A complementarity-determining region peptide of an anti-desmosome autoantibody may interact with the desmosomal plaque through molecular mimicry with a cytoplasmic desmoglein 1 sequence

The sera of patients with pemphigus, a group of autoimmune blistering skin diseases, contain autoantibodies directed against components of adhering junctions termed desmosomes. F12, a human monoclonal antibody derived from a pemphigus patient, recognizes an unknown polypeptide of the desmosomal and hemidesmosomal plaques. The third complementarity-determining region of the F12 heavy chain (VH-CDR3) was shown to share a four-amino-acid sequence (GSSG) with the intracellular domains of desmoglein 1 and bullous pemphigoid antigen 2 which interact with components of, respectively, the desmosomal and hemidesmosomal plaques. Computer modeling of F12 showed that the GSSG sequence protudes inside the antigen-combining site and thus might be involved in antigen interactions. The GSSG sequence is essential to F12 function, since a peptide containing the VH-CDR3 inhibited its binding to target antigens while VH-CDR3 peptides with specific modifications of the GSSG sequence did not. These data allow us to hypothesize that certain autoantibodies produced during the course of an autoimmune disease can behave as adhesion molecules, through the molecular mimicry of the motif involved in protein/protein adhesion, and to propose a new self-antigen binding mechanism for some autoantibodies.     

Pseudoinvasion with high-grade dysplasia in a colonic adenoma. Distinction from adenocarcinoma

High-grade dysplasia was found to extend to an area of pseudoinvasion in the submucosa of a colonic adenoma mimicking invasive carcinoma. The presence of both benign and cytologically malignant epithelium and residual foci of lamina propria among the submucosal glands distinguishes this entity from adenocarcinoma arising in an adenomatous polyp.     

Linkage of the horizontally acquired ypm and pil genes in Yersinia pseudotuberculosis

The superantigen-encoding ypm gene and the pil gene cluster governing type IV pilus biogenesis have been laterally acquired by Yersinia pseudotuberculosis. PCR assays on 270 unrelated strains from various environmental and animal sources revealed a significant association of ypm and pil in isolates.     

Activation-induced polarized recycling targets T cell antigen receptors to the immunological synapse; involvement of SNARE complexes

The mechanism by which T cell antigen receptors (TCR) accumulate at the immunological synapse has not been fully elucidated. Since TCRs are continuously internalized and recycled back to the cell surface, we investigated the role of polarized recycling in TCR targeting to the immunological synapse. We show here that the recycling endosomal compartment of T cells encountering activatory antigen-presenting cells (APCs) polarizes towards the T cell-APC contact site. Moreover, TCRs in transit through recycling endosomes are targeted to the immunological synapse. Inhibition of T cell polarity, constitutive TCR endocytosis, or recycling reduces TCR accumulation at the immunological synapse. Conversely, increasing the amount of TCRs in recycling endosomes before synapse formation enhanced their accumulation. Finally, we show that exocytic t-SNAREs from T cells cluster at the APC contact site and that tetanus toxin inhibits TCR accumulation at the immunological synapse, indicating that vesicle fusion mediated by SNARE complexes is involved in TCR targeting to the immunological synapse.     

Early recognition of newborn goat kids by their mother: II. Auditory recognition and evidence of an individual acoustic signature in the neonate

The vocal recognition of newborn kids by their mother at 2 days postpartum and the possible existence of interindividual differences in the voice structure of newborn kids were investigated in two separate studies. The ability of goats to discriminate between the bleats of their own versus an alien kid was tested at 2 days postpartum in mothers being prevented access to visual and olfactory cues from the young. Goats spent significantly more time on the side of the enclosure from which their own kid was bleating, looked in its direction for longer, and responded more frequently to the bleats of their own than to those of the alien kid (p < 0.05). In the second study, the sonograms of 13 kids, studied from Days 1 to 5, showed significant interindividual differences for the five variables taken into account and on each of the 5 days (duration of bleat, fundamental frequency, peak frequency, and numbers of segments and of harmonics). The potential for individual coding ranged between 1.1 and 4.1, indicating that for some variables variations between individuals were greater than intraindividual variations. Furthermore, when considering the five parameters together, the discriminating scores showed an average of 95% in the 78 combinations of any 2 kids for any given day. Finally, some significant intraindividual differences also were found between days, suggesting ontogenic changes in the characteristics of the kid's voice in early life. Therefore, mother goats are likely to recognize the vocalizations of their 48-hr-old kids, as they show sufficient interindividual variability to allow the existence of individual vocal signatures, even though some of the characteristics of the bleats change rapidly over time.     

Effect of ambient temperature on learning

After a three week exposure at 34, 25 or 10°C, three strains of mice (C57BL/6, BALB/c and A/J) underwent a conventional active two-way avoidance task. As compared to 25°C of ambient temperature, acquisition on the first day was severely impaired in the three strains at 34°C and in the C57BL/6, and A/J mice at 10°C. Learning scores on the second day were diminished in the C57BL/6 strain at 34°C and 10°C and in the BALB/c strain at 34°C. The mechanisms of such an impairment in learning at high or low temperature are discussed.     

Long-chain omega-3 fatty acids regulate bovine whole-body protein metabolism by promoting muscle insulin signalling to the Akt–mTOR–S6K1 pathway and insulin sensitivity

The ability of the skeletal musculature to use amino acids to build or renew constitutive proteins is gradually lost with age and this is partly due to a decline in skeletal muscle insulin sensitivity. Since long-chain omega-3 polyunsaturated fatty acids (LC n –3PUFA) from fish oil are known to improve insulin-mediated glucose metabolism in insulin-resistant states, their potential role in regulating insulin-mediated protein metabolism was investigated in this study. Experimental data are based on a switchback design composed of three 5 week experimental periods using six growing steers to compare the effect of a continuous abomasal infusion of LC n –3PUFA-rich menhaden oil with an iso-energetic control oil mixture. Clamp and insulin signalling observations were combined with additional data from a second cohort of six steers. We found that enteral LC n –3PUFA potentiate insulin action by increasing the insulin-stimulated whole-body disposal of amino acids from 152 to 308 μmol kg⁻¹ h⁻¹ ( P = 0.006). The study further showed that in the fed steady-state, chronic adaptation to LC n –3PUFA induces greater activation ( P < 0.05) of the Akt–mTOR–S6K1 signalling pathway. Simultaneously, whole-body total flux of phenylalanine was reduced from 87 to 67 μmol kg⁻¹ h⁻¹ ( P = 0.04) and oxidative metabolism was decreased ( P = 0.05). We conclude that chronic feeding of menhaden oil provides a novel nutritional mean to enhance insulin-sensitive aspects of protein metabolism.     

Undifferentiated embryonal sarcoma of the liver in an adult: a case report

Undifferentiated embryonal sarcoma of the liver is rare. It is usually observed in children and adolescents. We report one case of embryonal sarcoma of the liver arising in patient without any antecedent. The only symptom was right scapular pain. The liver scan showed a multicystic lesion suspicious for infectious origin or a tumor. Serologies for ecchinococcus, schistosomiasis and brucellosis were negative. The treatment was a right hepatectomy. On gross examination, the tumor was unencapsulated, multicystic and contained large areas of necrosis admixed with gelatinous areas. Microscopically, there were epithelioid and spindle tumor cells in a myxo?d stroma. Lipoblastic-like or rhabdomyoblastic-like, giant cells and PAS positive hyaline globules in the cell cytoplasm were present. The tumor cells expressed vimentin, cytokeratin (KL1), alpha-1-antitrypsin and smooth muscle actin. This observation shows that embryonal sarcoma of the liver may develop in adult patients and should be taken into consideration in any differential diagnosis of cystic hepatic tumor.     

Endometrial and colorectal tumors from patients with hereditary nonpolyposis colon cancer display different patterns of microsatellite instability

The colorectum and uterine endometrium are the two most commonly affected organs in hereditary nonpolyposis colon cancer (HNPCC), but the genetic basis of organ selection is poorly understood. As tumorigenesis in HNPCC is driven by deficient DNA mismatch repair (MMR), we compared its typical consequence, instability at microsatellite sequences, in colorectal and endometrial cancers from patients with identical predisposing mutations in the MMR genes MLH1 or MSH2. Analysis of non-coding (BAT25, BAT26, and BAT40) and coding mononucleotide repeats (MSH6, MSH3, MLH3, BAX, IGF2R, TGF beta RII, and PTEN), as well as MLH1- and MSH2-linked dinucleotide repeats (D3S1611 and CA7) revealed significant differences, both quantitative and qualitative, between the two tumor types. Whereas colorectal cancers displayed a predominant pattern consisting of instability at the BAT loci (in 89% of tumors), TGF beta RII (73%), dinucleotide repeats (70%), MSH3 (43%), and BAX (30%), no such single pattern was discernible in endometrial cancers. Instead, the pattern was more heterogeneous and involved a lower proportion of unstable markers per tumor (mean 0.27 for endometrial cancers versus 0.45 for colorectal cancers, P < 0.001) and shorter allelic shifts for BAT markers (average 5.1 bp for unstable endometrial cancers versus 9.3 bp for colorectal cancers, P < 0.001). Among the individual putative "target" loci, PTEN instability was associated with endometrial cancers and TGF beta RII instability with colon cancers. The different instability profiles in endometrial and colorectal cancers despite identical genetic predisposition underlines organ-specific differences that may be important determinants of the HNPCC tumor spectrum.     

Proposed criteria for mixed-dust pneumoconiosis: definition, descriptions, and guidelines for pathologic diagnosis and clinical correlation

We defined mixed-dust pneumoconiosis (MDP) pathologically as a pneumoconiosis showing dust macules or mixed-dust fibrotic nodules (MDF), with or without silicotic nodules (SN), in an individual with a history of exposure to mixed dust. We defined the latter arbitrarily as a mixture of crystalline silica and nonfibrous silicates. According to our definition of MDP, therefore, MDF should outnumber SN in the lung to make a pathologic diagnosis of MDP. In the absence of confirmation of exposure, mineralogic analyses can be used to support the pathologic diagnosis. The clinical diagnosis of MDP requires the exclusion of other well-defined pneumoconioses, including asbestosis, coal workers’ pneumoconiosis, silicosis, hematite miners’ pneumoconiosis, welders’ pneumoconiosis, berylliosis, hard metal disease, silicate pneumoconiosis, diatomaceous earth pneumoconiosis, carborundum pneumoconiosis, and corundum pneumoconiosis. Typical occupations associated with the diagnosis of MDP include metal miners, quarry workers, foundry workers, pottery and ceramics workers, and stonemasons. Irregular opacities are the major radiographic findings in MDP (ILO 1980), in contrast to silicosis, in which small rounded opacities predominate. Clinical symptoms of MDP are nonspecific. MDP must be distinguished from a variety of nonoccupational interstitial pulmonary disorders.