Panniculitis in childhood and adolescence

Background: The purpose of the present paper was to describe the clinical manifestations and treatment of patients with panniculitis. Methods: From January 1983 to December 2002, 4294 patients were treated for pediatric rheumatological diseases at Pediatric Rheumatology Unit, University of São Paulo, Brazil. Of these, 35 children and adolescents (0.8%) presented with panniculitis: erythema nodosum (EN) or Weber–Christian disease (WCD). Clinical characteristics, laboratory exams, biopsy of the lesion, treatment and clinical course were studied. Results: Of the 35 patients, 29 presented with EN and six with WCD, one of these with cytophagic histiocytic panniculitis. Mean age at symptom onset was 85 months (6–204 months) and the mean duration of follow up was 55 months (1–144 months). All the patients presented with inflammatory subcutaneous nodules. The patients with WCD presented with systemic manifestations and cutaneous atrophy. The principal etiologies of EN were streptococcal infection (42%), undetermined (13.5%), pulmonary tuberculosis (10%), and acute rheumatic fever (10%). Biopsy of the nodules indicated septal panniculitis in 14 patients with EN and lobular panniculitis without vasculitis in the patients with WCD, one of which had cytophagic histiocytic panniculitis. There was recurrence in 11 patients (38%) with EN and in all those with WCD. Non‐steroidal anti‐inflammatory drugs were used in 15 patients with EN and corticosteroids and/or immunosuppressive drugs in the six patients with WCD. Three patients died. Conclusions: EN is the most frequent panniculitis, with a benign course and is mainly associated with infections. WCD is a severe disease, with systemic involvement, that proceeds with cutaneous atrophy and requires the use of corticosteroids and or immunosuppressive drugs.     

Validity of an eyetracking method for capturing auditory–visual cross-format semantic priming

Introduction: Semantic priming paradigms are important for understanding lexical–semantic processing and the nature of linguistic deficits accompanying language performance in neurologically impaired individuals such as people with aphasia. Reaction-time-(RT)-based traditional semantic priming tasks entail potential confounds, especially problematic when applied to people with aphasia, who may have concomitant neurocognitive challenges that limit task performance. Some of these confounds include requirements of following complex instructions, making metalinguistic judgments, and using speech or limb-based motor actions to indicate overt responses. Eyetracking methods have great potential for avoiding some of these confounds. We tested the validity of an eyetracking method in capturing semantic priming in an auditory–visual cross-format priming paradigm (auditory word prime–visual image target).

Method: A total of 72 neurologically unimpaired adults participated in two phases: a stimulus development phase using traditional priming (n = 32) and an experimental eyetracking phase (n = 40). Each phase included two conditions, representing distinct levels of prime–target semantic relatedness: unrelated and related. Mean RT data from the traditional priming (stimuli development) phase guided image selection for the eyetracking experiment. Eyetracking indices of fixation duration and latency of fixation were recorded to capture semantic priming in the eyetracking experiment.

Results: Eye fixation data indicated that images related to auditory primes were attended to earlier and attracted significantly greater visual attention than unrelated images. These results mirrored RT data from the traditional priming method, which showed faster RT latencies and more accurate naming performance for related images than for unrelated images.

Conclusions: Results support the validity of eyetracking indices of semantic priming and offer a robust testing protocol for future studies in this line of research. Current clinical relevance for people with aphasia is highlighted. Further empirical testing of the psychometric properties of the eyetracking measures in various semantic priming contexts is recommended.     

The pentose phosphate pathway and pyruvate carboxylation after neonatal hypoxic-ischemic brain injury

The neonatal brain is vulnerable to oxidative stress, and the pentose phosphate pathway (PPP) may be of particular importance to limit the injury. Furthermore, in the neonatal brain, neurons depend on de novo synthesis of neurotransmitters via pyruvate carboxylase (PC) in astrocytes to increase neurotransmitter pools. In the adult brain, PPP activity increases in response to various injuries while pyruvate carboxylation is reduced after ischemia. However, little is known about the response of these pathways after neonatal hypoxia-ischemia (HI). To this end, 7-day-old rats were subjected to unilateral carotid artery ligation followed by hypoxia. Animals were injected with [1,2-¹³C]glucose during the recovery phase and extracts of cerebral hemispheres ipsi- and contralateral to the operation were analyzed using ¹H- and ¹³C-NMR (nuclear magnetic resonance) spectroscopy and high-performance liquid chromatography (HPLC). After HI, glucose levels were increased and there was evidence of mitochondrial hypometabolism in both hemispheres. Moreover, metabolism via PPP was reduced bilaterally. Ipsilateral glucose metabolism via PC was reduced, but PC activity was relatively preserved compared with glucose metabolism via pyruvate dehydrogenase. The observed reduction in PPP activity after HI may contribute to the increased susceptibility of the neonatal brain to oxidative stress.     

Immunological appraisal of wheat varieties in relation to chapatti-making characteristics

The current research work was conducted to characterize wheat proteins through immunochemical techniques and to find out their relationship with wheat quality traits. The results revealed that wheat variety AARI-11 possessed higher protein content (11.96%), wet gluten (31.39%), dry gluten (9.66%), Pelshenke value (190.52 min), and SDS-Sedimentation value (28.27 ml) than other tested varieties. The chapattis prepared from the wheat variety AARI-11 got significantly higher sensory scores owing to its higher protein contents. The wheat variety AARI-11 also exhibited significantly the highest antibody response against all the assessed protein fractions. The results of the present study suggest that anti-glutenin and anti-high molecular weight glutenin subunits (HMW-GS) antibody response was found positively correlated to the quality characteristics of flours and chapattis. The present study suggests that the use of antibodies response against glutenin and HMW-GS offers good tool for predicting quality and suitability of wheat to chapatti-making quality.     

Immunological appraisal of modified gluten to trim down celiac toxicity

The aim of the present research was to modify wheat gluten by binding methionine to gluten proteins to develop bread for celiac disease (CD) patients. The highest protein content, wet gluten content, dry gluten content and sodium dodecyl sulphate-sedimentation value were shown by the wheat variety AARI-11, therefore, it was selected for gluten modification. The bound methionine to gluten proteins was found increasing along the reaction time as the reaction proceeds and at a maximum near to 60 minutes and then it starts decreasing. The lowest immunoreactivity of the modified gluten was obtained near to 60 min of reaction at pH 10. The results for immunoglobulin A (IgA) index showed that the serum of each patient had positive IgA index to gliadins from unmodified gluten, but just sera of two patients had positive IgA index to gliadins from modified gluten and when these proteins were digested, the sera of no patient's serum had positive IgA reactivity. Among physical characteristics of breads 2 hours after baking, the specific volume of the modified gluten containing bread (4.13 ± 0.14 cm³/g) was lower than the control bread (4.59 ± 0.21 cm³/g). However, bread made with modified gluten had higher specific volumes than other gluten-free breads. Texture of the modified gluten was also affected by modification. Finally, the gluten content in the modified gluten bread was 79 ppm which is under the limits set by the Codex Alimentarius for food with reduced gluten content should have from 20 to 100 ppm. The study concludes that the incorporation of steric immensity into gluten proteins in order to shun immune recognition is the most promising approach to acquire wheat-based products that are tolerated by CD patients.     

TEL gene is involved in myelodysplastic syndromes with either the typical t(5;12)(q33;p13) translocation or its variant t(10;12)(q24;p13)

A t(5;12)(q33;p13) translocation is a recurrent chromosome abnormality in a subgroup of myeloid malignancies with features of both myeloproliferative disorders and myelodysplastic syndromes (MDSs). The molecular consequence of a t(5;12) is a fusion between the platelet- derived growth factor receptor-B gene on chromosome 5 and a novel ETS- like gene, TEL, on chromosome 12. We report on three patients with a t(5;12)(q33;p13) diagnosed as chronic myelomonocytic leukemia, and one case of a t(10;12)(q24;p13) in a progressive MDS, with eosinophilia and monocytosis. Involvement of the TEL gene in these chromosome translocations was investigated by fluorescence in situ hybridization (FISH) with cosmid probes containing selectively the 5' end or 3' end of TEL. Hybridization of these cosmids to the der(5)/der(10) or a der(12), respectively, demonstrated a rearrangement of TEL in both translocations, showing that the t(10;12) is a variant translocation of the t(5;12). Cloning of the fusion cDNA of one case of t(5;12) showed that the breakpoint occurred at the RNA level at exactly the same position as reported by Golub et al (Cell 77:307, 1994). In addition, the TEL gene on chromosome 12 could be localized between two probes previously mapped to 12p13, namely PRB1 and D12S178, leading to a better definition of the position of TEL in this chromosome region. Moreover, in the case involving chromosome 10, the breakpoint occurred between cKTN206 and cKTN312/LYT-10 at 10q24. Clinicohematological data in these studies as well as the restriction mapping of chromosomal breakpoints strongly suggest that (1) common features in MDSs involving the TEL gene are monocytosis and eosinophilia, (2) chromosomes other than no. 5 may be involved and at least a t(10;12)(q24;p13) variant chromosome translocation does exist in these MDSs, and (3) both standard and variant 12p/TEL translocations may be identified by FISH with appropriate probes.     

The cardiac atria are chambers of active remodeling and dynamic collagen turnover during evolving heart failure

OBJECTIVES: The role of atrial myocytes and extracellular matrix (ECM) changes in atrial chamber remodeling was studied in a canine model of heart failure (HF). BACKGROUND: Cardiac remodeling is a key process mediating the progression of HF. Studies of the structural mechanisms of cardiac remodeling have been limited to the left ventricle. The structural alterations associated with atrial chamber remodeling in evolving HF have not been studied. METHODS: Age- and weight-matched dogs were subjected to right ventricular pacing (240 beats/min) for one and three weeks to produce early and severe HF, respectively. Atrial tissues were assessed for myocyte and ECM changes. RESULTS: Right atrial and left atrial (LA) pressures were significantly increased in early and severe HF. The LA wall tension index was significantly increased at both HF stages by 116% and 443%, respectively. Atrial collagen synthesis and degradation were significantly increased in severe HF. Gelatinase activity was significantly increased at both early and severe stages of HF. Gelatin zymography showed increased matrix metalloproteinases (MMP)-9 with early HF and increased MMP-2 with severe HF. The LA wall tension index was significantly correlated with gelatinase activity and collagen synthesis. Although total atrial collagen content was not changed, disarray of collagen fibers was observed. Atrial myocyte hypertrophy without evidence of apoptosis was also present in severe HF. CONCLUSIONS: There is marked atrial chamber remodeling in canine pacing-induced HF, which is characterized by myocyte hypertrophy and dynamic collagen turnover. Atrial remodeling may contribute to the development of atrial arrhythmias and pulmonary hypertension and could offer a novel therapeutic target.