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Biomedical subjects

L F Brown

Publications and source records attributed to L F Brown.

At least 109 records · Page 6Linked to original sources
PubMed1989

Leaky vessels, fibrin deposition, and fibrosis: a sequence of events common to solid tumors and to many other types of disease.

Solid tumors must induce new blood vessels if they are to grow beyond minimal size. As an initial step in this process, tumors secrete a vascular permeability factor that renders the local microvasculature hyperpermeable to fibrinogen and to other plasma proteins. Extravasated fibrinogen is rapidly clotted to crosslinked fibrin gel. Over time, this gel is invaded by macrophages, fibroblasts, and endothelial cells and undergoes "organization," such that it is replaced by vascularized granulation tissue and finally by mature connective tissue. This sequence of events is not unique to tumors but occurs in wound-healing and in a wide variety of other disease processes, including some that prominently affect the lung.

Animals↗
PubMed1989

The theory and design of piezoelectric/pyroelectric polymer film sensors for biomedical engineering applications.

The unique properties of piezoelectric/pyroelectric polymers offer many new opportunities for biomedical engineering sensor applications. Since their discovery nearly 20 years ago, the polymer films have been used for many novel switching and sensor applications. Despite the prodigious exposure from many recent publications describing piezo film applications, methods of sensor fabrication and circuit interfacing still elude most engineers. This paper is presented as a tutorial guide to applying piezo polymers to biomedical engineering applications. A review of the fundamentals of piezoelectricity/pyroelectricity in piezo polymers is first presented. Their material properties are contrasted with piezoelectric ceramic materials. Some advantages and disadvantages of the films for biomedical sensors are discussed. Specific details on the fabrication of piezo film sensors are presented. Methods are described for forming, cutting, and mounting film sensors, and making lead connections. A brief discussion of equivalent circuit models for the design and simulation of piezoelectric/pyroelectric sensors is included, as well as common circuit interface techniques. Finally, several sources are recommended for further information on a variety of biomedical sensor applications.

Biomedical Engineering↗
PubMed1988

Fibrinogen influx and accumulation of cross-linked fibrin in mouse carcinomas.

125I-radiolabeled guinea pig fibrinogen was used to measure the influx (20 min) and accumulation (18 h) of fibrinogen/fibrin in three transplantable carcinomas (Lewis lung, TA3/St mammary, and MOT ovarian) growing in the subcutaneous space of syngeneic mice. Fibrinogen influx and, to an even greater extent, fibrin accumulation were substantially increased in all three tumors, as compared with normal control tissues. A significantly larger fraction of tumor-associated than control tissue radioactivity was insoluble in 3 M urea, a property of cross-linked fibrin. Positive identification of cross-linked fibrin was made by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography of tumor extracts. Tumor fibrin deposits were localized by immunoperoxidase staining of tissue sections. Fibrin accumulation was also significantly increased in premalignant hyperplastic alveolar nodules that had been transplanted to cleared mammary fat pads, as compared with normal mammary tissue, and was further increased in primary mammary carcinomas that arose from hyperplastic alveolar nodules. These findings generalize to the mouse the principles that tumor vessels are hyperpermeable to plasma proteins and that fibrin accumulates in transplantable and primary tumors. Further, they demonstrate that tumor fibrin is cross-linked and therefore analogous to the fibrin deposited in thrombi, wounds, and cellular immunity.

Animals↗
PubMed1988

Fibrinogen influx and accumulation of cross-linked fibrin in healing wounds and in tumor stroma.

Fibrinogen enters wounds and solid tumors, where it is clotted to fibrin that may subsequently be replaced by collagenous stroma. If, as has been suggested, the pathogenesis of wound healing and tumor stroma generation is similar and dependent on fibrin deposition, then the types and amounts of fibrin deposited in wounds and tumors might also be expected to be similar. To test this hypothesis, the authors injected homologous tracer fibrinogen (125I-GPF) intravenously into guinea pigs and measured its influx and accumulation in skin wounds and syngeneic carcinomas. In support of their hypothesis, the urea-insoluble product deposited in both wounds and tumors was identified as cross-linked fibrin by gel electrophoresis. Accumulation of both total and urea-insoluble 125I-GPF was quantitatively similar in wounds and tumors. However, influx and initial clotting of 125I-GPF in tumors exceeded that in wounds; given equivalent accumulation, these data suggest that fibrin turnover is more rapid in tumors than in wounds. Fibrinogen influx and fibrin accumulation declined toward normal a few days after wounding but remained consistently elevated in tumors. Thus, the magnitude and the persistence of microvascular hyperpermeability, as well as fibrin turnover, are major points of difference that distinguish tumors from healing wounds.

Animals↗
PubMed1987

Fibrin containing gels induce angiogenesis. Implications for tumor stroma generation and wound healing.

Fibrin deposition is a consistent early event in solid tumors and healing wounds and precedes new blood vessel ingrowth in both. We now demonstrate that fibrin gels of themselves induce an angiogenic response in the absence of tumor cells or platelets. Angiogenesis was enhanced when certain chemoattractants or mitogens were included in the fibrin gel. Newly devised, inert plastic chambers with one porous surface were filled with varying contents and were implanted in the subcutaneous space of guinea pigs. Chambers filled with cross-linked homologous fibrin or plasma induced an angiogenic response within 4 days. Vessels entered chambers through the surface pores and flared out radially; angiogenesis was quantitated by point counting. Vessels were functional and matured along a gradient that proceeded from distal (least mature) to proximal. The intensity of the angiogenic response was enhanced when zymosan activated serum, an N-formylmethionine tripeptide, or platelet-derived growth factor was included in the fibrin matrix. Prior aldehyde fixation or boiling of fibrin-filled chambers inhibited angiogenesis, as did high concentrations of hyaluronic acid. Chambers filled with type I collagen or agarose did not induce new blood vessel formation, but addition of collagen did not reduce fibrin's capacity to initiate angiogenesis. The novel assay introduced here offers several advantages that should facilitate the study of angiogenesis. These include reproducibility, low background, objective and quantitative scoring, and the capacity to evaluate native molecules in animals of several species. Taken together, our findings strongly implicate fibrin or related proteins in the pathogenesis of angiogenesis and offer a new approach for elucidating the underlying molecular mechanisms.

Animals↗
PubMed1987

Fibrin deposition in autochthonous Syrian hamster pancreatic adenocarcinomas induced by the chemical carcinogen N-nitroso-bis(2-oxopropyl)amine.

Immunofluorescence studies have demonstrated the presence of fib (a group of fibrinogen- and fibrin-related proteins that react with antibodies raised against fibrinogen) in the stroma of several transplantable animal and autochthonous human tumors. Acceptance of these reports was tempered by the possibility of artifactual clotting and fibrinolysis associated with tumor removal or tumor transplantation and by the relatively poor histology inevitable when immunofluorescence is performed on frozen tissue sections. An immunoperoxidase study therefore was undertaken of the ductal pancreatic carcinomas induced in female LGV Syrian hamsters by N-nitroso-bis(2-oxopropyl)amine [(BOP) CAS: 60599-38-4]. Artifactual clotting and fibrinolysis associated with tumor removal were avoided by systemic anticoagulation and antifibrinolysis. Fibronectin and residual fib were prominent components of tumor stroma. Prominent fib deposits also were found in a new location: the basement membrane zones of atypical pancreatic ducts and invasive carcinomas. In contrast, fib deposits were never found in the basement membranes of blood vessels, nerves, or pancreatic acini of BOP-treated or normal animals, or in the ductal basement membranes in the normal pancreas. Ducts with marked atypicality and invasive pancreatic carcinomas frequently exhibited discontinuous basement membrane staining for fib, which often paralleled loss of staining for the integral basement membrane proteins--type IV collagen and laminin. Loss of acquired fib basement membrane staining with malignant disease progression may serve as a new marker for local tumor invasion.

Adenocarcinoma↗
PubMed1984

Intraepithelial eosinophils in endoscopic biopsies of adults with reflux esophagitis.

A consecutive series of 50 adult patients was reviewed to evaluate the utility of endoscopic grasp biopsies of the esophagus in the diagnosis of reflux esophagitis. Endoscopic and histologic features were independently recorded and correlated. Measurements of basal zone thickness, papillary height, and vascular dilatation were possible in only 14% of the cases because of limited specimen orientation. However, 62% of the patients had other histologic features of esophagitis, including intraepithelial eosinophils, intraepithelial neutrophils, and epithelial necrosis. Intraepithelial eosinophils were the most frequent abnormality; they were noted in 52% of the cases and correlated best with the gross endoscopic features. Eosinophils were easily identified even in the poorly oriented grasp biopsies and were the only histologic finding in seven patients (23% of the abnormal cases). Thus, we conclude that esophageal grasp biopsies taken at the time of endoscopy are of value in the assessment of patients with suspected reflux esophagitis, and intraepithelial eosinophils are the most common and useful histologic criterion. This feature was previously observed in children and occurs as well in adults with reflux esophagitis.

Adolescent↗
PubMed1980

Enzymic inhibition assay for methotrexate with a discrete analyzer, the ABA-100.

We adapted an inhibition assay for methotrexate, involving dihydrofolate reductase from bovine liver, for use with a discrete analyzer (the ABA-100). The analyzer was used both for dilution and a 5-min pre-incubation of the sample with NADPH--enzyme reagent, and for the assay itself. The standard curve was linear between 10 and 120 microgram/L. Without pre-incubation the standard curve was nonlinear. The presence of albumin in the NADPH--enzyme reagent enhanced both enzyme activity and stability. Within-run precision (CV) was 2.0% (n = 24), run-to-run precision 7.1% (n = 49). Results obtained on patients' samples (29 sera, 15 urines, 18 cerebrospinal fluids) by the present method and a radioimmunoassay method did not differ statistically (p greater than 0.05) when the paired data were analyzed by use of the sign test and Wilcoxon's ranked sign test.

Albumins↗
PubMed1978

Effects of bilirubin on detection of hydrogen peroxide by use of peroxidase.

Bilitubin interferes with the quantitation of hydrogen peroxide in reagent systems in which peroxidase is used. Difference spectra suggest that this interference is a combination of chemical and spectral effects. The data presented are most consistent with the following interpretation: (a) bilirubin destroys part of the reactive intermediate formed in the peroxidase reaction and thus decreases the amount of chromophore formed and (b) the spectra for bilirubin and the chromaphore overlap, which also affects the results. The relevance of these results to reagent design and laboratory quality control are discussed.

Bilirubin↗