Dissecting the Structure and Mechanism of a Complex Duplication–Triplication Rearrangement in the DMD Gene

Pathogenic complex genomic rearrangements are being increasingly characterized at the nucleotide level, providing unprecedented opportunities to evaluate the complexities of mutational mechanisms. Here, we report the molecular characterization of a complex duplication–triplication rearrangement involving exons 45–60 of the DMD gene. Inverted repeats facilitated this complex rearrangement, which shares common genomic organization with the recently described duplication‐inverted triplication–duplication (DUP–TRP/INV‐DUP) events; specifically, a 690‐kb region comprising DMD exons from 45 to 60 was duplicated in tandem, and another 46‐kb segment containing exon 51 was inserted inversely in between them. Taking into consideration (1) the presence of a predicted PRDM9 binding site in the near vicinity of the junction involving two inverted L1 elements and (2) the inherent properties of X–Y chromosome recombination during male meiosis, we proposed an alternative two‐step model for the generation of this X‐linked DMD DUP–TRP/INV‐DUP event.     

Training and Education in Clinical Psychology in the Context of the Patient Protection and Affordable Care Act

The Patient Protection and Affordable Care Act of 2010 (ACA) is revamping the access, quality, and financing of the health and mental health systems. However, its impact on training and education in clinical psychology is unclear. This article aims to identify specific components of the ACA, in particular the Mental and Behavioral Health Education and Training Grants, that are expected to affect training and education in the field. The article further connects the ACA with four paradigm shifts in clinical psychology that have broad implications for training and education—evidence‐based practices, research methodology, interprofessionalism, and the quality indicator movement. The overarching goal of this article is to begin timely discussions on the future directions of the field under the current healthcare reform.     

Clinical variants of herpes zoster

The clinical course of herpes zoster has been analysed in 132 in-patients and a variety of the clinical forms shown which were initially disguised as the internal diseases. In addition to typical variants, the following types of herpes zoster have been found: gangrenous, bullous, hemorrhagic and disseminated.     

Thermographic semeiotics of food poisoning and its differential diagnosis

A thermographic study has revealed zones of hyperthermia in the epigastrium and other abdominal regions in 91.4 per cent of the patients with food poisoning. The temperature gradient in the epigastrium depended on the degree of severity of the disease (in mild course--0.60 +/- 0.11 degrees C, in moderately severe and severe course--1.15 +/- 0.09 degrees C). In salmonellosis a zone of hyperthermia was also found in the right iliac region. Clinical recovery in most cases preceded temperature normalization on the abdomen. In patients with acute dysentery the hyperthermic zone was constantly revealed in the left iliac region, in acute appendicitis in the right iliac region, in acute cholecystitis in the right hypochondrium, in acute pancreatitis in the epigastrium or in the hypochondrium with a clearly defined upper border. Thermography contributed to the differential diagnosis of food poisoning and the above diseases.     

An assessment of the therapeutic efficacy of gene-engineered human alpha 2-interferon in patients with acute viral hepatitis B

The clinical trials of alpha 2-interferon (alpha 2-IF) (reaferon) in 412 patients with acute viral hepatitis B (AVHB) permitted the establishment of the optimal therapeutic dose and the schedule for the drug use. The drug tolerance appeared satisfactory on the whole. alpha 2-IF was found to have a beneficial effect on the clinical course of VHB. The relationship was established between the therapeutic effectiveness of the drug and the clinical variants of the disease as well as the time of drug administration. The highest clinical effect (in 86.3%) was attained as a result of early (before the 7th day of jaundice) use of alpha 2-IF in patients with the acute-cyclic pattern of VHB. That effect consisted in the reduction of the treatment period (by 6-8 days), in a 2-fold reduction of the incidence of HBs-antigenemia, in rapid stimulation of the IF system, and in the initially low activity of natural killers. If the drug was administered later, the positive clinical effect was detectable only in 61% of the patients. In cholestatic VHB, alpha 2-IF did not produce any therapeutic effect.     

Prognosefaktoren für das Auftreten einer Peritonealcarcinose beim Magencarcinom

Einleitung: Zur Verbesserung der Behandlungsm?glichkeiten vor dem Hintergrund eines adjuvanten Therapiekonzepts des Magencarcinoms erscheint es sinnvoll, geeignete Prognosefaktoren für das Auftreten einer Peritonealcarcinose zu bestimmen. Damit wird eine enge Auswahl der m?glicherweise von einer intraperitonealen Chemotherapie profitierenden Patienten m?glich. Methoden: Im Zeitraum von 6/1975–12/1999 wurden 575 Magenresektionen bei Carcinomen in unserer Klinik durchgeführt. Seit dem 1.1.1986 werden die Daten der operierten Patienten prospektiv erfasst. Die zuvor operierten Patienten wurden retrospektiv ausgewertet. S?mtliche Daten zur pr?operativen Diagnostik, Operation, histopathologischen Ergebnissen, klinischem Verlauf und überleben werden in einer Exceldatei prospektiv gesammelt und statistisch ausgewertet. Ergebnisse: Die multivariate Auswertung mittels logistischer Regressionsanalyse erbrachte eine signifikante Korrelation nur für die Variablen pT3, pN2, G3 und für Carcinome des gesamten Magens sowie für Magenstumpfcarcinome. Bezüglich der Variablen Laurenklassifikation, Siegelringzellcarcinom, Auftreten von Lebermetastasen und Tumorlokalisation im distalen oder proximalen Magen konnte keine signifikante Korrelation gefunden werden. Allerdings hatte nur ein Drittel der Patienten mit einer Lebermetastasierung gleichzeitig eine Peritonealcarcinose (n = 29). Schlussfolgerungen: Die Ergebnisse zeigen den klinischen Zusammenhang zwischen der Tumorlokalisation, der Lymphknotenmetastasierung, der Serosainfiltration und dem Grading mit dem Auftreten einer Peritonealcarcinose. Die Daten bilden eine gute Grundlage für weitere immunhistochemische und molekularbiologische Untersuchungen, wie der Adh?sionsmoleküle zur Absch?tzung des Risikos einer peritonealen Metastasierung nach Magencarcinom.     

Peptidylarginine deiminase isoforms 1-3 are expressed in the epidermis and involved in the deimination of K1 and filaggrin

Post-translational conversion of arginine to citrulline residues is catalyzed by peptidylarginine deiminases (PAD). Although the existence of five isoforms of PAD has been reported in rodents and humans, their tissue distribution, substrate specificity, and physiological function have yet to be explored. In the epidermis, deimination of filaggrin and keratins is involved in maintaining hydration of the stratum corneum (SC), and hence the cutaneous barrier function. Here, RT-PCR, western blotting, and confocal microscopy analyses with anti-peptide antibodies highly specific for each of the PAD1-4 demonstrated that only PAD1-3 are expressed in mouse and human epidermis. PAD1 was detected in all layers, including the SC, and PAD2 in all the living layers, whereas PAD3 expression was shown to be restricted to the granular layer and lower SC. Moreover, PAD1 and 3 were observed to co-localize with (pro)filaggrin, and PAD2 to be located at the keratinocyte periphery in the stratum granulosum. We also detected PAD1 in extracts of superficial SC, where K1 is deiminated. Moreover, we showed that PAD1 and 3 are able to modify filaggrin in vitro. These data strongly suggest that each enzyme exerts a specific role in the course of epidermis differentiation.     

New polyurethanes based on diphenylmethane diisocyanate and 1,4:3,6-dianhydrosorbitol, 1. Model kinetic studies and characterization of the hard segment

1,4:3,6-Dianhydrosorbitol (DAS) seems to be an interesting reagent for the synthesis of polyurethanes. In the present work, the kinetics of the reaction of DAS with a monoisocyanate (p-tolyl isocyanate, p-TI) and with a diisocyanate (4,4′-diphenylmethane diisocyanate, MDI) were studied with the help of a chromatographic method (size exclusion chromatography, SEC). When the condensation reaction is performed in tetrahydrofuran (THF) solution, with dibutyltin dilaurate (SnDBDL) as catalyst, DAS exhibits two equireactive hydroxyl groups. The reaction rate can be well described by a second-order equation modified to include catalysis by the formed urethane functions. MDI and DAS were then condensed using two different experimental procedures (bulk and solution polycondensation in THF, in the presence of SnDBDL), and the characteristics of the resulting polyurethanes were compared. Bulk polycondensation led to an amorphous polymer, whereas the polyurethane prepared in solution was semi-crystalline. In both cases, we obtained a very high glass transition temperature ( ≈ 186°C). The synthesis of samples with various polymerization degrees gave a better understanding of the molecular weight distribution of segmented polyurethanes based on MDI and DAS.