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J K Frost

Publications and source records attributed to J K Frost.

At least 19 recordsLinked to original sources
PubMed1992

Centrifugal separation of carcinoma or atypical cells in voided urine.

A simple density gradient method was used to separate atypical and cancer cells from non-cancer cells in voided urine from patients with transitional cell atypia (moderate and grave atypia) and bladder cancer (squamous cell carcinoma and transitional cell carcinoma). Prior to cell separation, the Saccomanno preserved cells were dispersed by homogenization. After cell separation (5 min x 1400 rpm), atypical and cancer cells were enriched up to 20-fold. Also, most of the leucocytes (68-98%) and squamous cells (47-82%) were absent from density gradient specimen fractions containing the largest percentages of atypical and cancer cells. Peak purity ranges of atypical or cancer cells from different sample classes showed a large degree of overlap. This permitted the pooling of density gradient fractions enriched for atypical or cancer cells, thus increasing the efficiency of the method. Also, following centrifugation, the Papanicolaou-stained specimen fractions showed less background staining than the unprocessed controls, and the cells retained diagnostic morphologic features. We infer that this method may be a useful, low-cost approach for the morphologic study of developing cancers, not only from the urinary bladder, but also from the respiratory tract.

Carcinoma, Squamous Cell↗
PubMed1988

Nuclear grooves: a useful criterion in the cytopathologic diagnosis of papillary thyroid carcinoma.

A recent report emphasized the usefulness of the grooved nucleus as a diagnostic criterion of papillary thyroid carcinoma (PTC) in histopathologic material. The present study was undertaken to evaluate whether grooved nuclei can serve as an additional diagnostic criterion for PTC in cytologic material obtained by fine-needle aspiration (FNA). Slides from 124 consecutive thyroid FNAs were reviewed. Specimens included 11 PTCs, one follicular carcinoma, six follicular adenomas, eight follicular neoplasms not otherwise specified, 10 cases of chronic thyroiditis, and 88 colloid nodules/adenomatous goiters. Among the PTC cases, grooved nuclei were found in all 11 (100%), intranuclear inclusions in nine (82%), papillary fragments in seven (64%), and psammoma bodies in two (18%). Nuclear grooves were also observed in two of the 113 non-PTC cases (1.8%), both of which were colloid nodules, one with extensive Hurthle-cell change. The grooved nuclei were best identified on Papanicolaou-stained material. They were inconspicuous and difficult to identify in air-dried Diff-Quik-stained material. It appears that the recognition of grooved nuclei among tumor cells is a valuable diagnostic feature of PTC in cytologic material stained with polychromatic Papanicolaou stain.

Biopsy, Needle↗
PubMed1988

Sensitive and specific monoclonal antibody recognition of human lung cancer antigen on preserved sputum cells: a new approach to early lung cancer detection.

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.

Aged↗
PubMed1987

A quantitative method for the detection and localization of quantum-limited events from radionuclides in cells and tissue sections by computer-enhanced video microscopy.

Cellular dynamics often involve extremely low concentrations of biologically active substances, which can be radiolabeled and detected, localized and quantitated by autoradiography. The latter may require exposures from a few days to many months. The objective of this research was to demonstrate the feasibility of reducing this long period of data collection by one to two orders of magnitude, while maintaining or improving the spatial resolution and localization in tissues and the quantitative characteristics inherent in autoradiography. A mathematical model describing the complete system was generated using energy partition calculations to estimate photon production via scintillant per H3 beta particle emission and to estimate the subsequent photon capture based upon imaging system parameters and microscope geometry. Calculations showed that, typically, a single tritium beta particle produces a maximum of 5.8 X 10(3) photons. A photon-limited camera and microscope imaging system were selected and optimized in conjunction with a specially developed physical scintillation model. Results showed that the number of detected photoevents increases monotonically with both signal integration time and, independently, with the concentration of the radionuclide. Consequently, this work demonstrates that video microscopy imaging methods can spatially and temporally quantify very low concentrations of radiolabeled substances and can reduce data acquisition times.

Beta Particles↗
PubMed1986

Cytomorphologic evaluation of the neoplastic potential of 28 cell culture lines by a panel of diagnostic cytopathologists.

A panel of 7 diagnostic cytopathologists, i.e., physicians trained to diagnose the malignant potential of human cells in Papanicolaou-stained smears, was asked to evaluate two sets of microscope slides of stained coverslip preparations of 28 cell culture lines, 15 of which were neoplastic. Slide Set I consisted of 13 pairs of cell lines, one member of each pair being nontumorigenic and the other tumorigenic; the lines were of mouse (9 pairs), rat (3 pairs), and human (1 pair) origin. Slide Set II contained 4 human lines: one lung cancer, one melanoma, and two fibroblast lines. Of a total of 114 diagnostic decisions by the panel, 88 were correct (66/86, 77%) in choosing which member of a pair was neoplastic and 22 were correct (22/28, 79%) in choosing whether a given individual human line was or was not neoplastic. Two members of the panel were correct more frequently, with 16/17 (94%) correct diagnoses, each. Five nuclear morphologic criteria of malignancy used by cytopathologists were prominent in the tumorigenic lines: altered chromatin pattern characterized by increasing size of chromatin granules and chromatin clumping, sharp angularity of large nucleolar and/or chromocenter borders with spicule formation (pointed projection), irregular parachromatin clearing (increase in the clarity of the clear spaces between chromatin threads, granules and clumps), uneven thickness of chromatin at the nuclear border, and variability in nuclear size and shape from cell to cell. These markers of neoplastic transformation, when added to those previously reported, should increase overall accuracy in the diagnosis of neoplastic transformation of mammalian cells in culture.

Animals↗
PubMed1986

Centrifugal separation of cells in sputum specimens from patients with undifferentiated carcinoma.

Ethanol-fixed cells in sputum from patients with undifferentiated carcinoma of the lung were separated in aqueous Ficoll using a discontinuous density gradient centrifugation technique. The selective enrichment of small cell undifferentiated (e.g., oat cell) or large cell undifferentiated carcinoma cells was achieved while removing most of the leukocytes (80-90%) and macrophages (65-75%) from specimen fractions containing the greatest relative frequencies of cancer cells. The maximum purity of small cell carcinoma cells (0.04%) occurs in moderate density (rho = 1.121 g/ml) gradient fractions and results in a 2.4-fold enrichment relative to unprocessed specimens. In contrast, the maximum purity of large cell carcinoma cells (0.22%) is obtained in very high density (rho = 1.172 g/ml) gradient fractions and results in a 1.2-fold enrichment in comparison with unprocessed specimens. Microscopic examination of Papanicolaou-stained specimen fractions reveals that these enrichments were achieved while retaining diagnostically significant cytomorphologic and tinctorial features necessary for cancer screening and diagnosis. Peak purity ranges of undifferentiated cancer cells significantly overlap comparable ranges for material from bronchogenic adenocarcinoma and squamous cell carcinoma.

Carcinoma↗
PubMed1986

Sputum cytopathology: use and potential in monitoring the workplace environment by screening for biological effects of exposure.

Sputum cytopathologic monitoring detects squamous cell lung cancers at an extremely early stage (x-ray negative). It holds further potential for preventing disease by detecting epithelial alterations which reflect environmental hazards. The addition of sputum cytology screening to screening by chest x-ray film does not significantly reduce mortality from all types of lung cancer, but preliminary analysis of Johns Hopkins Lung Project data suggests that mortality from squamous cell carcinoma is reduced. Quantitative automated cytopathology systems and biochemical/immunological cell markers enhance understanding of these precursors and offer great promise for increasing capacity, accuracy, and usefulness in cytopathology screening of workers. Cytological specimens collected over years of screening workers considered at risk may be important to eventually understanding development and prevention of major occupational diseases.

Carcinoma, Squamous Cell↗
PubMed1986

Responses to partial nasal obstruction in sleeping infants.

Partial nasal obstruction was performed during a morning of quiet sleep (QS: non-REM) and active sleep (AS: REM) at ages 1 week, 2 weeks, 1, 2, 3, 4 and 6 months on 12 normal infants, 15 subsequent siblings of victims of the Sudden Infant Death Syndrome (SIDS) and 12 infants admitted for investigation of infant apnoea ('near-miss' SIDS). In all three groups the numbers failing to arouse after 240 s (FTA-240) in QS were significantly greater than those in AS. After 2 months of age all groups showed a decrease in the number FTA-240 in AS, whereas in QS the number did not change significantly. Subsequent siblings of SIDS had a significantly higher number FTA-240 in QS than controls. There was no significant difference in FTA-240 in QS between controls and infant apnoeas, although there was a trend for this to be higher in subsequent siblings of SIDS than infant apnoeas. It was concluded that arousal from AS is more marked than from QS, that after 2 months of age the ability to arouse from AS increases, and that in relation to SIDS, QS is the sleep state in which the infant is less able to arouse. Furthermore, subsequent siblings of SIDS differ from normal infants in their ability to arouse from QS.

Airway Obstruction↗
PubMed1986

Chromosomal radiosensitivity during the G2 cell cycle period and cytopathology of human normal x tumor cell hybrids.

The relationship between tumorigenicity and enhanced chromosomal radiosensitivity during the G2 cell cycle phase was examined through the use of nontumorigenic human cell hybrids and their nontumorigenic and tumorigenic segregants. The hybrid cells were produced by fusion of a normal and tumor cell. The parental lines, including HeLa and three fibroblast lines, one of skin and two of fetal lung origin, were also examined. The tumorigenic lines, which had cytological features associated with clinical cancer, showed a significantly higher incidence of chromatid breaks and gaps following X-irradiation during G2 than the normal skin line or the nontumorigenic hybrids. The hybrids and their nontumorigenic subclones had cytological features which are predominantly found with a benign clinical course and had the G2 chromosomal radiosensitivity more characteristic of the normal parental cells. Like tumorigenic cells, fetal cells exhibited enhanced G2 chromosomal radiosensitivity which could be suppressed in fetal X tumor cell hybrids. This observation suggests that the molecular basis for radiosensitivity in fetal cells differs from that of tumor cells. The enhanced G2 chromosomal radiosensitivity of a tumor cell, which appears to result from deficient DNA repair, is suppressed by fusion with a normal cell. Thus, the radiosensitivity, like tumorigenicity, behaves as a recessive trait. Although a Mendelian analysis is not possible with this material, the segregation of enhanced G2 chromosomal radiosensitivity with the neoplastic phenotype suggests that the two may be genetically linked.

Cell Line↗
PubMed1985

Automatic cell identification and enrichment in lung cancer: V. Adenocarcinoma and large cell undifferentiated carcinoma.

The aims of this study were to develop a protocol for the identification and enrichment of cancer cells from sputum obtained from patients with adenocarcinoma of the lung (n = 6) and large-cell undifferentiated carcinoma of the lung (n = 2), and to compare these findings with the results from our previous studies on other cell types from lung cancer. The hypotheses tested were: Cancer cells in sputum can be preserved following flow sorting. Enrichment for cancer cells from acridine orange (AO)-stained specimens can be achieved. Discrimination of cancer cells from noncancer cells is by AO green fluorescence and discrimination of lymphocytes from other cell types is by AO red fluorescence. Cancer cells are consistently enriched in the AO high green and red fluorescence region, although, for a given cell type, maximal enrichment is patient-dependent. Finally, cancer cell enrichment and lymphocyte exclusion can be done simultaneously. Cells from sputum were initially fixed, stained with AO, sorted on a dual parameter flow sorter, and classified into six groups corresponding to two ranges of green and three ranges of red fluorescence intensities. Cells of each region were stained by the method of Papanicolaou and differential counts were performed to determine the relative frequencies (i.e., purities) of leukocytes, macrophages, squamous cells, and cancer cells, in sorted and unsorted (i.e., control) samples. The average purity of leukocytes (81%), macrophages (6%), squamous cells (11%), and cancer cells (2%) varied markedly from sample to sample. However, the largest enrichment values (i.e., ratio of purity of a cell type in a sorted sample to its purity in the unsorted control sample) achieved for cancer cells consistently occurred for each patient sample in the region corresponding to high green and high red fluorescence intensities. Experimentally, a cancer cell average enrichment of sixteen-fold was obtained by this method. Additionally, fluorescence intensity ranges which increased the enrichment for macrophages by cell sorting typically excluded leukocytes and squamous cells, and vice versa. Finally, red fluorescence intensity was the primary discriminatory parameter for all cell types studied, although the additional use of green fluorescence intensity significantly increased cancer cell enrichment rates.(ABSTRACT TRUNCATED AT 400 WORDS)

Acridine Orange↗
PubMed1984

The National Cancer Institute Cooperative Early Lung Cancer Detection Program. Results of the initial screen (prevalence). Early lung cancer detection: Introduction.

This introduction provides a description of 3 cooperating studies on Screening for Early Lung Cancer conducted under the auspices of the National Cancer Institute. The next 3 reports detail the unique aspects and results of the individual screening studies. The final presentation summarizes the initial ("prevalence") screening for all 3 centers (approximately 30,000 men), and gives our conclusions.

Aged↗
PubMed1984

Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Johns Hopkins study.

The Johns Hopkins Lung Project was designed to determine whether the addition of cytologic screening to the radiographic screening of high-risk volunteers could enhance the early detection of asymptomatic lung cancer and whether early therapeutic intervention in detected cases could significantly reduce the mortality from this disease. Male volunteers, 45 yr of age and older, who smoked at least 1 pack of cigarettes per day were recruited from the Baltimore metropolitan area. All of the 10,387 acceptable high-risk volunteers received annual chest radiographic screening. By random assignment, one half received cytologic examination of induced sputum in addition to the roentgenogram. This report describes the results of the initial screening. Compared with usual methods of clinical diagnosis, screening by both roentgenography and cytology identified a greater proportion of the lung cancer cases at an earlier stage. Screening by sputum cytology was found to improve the detection only of squamous cell carcinoma. In the dual-screen group, sputum cytology accounted for 28% of the detected cases, and resulted in 39% additional detection of lung cancer over that achieved by roentgenography. There was no corresponding decrease in prevalence. Lung cancers detected by cytology alone were found at very early stages. Although there has been an increase in average survival, much of this increase, if not all, may have resulted from lead-time and sampling bias.

Adenocarcinoma↗
PubMed1984

Pathogenicity of Trichomonas vaginalis: cytopathologic and histopathologic changes of the cervical epithelium.

Virulence of 52 Trichomonas vaginalis isolates was estimated by the subcutaneous mouse assay. A positive linear relationship was found between the mean volumes of subcutaneous abscesses caused by the parasites in mice and severity of cervical epithelial abnormalities observed in the patients from whom these strains had been isolated. This relationship implies that virulence of the human urogenital trichomonad, as measured by the mouse assay, may be related to some factors associated with dysplastic changes in the cervical epithelium. No relationships appeared to exist between the results of the mouse assay and inflammation of the vagina and cervix as evaluated clinically or pathologically, although these data were not analyzed statistically; likewise, no relationships were found between the mouse assay and nonprotozoal microorganisms identified in donors of the trichomonad strains.

Abscess↗
PubMed1983

Expression and cellular compartmentalization of a herpes simplex virus type 2 protein (ICP 10) in productively infected and cervical tumor cells.

Antiserum to ICP 10, a herpes simplex virus type 2 (HSV-2) protein that is expressed in cells neoplastically transformed by viral DNA sequences within the Bgl II/Hpa I CD fragment, specifically precipitates the ICP 10 protein from HSV-2 infected cells and stains cells infected with HSV-2 for 4 to 16 hrs by indirect immunofluorescence. At 4 hr post infection (p.i.), the staining is primarily perinuclear, while at 16 hr p.i., it is cytoplasmic and intranuclear. Compartmentalization studies indicate that the 35S-[L]-methionine labeled ICP 10 is detectable in both the cytoplasmic and nuclear fractions early and late in infection. However, in its phosphorylated form, ICP 10 is undetectable in the nuclear fraction late in the viral reproductive cycle. Anti-ICP 10 serum stains a high (75%-83%) proportion of cervical tissue with pathological findings of dysplasia or carcinoma, as well as atypical exfoliated cells from these patients. Cervical tumor tissue from 4 of 12 patients also stains with antiserum to another purified viral protein complex designated ICP 12/14. In the majority of atypical cells with mild or moderate changes, ICP 10 localizes in the cytoplasm, while the majority of atypical cells with severe changes also display nuclear staining with anti-ICP 10 serum. While exfoliated atypical cells from 60% of patients with dysplasia are positive for ICP 10, those from only one half of these patients stain also with anti-ICP 12/14 serum and this staining is strictly cytoplasmic. Atypical cells from three patients in these series stain with the anti-HSV-2 serum but are negative for both ICP 10 and ICP 12/14. Exfoliated atypical cells from patients with CIS or invasive cancer stain equally well with all three antisera.

Antigens, Viral, Tumor↗
PubMed1982

Lung cancer mortality in males screened by chest X-ray and cytologic sputum examination: a preliminary report.

Observations from the continuing JHLP lung cancer screening study provide no clear evidence that mass screening by chest X-ray and sputum cytology, plus prompt appropriate treatment, reduces mortality du to lung cancer. No reduction in lung cancer deaths is observed in the JHLP when compared with the number of lung cancer deaths expected from the experience of two unscreened male populations of the same age and smoking status serving as population studies. Possible reasons for the lack of demonstrable decrease in mortality, even though "early" cases have been detected, include: (1) an insufficient passage of time for slowly growing cancers to become apparent in the control group, (2) ineffective therapy, and (3) the multifocal nature of pulmonary neoplasms. Additional study will be required to provide a definitive answer regarding the benefit, if any, of lung cancer screening.

Aged↗
PubMed1981

Centrifugal separation of cells in sputum specimens from patients with adenocarcinoma.

A Ficoll density gradient centrifugation technique was used to separate fixed cells from the sputa of patients with bronchogenic adenocarcinoma. The selective enrichment of leukocytes, squamous or cancerous cells was achieved while retaining the diagnostically significant cell morphologic features. This technique is shown to typically eliminate most of the leukocytes (96.9%) macrophages (86.7%), squamous cells (70.0%) and necrotic debris from specimen fractions containing the majority of cancerous cells. The maximum purity of cancer cells (14.6%) occurs in high density (p = 1.35 g/ml) gradient fractions and results in an average 12.2-fold enrichment for cancer cells in contrast to their relative frequency of occurrence in unprocessed specimens. Differential cell count analyses of serial density centrifugation fractions show that this technique produces comparable enrichment rates for material from bronchogenic adenocarcinoma and squamous cell carcinoma.

Carcinoma, Bronchogenic↗