Differential Effects of Gq Protein-Coupled Uridine Receptor Stimulation on IL-8 Production in 1321N1 Human Astrocytoma Cells.

G-protein-coupled receptors (GPCRs) trigger various physiological functions. GPCR-mediated effects largely depend on the receptor-associated G-protein subtypes. However, compelling evidence suggests that single receptor proteins activate multiple G-protein subtypes to induce diverse physiological responses. This study compared responses mediated by three different Gq-binding uridine nucleotide receptors, P2Y2, P2Y4, and P2Y6, by measuring Ca2+ signaling and interleukin (IL)-8 production. In 1321N1 human astrocytoma cells stably expressing these receptors, agonist stimulation evoked concentration-dependent intracellular Ca2+ elevation to a similar extent. In contrast, agonist-induced IL-8 production was prominent in P2Y6-expressing cells, but not in P2Y2- and P2Y4-expressing cells. In addition to inhibition of Gq signaling, G12 signal blockade attenuated uridine 5'-diphosphate (UDP)-induced IL-8 production, suggesting the involvement of a small G-protein pathway. The Rac inhibitor EHop-16 prevented UDP-induced IL-8 release. The P2Y6-triggered IL-8 production was also inhibited by extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and protein kinase B (Akt) inhibitors. These results suggest that P2Y6 receptor-induced IL-8 production requires Gq-mediated Ca2+ signaling as well as G12-mediated activation of Rac. The results also suggest the importance of considering the involvement of multiple G proteins in understanding GPCR-mediated functions.

[Psycho-oncological care in private practices: a survey among psychotherapists with and without licence for reimbursement with public health insurance]. / Psychoonkologische Versorgung bei niedergelassenen Psychotherapeuten: eine Befragung von Therapeuten mit und ohne Kassensitz.

Psycho-oncological care in private practices: a survey among psychotherapists with and without licence for reimbursement with public health insurance Objective: This study examined how certified psychotherapist working in an outpatient setting organise their practice to be able to treat cancer patients and what specific problems they encounter. We differentiated between therapists with and without licence. Methods: Out of the list of psychotherapists held by the German Cancer Information Service, a random sample of practices was selected. They received a mailed questionnaire. Per practice, only one therapist was selected. The questionnaire was developed by a group of psychotherapists from two psycho-oncological associations in Germany. Practices with and without licence were compared using chi-square, ranksum tests and multivariate regression analyses (adjusting for professional qualification and school of therapy). Results: Of 257 contacted practices, 160 therapists participated, and 144 were certified and could be included (62 without and 82 with licence). Waiting times for a first consultation for cancer patients were on average 10 days in practices of therapists without licence and 18 days with licence (p < 0.01). Crisis intervention within 3 days was possible for 62 % of the therapists without and for 44 % with licence (p = 0.08). There was no evidence for differences in what treatment options both types of therapists offered. Both groups reported that more than half of the cancer patients (60 % without and 58 % with licence) had to cancel their appointments at least once every 3 months, and 64 % of the therapists did not ask a fee for that. Financing of the treatment happened most frequently via compensation from health insurance companies via their licence in therapists with licence and via private payment or so called "Kostenerstattung" in therapists without licence. Discussion: In psycho-oncological practices, waiting times for a first consultation for cancer patients are on average 4 weeks shorter than in general, especially short in practices without licence. Cancellation of appointments by patients are relatively frequent in both groups of therapists, which bears financial risks for them. Special methods of compensation for services such as selective contracts are infrequently used..

Practice requirements for psychotherapeutic treatment of cancer patients in the outpatient setting-A survey among certified psychotherapists in Germany.

OBJECTIVE: The aim of this study was to delineate the challenges that psychotherapists encounter when they treat cancer patients and how they organise their practices to be able to treat them. METHODS: A random sample of certified psychotherapists, licensed by the health authorities, with training in psycho-oncology, was asked to complete a questionnaire covering the following issues: therapists' qualifications, organisation of the practice, dealing with appointment cancellations, financing, and networking. Practices with ≥50% cancer patients in their patient load were defined as "practices specialising in cancer" (PSC) and were compared to practices with a smaller proportion of cancer patients (non-PSC). RESULTS: Of 120 contacted therapists, 83 replied and 77 were eligible. The median waiting time for a first consultation was 10 days in PSC and 14 days in non-PSC (P = .05). Seventy-five of PSC and 56% of non-PSC can offer psychotherapy within 4 weeks. Time spent on dealing with the social problems of the patients was higher in PSC than in non-PSC (P = .04). They spent also more time communicating with other health care professionals such as private practice oncologists (P = .001). Cancer patients need to cancel appointments more frequently than noncancer patients (58% vs 48% cancel ≥1× per quarter). Sixty-six percent of the psychotherapists do not ask for financial reimbursement of these sessions. CONCLUSION: Psychotherapy for cancer patients in the outpatient setting requires different organisation of the practice. Sessions are cancelled more frequently, waiting time is considerably shorter, and psychotherapists communicate more often with other health care providers than in general psychotherapy.

HtpG, the prokaryotic homologue of Hsp90, stabilizes a phycobilisome protein in the cyanobacterium Synechococcus elongatus PCC 7942.

HtpG, a homologue of HSP90, is essential for thermotolerance in cyanobacteria. It is not known how it plays this important role. We obtained evidence that HtpG interacts with linker polypeptides of phycobilisome in the cyanobacterium Synechococcus elongatus PCC 7942. In an htpG mutant, the 30 kDa rod linker polypeptide was reduced. In vitro studies with purified HtpG and phycobilisome showed that HtpG interacts with the linker polypeptide as well as other linker polypeptides to suppress their thermal aggregation with a stoichiometry of one linker polypeptide/HtpG dimer. We constructed various domain-truncated derivatives of HtpG to identify putative chaperone sites at which HtpG binds linker polypeptides. The middle domain and the N-terminal domain, although less efficiently, prevented the aggregation of denatured polypeptides, while the C-terminal domain did not. Truncation of the C-terminal domain that is involved in the dimerization of HtpG led to decrease in the anti-aggregation activity, while fusion of the N-terminal domain to the middle domain lowered the activity. In vitro studies with HtpG and the isolated 30 kDa rod linker polypeptide provided basically similar results to those with HtpG and phycobilisome. ADP inhibited the anti-aggregation activity, indicating that a compact ADP conformational state provides weaker aggregation protection compared with the others.