Activation of bone morphogenetic protein/Smad signaling in bronchial epithelial cells during airway inflammation

Bone morphogenetic proteins (BMPs) are pleiotropic secreted proteins, structurally related to transforming growth factor (TGF)-beta and activins. BMPs play pivotal roles in the regulation of embryonic lung development and branching of airways and have recently been considered to influence inflammatory processes in adults due to their chemotactic activity on fibroblasts, myocytes, and inflammatory cells. In this study, we have investigated the possible involvement of BMPs in a model of experimental allergic-airway inflammation in situ using antibodies that detect activated Smad proteins, and have monitored the modulation of BMP ligands during the inflammatory response. Inflamed bronchial epithelial cells and a few scattered alveolar cells expressed levels of phosphorylated Smad1 (pSmad1/5), indicative of active BMP/Smad signaling. This was in contrast to healthy epithelium, which was devoid of immunoreactivity. A mechanistic explanation for increased pSmad1/5 staining during inflammation was provided by the upregulated expression of all the BMP type I receptors, i.e., activin receptor-like kinase (ALK)2, ALK3, and ALK6, in the inflamed bronchial epithelial cells. Furthermore, the mRNA and protein profiles for BMP ligands were significantly altered during airway inflammation with induction of BMP2, BMP4, and BMP6, and downregulation of BMP5 and BMP7. Collectively, our data demonstrate for the first time active BMP/Smad signaling during airway inflammation in bronchial epithelial cells and thus raise the possibility that BMPs could play a determining role in respiratory pathophysiology.     

Inappropriate peripheral blood lymphocyte responses to herpes viruses in patients with behçet's syndrome

Specific antibody production and the proliferative response of peripheral blood lymphocytes (PBLs) to a variety of viruses, including herpes simplex virus-type-1 (HSV-1) and varicella zoster (VZ), were studied in 7 patients with Behçet's syndrome. None of the patients produced an antibody response against HSV-1 or VZ. Furthermore, none of the patients showed a proliferative response to VZ, and three of them also failed to mount a response to HSV-I. These results suggest that the PBLs of patients with Behçet's syndrome make an inappropriately poor antibody and proliferative response when stimulated by HSV-1 and VZ.     

Laparoscopic bilateral inguinal hernia repair: Should it be the preferred technique?

Inguinal hernias are amongst the most common conditions requiring general surgical intervention. For decades, the preferred approach was the open repair. As laparoscopy became more popular and available and more surgeons became familiarized with this modality, laparoscopic inguinal hernia repair became an alternative. The aim of this study is to assess the effectiveness of laparoscopic inguinal repair, with a focus on bilateral inguinal hernias. Initial reports have shown promising clinical outcomes compared to those of conventional repair of bilateral hernias. However, there are only a few studies concerning laparoscopic repair of bilateral hernias. It is yet to be proven that laparoscopy is the “gold standard” in the treatment of bilateral inguinal hernias. So far, the choice of an inguinal hernia repair technique has been up to each surgeon, depending on their expertise and available resources after taking into consideration each patient’s needs.     

Awareness of thrombotic disease during lockdown: an unusual consequence of the COVID-19 pandemic

The adjusted global antiphospholipid syndrome score (aGAPSS) is a recently developed thrombotic risk assessment score that considers the antiphospholipid antibody (aPL) profile and conventional cardiovascular risk factors. In this retrospective study, we aimed to evaluate the validity of the aGAPSS in predicting clinical manifestations (criteria and extra-criteria) of antiphospholipid syndrome (APS) in a single centre cohort of patients. Ninety-eight patients with APS?±?systemic lupus erythematosus (SLE) were classified according to clinical manifestations as vascular thrombosis (VT), pregnancy morbidity (PM) or both (VT?+?PM). The aGAPSS was calculated for each patient as previously defined. Mean aGAPSS of the cohort was calculated as 10.2?±?3.8. Significantly higher aGAPSS values were seen in VT (n?=?58) and VT?+?PM (n?=?29) groups when compared to PM (n?=?11) group (10.6?±?3.7 vs 7.4?±?2.9, P?=?0.005; 10.7?±?4 vs 7.4?±?2.9, P?=?0.008, respectively), mainly due to lower frequencies of cardiovascular risk factors in PM. Higher aGAPPS values were also associated with recurrent thrombosis (11.6?±?3.7 vs 9.9?±?3.6, P?=?0.04). Regarding extra-criteria manifestations, patients with livedo reticularis (n?=?11) and APS nephropathy (n?=?9) had significantly higher aGAPSS values (12.9?±?3.4 vs 9.9?±?3.7, P?=?0.02; 12.4?±?2.9 vs 10?±?3.8, P?=?0.04, respectively). The computed AUC demonstrated that aGAPSS values ≥10 had the best diagnostic accuracy for thrombosis. Our results suggest that patients with higher aGAPSS values are at higher risk for developing vascular thrombosis (either first event or recurrence) and extra-criteria manifestations, especially livedo reticularis and APS nephropathy.

     

Prevalence of hemochromatosis gene (HFE) mutations in Greece

The frequencies of the hereditary hemochromatosis gene (HFE) mutations C282Y and H63D vary between different populations. There are a limited number of reports regarding the frequency of these mutations in populations of southeastern Europe. Two hundred and sixty-four adult individuals of Greek origin were examined for the C282Y and H63D mutations to determine the allele and genotype frequencies. The HFE gene region of DNA samples extracted from peripheral leukocytes was amplified by the polymerase chain reaction. Restriction enzyme analysis was performed using RSAI for C282Y and MBOI for H63D. None of the 264 individuals carried the mutation C282Y. Forty-three individuals (16.2%) were heterozygous carriers of the H63D allele and 2 were homozygous for this mutation (0.75%). The overall H63D allele prevalence is thus estimated at 8.9%. HFE mutation frequencies were low in the population studied and this may explain, in part, the relative rarity of clinical cases of hereditary hemochromatosis in Greece.     

Sternomastoid muscle function and fatigue in breathless patients with severe respiratory disease

In patients with severe respiratory disease, the work of breathing is increased and the respiratory muscles, particularly those of inspiration, may become fatigued. Hitherto, there has been little information on the incidence of respiratory muscle fatigue in acutely breathless patients. We studied 34 patients with severe respiratory disease on admission to hospital when they were most breathless, and then, if possible, 7 to 14 days later after recovery for evidence of sternomastoid muscle fatigue or increased fatigability. Frequency/force curves, numerically expressed as the 20:50 ratio, were carried out in all patients on admission. Three of the 34 patients had evidence of low frequency fatigue (i.e., greater than 15% reduction in 20:50 ratio) in the sternomastoid muscle on admission when first studied (mean +/- SEM 20:50 ratio, 56.3 +/- 1.2%; n = 3). The mean 20:50 ratio in the remaining 31 patients on admission was 75.7 +/- 1.6% (n = 31) compared with 77.8 +/- 1.4% (n = 25) when symptomatically better (p less than 0.05). The mean 20:50 ratio on admission was also significantly lower than the mean 20:50 ratio in a group of age- and sex-matched normal control subjects (i.e., 78.5 +/- 1.4%, n = 25; p less than 0.05). Twenty-five patients were studied completely both on admission and recovery, including a fatigability test that involved the performance of 50 fatiguing head lifts with measurements of the 20:50 ratio 10 and 60 min later. Sternomastoid muscle fatigability was significantly increased on admission when the patients were most breathless, compared with recovery when they were less breathless (p less than 0.001 at both 10 and 60 min).(ABSTRACT TRUNCATED AT 250 WORDS)     

A novel strategy for the determination of a rhabdovirus genome and its application to sequencing of Eggplant mottled dwarf virus

A novel strategy employing the rhabdovirus untranslated conserved intergenic regions was developed and applied successfully for the determination of the complete nucleotide sequence of Eggplant mottled dwarf virus (EMDV). The EMDV genome contains seven open reading frames with the same organization as Potato yellow dwarf virus (PYDV), the type species of the genus Nucleorhabdovirus. These two species encode five core genes [nucleocapsid (N), phosphoprotein (P), matrix (M), glycoprotein (G), and the polymerase (L)] like other viruses of the genus and an additional one (X), located between N and P, giving rise to a protein with currently unknown function. Furthermore, both EMDV and PYDV contain a gene (Y), inserted between P and M, which probably encodes the virus movement protein, in concordance with the rest of the plant-infecting rhabdoviruses. Phylogenetic analysis of the polymerase gene confirmed the classification of EMDV within the genus Nucleorhabdovirus and showed a close evolutionary relationship to PYDV. The novel sequencing strategy developed is a useful tool for the genome determination of yet uncharacterized rhabdoviruses.