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P J Dempsey

Publications and source records attributed to P J Dempsey.

At least 19 recordsLinked to original sources
PubMed1992

Possible role of transforming growth factor alpha in the pathogenesis of Ménétrier's disease: supportive evidence form humans and transgenic mice.

Ménétrier's disease is an uncommon disorder of unknown etiology characterized by enlarged gastric folds with foveolar hyperplasia and cystic dilatation of gastric glands. Biochemical features that are seen frequently include hypoproteinemia, hypochlorhydria, and increased gastric mucus. Because transforming growth factor alpha (TGF alpha) is an epithelial cell mitogen that inhibits gastric acid secretion and increases gastric mucin content, we hypothesized that its altered expression might be involved in the pathogenesis of this disease. Therefore, we characterized TGF alpha immunoreactivity in the gastric mucosa of 4 patients with Ménétrier's disease. In contrast to the normal pattern of TGF alpha immunostaining in which TGF alpha appears most concentrated in parietal cells, there was intense staining in the majority of mucous cells in the gastric mucosa of patients with Ménétrier's disease. In one patient from whom sufficient fresh tissue was obtained to isolate RNA, expression of TGF alpha and the epidermal growth factor receptor was higher in the gastric mucosa relative to a normal control. In addition, metallothionein-TGF alpha transgenic mice, which overexpress TGF alpha in gastric mucosa, show a number of features characteristic of Ménétrier's disease. These include foveolar hyperplasia and glandular cystic dilatation, increased gastric neutral mucin staining, and reduced basal and histamine-stimulated rates of acid production. Taken together, observations derived from the human material and correlation with data from a transgenic mouse model support an important role for TGF alpha in the pathogenesis of Ménétrier's disease.

Animals↗
PubMed1992

Increased production of transforming growth factor alpha following acute gastric injury.

Transforming growth factor alpha (TGF-alpha) production recently has been found in normal mammalian gastric mucosa. Inasmuch as TGF-alpha and epidermal growth factor (EGF) both stimulate epithelial cell migration and proliferation and suppress gastric acid secretion, the authors of the current study proposed that these growth factors may participate in tissue repair after acute gastric mucosal injury. Consequently, TGF-alpha and EGF production were examined after orogastric administration of either acidified taurocholate or 0.6 mol/L HCl to rats. TGF-alpha messenger RNA (mRNA) expression increased in a dose- and time-dependent manner after administration of taurocholate, whereas EGF mRNA expression was not detected. Radioimmunoassay of gastric mucosal scrapings obtained 6 hours after gastric injury induced by 0.6 mol/L HCl showed a 2.1-fold increase in immunoreactive TGF-alpha but no increase in immunoreactive EGF. In addition, there was a 68-fold increase in immunoreactive TGF-alpha in gastric juice within 30 minutes of gastric instillation of HCl and, again, no increase in immunoreactive EGF. There is a rapid appearance of TGF-alpha in the gastric juice within 30 minutes of injury, which is followed by increased expression of TGF-alpha mRNA and protein in the gastric mucosa. These studies suggest that locally produced TGF-alpha may participate in gastric mucosal repair following acute gastric injury to rats.

Animals↗
PubMed1992

Differential regulation of transforming growth factor alpha autoinduction in a nontransformed and transformed epithelial cell.

Addition of transforming growth factor alpha (TGF-alpha) to cultured human keratinocytes results in enhanced expression of TGF-alpha mRNA. This phenomenon of TGF-alpha autoinduction is also observed in a TGF-alpha responsive colon cancer cell line, LIM 1215. In the present study, regulation of TGF-alpha autoinduction is examined in these two cell types. In human keratinocytes, but not in LIM 1215 cells, the increase in steady-state TGF-alpha mRNA following administration of TGF-alpha is due to stabilization of the 4.8-kilobase TGF-alpha transcript, as determined by actinomycin D decay curves. Nuclear run-on experiments confirmed transcriptional control in LIM 1215 cells. Basal and TGF-alpha-stimulated TGF-alpha expression is mediated, at least in part, through a protein kinase C-dependent pathway in both cell types, as determined by the protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7), which attenuates TGF-alpha mRNA accumulation. In the keratinocytes, but not in the LIM 1215 cells, basal TGF-alpha expression is mediated through an epidermal growth factor receptor-dependent pathway, as determined by antibody blockade of the epidermal growth factor receptor. Thus, differential regulation of TGF-alpha autoinduction exists in these nontransformed and transformed epithelial cell types.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1990

Monoclonal antibodies that recognize human granulocyte-macrophage colony-stimulating factor and neutralize its bioactivity in vitro.

We have produced monoclonal antibodies to bacterially synthesized, human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and have studied in detail the characteristics of three strongly neutralizing antibodies. The antibodies reacted with GM-CSF at high dilution (EC50 = 0.1-1.7 nM) in an indirect ELISA but did not react with murine GM-CSF or other cytokines. They also recognized glycosylated hGM-CSF produced by human lymphocytes. The antibodies were able to immunoprecipitate rhGM-CSF, but only reacted weakly with rhGM-CSF on Western blots, indicating that they recognized a conformation-dependent epitope. Cross-blocking studies showed that the three antibodies recognized overlapping epitopes. The antibodies inhibited binding of 125I-labeled rhGM-CSF to HL-60 cells at nanomolar concentrations and neutralized GM-CSF activity in two different bioassays. These antibodies thus provide a useful tool for analyzing the specificity of bioassays and for further studies of the production and function of GM-CSF in vitro and in vivo.

Animals↗
PubMed1989

Cervical butterfly-block vertebra. A case report.

A new type of block vertebral malformation is described. A 42-year-old woman presented after an akinetic seizure. Routine cervical spine films, obtained because of a recent history of abnormal head posture, disclosed a vertebral anomaly. Computed tomography and conventional polytomography revealed that the lesion was composed of a butterfly vertebra as the upper portion of a pair of nonsegmented vertebrae. Vertebral fusion and segmentation anomalies are reviewed and compared with the specific features of this case.

Adult↗
PubMed1988

The importance of resolution in the clinical application of breast sonography.

Although in use for over thirty years, breast ultrasound continues a steady evolution both in technological development and in clinical application. It is now firmly established as a first line diagnostic modality to be used in conjunction with x-ray mammography. Its ability to provide qualitatively different parenchymal information in a slice-type, or tomographic format with excellent resolution makes it a clinically important instrument. The ultimate goal, however, still lies ahead. This is the detection and characterization of small masses within the breast, coupled with the ability to determine whether these foci are benign or malignant. This will likely involve not only scanners with better resolution, but also those, such as doppler, with the ability to obtain functional information as well.

Adult↗
PubMed1987

Epidermal growth factor stimulates the synthesis of cell-attachment proteins in the human breast cancer cell line PMC42.

The human breast cancer cell line PMC42 responds to the addition of epidermal growth factor (EGF) by proliferation and increased frequency of attachment of cell-organoid structures to the culture vessel. Antibodies to fibronectin and laminin reacted strongly, by immunoperoxidase, with the membranes of cells from organoids that became adherent following addition of EGF. This reaction was weak with membranes of cells of non-adherent organoids in cultures containing EGF and was negative with membranes of cells of free-floating organoids from cultures without EGF. An increase in biosynthetic labelling with 35S-methionine was found in cell lysates and supernatants of PMC42 cells cultured in the presence of EGF compared with control cells grown without EGF. One-dimensional SDS-polyacrylamide gel electrophoresis and 2-dimensional NEPHGE-PAGE of labelled cell proteins showed increased synthesis of several cellular proteins and the appearance in EGF-treated cells of 2 proteins which were not detected in cells from control cultures lacking EGF. Immunoprecipitation experiments using antibodies to fibronectin and laminin with lysates of 35S-methionine labelled PMC42 cells cultured with EGF showed strong immunoprecipitation at Mr 200 and 400 with anti-laminin, and at Mr 200 and 96 with anti-fibronectin. These immunoprecipitates were blocked specifically by purified laminin or fibronectin, respectively. No immunoprecipitates were detected with these antibodies in lysates from cells grown without EGF. EGF thus stimulates increased adherence of cultured PMC42 cell-organoid structures together with increased membrane expression of the cell-adhesive proteins laminin and fibronectin. These effects may play a role in normal development and neoplastic behaviour of breast epithelia.

Breast Neoplasms↗
PubMed1986

A monoclonal antibody CIBr17 recognizes a myoepithelium-specific antigen in human mammary gland.

A murine monoclonal antibody (MAb) CIBr17, raised against the human breast carcinoma cell line PMC42, reacts specifically with myoepithelial cells in normal human breast. This IgGl antibody recognizes a approximately 110kDa glycoprotein that is expressed on the cell surface and junctional membranes of PMC42 monolayer cultures. The CIBr17 antigen is present in two major glycosylated forms with approximate pls of 5.2 and 5.5 respectively in PMC42 cells. The tissue specificity of CIBr17 was assessed on frozen sections of PLP-fixed tissues by means of a 4-layer immunoperoxidase technique. CIBr17 has reacted with a variety of epithelium-derived tissues and some smooth muscle cells. Within many epithelial tissues, CIBr17 has demonstrated specific staining of particular epithelial cell types. Within normal breast and most benign breast lesions, antibody CIBr17 stained only myoepithelial cells. No staining of luminal epithelium, basement membranes or stromal elements was observed. In sclerosing adenosis, CIBr17 stained areas of pronounced myoepithelial differentiation, while in duct epitheliosis variable staining of proliferating cells was observed. In breast carcinomas, CIBr17 demonstrated variable antigen expression. In most tumors, CIBr17 either did not stain any tumor cells or stained only a small number of tumor cells spread randomly throughout the tumor. In several ductal carcinomas, however, CIBr17 stained the majority of tumor cells.

Antibodies, Monoclonal↗
PubMed1986

Development of monoclonal antibodies to the human breast carcinoma cell line PMC42.

In an attempt to identify antigens expressed during breast differentiation, three murine monoclonal antibodies, CIBr2, CIBr7, and CIBr18, were produced against the human pleomorphic breast carcinoma cell line PMC42. All three monoclonal antibodies reacted with previously undescribed antigenic determinants on the PMC42 cell line. Antibody CIBr18 reacted only with the immunizing cell line PMC42, whereas antibodies CIBr2 and CIBr7 showed minimal reactivity toward a panel of 34 human leukemia- and solid tumor-derived cell lines. The antigenic determinants detected by the three antibodies were distinct, and each showed variable expression in PMC42 monolayer and organoid cultures. The heterogeneity of staining seen on PMC42 cultures may reflect the fact that this cell line contains up to eight morphologically distinct cell types. Antigen expression correlated with cell type in some instances, whereas in other instances phenotypic subdivision within a cell type was apparent. Antigens recognized by antibodies CIBr7 and CIBr18 were characterized biochemically. In Western blotting, antibody CIBr7 identified a single band of an apparent molecular weight of 38,000 within PMC42 cell lysates. Sodium dodecyl sulfate-polyacrylamide gel analysis of polypeptides immunoprecipitated by antibody CIBr18 from [35S]methionine-labeled PMC42 cell lysates identified two glycoproteins of apparent molecular weights of 115,000 and 120,000, respectively. No biochemical data for the CIBr2 antigen are yet available. All three antigens were detected in human mammary epithelium and some non-breast tissues. The expression of these antigens in normal and neoplastic mammary epithelia is discussed in terms of antigen heterogeneity and changes in antigen expression upon conversion to the malignant state.

Adult↗
PubMed1979

Assessment of the postoperative course of excised brain abscess by computerized tomography.

We present two patients with brain abscess who underwent complete excision with a satisfactory clinical outcome although serial computerized tomography (CT) Scans in the early postoperative period seemed to indicate a large residual abscess in each case. We recommend treatment based on the clinical course rather than the CT scan appearance, indicate that earlier reports on this topic may be misleading, and suggest an explanation for these findings.

Brain Abscess↗
PubMed1978

Cholecystosonography for the diagnosis of cholecystolithiasis.

The gallbladder can be visualized by ultrasound (cholecystosonography) and gallstones seen as echo producing densities. Under cholecystosonographic observation the gallbladder can be demonstrated to contract following stimulation by cholecystokinin. This establishes patency of the cystic duct and excludes a diagnosis of acute obstructive cholecystopathy. The gallbladder has been identified in 84 of 86 patients. Stones have been identified sonographically in 64% of 42 patients with proven gallstones (75% of the last 20 cases). The gallbladder contracted following stimulation in 18 of 20 cases with a patent cystic duct. Cholecystosonography is simple, safe and economical. Cholecystonography with cholecystokinin stimulation is the first diagnostic study to be performed when cholecystolithiasis is suspected and the following circumstances exists: a) an acute right upper quadrant (RUQ) syndrome consistant with acute obstructive cholecystopathy. b) cholestasis or hepatic dysfunction. c) a history of allergy to contrast media. Cholecystosonography may detect gallstones in a gallbladder visualized by oral cholangiography when stones are of the same density as the contrast media.

Cholangiography↗
PubMed1978

Significance of biparietal diameter differences between twins.

Twins of dissimilar size have increased risks both at delivery and in the neonatal period. When dissimilar growth is severe, it should be reflected in birthweight and biparietal diameter (BPD) growth. Sonograms were done on 74 of 106 sets of twins delivered from July 1, 1973, to June 30, 1977. Excluding prematurity and birth trauma, the difference in BPD between twins with normal outcomes in the last scan prior to delivery was 1.32 +/- 0.20 mm (mean +/- SE) and the difference in birthweight was 250.3 +/- 31.4 g (mean +/- SE). In 7 sets of twins with poor outcomes (intrauterine fetal demise or severe intrauterine growth retardation) without central nervous system anomalies the difference in BPD between twins in the last scan, while both fetuses were alive, was 6.86 +/- 1.06 mm (mean +/- SE) and the difference in birthweight was 604.3 +/- 217.2 g (mean +/- SE). Both the BPDs and birthweights are significantly different at the P less than 0.01 level. Large differences in BPD between twins may possibly indicate compromise of one twin.

Female↗