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Biomedical subjects

B Atkinson

Publications and source records attributed to B Atkinson.

At least 37 records · Page 2Linked to original sources
PubMed1992

Use of bacterial trpE fusion vectors to express and characterize the bovine immunodeficiency-like virus core protein.

The gag coding region from Bovine Immunodeficiency-like Virus (BIV) was cloned into E. coli and expressed as a bacterial fusion protein. Six different clones spanning various regions of the gag open reading frame were generated. The resulting fusion proteins were expressed at high concentrations and readily purified. A panel of bovine immune sera specifically recognized the recombinant Gag proteins, as did immune sera from animals infected or immunized with lentiviruses related to BIV, such as Equine Infectious Anemia Virus (EIAV) and Human Immunodeficiency Virus (HIV). Analysis of the deletion clones, using the bovine immune sera panel, enabled us to identify at least one major epitope which was specifically recognized by all bovine sera examined. The ease of expression, purification, and specificity of these fusion proteins should enable a thorough study of the epidemiology of BIV infection.

Animals↗
PubMed1992

A prospective study of pulmonary function and gas exchange following liver transplantation.

Pulmonary function and gas exchange were prospectively studied in 95 patients before and 9 to 15 months following liver transplantation. Pretransplant, the most common PF abnormality was impaired efficiency of gas exchange as measured by Dss. As a group, the mean Dss was 78.0 +/- 16.6 percent predicted and was found to be less than 80 percent predicted in 50 patients. As a group, patients with the most severe liver diseases clinically (Child's C classification) had the lowest mean Dss pretransplant. Posttransplant, three findings were of clinical importance: PaCO2 significantly improved posttransplantation, suggesting a resolution of pretransplant respiratory alkalosis. Expiratory airflow obstruction, measured by a change in the FEV1/FVC, was extremely uncommon posttransplant. Mean Dss improved significantly in patients with Child's C severity of liver disease. The most frequent deteriorations in Dss statistically were associated with posttransplant thoracotomy, ARDS, nonspecific pneumonitis, significant pleural effusions and hepatic retransplantation.

Female↗
PubMed1991

Constitutive expression of multiple growth factor genes by melanoma cells but not normal melanocytes.

In a panel of metastatic melanoma cell lines we found steady-state mRNA transcripts for multiple growth factors including basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF)-A, PDGF-B, transforming growth factor (TGF)- beta 1, TGF- alpha, melanoma growth-stimulating activity (MGSA), interleukin (IL)-1 alpha, and IL-1 beta but not insulin-like growth factor (IGF)-1 or IGF-2. Expression of growth factor genes was constitutive because prior to RNA extraction melanoma cells were maintained in a chemically defined culture medium free of exogenous growth factors. Each of four cell lines had an individual pattern of expression of either two, four, five, or seven growth factors; however, all cell lines shared expression of the bFGF gene. Two strains of normal melanocytes expressed TGF- beta 1 but not bFGF, PDGF, TGF- alpha , or MGSA mRNA at detectable levels. We tested growth-modulatory effects of the growth factors most frequently expressed by melanoma cells (bFGF, TGF- alpha, TGF- beta, PDGF). None of these stimulated melanoma cell growth consistently, whereas exogenous, acid-activated TGF- beta inhibited melanoma growth at concentrations greater than 10 ng/ml, suggesting that bioactive TGF- beta may represent a physiologic growth inhibitor. Neither neutralizing antisera to PDGF or TGF- alpha nor a monoclonal antibody to the epidermal growth factor (EGF)-receptor inhibited melanoma cell growth. Our results indicate that multiple growth factors are expressed simultaneously and constitutively by melanoma cells but not normal melanocytes in culture. Expression of bFGF is a common feature underscoring the significance of bFGF as an autocrine factor for melanoma cells as described earlier. Secreted PDGF and TGF- alpha are apparently not involved in or not essential for autocrine growth stimulation of melanoma cells.

Blotting, Northern↗
PubMed1991

Interaction of subtype-selective antagonists with alpha 1-adrenergic receptor-mediated second messenger responses in rat brain.

The selective antagonists (+)-niguldipine and 5-methylurapidil (5-MU) were used to more clearly identify the alpha 1-adrenergic receptor subtypes involved in second messenger responses in slice and culture preparations of rat brain. The alpha 1-adrenergic receptor activating [3H]inositol phosphate (InsP) formation in neocortical and hippocampal slices appeared to have mixed characteristics. Although the low potency of (+)-niguldipine indicated involvement of the alpha 1B subtype, 5-MU had an alpha 1A-like potency at this subtype. (+)-Niguldipine did not inhibit the alpha 1 receptor-mediated potentiation of the cAMP response to either isoproterenol or adenosine in cortical slices, even at high concentrations. 5-MU inhibited both cAMP responses, although this inhibition appeared non-competitive. Thus, these receptors are clearly different from those mediating InsP formation. In primary glial cultures, (+)-niguldipine also had a low potency in blocking norepinephrine-stimulated [3H]InsP formation, consistent with involvement of the alpha 1B subtype. However, both 5-MU and WB 4101 had high potencies in blocking this response, suggesting involvement of the alpha 1A subtype. Inactivation of the alpha 1B subtype by pretreatment of cultures with chloroethylclonidine did not increase the potencies of any of these antagonists. The inhibition by 5-MU and WB 4101 was competitive in both control and chloroethylclonidine-pretreated cultures, whereas the inhibition by (+)-niguldipine was primarily noncompetitive. The use of these more selective antagonists shows that the current alpha 1A/alpha 1B subclassification scheme is inadequate to identify the receptors mediating these responses. None of the responses were blocked by (+)-niguldipine with the high potency expected at the alpha 1A subtype, although all InsP responses were blocked by 5-MU with a relatively high (alpha 1A-like) potency. In addition, very low affinity and noncompetitive effects of (+)-niguldipine were observed. These data raise the possibility of additional subtypes of alpha 1-adrenergic receptors or as yet unidentified functional interactions between known subtypes.

Adrenergic alpha-Antagonists↗
PubMed1990

Serum CEA and CA 19-9: potential future diagnostic or screening tests for gallbladder cancer?

The poor prognosis of gallbladder cancer and the presence of high-risk populations make the identification of a screening test for this disease very desirable. As part of an ongoing case-control study of gallbladder cancer being conducted in Mexico City, Mexico, and in La Paz, Bolivia, blood specimens were sought from all patients with cancer of the gallbladder and on controls of similar age and sex undergoing upper abdominal surgery. Each sample was analyzed for carcino-embryonic antigen (CEA) and CA 19-9. Using the specimens from Bolivia, a serum CEA cutoff of 4.0 ng/ml yielded a sensitivity of 50.0% and a specificity of 92.7%, while a serum CA 19-9 cutoff of 20.0 units/ml yielded a sensitivity of 79.4% and a specificity of 79.2%. Using ROC curve analysis, the latter was a much better test than the former (p less than 0.05). Using the tests in series or in parallel did not substantively improve the results. The specimens from Mexico were used for validation purposes, and yielded very similar results. In conclusion, serum CA 19-9 and CEA are fairly good tests for discriminating patients with gallbladder cancer from patients with gallstones and no cancer, the former being a better test than the latter. These tests may be useful in identifying disease recurrences. In addition, if a sufficiently high-risk population could be identified, this could potentially become a useful screening test for this serious disease, allowing early intervention. However, additional data are needed prior to recommending this clinically.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1990

Clinical, biochemical and immunoelectron microscopical evidence of dual hormone production in a mammosomatotroph cell adenoma.

This paper reports the occurrence of a rare, yet distinct pituitary adenoma which was surgically removed from a 42-year-old male with both clinical and biochemical evidence of acromegaly and mild hyperprolactinaemia. The monomorphic adenoma consisted of mature cells which were ultrastructurally indistinguishable from those of a prolactinoma. Electron immunocytochemistry, including a series of double-labelling techniques using selected colloidal gold particles as markers, indicated the presence of a pituitary adenoma in which the cells were capable of simultaneously producing growth hormone and prolactin and packaging them within the same secretory granule. This is thought to represent a mammosomatotroph cell adenoma.

Adenoma↗
PubMed1990

Components of image intensive diagnosis. Codifying visual features for effusion cytology.

Components of visual assessment in the diagnosis of effusions were analyzed using relative operating characteristic. Diagnostic performance in the assessment of malignancy and the specification of metastatic origin was measured for two expert cytologists. The component of performance attributable to feature interpretation was measured in protocols which minimized the effects of clinical information and visual search in the decision process. Feature interpretation, as a process, contributed significantly to the evaluation of malignancy and marginally to the specification of metastatic origin. For each of these diagnostic tasks, the process of feature interpretation was codified in the construction of explicit models. The expert cytologists were asked to define a set of localized visual features that incorporate essential visual elements for diagnosis. These features were evaluated for a set of test cases, and regression models were constructed defining malignancy and metastatic origin. Relative operating characteristic analysis indicated that the predictive value of the models for diagnosis was very similar to the component of human performance attributable to feature interpretation.

Computers↗
PubMed1989

Pathophysiology of tumor progression in human gallbladder: flow cytometry, CEA, and CA 19-9 levels in bile and serum in different stages of gallbladder disease.

Gallbladder epithelium is unique among the gastrointestinal cell types because proteins and protein levels in the fluid bathing the luminal side of the cells (bile) are different from and can be compared with those in the fluid bathing the basal side (serum). To help identify cellular changes that occur during the development of gallbladder cancer, we obtained gallbladder tissue, serum, and bile specimens from 20 patients with invasive adenocarcinoma of the gallbladder, three with high-grade dysplasia (carcinoma in situ), six with low-grade dysplasia, 12 with hyperplasia, and 10 with acute or chronic cholecystitis. We obtained serum samples from 40 patients with invasive adenocarcinoma and bile samples from 29 of these patients; serum samples from three with high-grade dysplasia and bile specimens from two of these; serum and bile samples from five with low-grade dysplasia; serum or bile samples from 126 with metaplasia, hyperplasia, or cholecystitis, including serum samples from 121 and bile samples from 110; and serum and bile samples from eight with normal biliary tracts. The study was conducted in Mexico City, Mexico, and La Paz, Bolivia. We performed flow cytometric DNA analysis on gallbladder tissue specimens and measured levels of carcinoembryonic antigen (CEA) and CA 19-9 antigen in the serum and bile specimens. Analysis of the cell cycle compartments by flow cytometry revealed marked variations of the proliferation index for the different disease states (P less than .0001). The proliferation index increased with progression from cholecystitis to invasive adenocarcinoma. Of the bile and serum measurements, only serum CA 19-9 values were correlated with flow cytometry measurements (r = -.49, P = .005). Overall, the serum and bile measurements were in agreement (P less than .01). However, with the exception of the correlations among serum measurements for the patients with invasive adenocarcinoma, most of the correlations could be explained by differences in the disease state. In particular, the progression from normal tissue to invasive adenocarcinoma involved no change in bile CA 19-9 level and only a slight change in bile CEA level but much larger changes in serum CEA and CA 19-9 levels. It appears that the progression from normal tissue to invasive adenocarcinoma results in increased production of these antigens and often in loss of cell polarity as well, i.e., inability to prevent leakage of the antigens into the serum.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1987

Tumor growth modulation by a monoclonal antibody to the epidermal growth factor receptor: immunologically mediated and effector cell-independent effects.

A monoclonal antibody of IgG2a isotype (425) is described that reacts with the epidermal growth factor receptor on human cells of different tissue origins. Monoclonal antibody 425 mediates tumor cytotoxicity in vitro using mouse and human effector cells and suppresses in vivo tumor cell growth of epidermoid (A 431) and colorectal (SW 948) carcinoma-derived cell lines. The tumoricidal effects in vitro are proportional to the antigen density on target cells. At concentrations higher than 1 nM, monoclonal antibody 425 inhibits growth of epidermal growth factor receptor-bearing A 431 cells, showing an epidermal growth factor-like agonist activity on the growth properties of these cells. A 431 cultures grown in the presence of growth-inhibiting doses of antibody or epidermal growth factor reveal a clear decrease of the relative number of cells in S phase. Additionally, cells treated with the antibody show a decrease of G2-M-phase cells in some, but not all, cultures tested.

Animals↗
PubMed1987

Radioimmunodetection of human glioma xenografts by monoclonal antibody to epidermal growth factor receptor.

Murine IgG2a monoclonal antibody (MAb) 425 specifically detects epidermal growth factor receptor, which is expressed on human gliomas and tumors of other tissue origin but rarely on normal brain tissues, and not at all on bone marrow and peripheral blood cells. 131I-labeled F(ab')2 fragments of this MAb injected into nude mice grafted with U-87 MG glioma cells preferentially localized in tumor tissue compared to normal mouse tissues, as determined by differential tissue counting of radioactivity. The mean tumor-to-tissue ratios of radioactivity ranged between 8.2 (blood) and 55.8 (muscle) at 2 days after the injection of 15 muCi of 131I-425 F(ab')2/mouse. Radiolabeled fragments of an anti-hepatitis virus IgG2a MAb did not localize in tumors. The localization index derived from the ratios of specific antibody to indifferent antibody in tumor tissue relative to blood was 9.94 at 2 days following the MAb injection. The labeled MAb did not localize in a xenograft of colorectal cancer tumor, which does not express the epidermal growth factor receptor. Tumors could be located by whole-body gamma-scintigraphy without background subtraction following the injection of 100 muCi of radiolabeled MAb 425 F(ab')2 fragments. The data suggest that MAb 425 is a likely candidate for clinical diagnostic and radioimmunotherapy trials.

Animals↗
PubMed1986

Flow cytometric DNA analysis of neuroblastoma. Correlation with histology and clinical outcome.

Clinical and histologic features of 38 cases of neuroblastoma were compared with data obtained by flow cytometric DNA analysis. Favorable clinical outcome was associated with an aneuploid stem line (P less than 0.01) and a low percentage of tumor cells in the S, G2, and M phases of the cell cycle (P less than 0.005). These favorable cytometric features were also associated with a favorable clinical stage (1, 2, 4s), and histologic evidence of Schwann's cell and ganglion cell differentiation. Consideration of cytometric data improved the sensitivity, specificity, and predictive efficiency of a current system for histologic grading of neuroblastoma.

Child↗
PubMed1986

Monoclonal antibody-defined antigens of human prostate cancer cell line PC3.

Over 600 hybridomas were derived from the immunization of mice with live cells and aqueous extracts of the human prostatic carcinoma cell line PC3. A total of 26 hybridomas with restricted reactivities were selected, subcloned and antibodies tested on a variety of tumor and normal cells. Seven monoclonal antibodies showed reactivity for prostate cancer and other tumor cell lines, including breast carcinomas. Three of the antibodies obtained after immunization with live cells reacted with live cells only and three of the four antibodies obtained after immunization with cell extract reacted with cell extracts and spent culture media. The fourth antibody in the latter group was reactive only in the immunoperoxidase staining assay. Antibody PrS5 recognized a 90,000 molecular weight molecule from 125I-surface-labeled cells in immunoprecipitation analysis. Antibodies PrE3 and PrD8 detected a nonacid glycolipid pentasaccharide from PC3 cells and meconium, and a glycoprotein of 115,000 molecular weight from 125I-surface-labeled red blood cells. The similar patterns of reactivity in RIAs and antigen analysis suggest that antibodies PrE3 and PrD8 recognize the same molecule. The results emphasize the usefulness of immunohistochemistry in the testing of monoclonal antibodies and the impact of the form in which the antigen is presented on the resultant antibody specificity.

Animals↗