Pulmonary Hodgkin's disease and Langerhans cell granulomatosis.
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Biopsy↗
Biomedical subjects
A Flint
Publications and source records attributed to A Flint.
Flow cytometry: DNA analysis of squamous cell carcinoma of the upper aerodigestive tract.
The flow cytometer is capable of analyzing a large number of cells or cell nuclei. The flow cytometer has been used to analyze the DNA content of tumor cells from squamous cell carcinomas of the upper aerodigestive tract using a modification of the Vindelov staining procedure. The main difficulty in analyzing solid tumors using flow cytometry technology is the disaggregation of the cells and the quantification of the diploid point (2N point). A set of internal standards was developed for establishing the 2N point, as well as a technique for disaggregation, which is described. A histogram characteristic of a more aggressive squamous cell carcinoma which tends to recur more quickly and more frequently than the other squamous cell carcinoma histogram types was identified. The flow cytometer proved to be a practical method of analysis allowing for quantitative measurement of DNA content from a large number of cells originating from a squamous cell carcinoma. The trend between recurrence and histogram type will require further study.
Animals↗
Simultaneous measurement of DNA content and detection of surface antigens of cervicovaginal cells by flow cytometry.
A method is described by which the measurement of the DNA content and the light scatter and the detection of a cervical carcinoma-associated antigen (CCA) of squamous epithelial cells can be simultaneously accomplished by flow cytometry (FCM). Cervicovaginal cellular samples obtained from 30 patients were analyzed by this method. Cell populations with an abnormal DNA content or with the presence of CCA were detected in 20 samples, 18 of which contained dysplastic cells as detected by routine cytologic screening. The remaining ten cases, which were interpreted as cytologically normal by routine screening, were also interpreted as normal by FCM analysis.
Antigens, Neoplasm↗
Pneumocystis carinii pneumonia. Cytologic manifestations and rapid diagnosis in routinely prepared Papanicolaou-stained preparations.
In this study of 28 immunocompromised patients, it was found that Pneumocystis carinii pneumonia could be easily and reliably diagnosed by examination of routinely prepared, Papanicolaou-stained cellular samples obtained by bronchoalveolar lavage, bronchial brushing, and bronchial washing. The distinctive intra-alveolar exudate of pneumocystosis observed in lung biopsy specimens was readily discernible in all of the cellular samples that demonstrated P. carinii by special stains. The exudate was not present in any of the P. carinii-negative samples. Routinely prepared, Papanicolaou-stained cellular samples can be relied upon for the rapid diagnosis of P. carinii pneumonia.
Bronchi↗
Adult respiratory distress syndrome in neutropenic patients.
The precise pathophysiologic mechanisms that cause the adult respiratory distress syndrome are unknown. Indirect evidence from human studies and extrapolations from animal models have suggested that phagocytic neutrophils are important in the pathogenesis of this disease. To further evaluate the role of neutrophils, the frequency of neutropenia in 18 bacteremic patients who had the adult respiratory distress syndrome was compared with that in a control group who had bacteremia alone. Three of 18 patients in the group with the adult respiratory distress syndrome were neutropenic as opposed to one of 18 in the control group (p greater than 0.6). Histologic examination of the lungs from two patients with the adult respiratory distress syndrome and neutropenia demonstrated the absence of neutrophils. It is likely that there are many pathways that lead to the adult respiratory distress syndrome. Although neutrophils may be involved in some of these processes, this study demonstrates that neutrophils are not required for the development of the syndrome. In the appropriate clinical setting, the diagnosis of the adult respiratory distress syndrome should not be excluded solely because of neutropenia.
Adult↗
Effect of amino acid substitutions on the catalytic and regulatory properties of aspartate transcarbamoylase.
Although intensive investigations have been conducted on the allosteric enzyme, aspartate transcarbamoylase, which catalyzes the first committed reaction in the biosynthesis of pyrimidines in Escherichia coli, little is known about the role of individual amino acid residues in catalysis or regulation. Two inactive enzymes produced by random mutagenesis have been characterized previously but the loss of activity is probably attributable to changes in the folding of the chains stemming from the introduction of charged and bulky residues (Asp for Gly-128 and Phe for Ser-52). Site-directed mutagenesis of pyrB, which encodes the catalytic chains of the enzyme, was used to probe the functional roles of several amino acids by making more conservative substitutions. Replacement of Lys-84 by either Gln or Arg leads to virtually inactive enzymes, confirming chemical studies indicating that Lys-84 is essential for catalysis. In contrast, substitution of Gln for Lys-83 has only a slight effect on enzyme activity, whereas chemical modification causes considerable inactivation. Gln-133, which has been shown by x-ray crystallography to reside near the contact region between the catalytic and regulatory chains, was replaced by Ala. This substitution has little effect on catalytic activity but leads to a marked increase in cooperativity. The Gln-83 mutant, in contrast, exhibits much less cooperativity. Since a histidine residue may be involved in catalysis and His-134 has been shown by x-ray diffraction studies to be in close proximity to the site of binding of a bisubstrate analog, His-134 was replaced by Ala, yielding a mutant with only 5% wild-type activity, considerable cooperativity, and lower affinity for aspartate and carbamoylphosphate. All of the mutants, unlike those in which charged or bulky residues replaced small side chains, bind the bisubstrate analog, which promotes the characteristic "swelling" of the enzymes indicative of the allosteric transition.
Amino Acid Sequence↗
Pulmonary histiocytosis X. Immunoperoxidase staining for HLA-DR antigen and S100 protein.
Immunoperoxidase staining for S100 protein and HLA-DR antigen was used to identify histiocytosis X (HX) cells in 23 cases of pulmonary histiocytosis X (PHX), three cases of idiopathic pulmonary fibrosis, and one case of hypersensitivity pneumonitis. S100 protein was present in HX cells in 22 of the PHX cases; HLA-DR antigen was present in HX cells from 16 cases. Varying numbers of peribronchiolar and interstitial cells were positive for either S100 or HLA-DR in two of the three cases of idiopathic pulmonary fibrosis, and in the case of hypersensitivity pneumonitis. Immunoperoxidase staining for chromogranin showed isolated neuroendocrine cells within the mucosa and wall or airways, sites in which HX cells were occasionally found. As other types of dendritic cells, as well as some neuroendocrine cells, may contain S100 protein, positive staining for S100 is not specific for HX cells.
Chromogranins↗
Noncaseating pulmonary granulomas associated with small cell carcinoma of the lung.
Noncaseating pulmonary granulomas are rarely associated with primary carcinoma of the lung. The patient described herein presented with constitutional symptoms and nodular pulmonary infiltrates associated with noncaseating granulomas without evident neoplasm in both transbronchial and open lung biopsy specimens. Despite corticosteroid therapy for presumed sarcoidosis, chest roentgenographic findings worsened and repeated transbronchial biopsy 12 months after the onset of initial symptoms revealed small cell carcinoma of the lung. Twenty-two months after initiation of chemotherapy, the patient is well with no evidence for carcinoma.
Antineoplastic Combined Chemotherapy Protocols↗
Alveolar soft part sarcoma of the uterine cervix.
Alveolar soft part sarcoma is a histologically distinctive neoplasm of uncertain histogenesis. Since its initial description in 1952, more than 200 cases have been reported. The extremities are most often the sites of involvement; the tongue, bones, and the orbit have been less commonly involved. The present paper describes a case of alveolar soft part sarcoma which was present only within the uterine cervix of a 37-year-old woman. Histologically, the tumor cells were arranged in the characteristic alveolar pattern; diagnostic PAS-positive diastase-resistant needle-shaped crystals were observed within the cytoplasm of the tumor cells. After the initial biopsy, the patient underwent a radical hysterectomy and pelvic lymph node dissection. Although no residual tumor was found within the cervix, a microscopic focus of tumor was detected in an obturator lymph node. The patient is at present clinically free of disease.
Adult↗
Construction of a human X-chromosome-enriched phage library which facilitates analysis of specific loci.
A human X-chromosome-enriched MboI-partial-digest recombinant library in phage lambda Charon30 has been constructed. Twelve out of the thirteen X-chromosome DNA sequences that were tested were present in the library. Most regions were covered in overlapping phage inserts; mean insert size was 13.7 kb. One phage from the library allowed detection of a 225-bp insertion of DNA into a region near the Duchenne muscular dystrophy (DMD) locus. Another recombinant phage represents an expansion of a region which exhibits extensive and varying homology with other human chromosomes, including the Y, as well as with rodent DNA. The present library should have widespread use for examining DNA sequences on the human X chromosome.
Bacteriophage lambda↗
Compartmentalization of algal bioluminescence: autofluorescence of bioluminescent particles in the dinoflagellate Gonyaulax as studied with image-intensified video microscopy and flow cytometry.
Compartmentalization of specialized functions to discrete locales is a fundamental theme of eucaryotic organization in cells. We report here that bioluminescence of the dinoflagellate alga Gonyaulax originates in vivo from discrete subcellular loci that are intrinsically fluorescent. We demonstrate this localization by comparing the loci of fluorescence and bioluminescence as visualized by image-intensified video microscopy. These fluorescent particles appeared to be the same as the previously described in vitro "scintillons." We attribute the endogenous fluorescence to that of the bioluminescence substrate, luciferin, because (a) the fluorescence excitation and emission characteristics are comparable, (b) the autofluorescence is lost after exhaustive stimulation of bioluminescence, and (c) the fluorescence of discharged particles in vitro can be restored by adding luciferin. The fluorescence in vivo exhibits a standard property of circadian (daily) rhythmicity: under constant environmental conditions, the intensity of the particle fluorescence fluctuates cyclically (it is maximal during the night phase and is low during the day). Thus, luciferin is localized within the cell at discrete loci from which the bioluminescence emanates; the cellular quantity of luciferin is rhythmically modulated by the circadian clock.
Dinoflagellida↗
Flow cytometric analysis of DNA in diagnostic cytology.
Flow cytometric analysis of nuclear DNA content and cell surface immunologic phenotyping were used in the evaluation of cytologic samples obtained from four patients. In each sample, a lymphoid cell population was present, which was difficult to evaluate by traditional cytopathologic methods. In two of the cases, the flow cytometric demonstration of monoclonal populations of lymphoid cells characterized by abnormal amounts of nuclear DNA gave support to the cytologic interpretation of malignancy. In a third sample, a lymphoid cell population that could not be cytologically distinguished from malignant lymphoma cells of small lymphoid cell type was shown to be composed of euploid, polyclonal cells. In the fourth case, the demonstration of euploidy in morphologically distinctive cell populations was helpful in interpreting the fine-needle aspirate of the thyroid gland. The authors conclude that flow cytometry can be used to great advantage in the evaluation of cytologic samples as well as in predicting biologic behavior.
Adult↗
Development and use of metaphase chromosome flow-sorting methodology to obtain recombinant phage libraries enriched for parts of the human X chromosome.
Metaphase chromosomes isolated from human lymphoblastoid cell lines containing structurally abnormal X chromosomes have been stained with the bisbenzimidazole dye Hoechst 33258 and analyzed on a FACS II flow system equipped with a 5-W all-lines argon ion laser. The chromosomal fluorescence has been highly resolved at flow rates of 1,000-3,000 chromosomes per second. With the goal of obtaining recombinant DNA libraries from parts of the human X chromosome, fluorescence populations enriched for a dicentric X (Xpter- greater than Xq24::Xq24-greater than Xpter) chromosome and an isochromosome of the long arm of the X [i(Xq)] have been identified. The dicentric X chromosome has been resolved as a discrete peak in the fluorescence flow histogram. In contrast, the fluorescence intensity of the isochromosome is indistinguishable from that of chromosomes 3 and 4. Recombinant DNA libraries from the flow-sorted chromosomes have been constructed in the lambda phage, Charon 21A, and consist of 1.6 X 10(5) and 0.7 X 10(5) plaque-forming units in the case of the dicentric X and the isochromosome, respectively. Ninety percent of the phage in both recombinant libraries contain inserts which hybridize to highly repetitive human DNA sequences. The recombinant phage library from the flow-sorted dicentric X chromosome, which could be assigned to a discrete fluorescence peak, has been further characterized and shows at least a tenfold enrichment for X chromosome-specific DNA sequences as determined by Southern blot hybridization of cloned fragments.
Bacteriophage lambda↗
Isolation of human chromosome 13-specific DNA sequences cloned from flow sorted chromosomes and potentially linked to the retinoblastoma locus.
A recombinant DNA library has been constructed using flow sorted chromosome #13 DNA and the phage vector, Charon 21A. Roughly 90% of the phage inserts in the library hybridize to human repetitive DNA. Phage containing human nonrepetitive inserts have been screened for chromosome #13 specificity by Southern blot analysis using the genomic DNA of human-rodent cell hybrids containing different regions of the human #13 autosome. Of 18 phage inserts characterized, 13 have been assigned to the 13q12----q22 subregion, three appear to be localized in the 13pter----q12 region, and two are not #13-specific. By Southern blot analysis of the DNA of a retinoblastoma patient exhibiting a deletion of band 13q14 and of karyotypically normal individuals, two phage inserts have been putatively assigned to band 13q14, the currently accepted locus for a genetic determinant for retinoblastoma. These two DNA probes show quantitative differences in hybridization band intensity in the genomic DNA of the 13q--patient relative to that of the normals. In situ hybridization data support these conclusions. A recombinant phage library that shows an approximate 90% enrichment for human chromosome #13-specific DNA fragments should prove useful not only in studies related to retinoblastoma, but also in the molecular analysis of the structure and function of chromosome #13.
Animals↗
Infarction and squamous metaplasia of intraductal papilloma: a benign breast lesion that may simulate carcinoma.
Infarction of intraductal papillomas is uncommon. Six lesions of this type was referred to the authors as diagnostic problems, and two additional cases were found in a review of in-patient material. The patients' median age was 62 years (range, 30 to 81 years), and in each case the mass had been asymptomatic. Although the architectural pattern of the papillomas remained intact, ischemic necrosis rendered histologic evaluation difficult. Squamous metaplastic epithelium was present in three cases. Distortion of residual viable ductal epithelium by fibrosis at the periphery of the papillomas closely simulated invasive carcinoma. The appearance of the lesion on low-power magnification, the absence of malignancy elsewhere in the sample, and the absence of cytologic features of malignancy are useful criteria for distinguishing this lesion from carcinoma. None of these lesions recurred in the six patients for whom follow-up information was available (follow-up period, one to 20 years).
Adult↗
The preparation of electronically sorted hematopoietic cells for visual analysis.
The authors describe a simple method of collecting and preparing electronically sorted hemic cells for visual analysis. Wright-stained preparations were obtained easily by this method and offered excellent preservation of morphologic features. Flow cytometer-derived data thus can be correlated with the morphologic characteristics of immunologically distinctive subsets of hemic cells.
Cell Separation↗
Reproducibility in morphologic classification of non-Hodgkin's lymphomas using the Lukes-Collins system. The Southeastern Cancer Study Group experience.
Five pathologists of the Southeastern Cancer Study Group reviewed routinely prepared histologic sections from 249 cases of non-Hodgkin's lymphoma. They classified these cases morphologically, using criteria of the Lukes-Collins classification system. To evaluate reproducibility in classification, the individual interpretations of each pathologist were compared with a consensus interpretation. The pathologists recognized general morphologic features of follicular center cell lymphomas in 87-94% of such cases, but they identified specific morphologic types much less consistently. Significant differences of interpretation were encountered with respect to small cleaved follicular center cell, large cleaved follicular center cell, and large transformed (large noncleaved) follicular center cell types. Inadequacies of routine histologic sections contributed substantially to these disagreements. Ancillary immunologic technics may be required to improve consistency in recognition of some morphologic types, as well as to characterize cases that are not classified easily by morphology alone.
Evaluation Studies as Topic↗
Malakoplakia and malakoplakialike lesions of the upper gastrointestinal tract.
This report describes the clinical and pathologic features of 3 cases of unusual lesions that bear a striking similarity to malakoplakia. The lesions were located in the stomach, submental region, and oropharyngeal soft tissues. The cellular infiltrates were composed of sheets of mononuclear cells with abundant, granular, eosinophilic cytoplasm. Nuclei were small and bland, and mitoses were extremely rare. Lymphocytes and plasma cells were present in varying numbers. Ultrastructural studies revealed unusual crystalline structures within dilated cisternae of rough surfaced endoplasmic reticulum of plasmacytoid cells in all 3 cases. The 3 cases may represent a morphologic spectrum of chronic immunologic stimulation, with the crystalline structures limited to stimulated lymphocytes of gastrointestinal tract lesions.
Aged↗