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R J Coffey

Publications and source records attributed to R J Coffey.

18 recordsLinked to original sources
PubMed1992

Amphiregulin messenger RNA is elevated in psoriatic epidermis and gastrointestinal carcinomas.

Amphiregulin (AR) is a heparin-regulated, epidermal growth factor-like growth factor capable of stimulating the proliferation of non-tumorigenic cells while inhibiting cell proliferation in some human tumor cell lines in vitro. In the present study, we have investigated AR mRNA expression in normal, hyperproliferative, and neoplastic human epithelium. Our results demonstrate that, compared with the adjacent uninvolved epithelium, AR mRNA expression is markedly elevated in epidermal biopsies derived from three human psoriatic lesions as well as in biopsies derived from five human colon carcinomas and three human stomach carcinomas. Moreover, analysis of a colon carcinoma by in situ hybridization revealed that AR mRNA is localized to the epithelium.

Amphiregulin↗
PubMed1992

Transforming growth factors and related peptides in gastrointestinal neoplasia.

Transforming growth factor alpha and beta 1 (TGF alpha and TGF beta 1) are representative members of two distinct and expanding families of polypeptide growth factors. TGF alpha is an epithelial cell mitogen, whereas TGF beta 1 inhibits epithelial cell growth; the role of these factors in contributing to the transformed phenotype is uncertain. Steady state mRNA expression for these growth factors and their receptors in a panel of human colon cancers and adjacent normal mucosa is presented. Based in part on results from transgenic mice in which TGF alpha is selectively overproduced in the mammary gland, a possible role for TGF alpha as a tumor promoter in the process of transformation is discussed.

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

Integrating total quality management and quality assurance at the University of Michigan Medical Center.

Staff members from the University of Michigan Medical Center (UMMC), 1990 winner of the Commitment to Quality Award, describe how they integrated its quality assurance (QA) program into its total quality management (TQM) strategy. The QA program has changed in recent years to establish quality as a central priority, to educate staff in the importance of quality, and to disseminate information more effectively. While these initiatives were underway, UMMC began to embrace TQM as an operating philosophy. Recognizing both the strengths and weaknesses of QA, staff members have worked to apply TQM principles (eg, focus on processes) to QA while using the ongoing monitoring of QA to identify opportunities for improvement within the organization's TQM management system.

Forms and Records Control↗
PubMed1992

Transforming growth factor alpha protection against drug-induced injury to the rat gastric mucosa in vivo.

This study was designed to determine whether transforming growth factor alpha (TGF alpha) protects rat gastric mucosa against ethanol- and aspirin-induced injury. Systemic administration of TGF alpha dose-dependently decreased 100% ethanol-induced gastric mucosal injury; a dose of 50 micrograms/kg delivered intraperitoneally 15 min before ethanol decreased macroscopic mucosal injury by > 90%. At the microscopic level, TGF alpha prevented deep gastric necrotic lesions and reduced disruption of surface epithelium. Pretreatment with orogastric TGF alpha (200 micrograms/kg) only partially (40%) decreased macroscopic ethanol damage. Intraperitoneal administration of TGF alpha at a dose of 10 micrograms/kg, which does not significantly inhibit gastric acid secretion, decreased aspirin-induced macroscopic damage by > 80%. TGF alpha protection does not seem to be mediated by prostaglandin, glutathione, or ornithine decarboxylase-related events, as evidenced by lack of influence of the inhibition of their production. Pretreatment with the sulfhydryl blocking agent N-ethylmaleimide partially abolished (40%) the protective effect of TGF alpha. In addition, systemic administration of TGF alpha resulted in a two-fold increase in tyrosine phosphorylation of phospholipase C-gamma 1 and in a time- and dose-dependent increase in levels of immunoreactive insoluble gastric mucin; these events occurred in a time frame consistent with their participation in the protective effect of TGF alpha.

Animals↗
PubMed1992

Distinctive patterns of hyperplasia in transgenic mice with mouse mammary tumor virus transforming growth factor-alpha. Characterization of mammary gland and skin proliferations.

Eight lines of transgenic mice expressing a mouse mammary tumor virus (MMTV) human transforming growth factor-alpha (TGF alpha) fusion gene were established. Three lines with distinctive phenotypes are presented. All have proliferative changes of the mammary gland. One line has sebaceous gland hyperplasia of the skin. Five histologic patterns of mammary gland hyperplasia based on two of these lines were identified: cystic hyperplasia, solid hyperplasia, dysplasia, adenoma, and adenocarcinoma. Human TGF alpha mRNA and protein were produced in all patterns but appeared reduced in solid hyperplasia, dysplasia, and adenocarcinoma. TGF alpha immunoreactivity in the mammary tissue, cystic fluid, and serum did not show significant differences; hyperplasia developed in 65% of multiparous mice and 45% of virgin mice by 12 months of age. Adenocarcinoma developed in 40% of multiparous mice and 30% of virgin mice by 16 months of age. These transgenic lines may provide useful models of mammary and sebaceous gland hyperplasia analogous to human disease.

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↗
PubMed1992

Gamma knife surgery for sellar and suprasellar tumors.

Recent advances in neuroimaging, coupled with stereotactic delivery of ionizing radiation, permit precise, single-treatment irradiation of various intracranial tumors. This article describes the authors' experience with the 201-source 60Co gamma knife. Initial results indicate a potential therapeutic role for radiosurgery in controlling tumor growth and hormone hypersecretion in most patients. The authors believe that radiosurgery should be considered for small pituitary adenomas when prior microsurgery has failed to control tumor growth. Radiosurgery is a primary treatment alternative for patients who are elderly, medically infirm, or refuse microsurgical removal. Further follow-up is necessary to evaluate the long-term tumor control rate, hormonal effects, and tolerance of surrounding critical structures to stereotactic radiosurgery.

Adenoma↗
PubMed1992

The role of radiosurgery in the treatment of malignant brain tumors.

Most studies describing the results of radiosurgery have concentrated on the definitive treatment of small, histologically benign lesions such as vascular malformations, acoustic neurinomas, and pituitary adenomas. More recently, the role of radiosurgery using the gamma knife or LINAC-based systems to treat malignant neoplasms has become better defined. Most solitary metastases, ependymomas, well-circumscribed (on imaging studies) AAs, and a few glioblastomas (and other tumors) have responded dramatically to radiosurgery. Provided that the tumor volume was small (less than or equal to 14 cm3; 30-mm diameter), radiosurgery safely has caused tumor disappearance, shrinkage, or stabilization, regardless of prior surgery, conventional fractionated irradiation, or tumor radioresistance. For patients with recurrent or persistent, small, malignant intracranial tumors, radiosurgical treatment has obviated the need for prolonged hospitalization and has eliminated the risks associated with general anesthesia and open craniotomy.

Adolescent↗
PubMed1991

Elevated content of the tyrosine kinase substrate phospholipase C-gamma 1 in primary human breast carcinomas.

Phospholipase C-gamma 1 (PLC-gamma 1) is a substrate for several receptor tyrosine kinases and its catalytic activity is increased by tyrosine phosphorylation. However, the biological significance of this molecule in normal or malignant human epithelial cell proliferation is unknown. We determined the relative content of PLC-gamma 1 in primary human mammary carcinomas and in nonmalignant mammary tissues. By Western blot and immunohistochemistry, considerably higher levels of PLC-gamma 1 protein were detectable in the majority of carcinomas and in one of two benign fibroadenomas compared to normal breast tissues. In 18 of 21 carcinomas that contained high levels of PLC-gamma 1, the presence of phosphotyrosine on PLC-gamma 1 could also be detected. All carcinomas in which tyrosine phosphorylated PLC-gamma 1 was present also expressed detectable levels of the epidermal growth factor receptor or erbB-2, two tyrosine kinases known to phosphorylate this enzyme. Thus, a high percentage of mammary carcinomas concomitantly display increased levels of receptor tyrosine kinases and a direct tyrosine phosphorylation substrate, thereby potentially amplifying two successive steps in a signal transduction pathway.

Amino Acid Sequence↗
PubMed1991

Radiosurgery for solitary brain metastases using the cobalt-60 gamma unit: methods and results in 24 patients.

To define the role of stereotactic radiosurgery in the treatment of metastatic brain tumors we treated 24 consecutive patients (20 men, 4 women) with the 201-source 60Co gamma unit between May 1988 and March 1990. The primary tumors included malignant melanoma (n = 10), non-small cell lung carcinoma (n = 6), renal cell carcinoma (n = 3), colorectal carcinoma (n = 1), oropharyngeal carcinoma (n = 1), and adenocarcinoma of unknown origin (n = 3). All tumors were less than or equal to 3.0 cm in greatest diameter. Twenty patients received a planned combination of 30-40 Gy whole brain fractionated irradiation and a radiosurgical "boost" of 16-20 Gy to the tumor margins; one patient refused conventional fractionated irradiation. Three patients with recurrent, persistent, or new non-small cell lung carcinomas had radiosurgical treatment 12-20 months after receiving 30-42.5 Gy whole-brain external beam irradiation. Stereotactic computed tomographic imaging was used for target coordinate determination and imaging-integrated dose planning. All tumors were enclosed by the 50-90% isodose shell using one (n = 22), two (n = 1), or three (n = 1) irradiation isocenters. During this 23-month period (median follow-up of 7 months) no patient died from progression of a radiosurgically-treated brain metastasis. Ten patients died of systemic disease (n = 8) or remote central nervous system metastasis (n = 2) between 1 week and 10 months after radiosurgery. One patient had tumor progression and underwent craniotomy and tumor excision 5 months after radiosurgery. To date, median survival after radiosurgery has been 10 months; 1-year survival was 33.3%. Stereotactic radiosurgery eliminated the surgical and anesthetic risks associated with craniotomy and resection of solitary brain metastases. Radiosurgery also effectively controlled the growth of tumors considered "resistant" to conventional irradiation.

Adult↗
PubMed1990

Expression and regulation of mRNA coding for acidic and basic fibroblast growth factor and transforming growth factor alpha in cells derived from human skin.

We investigated the regulation of mRNAs coding for acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), and transforming growth factor-alpha (TGF alpha) in cultures of human neonatal foreskin fibroblasts, keratinocytes, and melanocytes. Each cell type was propagated in an optimized serum-free medium. In rapidly growing fibroblasts, the addition of fetal bovine serum caused a modest induction of aFGF message within 2 h in conjunction with a concomitant elevation of bFGF transcripts. In these same cells, TGF alpha mRNA could not be detected in any experimental condition. In contrast, keratinocytes rapidly growing in the presence of epidermal growth factor (EGF) contained transcripts for TGF alpha that increased substantially when these cells were treated with serum. This observation suggests that factors present in serum can elevate the levels of TGF alpha mRNA beyond the levels already present in keratinocyte cultures growing in the presence of EGF. These same keratinocyte cultures had low to undetectable levels of bFGF or aFGF message, and the levels of these mRNAs were not affected by serum treatment. Treatment of keratinocytes proliferating in the presence of EGF with TGF beta for 48 h caused expression of bFGF mRNA in four of six independent cell strains. TGF beta-enhanced expression of bFGF mRNA occurred as early as 12-24 h after TGF beta exposure. TGF beta did not enhance the expression of mRNA for aFGF or TGF alpha in keratinocytes. Melanocytes failed to express detectable levels of mRNA coding for any of these growth factors in the presence of absence of TGF beta or serum.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood↗
PubMed1979

Propranolol therapy in thyrotoxicosis. A review of 84 patients undergoing surgery.

The effect of propranolol on the surgical course of 84 thyrotoxic patients undergoing partial thyroidectomy or extrathyroidal surgery was evaluated. Seventy-two patients (group 1) underwent surgery with propranolol as their sole preparatory medication, whereas in 12 (group 2) surgery was carried out after a rather prolonged period of thionamide preparation with the addition of propranolol preoperatively as an adjunctive therapeutic agent. Preoperative pulse rate and systolic blood pressure levels fell in both groups, and the clinical features of thyrotoxicosis were rapidly ameliorated with an average dose of propranolol of 330 mg (range 40 to 1,280 mg) daily. Maximal clinical response occurred within 48 to 72 hours of starting propranolol therapy. In 14 patients in group 1, paired serum calcium levels were reduced by the administration of propranolol preoperatively; serum thyroxine levels were unchanged. Serum thyroxine decay, evaluated postoperatively in the patients in group 1, was decreased. The half life of thyroxine was inversely related to the initial thyroxine levels. Analysis of these data indicates that the administration of propranolol alone provides rapid, safe and effective preparation of thyrotoxic patients for emergency or for elective thyroidal or extrathyroidal surgical procedures.

Adolescent↗
PubMed1977

The surgical treatment of primary hyperparathyroidism: a 20 year experience.

Analysis of a series of 200 surgically treated cases of primary hyperparathyroidism was carried out in an effort to identify not only the changing clinical patterns and improved diagnostic methods but also to assess the long term results of our conventional operative methods in light of recent reports of a high incidence of diffuse hyperplasia and a high recurrence rate when surgery is restricted to removal of the adenoma. As reported by others the "chemical diagnosis" of primary hyperparathyroidism, the clinical setting in which unsuspected hypercalcemia is demonstrated on routine blood analysis, accounts for the majority of diagnoses today. Impending or actual "parathyroid crisis" has been observed with alarming frequency. The use of the thiazide challenge test provides a useful diagnostic aid in many instances. The incidence of diffuse hyperplasia was 6% in this series while an adenoma was present in 88%. No instance of recurrence was observed in either the cases of adenomas or diffuse hyperplasia.

Adenoma↗
PubMedDate not supplied

Roles for transforming growth factor-alpha in gastric physiology and pathophysiology.

Transforming growth factor alpha (TGF alpha) is a 5.6 kd single-chain polypeptide that acts through binding to the epidermal growth factor receptor (EGFR). TGF alpha is produced in a wide range of normal as well as embryonic and neoplastic cells and tissues. TGF alpha and EGFR, but not EGF, are expressed in normal gastric mucosa. We have identified the following biological roles for TGF alpha in the stomach, using a variety of primate and rodent models: inhibition of acid secretion; stimulation of mucous cell growth; protection against ethanol- and aspirin-induced injury. This last effect is associated with a time- and dose-dependent increase in levels of insoluble gastric mucin. Based on these known biological actions of TGF alpha, we have examined TGF alpha production in Ménétrier's disease, a disorder characterized by foveolar hyperplasia, hypochlorhydria, and increased gastric mucin content. In four patients with Ménétrier's disease, there was enhanced TGF alpha immunostaining throughout the gastric mucosa. Furthermore, metallothionein (MT)-TGF alpha transgenic mice which overproduce TGF alpha in the stomach exhibit histopathological and biochemical features characteristic of and consistent with the diagnosis of Ménétrier's disease. Thus locally produced TGF alpha may mediate a number of biological processes in the stomach, and its altered production may participate in the pathogenesis of selected pathological states.

Amino Acid Sequence↗