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Biomedical subjects

A Flint

Publications and source records attributed to A Flint.

At least 73 records · Page 4Linked to original sources
PubMed1991

A new class of reversible cell cycle inhibitors.

The effects of three compounds on the cell cycle of HL-60 promyeloid leukemia cells has been examined. Ciclopirox olamine, an antifungal agent, and the compound Hoechst 768159 reversibly block the cell cycle at a point occurring roughly 1 h before the arrest mediated by aphidicolin, an inhibitor of DNA polymerase alpha activity, which acts in early S phase. Similar results are also obtained with the compound mimosine, a plant amino acid. Based on these data, it is concluded that all three agents inhibit cell cycle traverse at or very near the G1/S phase boundary and identify a previously undefined reversible cell cycle arrest point.

Antifungal Agents↗
PubMed1991

Mimosine reversibly arrests cell cycle progression at the G1-S phase border.

It has previously been demonstrated that the compound mimosine inhibits cell cycle traverse in late G1 phase prior to the onset of DNA synthesis (Hoffman BD, Hanauske-Abel HM, Flint A, Lalande M: Cytometry 12:26-32, 1991; Lalande M: Exp Cell Res 186:332-339, 1990). These results were obtained by using flow cytometric analysis of DNA content to compare the effects of mimosine on cell cycle traverse with those of aphidicolin, an inhibitor of DNA polymerase alpha activity. We have now measured the incorporation of bromodeoxyuridine into lymphoblastoid cells by flow cytometry to determine precisely where the two inhibitors act relative to the initiation of DNA synthesis. It is demonstrated here that mimosine arrests cell cycle progression at the G1-S phase border. The onset of DNA replication occurs within 15 min of releasing the cells from the mimosine block. In contrast, treatment with aphidicolin results in the accumulation of cells in early S phase. These results indicate that mimosine is a suitable compound for affecting the synchronous release of cells from G1 into S phase and for analyzing the biochemical events associated with this cell cycle phase transition.

Aphidicolin↗
PubMed1991

Diagnostic usefulness of nasal biopsy in Wegener's granulomatosis.

Wegener's granulomatosis (WG) frequently involves the upper respiratory tract, and nasal mucosal biopsy is often initially used to establish the diagnosis. To evaluate the diagnostic efficacy of nasal biopsy in WG, we reviewed the pathologic features of 30 such biopsy specimens from 17 patients with well-documented WG. Active vasculitis (granulomatous or nongranulomatous) was identified in seven of the patients (41%). The presence of extravascular foci of necrosis in lung biopsy samples has recently received attention as a characteristic feature of WG. Similar foci were found in the nasal samples from six of our patients, although vasculitis was absent in the samples from two of them. If extravascular foci of necrosis are regarded as characteristic or even diagnostic of WG, two additional patients in our series could be regarded as having had diagnostic nasal biopsies (nine of 17 patients). Nasal biopsy could thus be considered as diagnostic in 53% of the patients. Samples larger than 5 mm in greatest dimension were more likely to contain diagnostic features than were smaller samples (P = 0.002).

Adolescent↗
PubMed1991

Quantitative assessment of lung pathology in idiopathic pulmonary fibrosis. The BAL Cooperative Group Steering Committee.

The diagnosis and classification of most interstitial lung diseases requires histologic evaluation of lung tissue, obtained by an open lung biopsy to confirm the diagnosis. In addition, it is generally accepted that response to therapy in idiopathic pulmonary fibrosis (IPF) is related to the relative degree of cellularity and fibrosis present. Because only a qualitative assessment of the relative extent and severity of these changes is generally provided, correlation with clinical and physiologic alterations is difficult. This report describes results of a semiquantitative assessment by four pathologists of inflammatory/exudative changes, fibrotic/reparative changes, and airway alterations, in addition to an overall assessment of cellularity and fibrosis in 50 patients with IPF. In 10 randomly selected biopsies examined twice in a blinded fashion, absolute agreement between assessments for a given pathologist varied between 54 and 64% (mean = 57.5%) and in the majority of instances the agreement was greater than would have occurred by chance. There was good agreement for most variables across the four raters on the 101 samples. The mean score for some of the parameters reported by a given rater deviated occasionally from those of the other raters, but no single rater was consistently different from the other raters. A principal component factor analysis revealed that the pathologic features fell into four general groupings: alveolar wall metaplasia, fibrosis, honeycombing, smooth muscle, and vascular changes fell into one group; severity and extent of cellularity in the alveolar wall into a second group; severity and extent of cellularity in the alveolar space into a third group; and interstitial young connective tissue along with granulation tissue in the airways formed the fourth group.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗
PubMed1991

The tall cell variant of papillary carcinoma of the thyroid gland. Comparison with the common form of papillary carcinoma by DNA and morphometric analysis.

The tall cell variant of papillary carcinoma of the thyroid manifests a more aggressive behavior than the usual form of papillary carcinoma of the thyroid. Morphometric analysis of nuclear features and DNA analysis may yield information predictive of aggressive behavior. Accordingly, the DNA content and morphometric features of the neoplastic cells of the tall cell variant were measured and compared with measurements obtained from neoplastic cells of the usual form of papillary carcinoma. Six of the 11 tall cell neoplasms were aneuploid, as were four of the eight usual papillary neoplasms. Although benign cells were separated from malignant cells in each case, differences between tall and usual papillary carcinoma cells were not observed regarding DNA content, chromatin texture, or nuclear size and shape. Differences in the clinical behavior of these neoplasms will likely need to be explained on the basis of other characteristics.

Carcinoma, Papillary↗
PubMed1990

Neurofibroma of the ovary.

We report an unusual example of ovarian neurofibroma in a woman with neurofibromatosis (von Recklinghausen's disease). The neoplasm caused ovarian enlargement which surgically simulated malignant neoplasm. Ovarian neurofibromas are extremely rare and may arise from small myelinated nerves in the ovarian hilum.

Female↗
PubMed1990

Comparison of antigen expression on normal urothelial cells in tissue section and tissue culture.

Antigenic characterization of urothelial cells cultured from normal adult ureter was performed. These cells were cultured using a simplified isolation and culture technique and a commercially available serum-free medium. The cells growing in these cultures had epithelioid morphology and normal quantities of DNA. The antigen expression on these cultured normal urothelial cells was evaluated using a panel of monoclonal antibodies: 5G6.4, AN43, URO-5, anti-keratin and anti-blood group antibodies, and 425 (anti-epidermal growth factor receptor). Lower levels of anti-A and AN43 binding on cultured cells were observed than are seen on urothelial cells in sections of normal ureter, while the binding of anti-blood group H, 5G6.4, and URO-5 was unchanged. Binding of anti-epidermal growth factor receptor antibody 425 was improved if the cells were grown in medium lacking epidermal growth factor. These results confirm the urothelial origin of these cultured urothelial cells but indicate that some antigenic differences between cultured normal urothelial cells and urothelial cells in situ in the normal ureter exist.

ABO Blood-Group System↗
PubMed1990

Fibronectin distribution in normal and malignant urothelium.

Fibronectin is a glycoprotein that mediates the attachment of BCG to the murine bladder. To assess the potential role of fibronectin on bladder cancer cells as a specific substrate for BCG binding in man, a semi-quantitative method was employed to evaluate the presence of fibronectin on normal urothelium and bladder cancer. Monoclonal anti-fibronectin binding to normal and malignant urothelial tissues was evaluated by an immunoperoxidase assay. Human tumor cell lines were evaluated with mixed hemadsorption and immunoperoxidase assays. In both systems, immunoreactive fibronectin had low expression on unfixed normal and malignant urothelium. With fixation, immunoreactive fibronectin decreased on supporting stroma and increased in normal and malignant urothelium. Fibronectin distribution did not show tumor specificity either with fixed or unfixed specimens.

BCG Vaccine↗
PubMed1990

Hürthle-cell neoplasms of the thyroid gland.

The difference in biologic behavior of Hürthle-cell neoplasms as reported in several series may be explained by the use of different diagnostic pathologic criteria, and the selection of patients with neoplasms of varying clinical stages (treatment at the time of initial diagnosis versus treatment for advanced disease, or initial diagnosis at an advanced stage). On the basis of all of the available evidence, it appears that Hürthle-cell neoplasms exhibit a biologic behavior similar to that of corresponding follicular neoplasms although these latter tumors may have a slightly higher propensity to metastasize. Survival and cure rates are lower than those for papillary cancer and are comparable to those for follicular carcinoma. DNA analysis may be of some help in predicting clinical behavior; aneuploid neoplasms are more often associated with the pathologic features of malignant tumors and may follow a more aggressive clinical course. At present, however, we are unaware of specific surgical strategies that are based upon DNA analysis. Tumor size and morphometric analysis of cytological features have not been particularly valuable for estimating the clinical course of these tumors.

Adenoma↗
PubMed1989

Identification by monoclonal antibodies of an antigen shed by human bladder cancer cells.

The reactivities of two anti-bladder cancer monoclonal antibodies, AN43 and BB369, were characterized. AN43 and BB369 reacted with a majority (greater than 50%) of bladder cancer tissue sections tested by immunoperoxidase staining. When tested against a panel of 27 normal human tissues, AN43 and BB369 reacted only with urothelium and stomach. AN43 and BB369 showed identical binding patterns and competed for binding on bladder cancer cells, suggesting that the two antibodies react with identical or spatially close epitopes. Bound BB369 antibody was rapidly shed from the surface of viable UM-UC-9 human bladder cancer cells. The antigen was found in spent tissue culture medium from the UM-UC-9 human bladder cancer cell line. AN43 and BB369 define a shed bladder tumor-associated antigen with limited distribution on normal tissues. The antigen is different from bladder tumor-associated antigens defined by other monoclonal antibodies and may be useful for the diagnosis and follow-up of patients with bladder cancer.

Antibodies, Monoclonal↗
PubMed1988

Cytophotometric measurements of Hürthle cell tumors of the thyroid gland. Correlation with pathologic features and clinical behavior.

The DNA content and nuclear size and shape of 21 Hürthle cell neoplasms of the thyroid were analyzed with a CAS 100RS Image Analyzer (Cell Analysis Systems, Lombard, IL) in order to distinguish between benign and malignant lesions. Neoplasms were considered malignant if documented metastatic disease or pathologic evidence of vascular or capsular invasion was present. Of the ten neoplasms classified as malignant, eight were aneuploid and two were diploid. Nine of the 11 benign neoplasms were diploid, the remaining two neoplasms were aneuploid. Two of the four malignant neoplasms which recurred or metastasized were aneuploid, the other two were diploid. A statistically significant association was found between aneuploidy and tumor invasion (P = 0.007). However, measurement of the percentage of cycling tumor cells as well as nuclear size and shape were not useful in separating benign from malignant neoplasms.

Adenoma↗
PubMed1988

Cervical carcinoma antigen: distribution in neoplastic lesions of the uterine cervix and comparison to other tumor markers.

Four antibodies (anti-CCA, anti-CEA, Ca-l, and anti-EMA) were used to study the distribution of antibody-binding sites in normal endocervical mucosa, metaplastic squamous epithelium, squamous epithelium exhibiting varying grades of intraepithelial neoplasia, and invasive squamous cell carcinoma. Anti-CCA, a novel monoclonal antibody raised against an extract of squamous cell carcinoma of the cervix, recognizes dysplastic, neoplastic, and metaplastic cervical epithelial cells. While anti-CCA and Ca-l rarely stained normal glandular epithelium, 31.4 and 45.7% of the samples stained positively for CEA and EMA, respectively. There did not appear to be significant differences between anti-CCA and the other antibodies in the frequency with which neoplastic conditions were stained. Based upon these observations, it appears that none of the antibodies tested can be regarded as a specific tumor marker.

Antigens, Neoplasm↗
PubMed1988

Bronchogenic carcinoma metastatic to normal-sized lymph nodes: frequency and significance.

CT staging of mediastinal lymph node metastases from bronchogenic carcinoma is a subject of considerable controversy. The frequency of metastases to normal-sized lymph nodes is a critical issue related to the sensitivity of CT. The authors prospectively examined 42 patients with bronchogenic carcinoma with CT; in 39, careful surgical-pathologic correlation of mediastinal lymph node status was possible. Only 7% had metastases limited to mediastinal lymph nodes that were normal-sized at CT. This reflected a low overall frequency of metastases to normal-sized nodes and several diagnostic factors that converted potentially false-negative studies into true-positive CT studies. In this small series, metastases to enlarged nodes were more likely to have extracapsular spread of tumor, a poor prognostic factor. Overall, the authors do not consider metastases to normal-sized mediastinal lymph nodes to be a major problem in CT staging of non-small cell lung cancer.

Adenocarcinoma↗
PubMed1988

Cytophotometric measurements of metaplastic carcinoma of the breast: correlation with pathologic features and clinical behavior.

The DNA content of the various neoplastic elements of 12 Feulgen-stained metaplastic breast carcinomas was measured by image analysis. Spindle cell, osseous, chondroid, rhabdomyoid, or squamous cell metaplastic elements comprised at least half of each neoplasm in which an invasive ductal carcinoma component also was identified. The epithelial elements in all of the neoplasms were aneuploid, as was the metaplastic component in 11 of the cases. Multiple stem cell lines were detected in the ductal carcinoma component in 4 cases and in the metaplastic components in 5 cases. Our findings lend support to the view that metaplastic elements are derived from malignant epithelial cells, rather than from benign stromal cells. Neither aneuploidy nor the presence of multiple stem cell lines was a useful predictor of the biologic behavior of these 12 neoplasms.

Adult↗
PubMed1987

Direct hybridization to DNA from small numbers of flow-sorted nucleated newborn cells.

A technique is described that allows direct hybridization to the DNA of cells flow sorted onto nitrocellulose filters, which obviates an intervening DNA isolation step. The feasibility of this technique for studying small numbers of cells is demonstrated with human cord blood, which has a high proportion of nucleated cells. The cells are stained with fluorescein-conjugated anti-HLe-l, a monoclonal antibody that recognizes mature leucocytes. Anti-HLe-l-positive cells are all nucleated, and a controlled, precise number of them may be sorted directly onto a nitrocellulose membrane. In cord blood, a small percentage of anti-HLe-l-negative cells are nucleated erythrocytes, which may also serve as a source of DNA. Studies were performed on male or female newborn cells flow sorted onto nitrocellulose membranes and hybridized with either a non-specific human repeat DNA probe or a Y chromosome-specific probe. Importantly, the sex of the newborn could be determined at the DNA level from as few as 50 sorted cord blood leucocytes or 5,000 HLe-l-negative cells. Since nucleated erythrocytes are common in fetal blood but rarely found in the peripheral circulation of adults, the method has potential application for the determination of fetal sex from analysis of flow-sorted nucleated erythrocytes present in the maternal circulation during pregnancy.

Cell Separation↗
PubMed1987

Construction of a chromosome 16-enriched phage library and characterization of several DNA segments from 16p.

A flow sorted chromosome 16-enriched recombinant library was produced to isolate DNA probes useful for constructing a linkage map of 16p, primarily for the study of adult polycystic kidney disease (APKD). The APKD locus has been mapped to chromosome 16 by linkage with the probe 3'HVR, which is located in the region 16p12----pter. Of the 48 single-copy fragments isolated from this new phage library, 39 (81%) were found to be chromosome 16 specific. Probes mapping to chromosome 16 were regionally localized by hybridizing to flow-sorted spot blots of translocation products from lymphoblastoid cell lines containing the rearrangements t(1;16) or t(11;16). Translocation breakpoints at 16p13.11 and 16p11.1 were utilized to subdivide chromosome 16 into three regions: Twenty-six probes were mapped to 16p11.1----16qter, two to 16p11.1----16p13.11, and eleven to 16p13.11----16pter. Probes from 16p were examined for their recognition of restriction fragment length polymorphisms (RFLPs). Seven polymorphic probes were found which recognized eleven RFLPs. Six of the seven probes have RFLPs which are reasonably informative (polymorphism information contents (PIC) of over 0.25). Two of these identify polymorphisms with three different alleles, one of which has a PIC value of over 0.4. These probes may aid in the diagnosis of APKD and contribute towards a linkage map of chromosome 16.

Animals↗
PubMed1987

Crack lung: pulmonary disease caused by cocaine abuse.

A patient developed 3 separate episodes of fever, transient pulmonary infiltrates, and bronchospasm after inhalation of cocaine. The illness was associated with eosinophilia, pruritus, and an elevated IgE level, indicating an immunologic pathogenetic mechanism. This is a complication of cocaine abuse not previously reported.

Cocaine↗