Strain Dependent Variation of Immune Responses to A. fumigatus: Definition of Pathogenic Species

For over a century microbiologists and immunologist have categorized microorganisms as pathogenic or non-pathogenic species or genera. This definition, clearly relevant at the strain and species level for most bacteria, where differences in virulence between strains of a particular species are well known, has never been probed at the strain level in fungal species. Here, we tested the immune reactivity and the pathogenic potential of a collection of strains from Aspergillus spp, a fungus that is generally considered pathogenic in immuno-compromised hosts. Our results show a wide strain-dependent variation of the immune response elicited indicating that different isolates possess diverse virulence and infectivity. Thus, the definition of markers of inflammation or pathogenicity cannot be generalized. The profound understanding of the molecular mechanisms subtending the different immune responses will result solely from the comparative study of strains with extremely diverse properties.     

High-grade mucoepidermoid carcinoma of the breast. Fine needle aspiration cytology and clinicopathologic study of a case

A primary high-grade mucoepidermoid carcinoma of the breast was evaluated preoperatively by fine needle aspiration (FNA) cytology in a 72-year-old woman. The smears showed a mixed pattern consisting of clusters of poorly differentiated squamous cells, keratinized squamous cells and vacuolated mucin-secreting cells. The subsequent mastectomy specimen showed a tumor with the features of a high-grade mucoepidermoid carcinoma. Electron microscopy confirmed the diagnosis, reflecting the epidermoid and glandular differentiation of the tumor. The course was rapidly fatal, and the patient died a few months after presentation. A review of the literature indicated that mucoepidermoid carcinoma of the breast is a very rare neoplasm; the FNA cytologic features described in this report may constitute a basis to preoperatively recognize this tumor.     

Primary multilobated T-cell lymphoma of the breast diagnosed by fine needle aspiration cytology and immunocytochemistry

The fine needle aspiration (FNA) cytologic, immunocytochemical and ultrastructural findings of a primary multilobated T-cell lymphoma arising in the breast of a 61-year-old woman are described. Large pleomorphic multilobated malignant cells were primarily identified as lymphomatous in origin and phenotypically as T-cells by a selected panel of monoclonal antibodies applied to the original smears obtained by FNA biopsy. This appears to be the second report of a multilobated lymphoma arising in the breast and the first with a T-cell phenotype in this anatomic site.     

A comparative study on axial coordination and ligand binding in ferric mini myoglobin and horse heart myoglobin

The absorption and resonance Raman spectra and the azide binding kinetics of ferric horse heart myoglobin (Mb) and mini myoglobin (a chemically truncated form of horse heart Mb containing residues 32-139) have been compared. The steady-state spectra show that an additional six-coordinated low-spin form (not present in entire horse heart Mb, which is purely six-coordinated high spin) predominates in mini Mb. The distal histidine is possibly the sixth ligand in this species. The presence of two species corresponds to a kinetic biphasicity for mini Mb that is not observed for horse heart Mb. Azide binds to horse heart Mb much more slowly than to sperm whale Mb. This difference may result from a sterically hindered distal pocket in horse heart Mb. In both cases, the rate constants level off at high azide concentrations, implying the existence of a rate-limiting step (likely referable to the dissociation of the axial sixth ligand). The faster rate constant of mini Mb is similar to that of sperm whale Mb, whereas the slower one is similar to that of entire horse heart Mb.     

Attenuation of pulmonary and systemic vasoconstriction with pentoxifylline and aminophylline

The effects of acute administration of therapeutic doses (1-10 mg/kg) of pentoxifylline and aminophylline on the resistance of the systemic and pulmonary circuits in anaesthetized dogs and pigs were tested. During room air breathing, neither of the two substances caused a significant change in systemic vascular resistance (SVR) or pulmonary vascular resistance (PVR). During hypoxia (10% O2 and nitrogen), however, both substances caused a significant reduction in PVR (p less than 0.05) without affecting SVR. The largest dose of pentoxifylline decreased PVR from 7.8 +/- 2.8 to 4.4 +/- 1.5 in dogs and from 9.9 +/- 1.4 to 5.8 +/- 0.6 mmHg.L-1.min in pigs. Aminophylline was equally effective and selective in lowering PVR but not SVR during hypoxia. When SVR was elevated in dogs by continuous infusion of angiotensin, pentoxifylline lowered SVR from 139 +/- 27 to 83 +/- 20 mmHg.L-1.min (p less than 0.05). The simultaneous small elevation in PVR during angiotensin infusion was also attenuated to base-line value by pentoxifylline injection. These results suggest that xanthines, in therapeutic doses, can have a profound vasodilator effect on either the systemic or on the pulmonary circuit, only wherever the vessels are constricted. The vasodilatory effect of pentoxifylline is viewed as a second beneficial effect besides the benefit derived from its action on erythrocyte deformability.     

A novel cross-shear metric for application in computer simulation of ultra-high molecular weight polyethylene wear

Wear testing of polyethylene in total joint replacements is common and required for any new device. Computational wear modelling has obvious utility in this context as it can be conducted with much greater economy than physical testing. Archard's law has become the accepted standard for wear simulation in total joints but it does not account for cross-shear, which is known to increase wear significantly relative to unidirectional sliding. The purpose of this study was to develop a robust cross-shear model applicable to any interface geometry under any kinematic conditions. The proposed metric, x ^*, is distinguished from existing cross-shear models by the fact that it measures cross-path motion incrementally throughout a motion cycle and quantifies cross-shear based on incremental changes in sliding direction. Validation showed strong support for the predictive capability of x ^* when applied to pin-on-disc test data.     

Detecting clinical activity in systemic lupus erythematosus with an archaeal poly(ADP-ribose) polymerase-like thermozyme: a pivotal study

The clinical usefulness of an immunotest was evaluated by using purified poly(adenosine diphosphate (ADP)-ribose) polymerase from Sulfolobus solfataricus (PARPSso) as an antigen to detect the presence of abnormal anti-PARP antibodies in the sera of patients with systemic lupus erythematosus (SLE) at different clinical stages. Sera from 44 patients with SLE, subgrouped on the basis of disease activity (16 with inactive disease, 28 with active disease) were analysed with a new immunotest to detect anti-PARP antibodies, and with an immunofluorescent (IIF) assay for antinuclear antibodies (ANA) detection. ANA detection by IIF revealed that sera of healthy subjects were negative, whereas sera from patients with SLE were positive in all cases (13 positive at 1:80, 15 at 1:160, 15 at 1:320, 1 at 1:640, v/v). Anti-PARP activity was higher in ANA-positive patients than in controls (p?=?0.005). Within the group of SLE sera, disease and anti-PARP activity was increased more significantly in patients with active than in those with inactive disease (p?p?=?0.001, respectively). Correlation between anti-PARP and disease activity in SLE patients was statistically significant (p?Sso seems to be suitable for detecting anti-PARP antibodies and could play a role as a serological marker of disease activity in patients with SLE.     

FAM111A Mutations Result in Hypoparathyroidism and Impaired Skeletal Development

Kenny-Caffey syndrome (KCS) and the similar but more severe osteocraniostenosis (OCS) are genetic conditions characterized by impaired skeletal development with small and dense bones, short stature, and primary hypoparathyroidism with hypocalcemia. We studied five individuals with KCS and five with OCS and found that all of them had heterozygous mutations in FAM111A. One mutation was identified in four unrelated individuals with KCS, and another one was identified in two unrelated individuals with OCS; all occurred de novo. Thus, OCS and KCS are allelic disorders of different severity. FAM111A codes for a 611 amino acid protein with homology to trypsin-like peptidases. Although FAM111A has been found to bind to the large T-antigen of SV40 and restrict viral replication, its native function is unknown. Molecular modeling of FAM111A shows that residues affected by KCS and OCS mutations do not map close to the active site but are clustered on a segment of the protein and are at, or close to, its outer surface, suggesting that the pathogenesis involves the interaction with as yet unidentified partner proteins rather than impaired catalysis. FAM111A appears to be crucial to a pathway that governs parathyroid hormone production, calcium homeostasis, and skeletal development and growth.     

Dynamic changes in microbiota and mycobiota during spontaneous ‘Vino Santo Trentino’ fermentation

Vino Santo is a sweet wine produced from late harvesting and pressing of Nosiola grapes in a small, well‐defined geographical area in the Italian Alps. We used metagenomics to characterize the dynamics of microbial communities in the products of three wineries, resulting from spontaneous fermentation with almost the same timing and procedure. Comparing fermentation dynamics and grape microbial composition, we show a rapid increase in a small number of wine yeast species, with a parallel decrease in complexity. Despite the application of similar protocols, slight changes in the procedures led to significant differences in the microbiota in the three cases of fermentation: (i) fungal content of the must varied significantly in the different wineries, (ii) Pichia membranifaciens persisted in only one of the wineries, (iii) one fermentation was characterized by the balanced presence of Saccharomyces cerevisiae and Hanseniaspora osmophila during the later phases. We suggest the existence of a highly winery‐specific ‘microbial‐terroir’ contributing significantly to the final product rather than a regional ‘terroir’. Analysis of changes in abundance during fermentation showed evident correlations between different species, suggesting that fermentation is the result of a continuum of interaction between different species and physical–chemical parameters.     

The beta subunit of E. coli glycyl-tRNA synthetase plays a major role in tRNA recognition.

The contributions made by the alpha and beta subunits of E. coli glycyl-tRNA synthetase to the recognition of tRNA have been investigated via binding and immunological methods. Using the nitrocellulose filter assay, we have shown that isolated beta subunit, but not the alpha subunit, binds [14C]glycyl-tRNA with an affinity comparable to that of the native enzyme. Further, the data indicate that the beta subunit possesses one binding site for glycyl-tRNA while the native or reconstituted enzyme (alpha 2 beta 2) has two sites. Rabbit antibodies directed at the beta subunit or the holoenzyme inhibit efficiently the ability of the enzyme to aminoacylate tRNA while alpha-subunit antibodies have a smaller effect. Since none of the antisera have an appreciable effect on the ATP-PPi exchange activity of the enzyme under these conditions, the beta-subunit (and holoenzyme) antisera evidently interfere with productive tRNA binding. Taken together, the data indicate that the larger, beta subunit of glycyl-tRNA synthetase plays a major role in tRNA recognition.