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Biomedical subjects

D L Barrett

Publications and source records attributed to D L Barrett.

7 recordsLinked to original sources

Pyrrole mannich bases as potential antipsychotic agents.

Recently, we reported on a series of arylpiperazines 4 which exhibit high affinity for the serotonin 5-HT-1A and 5-HT-1B binding sites. Although these compounds interact weakly with dopamine D-1 and D-2 receptors, they are reasonably potent in inhibiting conditioned avoidance responding (CAR) in the rat, an indication of potential antipsychotic activity. Conversion of these arylpiperazines to pyrrole Mannich bases has provided a series of compounds (10-44) which exhibit potent inhibition of CAR when given po and have strong affinity for both the D-2 and 5-HT-1A binding sites. Some of these agents also fail to produce catalepsy. The D-2 binding data and the block of CAR suggest that they are potential antipsychotic agents and the lack of cataleptogenic potential suggests some might possess less liability for producing extrapyramidal side effects and tardive dyskinesias in man.

Animals

Flow cytometry of human gynecologic specimens using log chromomycin A3 fluorescence and log 90 degrees light scatter.

Flow cytometry and electronic cell sorting are being investigated to screen gynecologic specimens for cervical neoplasia. Cellular DNA content is quantitated by Chromomycin A3 fluorescence and cell size is quantitated by 90 degrees light scatter; the logarithms of the measured intensities are used to produce a two parameter histogram. To determine the cell types responsible for signals in various histogram regions, systematic electronic cell sorting is performed. The sorted fractions are sedimented into microscope slides and stained by the Papanicolaou technique. The cells in each fraction are identified by conventional cytomorphologic criteria. Morphologic analysis of sorted cells reveals histogram regions corresponding to specific cell types. One very important region contains the highest concentration of signals from abnormal cells and is therefore the best region to analyze for specimen abnormality. However, because a significant number of signals in this region are from normal cells, specimens cannot be diagnosed by their analysis. Another important histogram region is composed primarily of signals from endocervical columnar and metaplastic cells. The presence of such cells is a good criterion for specimen adequacy, therefore analysis of signals in this region is essential to assess specimen adequacy for automatic screening.

Cervix Uteri

A cytomorphologic approach to standardization of cell dispersal evaluation for gynecologic specimens.

Dispersal of cells in gynecologic specimens is a major concern in sample preparation for automated systems. A variety of dispersal techniques has been tested, with varying degrees of success reported by many laboratories. In order to have a more meaningful comparison of the results of different techniques and among investigators, a standardized evaluation procedure is desirable. The cytomorphologic element of evaluation of cell dispersal has been developed and tested in this laboratory and might be applied toward this purpose. This evaluation reveals the changes in relative numbers of single cells according to cell type and estimates cell loss as well as changes in cellular preservation. Groups of cells are tabulated according to whether they appear as definite tissue groups or as clumps of single cells. Because abnormal cells and cells from the transformation zone often occur in tissue groups, special emphasis is placed on dispersal analysis by cell type to reveal whether the diagnostically important cells and cells relating to specimen adequacy were optimally dispersed. Furthermore, the format of evaluation allows assessment of the applicability of dispersal procedures to preparation for both flow and slide-based systems of automated cytology.

Autoanalysis

Comparison of cellular recovery rates and morphologic detail obtained using membrane filter and cytocentrifuge techniques.

Two methods commonly used for collecting cells from a large volume of fluid-membrane filters (Millipore, Gelman, and Nuclepore) and cytocentrifugation-were compared for percentage of cell recovery and degree of cell preservation. Twenty samples of body cavity fluid were centrifuged, and the buffy coat of each was resuspended in a balanced electrolyte solution. The cellularity of each suspension was determined using both Coulter Counter and hemocytometer. Exact aliquots of each sample were collected on Millipore, Gelman, and Nuclepore filters and on slides by cytocentrifugation (Shandon). The resultant material was fixed in alcohol (95% ethanol), stained by the Papanicolaou method, mounted, and then evaluated with respect to the number of cells present and the diagnostically significant morphologic detail of the cells. Cell recovery was estimated by counting cells in known areas of each preparation and then ascertaining the total area. The Millipore filter technique consistently recovered the highest percentage of cells and preserved the best morphologic detail.

Body Fluids

The incidence and significance of intracytoplasmic calcifications in nipple aspirate specimens.

Intracytoplasmic deposits demonstrated to be calcifications have been identified in nipple aspirates from 3.6 per cent of breasts with satisfactory cytology. The deposits occurred almost exclusively in epithelial groups, and their structure ranged from dust-like particles and spiculated forms to psammoma bodies; all exhibited characteristic density, refractility and well-defined, irregular borders. Nipple aspirates containing calcifications were typically characterized by the presence of numerous epithelial groups, frequently of papillary type. This association was supported histologically by the fact that 11 of the 14 available tissue specimens contained papillary lesions in the duct system, including three with papillary carcinoma in situ. Cytologic abnormality was significantly associated with the presence of calcifications, and marked cellular changes were found four times as often in this group as in the total population with satisfactory cytology. Calcific deposits were found in six of the fourteen available tissue specimens, four of which contained breast carcinoma. Calcifications were noted in only 23 per cent of 97 available mammograms, but further investigation has revealed other significant radiologic findings. Cytologic calcifications were found most frequently in aspirates from women between the ages of 41 and 60 and were often associated with clinical findings of breast disease. Preliminary findings indicate an increased prevalence of breast carcinoma in patients with cytologic calcifications and suggest that such patients may require closer than normal follow-up.

Adult

Cytomorphology of gynecologic specimens analyzed and sorted by two-parameter flow cytometry.

The purpose of this study was to define the fluorescence and light scatter properties of the different cell types encountered in gynecologic specimens. Samples stained with Chromomycins A3 were analyzed on a laser-activated electronic cell sorter, and two-parameter histograms of the cell populations were generated from measurements of nuclear fluorescence and small angle light scatter. Cell populations with defined scatter and fluorescence ranges were sorted, stained by a modified Papanicolaou technique, and evaluated using conventional cytomorphologic criteria. We focused on determining which regions of the histogram corresponded with abnormal cells and cells defining specimen adequacy (columnar and metaplastic cells). Sorted cells corresponding with the main fluorescence region are single, benign, mononuclear cells. Relative proportions of the different types of cells in this region vary with light scatter. Leukocytes predominate at low scatter, mature squamous cells predominate at high scatter, and metaplastic and endocervical cells occur throughout this range. Cells sorted with higher values of nuclear fluorescence include dysplastic and malignant cells as well as benign cells occurring as groups, multinucleates, or with adherent leukocytes or bacteria. This study demonstrates that cytomorphology is a useful method for monitoring and interpreting flow cytometry data.

Chromomycin A3