HLA class II regulation and structure. Analysis with HLA-DR3 and HLA-DP point mutants.

Point mutations that affect HLA-DR structure or expression have not previously been described. In the present study, we isolated such mutants by immunoselection of an ethyl methanesulfonate-mutagenized HLA-DR3 cell line with an anti-HLA-DR3 monoclonal antibody, 16.23. To facilitate analysis, we used a parent cell line with a preexisting deletion of one haplotype encompassing DR and DQ alpha and beta. The selection yielded two sets of mutants, one with defects in DR3 structure, the other with defects in different steps leading to DR expression. Of the expression-defective mutants, one had undergone a second deletion removing the remaining DR alpha gene but no other class II genes. It had a normal abundance of DR beta mRNA but had lost binding of DR monomorphic antibodies, indicating that DR beta chains do not form noncognate dimers. A second mutant had an abnormally large DR alpha mRNA, probably resulting from a splice site mutation. Several mutants had marked reductions in DR beta mRNA levels; in two of these, the lesion appeared to be transcriptional because the reduction in DR beta mRNA was paralleled by an altered methylation pattern of one of the DR beta genes. Other expression-defective mutants had different posttranscriptional defects. Some of the mutations were similar to those that have been found in mouse strains defective in I-E expression, whereas others have no known natural counterpart. The matrix of reactivities of anti-HLA class II monomorphic antibodies with these and similar mutants allowed us to define the gene products recognized by these antibodies. A set of seven mutants were "epitope defective," that is, they expressed normal or near normal levels of HLA-DR3 but no longer bound 16.23. Unexpectedly, each of the epitope mutants had decreased DR dimer stability. These mutants should be useful in localizing the DR3 alloepitope and in elucidating its contribution as a restriction element in the presentation of soluble antigen to immune T cells

Developing textile entrepreneurial inclination model by integrating experts mining and ISM-MICMAC

The Indian textile industry is lacking in an entrepreneurial inclination of a skilled young generation; because of this, the industry is facing a challenge to achieve sustainable development and growth. To overcome this problem, the goal of this work is to build an entrepreneurial inclination model in the context of the textile industry. For achieving this goal, a combined approach of an extensive literature review and experts mining has been used to establish the entrepreneurial inclination factors in phased of the study. In the second phase, an Interpretive Structural Modelling (ISM) with Matrice d'Impacts Croisés Multiplication Appliqués à un Classement (MICMAC) has been applied to build a structural model and to find the driving force factors and dependence power. The results show that effective entrepreneurship courses, institutional policy, training and internship, institutional corporation and the involvement of institutional heads play a very significant role in encouraging youth towards entrepreneurship. The outcomes of the study can help both the government and academic institutes to draw up effective policy and develop an entrepreneurial culture which can help to create more entrepreneurs in the textile field.N

Prospective Analysis of STRATAFIX™ Symmetric PDS Plus Suture for Fascial Closure in Spinal Surgery: A Pilot Study

Wound closure is an integral part of every spinal procedure. Effective and secure wound closure is paramount in the prevention of infection, wound dehiscence and the preservation of cosmesis. Barbed suture technologies such as STRATAFIX™ Symmetric have been studied and are used in a variety of specialties, including obstetrics and orthopedic surgery, but is underutilized in neurosurgery. This study aims to assess the time and rate of closure using STRATAFIX™ Symmetric technology for fascial closure and compare this method to the more traditionally used method of fascial closure using braided absorbable sutures below the epidermis. 20 patients were recruited for the study. 10 patients underwent fascial approximation with braided absorbable sutures and definitive fascial closure with STRATAFIX™ Symmetric. In the control group, fascial closure was completed entirely with interrupted braided absorbable stitches. Patients assigned to STRATAFIX™ Symmetric group had shorter mean time for fascial closure, faster rate of average fascial closure, and lower number of total sutures used. The use of barbed suture technology such as STRATAFIX™ Symmetric may reduce the time to closure in thoracolumbar spine surgery without increasing the risk of adverse events. This pilot study forms the framework for a larger randomized, controlled trial appropriately powered for such an analysis

Preoperative Teleconsultation Visits are as Efficient as In-person Appointments in Avoiding Unnecessary Cancellation of Elective Surgical Procedures

The COVID-19 pandemic has presented many challenges in health care, not the least of which was the need to find alternatives to an in-person evaluation to reduce the risk of transmission of the virus. Despite the discontinuation of elective procedures at Thomas Jefferson University Hospital in Philadelphia (TJUH), Pennsylvania in March 2020, there was a subset of patients that required urgent surgical procedures. Consequently, there needed to be a different approach to the presurgical assessment of these patients. At our institution teleconsultation had gained acceptance by patients and providers prior to the COVID-19 pandemic, therefore a program was rapidly developed utilizing teleconsultation to assess these patients. The question we sought to answer was, in patients undergoing surgery, does completing the preoperative surgical consult through teleconsultation affect the cancellation rate on the day of surgery? Definitions - Teleconsultation – refers to synchronous visits in which a nurse practitioner or physician interfaces in real-time with a patient by video-conferencing. - Medically Optimized – patient completed the pre-admission testing process and was deemed an acceptable risk for surgery

Revertants from the HLA class II regulatory mutant 6.1.6: implications for the regulation of Ia gene expression.

Abstract Class II (Ia) genes of the human MHC code for developmentally regulated, highly polymorphic cell surface glycoproteins. The control of expression of this highly complex genetic region has not been extensively investigated. We used 6.1.6, a variant of a normal B lymphoblastoid cell that has lost expression of all class II molecules, to study this question. In previous studies, we have shown that the structural genes for class II molecules are intact but are not expressed in 6.1.6 (6), and that the defect is at the transcriptional level (7). In this report, we describe the isolation and characterization of revertants of 6.1.6 that reexpress class II molecules. These revertants have four unusual properties: 1) they are found at a higher frequency (0.7%) than would be expected for a mutational event; 2) they are unstable; 3) they reexpress only a subset of class II molecules; and 4) they have only been found in tetraploid cells. On the basis of previous work with 6.1.6 and the properties of reversion in 6.1.6, we propose a hypothesis for the nature of the defect in 6.1.6 and a model for the regulation of class II molecules.</jats:p

Exogenously provided peptides fail to complex with intracellular class II molecules for presentation by antigen-presenting cells.

Abstract Exogenously supplied antigenic peptides can bind to and be presented by cell surface class II molecules of APCs without prior processing. However, it has been unclear whether peptide Ags exogenously supplied to APCs can also form complexes with nascent intracellular class II molecules that contribute to Ag presentation. We found that exogenously provided peptide Ags, unlike whole protein Ags, are presented as efficiently by fixed as by unfixed B lymphoblastoid APCs, suggesting that intracellular processes do not contribute to the presentation of exogenously supplied peptides by unfixed APCs. Consistent with this finding, exogenously provided peptides do not bind detectably to nascent intracellular class II molecules. We studied the basis for this failure. First, as compared with whole proteins, exogenously supplied peptides accumulate very poorly intracellularly. Second, peptides are more rapidly exocytosed. The limited ability of APCs to accumulate exogenously supplied peptides intracellularly provides a likely explanation for the failure of these peptides to associate with nascent intracellular class II molecules. Exogenously supplied peptides probably never reach the intracellular vesicles in which peptide loading of class II molecules occurs. These findings have implications for the use of peptides therapeutically to block presentation of autoantigens in autoimmune disease.</jats:p