Telephone use and costs in a group subspecialty practice.
Explore the source record for details and available documents.
Costs and Cost Analysis↗
Biomedical subjects
J M Alcorn
Publications and source records attributed to J M Alcorn.
Stimulation of the collagen alpha 1 (I) endogenous gene and transgene in carbon tetrachloride-induced hepatic fibrosis.
Cirrhosis is characterized by a marked increase in the deposition of type I collagen and in the expression of the type I collagen genes alpha 1(I) and alpha 2(I). Although alpha 1(I) gene regulation has been extensively studied in cultured cells, these results may not be applicable to hepatic fibrogenesis in vivo. Therefore the regulation of the alpha 1(I) endogenous gene and an alpha 1(I) transgene was studied in a transgenic mouse model that has a single copy of a human alpha 1(I) gene segment containing the structural gene and 1.6 Kb of 5' DNA and 20 Kb of 3' DNA. To initiate hepatic fibrogenesis, we treated mice with the hepatotoxin carbon tetrachloride, either in a single dose or in biweekly doses for a period of 3 to 8 wk. Subsequently, hepatic alpha 1(I) messenger RNA levels were determined by a species-specific RNase protection assay. Carbon tetrachloride injections coordinately increased the messenger RNA levels of the alpha 1(I) endogenous gene and the transgene, both immediately and after 8 wk. These experiments demonstrate that this alpha 1(I) transgene fragment contains information sufficient for appropriate basal and carbon tetrachloride-stimulated hepatic expression. They further demonstrate that sufficient homology exists between the human and mouse regulatory elements for the recognition of human cis-acting elements by mouse trans-acting factors. Thus transgenic mice provide a unique model in which to characterize the collagen alpha 1(I) regulatory elements that are required in vivo for pathophysiological responses.
Animals↗
The acute-phase response protects mice from D-galactosamine sensitization to endotoxin and tumor necrosis factor-alpha.
D-Galactosamine is an hepatocyte-specific inhibitor of RNA synthesis. It has been used to sensitize animals both to the lethal effects of bacterial endotoxin (lipopolysaccharide) and to a principal lipopolysaccharide-induced mediator of shock, tumor necrosis factor-alpha. The mechanism by which this sensitization occurs is unknown. Because lipopolysaccharide, acting through a network of cytokines, provokes the transcription of a number of hepatic acute-phase proteins, we postulated that the lipopolysaccharide-sensitizing effect of D-galactosamine could be caused by its inhibition of acute-phase product transcription. We confirmed that the acute-phase response to lipopolysaccharide was attenuated by simultaneous administration of D-galactosamine. However, when the acute-phase response was induced by subcutaneous turpentine 24 hr before D-galactosamine administration, the effect of D-galactosamine on circulating acute-phase reactants was negligible. Furthermore, induction of an a priori acute-phase response protected mice from both D-galactosamine/lipopolysaccharide and D-galactosamine/tumor necrosis factor-alpha-induced death. The turpentine-induced acute-phase response did not decrease endogenous tumor necrosis factor-alpha production after lipopolysaccharide, nor did it affect the clearance of larger doses of injected tumor necrosis factor-alpha. Thus we suggest that the acute-phase response protects against death in D-galactosamine-sensitized mice through an interaction with mediators of shock subsequent to tumor necrosis factor-alpha release.
Absorption↗
Beam-shaping device for long-film angiography.
Uniform radiologic exposure from the pelvis to the ankles is often difficult to achieve when long films (51-inch) are used for femoral angiography. A unique device developed to shape the x-ray beam accomplishes this task by using a movable shutter to obscure a portion of the x-ray beam. A microprocessor-controlled stepper motor modulates the amount of beam cutoff by regulating the movement of the shutter from the foot end of the film. The goal is to match exposure factors to the patient's body shape. This beam-shaping device has been evaluated and tested in examinations of 500 patients over the past year. A substantial improvement in image quality over that achieved with earlier systems of graduated screens and multiple wedge filters was seen in all cases. The system is esy to use, flexible, and especially valuable in imaging obese patients or those who have legs disproportionately smaller than their pelvis or abdomen.
Abdomen↗
Aortic dissection and hepatic ischemia.
Explore the source record for details and available documents.
Aged↗
Colorectal cancer prevention: a primary care approach.
Colorectal cancer is a prevalent, deadly disease of the elderly. It is typically asymptomatic until advanced, and then responds poorly to treatment. Asymptomatic precursor lesions may afford both an opportunity to study carcinogenesis and to intervene and prevent cancer deaths. Prevention strategies focus on either primary prevention of polyps and cancers (mainly through dietary measures) and secondary detection and removal of precursor polyps and early cancers. Despite shortcomings in both strategies, dietary recommendations and screening tests for select patients may play an important role in reducing mortality.
Aged↗
Left ventricular diastolic dysfunction presenting as ascites: the importance of clinically assessing central venous pressure.
A 66-year-old man without history of heart disease or symptoms of left ventricular (LV) failure was admitted with transudative ascites. Echocardiography showed no valvular or pericardial disease and normal LV function. Gated pool scintigraphy confirmed normal LV systolic function but demonstrated severe right ventricular systolic dysfunction. Catheterization revealed left ventricular diastolic dysfunction as the cause of right-sided failure. The clinician evaluating transudative ascites cannot exclude LV failure on the basis of noninvasive assessment of systolic function alone. Appreciation of an elevated central venous pressure remains the most important evidence of a cardiac source of ascites.
Aged↗
Biliary obstruction caused by epithelioid angiomatosis in a patient with AIDS.
Explore the source record for details and available documents.
Acquired Immunodeficiency Syndrome↗
Therapy for hepatic fibrosis.
Although there is no established therapy for the fibrogenesis of hepatic cirrhosis, many potential therapies are now emerging. The requirements for the "perfect therapy" for hepatic fibrosis can be listed: (1) the pharmacologic agent should be active only in the liver; (2) its effect should be specific for collagen (or another critical extracellular matrix component); and (3) it should not be toxic. To date no agents fulfill these criteria. Of the agents we reviewed, only colchicine appears sufficiently safe for use outside of controlled clinical trials for cirrhotic patients whose underlying disease is not otherwise treatable. However, confirmation of the efficacy of colchicine in additional well-controlled clinical trials is still required. Agents such as collagen propeptides require extensive in vitro development, while trials in animal models are required for prolyl 4-hydroxylase inhibitors, proline analogues, and prostaglandins. For more developed agents, such as malotilate and gamma-interferon, there is now a need for well-designed long-term clinical trials.
Colchicine↗
Expression of collagen genes in the liver.
Hepatic production of type I collagen is markedly increased in liver cirrhosis. Previous studies using primary liver cell cultures have demonstrated that hepatocytes, lipocytes and endothelial cells are all capable of producing collagen. In this study in situ hybridization and hepatic cell sorting have been used to identify which cells are expressing the type I collagen gene, alpha 1(I), in normal rat liver. Northern blotting of mRNAs from purified hepatic cell populations demonstrated that both hepatocytes and several types of non-parenchymal cells express the collagen alpha 1(I) gene. Calculations based on cell numbers, yields of mRNA, and cellular mRNA concentration demonstrated that the majority of collagen alpha 1(I) mRNA originates from the hepatocytes in the normal liver. Localization of a collagen alpha 1(I) mRNA by in situ hybridization confirmed that both hepatocytes and non-parenchymal cells express this gene. Furthermore, collagen alpha 1(I) gene expression in hepatocytes was obtained by transfecting a reporter gene driven by the collagen alpha (I) 5' regulatory segment in primary liver cell cultures. Future experiments will further characterize the regulation of collagen alpha 1(I) gene expression in the liver.
Animals↗