Amino acid variations at a single residue in an autoimmune peptide profoundly affect its properties: T-cell activation, major histocompatibility complex binding, and ability to block experimental allergic encephalomyelitis.

Myelin basic protein (MBP) or helper T cells reactive against MBP induce an autoimmune disease, experimental allergic encephalomyelitis, in B10.PL and PL/J inbred mice. In both strains, virtually the entire repertoire of MBP-specific T cells recognize an N-terminal peptide fragment in the context of the I-Au molecule encoded by the major histocompatibility complex (MHC) and utilize a very limited set of T-cell receptor genes. To delineate the nature of the trimolecular complex, consisting of the T-cell receptor, MBP-peptide fragment, and MHC molecule (I-Au), we have synthesized 13 variants of the 9-mer N-terminal immunodominant peptide differing at residue 4 and studied their immune recognition in vitro and in vivo. These substitutions have a striking range of effects on T-cell activation, ability to bind to the MHC molecule, and initiation of immune responses in vivo. An understanding of the autoimmune peptide/MHC/T-cell receptor interactions allowed us to design variant 9-mer peptides that have high affinity for an MHC molecule and are effective in blocking experimental allergic encephalomyelitis, possibly through two distinct mechanisms, peripheral T-cell tolerance and the inhibition of binding of the encephalitogenic peptide to the MHC molecules.     

Pharmacist involvement in clinical assessment and laboratory testing for heparin-induced thrombocytopenia

Journal of Thrombosis and Thrombolysis - Heparin-induced thrombocytopenia (HIT) is a rare adverse drug reaction. The anti-PF4 antibody assay (ELISA) is utilized to assist in the clinical evaluation...     

Round Pendant Around the Neck–Thyroid. A Review

The rare situation of thyroid stone is discussed with literature review and case report. A case of isolated solitary stone of the thyroid is documented here. There are incidences of calcification in the thyroid gland commonly associated with carcinoma thyroid and multinodular goiter. But solitary stone of thyroid is reported rarely and one such case is reported from India. The possibility of malignancy is high, in case of calcification of thyroid swellings. Hence, isolated calcification should be surgically treated even if fine needle aspiration cytology is negative for malignancy.     

Differences in t cell receptor restriction fragment length polymorphisms in patients with rheumatoid arthritis

Objective. The purpose of this study was to determine whether a T cell receptor (TCR) polymorphism, either by itself or in combination with particular HLA polymorphism, leads to susceptibility to rheumatoid arthritis (RA). Methods. Eight restriction fragment length polymorphisms (RFLPs) detected with TCR gene segments were investigated in 46 individuals with RA and were compared with data from normal control subjects. Results. A statistically significant difference in the genotype frequencies of a Taq I RFLP detected with the TCRα constant region (C_α) gene was noted. In addition, when the DR4+ subpopulations were examined, the allelic frequency of a 2-kb Bam HI fragment detected with a V_β8 gene was increased in the samples from RA patients (P < 0.0086). Conclusion. The results of this study suggest that germline differences in the TCR repertoire may be associated with RA, and that there is a contributory effect of DR4+ haplotypes with certain TCR haplotypes in susceptibility to RA.     

INTERVIEW TRAINING: helping adults with mental handicaps to find jobs

Although many adults with mental handicaps have the skills to hold down jobs in the community, they often fail to present themselves adequately when they go for an interview or a meeting to discuss a job with a prospective employer. This paper argues for the feasibility of interview training. It outlines a three-stage programme, with critical interview skills, which is reasonably straightforward to cover with adults with mental handicaps. Two case studies are presented which describe the sorts of problems which can be dealt with in interview training and illustrate the progress which can be achieved.     

Induction of vitellogenin in primary monolayer cultures of cockerel hepatocytes.

A primary monolayer culture system from cockerel hepatocytes was established. The cultures synthesize and secrete proteins that comigrate with authentic serum proteins on polyacrylamide gels and are found in the same relative abundance. Addition of estradiol increased the synthesis of apoprotein B, found in very low density lipoprotein, under all culture conditions. Vitellogenin synthesis could not be induced directly by estradiol. However, when serum was obtained from cockerels injected with estradiol 4 days before blood collection and included in the culture medium, the cultures secreted a protein identified immunologically as vitellogenin by affinity chromatography. Furthermore, addition of growth hormone or prolactin to cultured cockerel hepatocyte monolayers resulted in the synthesis and secretion of a polypeptide that comigrates with authentic vitellogenin on polyacrylamide gels.