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Biomedical subjects

C Molnar

Publications and source records attributed to C Molnar.

11 recordsLinked to original sources

Interleukin-6 stimulates thrombopoiesis through thrombopoietin: role in inflammatory thrombocytosis.

Baseline platelet production is dependent on thrombopoietin (TPO). TPO is constitutively produced and primarily regulated by receptor-mediated uptake by platelets. Inflammatory thrombocytosis is thought to be related to increased interleukin-6 (IL-6) levels. To address whether IL-6 might act through TPO to increase platelet counts, TPO was neutralized in vivo in C57BL/10 mice treated with IL-6, and hepatic TPO mRNA expression and TPO plasma levels were studied. Transcriptional regulation of TPO mRNA was studied in the hepatoblastoma cell line HepG2. Furthermore, TPO plasma levels were determined in IL-6-treated cancer patients. It is shown that IL-6-induced thrombocytosis in C57BL/10 mice is accompanied by enhanced hepatic TPO mRNA expression and elevated TPO plasma levels. Administration of IL-6 to cancer patients results in a corresponding increase in TPO plasma levels. IL-6 enhances TPO mRNA transcription in HepG2 cells. IL-6-induced thrombocytosis can be abrogated by neutralization of TPO, suggesting that IL-6 induces thrombocytosis through TPO. A novel pathway of TPO regulation by the inflammatory mediator IL-6 is proposed, indicating that the number of platelets by themselves might not be the sole determinant of circulating TPO levels and thus of thrombopoiesis. This regulatory pathway might be of relevance for the understanding of reactive thrombocytosis.

Animals↗

Addressing challenges, creating opportunities: fostering consumer participation in Medicaid and Children's Health Insurance managed care Programs.

With more than half of the Medicaid population enrolled in managed care and with enrollment in Medicaid managed care and Children's Health Insurance Programs continuing to accelerate, policy makers and program administrators must quickly come to consensus on the role of the consumer in the planning, implementation, and oversight of Medicaid and S-CHIP managed care. This article explores the barriers to consumer participation and makes concrete policy and programmatic recommendations to increase consumer participation in public managed care programs. To fully comply with existing federal and state requirements for consumer participation and for this participation to have an impact on the quality of managed care programs, states need to provide more education and support to consumers on: how to choose a health plan; how to access the health plan services and out-of-network benefits; and how to use grievance procedures. In addition, more work needs to be done to make the growing availability of health plan and provider performance data meaningful and available to Medicaid and S-CHIP consumers. Finally, states must address the lack of resources, lack of information, and lack of training that prevent many consumers from being able to sustain their involvement in system-level advisory and oversight bodies.

Child↗

Hepatocyte growth factor plasma levels after myocardial infarction are not affected by recombinant tissue-type plasminogen-activator therapy.

Hepatocyte growth factor (HGF), a cytokine involved in tissue regeneration, angiogenesis and lateral vessel growth, is secreted as a biological-inactive, single-chain precursor named pro-HGF. In case, of tissue injury pro-HGF is proteolytically cleaved at the extracellular locus by serine proteases. Results obtained from in vitro experiments showed that urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) can cleave single-chain HGF. In this study we measured serum HGF levels in patients with acute myocardial infarction (MCI). Two groups of patients were compared. One group (n = 7) was treated with a conventional therapy and the other group (n = 7) was subjected to a thrombolytic therapy with recombinant tissue-type plasminogen activator (rtPA). Serum samples were collected at time of admission and subsequently 12-16 hours, 20-30 hours and 50-60 hours after onset of chest pain. At admission and before administration of rtPA, serum HGF levels peaked at 16.8 +/- 2.2 ng/ml in the lysed group and at 20.7 +/- 6.5 ng/ml in the non-lysed group. Levels then continuously declined, reaching lowest values 50-60 hours after onset of chest pain (3.2 +/- 1.3 ng/ml in the group treated with rtPA versus 4.4 +/- 0.9 ng/ml in the non-lysed group). No statistical significant difference could be detected between the two groups at any time. We suggest that serine proteases other than tPA are involved in HGF activation in vivo.

Acute Disease↗

Differential regulation of interleukin 4 and interleukin 13 production by interferon alpha.

Interferon alpha (IFN-alpha) has proven its clinical usefulness in a variety of diseases of diverse pathogenesis. In addition to direct antiviral effects, recent evidence suggests that its interaction with the cytokine cascade might contribute to its mechanism of action. This study was undertaken to determine whether IFN-alpha influences the synthesis of interleukin 4 (IL-4) and IL-13, two cytokines which share many biological properties on various cells and tissues and which have a profound role in regulating immunological and inflammatory responses. Peripheral blood mononuclear cells (PBMC) from healthy volunteers were stimulated with Concanavalin A (ConA), phorbol myristate acetate (PMA), anti-CD3/CD28 mAbs, either alone or in various combinations, and incubated with increasing concentrations of IFN-alpha. IL-4 and Il-13 mRNA was determined by Northern hybridizations and IL-4 and IL-13 protein synthesis was evaluated by specific enzyme-linked immunosorbent assay (ELISA). IFN-alpha led to a profound decrease of IL-13 mRNA expression after an incubation period of 5 h with ConA alone or in combination with PMA, whereas it showed no regulatory effect on IL-4 mRNA expression. After an incubation period of 24 h, the decrease in IL-13 mRNA expression after addition of IFN-alpha was even more pronounced. At the protein level, IFN-alpha increased IL-4 synthesis dose dependently regardless of the mode of activation. This increase was most pronounced after stimulation with ConA or anti-CD28/PMA. In contrast, IL-13 synthesis was strongly downregulated by IFN-alpha in a dose-dependent manner irrespective of the activating agent. It is concluded that IL-4 and IL-13, although showing similar biological effects, are differentially regulated by IFN-alpha.

Gene Expression Regulation↗

Change in rape narratives during exposure therapy for posttraumatic stress disorder.

This paper presents a coding system developed to explore changes in narratives of rape during therapy for posttraumatic stress disorder (PTSD) involving repeated reliving and recounting of the trauma. Relationships between narrative categories hypothesized to be affected by the treatment and treatment outcome were also examined. As hypothesized, narrative length increased from pre- to post-treatment, percentage of actions and dialogue decreased and percentage of thoughts and feelings increased, particularly thoughts reflecting attempts to organize the trauma memory. Also as expected, increase in organized thoughts was correlated negatively with depression. While indices of fragmentation did not significantly decrease during therapy, the hypothesized correlation between decrease in fragmentation and reduction in trauma-related symptoms was detected.

Adolescent↗

Aspiration after percutaneous gastrostomy. Assessment by Tc-99m labeling of the enteral feed.

Aspiration pneumonia, a recognized complication of enteral feeding via a nasogastric tube, is considered uncommon with percutaneously placed gastrostomy tube feeding. We report aspiration pneumonia during enteral alimentation in a neurologically compromised but conscious patient. Aspiration continued despite changing the route of enteral feeding from nasogastric to percutaneous gastrostomy. Quantitative scintigraphic studies with Tc-99m-labeled enteral infusion demonstrated frequent episodes of gastroesophageal reflux and aspiration of gastric contents, which increased when the infusion rate was speeded up for nutritional replacement. Gastric retention also occurred at the higher infusion rate. Thus, percutaneous gastrostomy may not decrease the frequency of aspiration in patients at risk.

Adult↗

Inflated perception of responsibility for harm in obsessive-compulsive disorder.

The present study examined the proposition that inflated responsibility is implicated in obsessive compulsive disorder (OCD). Compared to non-anxious control participants (NACs), and an anxious control group with generalized social phobia (GSPs), we predicted that individuals with OCD (OCs) would exhibit a greater urge to rectify situations involving potential risk, would report more distress upon leaving such situations unrectified, and would feel more personal responsibility if the unrectified situations resulted in harm. Fifteen OCs, 15 NACs, and 15 GSPs completed the Obsessive Compulsive Responsibility Scale (OCRS), which included low-risk, OC-relevant, and high-risk situations. Compared to NACs and GSPs, OCs reported more urges, distress, and responsibility in low-risk and OC-relevant situations; no group differences were detected on high-risk situations. GSPs and NACs differed only in their responsibility in OC-relevant situations, with GSPs reporting higher responsibility than controls. Our results suggest that compared to OCs, NACs, and GSPs can better differentiate between situations that merit concern and ones that do not.

Adult↗

Implicit and explicit memory in obsessive-compulsive disorder.

We examined implicit and explicit memory in obsessive-compulsive disorder (OCD) patients an in non-patients. Implicit memory was measured by the effect of prior presentation on ratings of noise volume. Explicit memory was examined via a recognition task. We also investigated participants' confidence in the accuracy of their recognition. OCD patients rated noise accompanying contamination and neutral sentences as louder than did non-patients. Both groups rated noise accompanying contamination sentences as louder than noise accompanying neutral sentences. Also, both groups were less confident in their recognition of new contamination sentences compared to new neutral sentences, but this difference was less pronounced in the OCD group. The findings are discussed in light of previous research on memory in anxiety disordered individuals.

Adult↗