The antigen presentation pathway yields peptide-MHC class I complexes on the antigen presenting cell (APC) surface for recognition by appropriate T-cells. Expression of the peptide-MHC complex on APC surface is preceded by several steps that include the generation of peptide fragments in the cytoplasm and their assembly with MHC molecules in the endoplasmic reticulum. It is now clear that MHC binding to optimally processed peptides in the endoplasmic reticulum is obligatory for their stable expression on the cell surface. However, whether a similar obligatory relationship exists between generation of processed peptides and their expression as peptide-MHC on APC surface is not known. Here, we addressed this question by analyzing the processing of ovalbumin (aa257-264, SL8) or influenza nucleoprotein (aa366-374, AM9) analogs. We examined the generation of naturally processed peptides using precursors that did, or did not, contain residues flanking the optimal MHC-binding peptides. By characterizing the peptides generated from these precursors by T-cell stimulation assays and by high performance liquid chromatography analysis, we established that intracellular assembly of peptide-MHC complexes and their expression on the cell surface can occur with peptides that lack flanking residues. The presentation of these endogenously synthesized perfect fit peptides demonstrates that the cleavage of precursor polypeptides is an independent step in the antigen presentation pathway.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1995

Swallowing therapy of neurologic patients: correlation of outcome with pretreatment variables and therapeutic methods.

The results of swallowing therapy in 58 patients with neurologic disorders are presented. All patients received tube feeding, either partially or exclusively, at admission, and successful outcomes, defined as exclusively oral feeding, were achieved in 67% of patients over a median treatment interval of 15 weeks. A subset of 11 patients who had experienced disease onset 25 weeks or more prior to admission nonetheless had a similar success rate of 64%. No other pretreatment variable, including age, localization of lesion, type or degree of aspiration, or cognitive status, correlated with successful outcome. Indirect therapy methods such as stimulation techniques and exercises to enhance the swallowing reflex, alter muscle tone, and improve voluntary function of the orofacial, lingual, and laryngeal musculature were utilized in all but 1 patient. Direct methods including compensatory strategies such as head and neck positioning, and techniques such as supraglottic swallowing and the Mendelsohn maneuver were additionally employed in nearly one-half of patients. Swallowing therapy is associated with successful outcome, as defined by exclusively oral feeding, among patients with neurogenic dysphagia, regardless of pretreatment variables including time since disease onset. Indirect treatment methods appear to be effective when used either alone or in combination with direct methods. Achievement of oral feeding is not associated with undue risk of pneumonia. Further rigorous scientific studies are needed.

Adult↗

PubMed1995

Interrater reliability of an etiologic classification of ischemic stroke.

BACKGROUND AND PURPOSE: Precise identification of the cause of stroke is critical to research and clinical practice. Published series of ischemic stroke show considerable variation in the proportion of cases classified as atherosclerotic large-vessel disease, lacunar infarct, cardioembolic stroke, stroke of other known cause, and stroke of undetermined etiology. We describe the development and use of an etiology-specific classification of ischemic stroke. The interrater reliability of the classification is then evaluated. METHODS: A total of 160 cases of ischemic strokes in young adults were reviewed by paired neurologists who assigned cases to prioritized categories. The results of paired ratings were evaluated for each of the potential causes. Interrater agreement was assessed by means of kappa, which is the chance-adjusted percent agreement. RESULTS: For standard pairs, kappa was fair to good for all causes except lacunar stroke (kappa = 0.31); however, pair-to-pair variation was greatest for lacunar strokes. Strokes of undetermined cause and hematologic/other cause were of borderline fair reliability. CONCLUSIONS: The utility of a stroke classification system is dependent on its intended use. An etiologic classification is useful in studies of the epidemiology and pathophysiological basis of stroke. Fair to good reliability for an etiologic classification of stroke can be obtained when criteria are explicit.

Adolescent↗

PubMed1994