What is ideal genetic counselling? A survey of current international guidelines

The objective of this article is to review guidelines that address counselling in the context of genetic testing in order to summarise what aspects of counselling they consider most important, and to examine how they construct the ideal of genetic counselling. Guidelines were collected by examining the websites of different international professional, political, ethical and patient organisations, either previously known or found with the help of the Google search engine, and also using references listed in other studies. The most frequently mentioned topics in the collected 56 guidelines were sought, and this was carried out with the software package Qualitative Solutions and Research for Non-numerical Unstructured Data Indexing Searching and Theorizing. Topics related to genetic counselling that were mentioned in at least 30 of 56 collected documents were considered to be the most important aspects of genetic counselling. The ideal of genetic counselling is expressed in the analysed guidelines as being composed of (1) an appropriately trained professional who understands genetics and its ethical implications well; (2) relevant and objective information; (3) assurance of the counsellee's understanding; (4) psychological support; (5) informed consent; (6) confidentiality of genetic information; (7) considering familial implications; (8) appropriate handling of potential discrimination of testing; and (9) assuring autonomous decision-making by the counsellee. The ideal of genetic counselling is rather consistent in the guidelines, but there are some contradictions between the requirements of objective information-giving and adapting counselling to counsellee's circumstances.     

High expression of prostate-specific membrane antigen in the tumor-associated neo-vasculature is associated with worse prognosis in squamous cell carcinoma of the oral cavity

Prostate-specific membrane antigen (PSMA) is a transmembrane protein expressed in prostate cancer as well as in the neo-vasculature of nonprostatic solid tumors. Here, we determined the expression pattern of PSMA in the vasculature of oral squamous cell carcinoma. Using a previously validated antibody, PSMA staining distribution and cyclooxygenase 2 (COX2) expression status was evaluated in a cohort of patients with squamous cell carcinoma of the oral cavity (n=96) using immunohistochemistry and was correlated with clinicopathological features as well as outcome. Twenty-four (25%) cases showed no detectable PSMA staining, 48 (50%) demonstrated positive immunoreactivity for PSMA in less than 50% of microvessels and 24 (25%) cases showed strong endothelial PSMA expression in more than 50% of tumor-associated microvessels. High endothelial PSMA expression was associated with greatly reduced survival (18.2 vs 77.3 months; P=0.0001) and maintained prognostic significance after adjusting for grade and stage in multivariate analysis (hazard ratio=2.19, P=0.007). Furthermore, we observed a strong association between endothelial PSMA and cancer cell-specific COX2 expression. In conclusion, we provide the first evidence for the prognostic significance of endothelial PSMA expression in oral squamous cell carcinoma and, suggest a potential interaction between arachidonic acid metabolites and endothelial PSMA expression in the tumor neo-vasculature.     

Diets high in corn oil or extra-virgin olive oil provided from weaning advance sexual maturation and differentially modify susceptibility to mammary carcinogenesis in female rats

Based on the importance of early-life events in breast cancer risk, we have investigated the effects of high-fat diets on maturation, mammary gland development, and its susceptibility to transformation. Female Sprague-Dawley rats were fed a lowfat (LF), high corn oil (HCO), or high extra-virgin olive oil (HOO) diet from weaning and gavaged with 7,12-dimethylbenz[a]anthracene. Body weight and mass increased in the HCO group compared to the LF group. The vaginal opening was advanced in both high-fat groups, especially in the HCO group. This HCO group also had increased body weight around puberty, more corpora lutea at post-puberty, and tended to have higher kisspeptin levels in the hypothalamus. Both high-fat diets induced subtle modifications in the morphology of the mammary gland, with no changes on β-casein or hormone receptors expression in the gland. The HCO diet had a clearly stimulating effect of carcinogenesis, inducing the earliest appearance of tumors and the highest tumor incidence and yield, whereas the HOO diet seemed to have a weak enhancing effect, increasing tumor yield. Our data suggest a strong influence of the HCO diet in sexual maturation and mammary cancer risk, while rats fed the HOO diet were more similar to the controls.     

Involvement of protein kinases in the induction of NO synthase II in human DLD-1 cells

1. Protein phosphorylation is involved in the induction of nitric oxide synthase II (NOS II, iNOS) in several types of animal cells. Here we have investigated the possible involvement of major protein kinases in the induction of NOS II expression in human DLD-1 cells.
2. In DLD-1 cells, interferon-γ alone induced a submaximal NOS II expression; a cytokine mixture consisting of interferon-γ, tumour necrosis factor-α and interleukin-1β produced maximal NOS II induction.
3. Activators of protein kinase A (forskolin, 8-dibutyryl-cyclic AMP), of protein kinase C (tetradecanoylphorbol-13-acetate), and of protein kinase G (8-bromo cyclic GMP) did not induce NOS II mRNA by themselves, nor did they alter NOS II mRNA induction in response to cytokines.
4. Inhibitors of protein kinase A (compound H89), of protein kinase C (bisindolylmaleimide, chelerythrine or staurosporine), of phosphatidylinositol 3-kinase (wortmannin), of p38 mitogen-activated protein kinase (compound SB 203580) and of extracellular signal-regulated kinase (compound PD 98059) also had no influence on basal or cytokine-induced NOS II mRNA expression.
5. Immunoprecipitation kinase assays showed no activation of extracellular signal-regulated kinase or p38 mitogen-activated protein kinase in cytokine-incubated DLD-1 cells. The c-Jun NH₂-terminal kinase was activated by cytokines, but the most efficacious cytokine was tumour necrosis factor-α which did not induce NOS II by itself.
6. In contrast, the protein tyrosine kinase inhibitor tyrphostin B42 (a specific inhibitor of interferon-γ-activated janus kinase 2) and the protein tyrosine kinase inhibitor tyrphostin A25 both reduced CM-induced NOS II mRNA expression in a concentration-dependent manner.
7. These results suggest that activation of NOS II expression in DLD-1 cells is independent of the activities of protein kinases A, C and G, phosphatidylinositol 3-kinase, extracellular signal regulated kinase and p38 mitogen-activated protein kinase, but seems to require protein tyrosine kinase activity, especially the interferon-γ-activated janus kinase 2.

     

Psychiatrie und gerichtliche Psychologie

Ohne Zusammenfassung     

Acupotomy versus sodium hyaluronate for treatment of knee osteoarthritis in rabbits

Objective

To investigate the possible advantages of acupotomy over sodium hyaluronate injection for the treatment of knee osteoarthritis (KOA).

Novel variants and clinical symptoms in four new ALG3‐CDG patients,review of the literature,and identification of AAGRP‐ALG3 as a novel ALG3 variant with alanine and glycine‐rich N‐terminus

ALG3‐CDG is one of the very rare types of congenital disorder of glycosylation (CDG) caused by variants in the ER‐mannosyltransferase ALG3. Here, we summarize the clinical, biochemical, and genetic data of four new ALG3‐CDG patients, who were identified by a type I pattern of serum transferrin and the accumulation of Man₅GlcNAc₂‐PP‐dolichol in LLO analysis. Additional clinical symptoms observed in our patients comprise sensorineural hearing loss, right‐descending aorta, obstructive cardiomyopathy, macroglossia, and muscular hypertonia. We add four new biochemically confirmed variants to the list of ALG3‐CDG inducing variants: c.350G>C (p.R117P), c.1263G>A (p.W421*), c.1037A>G (p.N346S), and the intron variant c.296+4A>G. Furthermore, in Patient 1 an additional open‐reading frame of 141 bp (AAGRP) in the coding region of ALG3 was identified. Additionally, we show that control cells synthesize, to a minor degree, a hybrid protein composed of the polypeptide AAGRP and ALG3 (AAGRP‐ALG3), while in Patient 1 expression of this hybrid protein is significantly increased due to the homozygous variant c.160_196del (g.165C>T). By reviewing the literature and combining our findings with previously published data, we further expand the knowledge of this rare glycosylation defect.