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.     

Quantification of in-plane motion of the coronary arteries during the cardiac cycle: Implications for acquisition window duration for MR flow quantification

Motion of the coronary arteries during the heart cycle can result in image blurring and inaccurate flow quantification by MR. This condition applies particularly for longer acquisition windows that are typical of breath-hold coronary flow measurements. To determine the sensitivity of the technique to in-plane motion of different coronary arteries, the temporal variation in coronary position was measured in a plane perpendicular to the proximal portion of the vessel. The results indicated the presence of substantial displacement of the coronary arteries within the cardiac cycle, with a magnitude of motion approximately twice as large for the right as for the left coronary arteries. An estimation of the resulting vessel blurring was calculated, showing that the duration of the acquisition window for high spatial resolution coronary flow acquisitions should be less than 25 to 120 msec, depending on the specific coronary artery studied. In addition, these data specify optimal acquisition window placement for high resolution coronary angiography.     

THE CASE AGAINST OPEN NECK BIOPSY

Many patients present with lateral neck lumps due to benign or malignant conditions, and they may be difficult to differentiate clinically. It is detrimental to perform an open neck biopsy on a patient with a cancer originating from the head and neck region (upper aerodigestive tract or skin) prior to definitive treatment. The biopsy interferes with the assessment and management of the neck, increasing morbidity. It may also decrease curability and perhaps induce fungation. A protocol to avoid the need for an open biopsy, using fine needle aspiration cytology and a thorough examination of the upper aerodigestive tract is recommended. The authors also recommend combined radical radiotherapy and surgery for the patient who has had an open biopsy. A thoughtless biopsy is both needless and harmful.     

Empirical treatment without bronchoscopy for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome.

An empirical approach to treating Pneumocystis carinii pneumonia was adopted in a prospective study of 73 men with antibodies to human immunodeficiency virus 1 (HIV-1) presenting with respiratory problems. At presentation 49 patients (group 1) were thought to have a history, findings at clinical examination, chest radiograph, and arterial blood gas tensions typical of pneumocystis pneumonia, and empirical treatment was begun immediately. Twenty four patients (group 2) were thought to have features not typical of pneumocystis pneumonia. All patients were subsequently referred for bronchoscopy to determine the diagnosis. In group 1 four patients were excluded from the analysis because bronchoscopy was not possible. Of the remaining 45, 42 had pneumocystis pneumonia, which was diagnosed at bronchoscopy in 40, and on the basis of the clinical response to co-trimoxazole in two who had negative results from investigations. Of the three patients without pneumocystis pneumonia, one patient with lymphoid interstitial pneumonitis and Branhamella catarrhalis infection would have failed to respond to empirical treatment. The other two had multiple bacterial pathogens at bronchoscopy; one already had Kaposi's sarcoma and the other would have been misdiagnosed as having AIDS. In group 2 a specific diagnosis was made at bronchoscopy in 21 cases, including pneumocystis pneumonia in seven (all had atypical chest radiographs). In three cases no diagnosis was made and spontaneous recovery occurred. Adopting an empirical approach to treatment for typical pneumocystis pneumonia (group 1) led to the correct treatment in 43 of 45 cases (95%) and would have saved 44 of the 45 of bronchoscopies in this group. Adopting an empirical approach would have caused one patient to be misdiagnosed as having AIDS. Overall, 44 out of 69 bronchoscopies (64%) would have been saved; the specificity for the diagnosis of pneumocystis pneumonia was 85% and the sensitivity was 85%. Adopting an "empirical" treatment policy for typical pneumocystis pneumonia will cause a large reduction in the number of "high risk" bronchoscopies performed.     

Research fellowship in behavioral AIDS research

Announcement

Research fellowship in behavioral AIDS research