De novo mutation in DMD gene in a patient with combined hemophilia A and Duchenne muscular dystrophy

We report an unusual case of a patient with two combined X-linked diseases, severe hemophilia A (HA) and Duchenne muscular dystrophy (DMD), of which only HA was hereditary. There was no family history of muscular dystrophy. Genetic analysis revealed that HA was caused by the hereditary coagulation factor VIII (F8) intron 22 inversion (distal/type I inversion), whereas DMD was caused by a de novo deletion in the dystrophin gene. This is the first report of a patient with two severe X-linked diseases, of which only HA was hereditary. Despite the fact that the probability of acquiring two X-linked abnormalities, one hereditary and one de novo, is extremely low, the emergence of such cases indicates that genetic testing for distinct X-linked diseases could be of importance in patients with hereditary hemophilia.     

Genetic characterization of a mumps virus isolate during passaging in the amniotic cavity of embryonated chicken eggs

The aim of this study was the molecular characterization of a historical mumps isolate (an alleged individual sample). After RNA extraction and cDNA synthesis, selective nested PCR amplification with specific primers, automated DNA sequencing and RFLP analyses were performed. The relative ratios of the detected virus sequences were determined by GeneScan electrophoresis. Phylogenetic tree based on the 316 nucleotide region of the SH gene of the mumps virus was generated by the neighbor-joining method. Results obtained by the described molecular approach show: (a) there are two mumps virus variants, A and B, detected in the fourth passage of wild type virus in the amniotic cavity of embryonated chicken eggs (ECE); (b) variants A and B belong to different genotypes; (c) variants A and B differ in the HN and NP genes which code for amino acid sequences comprising immunogenic epitopes; (d) variant B contains one or more minor variants. We discuss whether the observed differences between the two variants are a consequence of natural heterogeneity or of laboratory contamination in the early passages.     

Polymerization of phenylacetylene with WOCl4/tetraphenyltin catalyst in benzene/1,4-dioxane. Synthesis of high-molecular-weight poly(phenylacetylene)

Phenylacetylene was polymerized with WOCl₄/tetraphenyltin (mole ratio 1:2) catalyst in benzene and benzene/1,4-dioxane mixtures. The resulting polymers were characterized by means of multidetector size-exclusion chromatography and ¹H NMR and IR spectroscopy. 1,4-Dioxane used as a co-solvent was found to increase both the content of cis units and the molecular weight of poly(phenylacetylene) (PPhA); a weight-average molecular weight of M?_w = 1 · 10⁶ was reached. In spite of the high mole ration monomer: catalyst (1260:1) used in the polymerizations high yields of PPhA were attained. No effect of an alteration in PPhA microstructure upon its degradation in tetrahydrofuran solution exposed to air has been observed.     

Criteria for regular spacing of reacting Mach stems

Nonlinear geometric optics is developed to construct translating self-similar high-frequency nonlinear wave patterns as perturbed solutions behind reacting shock waves. The geometric conditions involving these wave patterns that yield the maximum acoustic amplification lead to criteria for both the formation and regular spacing dimension for Mach stems in reacting gases.     

Normal forms for reduced stochastic climate models

The systematic development of reduced low-dimensional stochastic climate models from observations or comprehensive high-dimensional climate models is an important topic for atmospheric low-frequency variability, climate sensitivity, and improved extended range forecasting. Here techniques from applied mathematics are utilized to systematically derive normal forms for reduced stochastic climate models for low-frequency variables. The use of a few Empirical Orthogonal Functions (EOFs) (also known as Principal Component Analysis, Karhunen–Loéve and Proper Orthogonal Decomposition) depending on observational data to span the low-frequency subspace requires the assessment of dyad interactions besides the more familiar triads in the interaction between the low- and high-frequency subspaces of the dynamics. It is shown below that the dyad and multiplicative triad interactions combine with the climatological linear operator interactions to simultaneously produce both strong nonlinear dissipation and Correlated Additive and Multiplicative (CAM) stochastic noise. For a single low-frequency variable the dyad interactions and climatological linear operator alone produce a normal form with CAM noise from advection of the large scales by the small scales and simultaneously strong cubic damping. These normal forms should prove useful for developing systematic strategies for the estimation of stochastic models from climate data. As an illustrative example the one-dimensional normal form is applied below to low-frequency patterns such as the North Atlantic Oscillation (NAO) in a climate model. The results here also illustrate the short comings of a recent linear scalar CAM noise model proposed elsewhere for low-frequency variability.     

Melanoma with second myxoid stromal changes after personally applied prolonged phototherapy

Most malignant melanomas are easily diagnosed; however, melanoma is also one of the lesions most frequently reported to mimic other tumors. One of the most difficult patterns to recognize is characterized by prominent myxoid matrix. A case is presented of primary cutaneous melanoma with abundant myxoid matrix in a patient who underwent prolonged phototherapy. Three years before, after getting sunburns, the patient noticed changes of a congenital nevus located in the area of sunburns. It became darker, started to blanch, and grew, with occasional bleeding. Without consulting a physician, the patient applied phototherapy onto the area for 30 months. He used a Bioptron lamp with polarized, polychromatic, incoherent light, at a wavelength from 480 to 3400 nm, without ultraviolet radiation. Clinically, the lesion was unevenly pigmented, ulcerated, covered with hemorrhagic crust, and measuring 3.5 cm in greatest dimension, with a satellite nodule. Multiple metastatic subcutaneous nodules were also found on the scalp and trunk. Histologically, the primary tumor and metastases were composed of nests and pseudotubular formations of polygonal, spindle, and stellate cells embedded in abundant myxoid stroma that comprised more than 80% of the tumor mass. Focally, in the epidermis and papillary dermis, nests of atypical melanocytes and numerous melanophages were observed. Chemotherapy and immunotherapy were administered as suggested by an oncologist. The patient died from distant metastases 6 months after the diagnosis. Although some authors believe that myxoid changes do not seem to alter the behavior of melanoma, it remains an important differential diagnosis issue.     

The expression of syndecan-1 in psoriatic epidermis

Psoriasis is a chronic inflammatory skin disease characterized by exaggerated keratinocyte proliferation. Current opinion indicates that psoriasis is driven by T cell-mediated immune responses targeting keratinocytes. However, psoriasis cannot be explained solely on the basis of T-cell activation, and it is likely that an intrinsic alteration in epidermal keratinocytes plays a very important role in disease expression. Syndecans comprise a major family of cell surface heparan sulfate proteoglycans. Several studies indicate their role in adhesion, cell-extracellular matrix interactions, migration, keratinocyte proliferation and differentiation, inflammation, and wound healing. To determine the expression of syndecan-1 in psoriasis, skin samples from 29 patients with fully developed psoriasis and skin samples from 14 healthy volunteer persons with no personal or family history of psoriasis were immunohistochemically examined using monoclonal antibody against syndecan-1. The expression of syndecan-1 was analyzed in whole mount section of psoriatic and non-psoriatic skin biopsies under high magnification (400x). In addition, the intensity and topography of reaction in the cell, as well as localization of positive cells in the epidermis were evaluated. Strong syndecan-1 reactivity in epidermal cells in all non-psoriatic and psoriatic samples was observed. Statistical analysis showed no significant differences between two analyzed groups (P > 0.05). In normal skin syndecan-1 was expressed in full thickness of the epidermis. The strongest reaction was observed in membranes and intercellular junctions of spinous and granular layer while basal cells showed weaker expression that was confined to cytoplasm. In psoriatic skin syndecan-1 was expressed in the membrane and intercellular junction of cells located in thickened and elongated rete ridges of the epidermis. The strongest reaction was in basal and suprabasal layers and expression diminished through spinous layer. Cells in spinous layer lose syndecan-1 expression, which is opposite pattern to normal skin. Our results suggest that aberrant skin expression of syndecan-1 may be involved in the development of psoriasis.     

An unusual pattern of pseudoepitheliomatous hyperplasia associated with cutaneous primary melanoma: report of two cases with analysis of p53 and bcl-2 immunoreactivity

Pseudoepitheliomatous hyperplasia (PEH) is a benign, reactive epithelial proliferation. PEH is characterized by hyperplasia of the epidermis or adnexal epithelium into irregular squamous strands that extend deep down into the subjacent dermis. PEH occurs in response to underlying infections, inflammatory or neoplastic conditions. The presence of PEH overlying cutaneous melanoma is rare. The clinical and histological features of PEH can closely mimic squamous cell carcinoma and could be misinterpreted. We report two cases of cutaneous primary melanoma associated with PEH and discuss differential diagnoses and potential role of p53 and bcl-2 in the pathogenesis of PEH.     

Evidence that intracellular cyclophilin A and cyclophilin A/CD147 receptor-mediated ERK1/2 signalling can protect neurons against in vitro oxidative and ischemic injury

We previously reported that cyclophilin A protein is up-regulated in cortical neuronal cultures following several preconditioning treatments. In the present study, we have demonstrated that adenoviral-mediated over-expression of cyclophilin A in rat cortical neuronal cultures can protect neurons from oxidative stress (induced by cumene hydroperoxide) and in vitro ischemia (induced by oxygen glucose deprivation). We subsequently demonstrated that cultured neurons, but not astrocytes, express the recently identified putative cyclophilin A receptor, CD147 (also called neurothelin, basigin and EMMPRIN), and that administration of purified cyclophilin A protein to neuronal cultures induces a rapid but transient phosphorylation of the extracellular signal-regulated kinase (ERK) 1/2. Furthermore, administration of purified cyclophilin A protein to neuronal cultures protects neurons from oxidative stress and in vitro ischemia. Interestingly, we detected up-regulation of cyclophilin A mRNA, but not protein in the hippocampus following a 3-min period of sublethal global cerebral ischemia in the rat. Despite our in vivo findings, our in vitro data show that cyclophilin A has both intracellular- and extracellular-mediated neuroprotective mechanisms. To this end, we propose cyclophilin A's extracellular-mediated neuroprotection occurs via CD147 receptor signalling, possibly by activation of ERK1/2 pro-survival pathways. Further characterization of cyclophilin A's neuroprotective mechanisms may aid the development of a neuroprotective therapy.     

Platelet‐rich plasma as a novel treatment for lichen planopillaris

Treatment of lichen planopillaris (LPP) remains a significant challenge due to the irreversible damage inflicted on hair follicles combined with the low efficacy of existing treatments. We hypothesized that growth factors released by the use of platelet‐rich plasma (PRP) may arrest the development of LPP. To test our hypothesis, we treated an LPP patient that has failed previous treatments with a new PRP regimen. Following PRP treatment and six months follow‐up, the patient experienced complete regression of itching and hair shedding. To the best of our knowledge, this is the first report of successful treatment of LPP with a PRP regimen.