On antisense peptides: the parathyroid hormone as an experimental example and a critical theoretical view

We followed an approach which predicts that translation of two complementary RNA strands into protein generates pairs of "antisense" peptides which bind each other with specific and high affinity (Bost et al. Proc. Natl. Acad. Sci. (1985) 82, 1372). We used human parathormone as an experimental example, and we analysed by computer homologies between antisense peptide sequences and their published receptor sequences. We conclude that there is no experimental indication that parathormone binds to a synthetic peptide, the sequence of which was derived from the antisense RNA sequence. Based on homology scores and antigenicity indexes (Hopp) the analysis shows that the peptide ligand itself, or a random artificial peptide, are as good candidates as the antisense peptide in producing antibodies, presumably recognizing the receptor. We therefore question the general applicability of this approach.     

Affinity labeling of rat liver and kidney type I 5'-deiodinase. Identification of the 27-kDa substrate binding subunit

Extrathyroidal production of 3,3',5-triiodothyronine from the thyroid secretory product, thyroxine, is catalyzed by tissue-specific iodothyronine 5'-deiodinases. Type I 5'-deiodinase (5'D-I) produces greater than 75% of the T3 found in the circulation and in thyroid hormone-responsive tissues and is most abundant in rat liver and kidney. In this study, we used the bromoacetyl derivatives of T4 (N-bromoacetyl-[125I]L-thyroxine, BrAcT4) and T3 (N-bromoacetyl-[125I]3,3',5-triiodothyronine, BrAcT3) as alkylating affinity labels to identify 5'D-I-related protein(s). BrAcT4 and BrAcT3 rapidly and irreversibly inactivated 5'D-I activity in liver and kidney microsomes. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of affinity labeled 5'D-I preparations showed that approximately 80% of the affinity label was incorporated into a protein with a Mr of 27,000 (p27). 5'D-I substrates and inhibitors specifically blocked affinity labeling of p27 with a rank order of potency (BrAcT4 greater than BrAcT3 greater than 3,5,3'-triiodothyronine (rT3) approximately flavone EMD 21388 greater than iodoacetate greater than N-acetyl-T4 (NAcT4) greater than N-acetyl-T3 (NAcT3] identical to that determined for inhibition of 5'-deiodination. Hyper- and hypothyroidism-induced increases and decreases in 5'D-I activity, respectively, were matched by comparable changes in the quantity of affinity labeled p27. BrAcT3 was a less effective affinity label for p27 and minor labeling of a new band with 53 kDa was observed. Molecular sieve chromatography of detergent-solubilized 5'D-I showed coincident peaks of p27 and 5'-deiodinating activity with an apparent Mr approximately 51,000. Two-dimensional gel electrophoresis showed that p27 was a single polypeptide with a pI of 6.1. Approximately 2-5 pmol of p27 were present per mg of liver microsomal protein, equal to previous estimates for 5'D-I content. Our results suggest that p27 represents the substrate binding subunit of type I 5'-deiodinase, the enzyme catalyzing the key reaction in the activation of T4 to the thyromimetically active T3.     

Therapy-relevant factors in adult ADHD from a cognitive behavioural perspective

Adult individuals with attention-deficit hyperactivity disorder (ADHD) have been suffering from this neurobiological and highly heritable disorder chronically since childhood. Resulting from their longstanding neuropsychological impairments, such as attentional problems, emotional instability, and disinhibition, they are familiar to a multiplicity of negative life outcomes and underachievement. Furthermore, a large part of this population suffers from psychiatric comorbidity. This accumulation of negative experiences has an impact on therapy-relevant factors such as the individual's self-esteem, self-efficacy, development of core beliefs/schemas, and coping strategies. Based on negative beliefs about the self, individuals confronted with difficult situations develop maladaptive coping strategies, for instance avoidance and procrastination. These strategies lead to maintenance and reinforcement of maladaptive beliefs, and as such they acquit themselves as schema-confirming. Captured in this vicious cycle, the individual sees her negative view of the self confirmed. The purpose of this paper is to illuminate these interactive factors that influence the aforementioned cycle in order to emphasize the cognitive behavioural interventions tailored to those factors on the basis of latest research. Furthermore, the authors want to attract notice to the resources people with ADHD are said to have, namely creativity and resilience. These postulated resources could be therapy-relevant by creating positive beliefs about the self, hence improving coping skills and breaking the vicious circle of negative appraisal. Taking into account personal resources and their fostering may be an important fundament for the treatment plan of adult ADHD. Information on the current state of research and theoretical approaches concerning the below-mentioned key words was gathered through MEDLINE, PsycINFO, PSYNDEXplus, and PubMed databases.     

Regulation of thyroid hormone metabolism in rat liver fractions.

The nature of the conversion of thyroxine (T4) to triiodothyronine (T3) and reverse triiodothyronine (rT3) was investigated in rat liver homogenate and microsomes. A 6-fold rise of T3 and 2.5-fold rise of rT3 levels determined by specific radioimmunoassays was observed over 6 h after the addition of T4. An enzymic process is suggested that converts T4 to T3 and rT3. For T3 the optimal pH is 6 and for rT3, 9.5. The converting activity for both T3 and rT3 is temperature dependent and can be suppressed by heat, H2O2, merthiolate and by 5-propyl-2-thiouracil. rT3 and to a lesser degree iodide, were able to inhibit the production of T3 in a dose related fashion. Therefore the pH dependency, rT3 and iodide may regulate the availability of T3 or rT3 depending on the metabolic requirements of thyroid hormones.     

A Systematic Review on the Characteristics,Treatments and Outcomes of the Patients with Primary Spinal Glioblastomas or Gliosarcomas Reported in Literature until March 2015

Our aim was to determine the characteristics, treatments and outcomes of patients with primary spinal glioblastomas (GB) or gliosarcomas (GS) reported in literature until March 2015. PubMed and Web of Science were searched for peer-reviewed articles pertaining to cases of glioblastomas / gliosarcomas with primary spinal origin, using predefined search terms. Furthermore we performed hand searches tracking the references from the selected papers. Eighty-two articles published between 1938 and March 2015 were eligible. They reported on 157 patients. Median age at diagnosis was 22 years. The proportion of patients who received adjuvant chemo- or radiotherapy clearly increased from the time before 1980 until present. Median overall survival from diagnosis was 8.0 ± 0.9 months. On univariate analysis age influenced overall survival, whereas tumor location, gender and the extent of initial resection did not. Outcomes did not differ between children (< 18 years) and adults. However, the patients who were treated after 1980 achieved longer survival times than the patients treated before. On multivariable analysis only age (< 60 years) and the time period of treatment (≥ 1980) were confirmed as positive independent prognostic factors. In conclusion, primary spinal GB / GS mainly affect younger patients and are associated with a dismal prognosis. However, most likely due to the increasing use of adjuvant treatment, modest therapeutic progress has been achieved over recent decades. The characteristics and treatments of primary spinal glioblastomas should be entered into a central registry in order to gain more information about the ideal treatment approach in the future.