Murine monoclonal antibodies (Mabs) to a glycolipid antigen of small-cell (SCC) and a protein antigen of non-small-cell lung cancer (NSCC) were applied to preserved sputum specimens from individuals who participated in The Johns Hopkins Lung Project (JHLP). In that study, undertaken in 1973 to evaluate the efficacy of sputum cytology screening, half of the high-risk participants (5,226 men, greater than or equal to 45 years of age, currently smoking greater than or equal to 1 pack of cigarettes per day) were randomly assigned to produce specimens for cytopathological analysis. During regular screenings over the next 5 to 8 years, 626 (12%) showed moderate (or greater) atypia. Sixty-nine of these (26 who progressed to cancer, 43 who did not) were randomly selected for a blinded improved Mab immunostaining protocol in the present study. Satisfactory specimens with morphologic atypia immunostained positively in 14 of the 22 patients who eventually progressed to cancer (sensitivity 64%), and were nonreactive in 35 of the 40 patients who did not progress to lung cancer (specificity 88%). Review of the true positive specimens (14/22 atypias) showed that they were collected 24 months in advance of diagnosis. In contrast, the 8/22 false negative atypias (failure to stain) showed that they were collected for an average of 57 months preceding the diagnosis of cancer. Subsequent specimens (average, 26 months before cancer) from participants who were originally considered "false negative" did stain positively improving sensitivity to 91% among specimens collected for an average of 2 years in advance of the clinical appearance of lung cancer. Specificity remained at 88%. Recognition of neoplastic antigen expression 2 years in advance of clinical cancer may be a valuable intermediate end point in studies of lung cancer prevention, detection, and therapy.
A new amplification technique is described for the detection of small amounts of antigen in ethanol-fixed cytologic specimens and formalin-fixed tissues. By adding a third antibody layer to the already sensitive avidin-biotin immunoperoxidase system, we have demonstrated a considerable increase in both the quantitative and qualitative aspects of this immunostaining method. In evaluating this technique, we employed a previously defined small cell lung carcinoma cell surface antigen system and monoclonal antibodies.
The value of the Papanicolaou-stained vaginopancervical (Fast) smear in the detection of chlamydial infection has been disputed. We examined 116 satisfactory Fast smears from 203 women enrolled in the Johns Hopkins Fertility Control Clinic and compared tissue-culture results with cytopathologic detection using various published morphologic criteria. All Chlamydia culture-positive cases were reviewed, and certain cytologic features considered helpful in the detection of chlamydial infection in cervical smears obtained from this selected high-risk population were identified. The changes that had the highest correlation with tissue culture included fine vacuolation of metaplastic endocervical cells, giving their cytoplasm a rarefied "moth-eaten" appearance. Using these criteria, cytopathologic changes of chlamydial infection were observed in 24 of 28 cases of tissue-culture-positive cases and in 8 of 88 tissue-culture-negative cases. The sensitivity and specificity of the Fast-smear cytodiagnosis of Chlamydia infection utilizing these morphologic changes and compared with tissue culture were 86% and 91%, respectively. Other cytologic features, including inflammatory background and intracytoplasmic structures consistent with initial and intermediate chlamydial bodies within the metaplastic cells, were found to be useful although less specific and less sensitive. The implications of these diagnostic features, the conditions to be considered in their differential diagnosis, and the pitfalls of chlamydial cytodiagnosis and the chlamydia culture studies have been critically reviewed. Study design and the high unsatisfactory cervical smear rate are discussed.
The Department of Mathematical Sciences at the United States Military Academy is prepared to lead the young minds of America into the 21st century with a bold and innovative curriculum coupled with student and faculty growth models and interdisciplinary lively applications. In 1990, the mathematics department began its first iteration of their "7 into 4" core curriculum. Each year improvements have been incorporated into the core mathematics program. In 1992 , interdisciplinary applications appeared in the core program as an opportunity t o communicate and work with the academic disciplines. Our core curriculum is tied together both vertically and horizontally with threads. These threads tie together both the content within each course as well as among all the courses. Student attitudes are measured through course surveys as we attempt to develop "life long learners". Student performance is measured or calibrated throughout their four years.
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