple GISTs, lentigines, malignant melanoma, and an angioleiomyoma were identified in relatives. A previously reported gain-of-function missense mutation in KIT exon 11 (T --> C) that results in a V559A substitution within the juxtamembrane domain was identified in three family members. The proband's recurrent gastric GIST had a 44,XY-14,-22 karyotype and immunohistochemical evidence of strong diffuse cytoplasmic KIT expression without expression of actin, desmin, or S-100. Immunoblotting showed strong expression of phosphorylated KIT and downstream signaling intermediates (AKT and MAPK) at levels comparable with those reported in sporadic GISTs. cDNA array profiling demonstrated clustering with sporadic GISTs, and expression of GIST markers comparable to sporadic GISTs. CONCLUSION: These studies provide the first evidence that gene expression and mechanisms of cytogenetic progression and cell signaling are indistinguishable in familial and sporadic GISTs. Current investigations of molecularly targeted therapies in GIST patients provide opportunities to increase the understanding of features of the hereditary syndrome, and risk factors and molecular pathways of the neoplastic phenotypes.     

Diet and the risk of papillary and follicular thyroid carcinoma: a population-based case-control study in Sweden and Norway

A population-based case-control study was conducted in two regions ofSweden and Norway to investigate the association between dietary habits andthe risk of thyroid cancer. The consumption of selected foods was reported ina self-completed food-frequency questionnaire by 246 cases withhistologically confirmed papillary (n = 209) and follicular (n = 37) thyroidcarcinoma, and 440 age- and gender-matched controls. Odds ratios (OR) andtheir 95 percent confidence interval (CI) were calculated as estimates of therelative risk using conditional logistic regression. High consumption ofbutter (OR = 1.6, CI = 1.1-2.5) and cheese (OR = 1.5, CI = 1.0-2.4) wasassociated with increased risks. Residence in areas of endemic goiter inSweden was associated with an elevated risk, especially among women (OR =2.5, CI = 1.3-4.9). High consumption of cruciferous vegetables was associatedwith increased risk only in persons who ever lived in such areas. A decreasedrisk was associated with consumption of iodized salt in northern Norway, andwith use of iodized salt during adolescence among women (OR = 0.6, CI =0.6-1.0). The results of this study suggest a role of diet and environment inthe risk of thyroid cancer.     

Depression,anxiety and disease-related distress in couples affected by advanced lung cancer

Objectives

Lung cancer patients and their partners are prone to high levels of depression and anxiety or severe distress related to the poor prognosis of the illness. However, there remain doubts regarding the extent to which this distress exceeds levels in the general population. This study explored levels of depression and generalized anxiety for comparison with matched data of a representative sample from the general population. Additionally, covariance of distress between the two partners, together with disease-specific components and differences were investigated.

Materials and methods

In a cross-sectional survey, 54 pairs of lung cancer patients and their partners (n = 108) were assessed for depression and anxiety, cancer-related distress, unmet needs and disclosure in communication. Comparisons between distress levels of participating couples and matched community-comparisons (n = 162) were conducted. Additionally, multilevel analysis for estimating intra-dyadic associations of anxiety and depression was computed. Components of distress, needs and aspects of communication were explored via item mean values.

Results

Lung cancer patients as well as their partners exhibited significantly higher levels of depression and anxiety when compared to community-based comparison subjects (patients: mean difference of 1.01 for depression with a relative risk (RR) of 4.5 and 0.84 for anxiety with RR = 6.1; partners: 1.17 for depression with RR = 4.6 and 1.59 for anxiety with RR = 7.6). Partial intraclass correlations between patients and partners were weak (PIC = .29 for depression; PIC = .21 for anxiety). Fear of progression emerged as main component of distress for both patients and partners, although differing stressors were described.

Conclusion

Lung cancer-affected couples exhibit levels of depression and anxiety far exceeding those of the general community. In clinical practice, patients and partners should be assessed separately for distress against the background of weak intra-dyadic associations. In cases of significant depression or anxiety, referral for psychosocial treatment is indicated and has been shown to improve quality of life.