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Biomedical subjects

Mary Richardson

Publications and source records attributed to Mary Richardson.

16 recordsLinked to original sources
PubMed2006

Relationships among tumor burden, tumor size, and the changing concentrations of fibrin degradation products and fibrinolytic factors in the pleural effusions of rabbits with VX2 lung tumors.

The VX2 tumor is derived from a papilloma virus-induced rabbit epithelial cell line. If VX2 tumor cells (trapped in a plasma clot) are introduced intravenously into NZW rabbits, the cells lodge in the lung capillary bed and produce tumors. Independently of the tumor burden (ie, the total tumor weight per rabbit), approximately 15% of rabbits with VX2 lung tumors accumulate an effusion in the interpleural space and this pleural effusion contains products of hemostasis. We hypothesized that these products were of intra-tumoral origin and that they changed in concentration as tumor burden increased. Interrelationships among lung-, tumor-weights, and pleural effusion volumes, and the concentrations of fibrinolytic factors, their catabolic products, and other proteins of pleural effusions were measured in rabbits with a wide range of tumor burdens. Positive correlations between tumor burden and total lung weight and between pleural effusion volume and net lung weight suggested that interstitial fluid from the stroma of tumors passed directly into the extravascular space of the lung(s) and into the interpleural space(s). Analyses of pleural effusions indicated that plasminogen-, alpha(2)-antiplasmin-, and plasminogen activator inhibitor-1-related proteins, urokinase-like- and tissue-plasminogen activator activities, and vascular endothelial growth factor increased in concentration up to a tumor burden of approximately 20-25 g. Plasmin activity and intact fibrinogen were absent. The concentration of fibrin(ogen) degradation products did not change significantly up to a tumor burden of approximately 25 g but increased substantially as tumor burdens exceeded 25 g. In conclusion, interstitial fluid from tumors enters the extravascular space of the host and may accumulate with fluid from non-tumor sources as a pleural effusion. The concentrations of fibrinolytic factors and their products in pleural effusions reflect the tumor burden of the rabbit. Conceivably, the components of a malignant effusion contain much information about the extent of tumor growth.

Animals↗
PubMed2006

Home Study Course: summer 2006.

OBJECTIVE: The Home Study Course is intended for the practicing colposcopist or practitioner who is seeking to develop or enhance his or her colposcopic skills. The goal of the course is to present colposcopic cases that are unusual or instructive in terms of appearance, presentation, or management, or that demonstrate new and important knowledge in the area of colposcopy or pathology. Participants may benefit from reading and studying the material or from testing their knowledge by answering the questions. ACCME ACCREDITATION: The American Society for Colposcopy and Cervical Pathology (ASCCP) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The American Society for Colposcopy and Cervical Pathology designates this educational activity for a maximum of 1 AMA PRA Categorys I Creditt. Physicians should only claim credit commensurate with the extent of their participation in the activity. ASCCP also designates their educational activity for 1 Category 1 credit hour of the ASCCP's Program for Continuing Professional Development. Credit is available for those who choose to apply. The Home Study Course is planned and produced in accordance with the ACCME's Essential Areas and Elements. DISCLOSURES: The clinical history and images in the Home Study Course may represent an actual case, but not always. To improve educational quality, some gross, cytological, or histological images may come from photographic libraries. Good teaching cases are often difficult to obtain, and we encourage our readers to submit cases with high-quality images to the Home Study Course editor or executive editor to consider for publication. Lastly, faculty must disclose any significant financial interest or relationship with proprietary entities that may have a direct relationship to the subject matter. For this course, the authors had no such relationship to report.

Adult↗
PubMed2006

Turnover and fate of fibrinogen and platelets at the rabbit aorta wall immediately after a balloon de-endothelializing injury in vivo.

A de-endothelializing injury to the artery wall in vivo results in a rapid procoagulant response at the surface of the exposed subendothelium. Activated tissue factor (TF)-bearing cells and hemostasis factors located at the site of injury respond by producing thrombin, and within minutes the principal thrombus-forming, blood-borne components (platelets, fibrinogen) accumulate at the site. To compare their behaviors, the rates of uptake and turnover of rabbit (51)Cr-platelets and rabbit (125)I-fibrinogen were quantified simultaneously during the initial 100-min interval after a balloon catheter injury to the rabbit aorta in vivo. Platelets ( approximately 70,000/mm(2)) and fibrin(ogen) ( approximately 2.8 pmol/cm(2)) saturated the ballooned aorta surface within five minutes after injury. Whereas the adherent platelet and fibrinogen concentrations remained steady at the aorta surface, fibrin(ogen)-related products continued to accumulate slowly in the tunica media (TM) for at least 100 minutes. A relatively small proportion (3.7%/min) of adhered platelets turned over at the ballooned aorta surface at 10 minutes, decreasing to 1.2%/min at 100 minutes. By contrast, a larger proportion of fibrin(ogen) ( approximately 20%/min) was turned over within the platelet layer at 10 minutes, decreasing to 6%/min at 100 minutes. As verified by immunostaining aorta sections and by protein analysis of TM extracts, the uptakes of platelets and fibrinogen at the site of injury contributed to an accumulation of products of platelet releasate and fibrin(ogen) degradation (FDPs) within the TM. These observations improve our understanding of the hemostatic processes and subsequent events that occur after an arterial injury in vivo.

Animals↗
PubMed2006

Steroid hormone receptor expression in nasopharyngeal angiofibromas. Consistent expression of estrogen receptor beta.

Nasopharyngeal angiofibroma is an uncommon tumor arising in adolescent males, suggesting that the tumor may be hormonally responsive. Previous studies have found androgen receptor (AR) expression but variable expression of estrogen receptor (ER). The recently described ss receptor for estrogen has not been analyzed in angiofibroma. We analyzed 13 cases of nasal angiofibroma by immunohistochemical analysis for the presence of ARs, progesterone receptors (PR), and ER-a and ER-ss. All 13 cases were positive for ER-ss, in stromal pericytic and endothelial cells, and 12 of 13 stained strongly. Five cases were positive for AR in stromal cells, most staining weakly, and with no staining in endothelial or pericytic cells. None of the cases displayed staining for ER-a or PR. The findings confirm that nasopharyngeal angiofibromas express ER and suggest that new modulators of ER-ss activity may provide an alternative therapy for these lesions.

Angiofibroma↗
PubMed2005

Inhibition by doxycycline of angiogenesis in the chicken chorioallantoic membrane (CAM).

Doxycycline, a tetracycline derivative, has many properties in addition to its antibiotic activity, including inhibition of matrix metalloproteinases (MMPs) and the ability to chelate divalent cations including Ca(2+). It has been shown to inhibit endothelial cell growth in vitro, and reduce the development of experimental tumours, especially bone metastasis in a model of breast cancer. We examined the effects of doxycycline on angiogenesis in the chicken chorioallantoic membrane (CAM) model, and showed that doxycycline will cause loss of the chorionic plexus in CAMs when applied at day 8 of incubation, and the duration of this inhibition was dose-dependent. Repeated doses prolonged the inhibition, but following removal of the doxycycline there was rapid recovery of the chorionic plexus. The effects of doxycycline are in part mimicked by the MMP inhibitor 1,10-phenanthroline, and more closely by the Ca(2+)-chelating agent EGTA. Doxycycline was equally effective in causing loss of the chorionic plexus by day 11 in CAMs, a time at which the blood vessels are established. Doxycycline has important potential as an antiangiogenic treatment. It is capable of inhibiting angiogenesis in an in vivo model, including the removal of comparatively mature endothelial cells. The response is sensitive to the dosing regimen and the effect is rapidly reversible.

Animals↗
PubMed2005

Early intervention in migraine with sumatriptan tablets 50 mg versus 100 mg: a pooled analysis of data from six clinical trials.

BACKGROUND: In clinical trials evaluating sumatriptan in the treatment of moderate or severe migraine pain, the 50- and 100-mg doses have been comparably effective and well tolerated. OBJECTIVE: To assess the dose-efficacy relationship of sumatriptan tablets given early for mild pain, data from 6 randomized, double-blind, placebo-controlled, early-intervention studies of sumatriptan tablets 50 mg and 100 mg (5 of which have been published) were pooled for analysis. These constitute all the studies conducted to date of sumatriptan tablets prospectively given early for mild pain. METHODS: The primary efficacy end point in all the studies was the proportion of patients reporting a pain-free result (ie, mild, moderate, or severe pain reduced to none) 2 hours postdose. Other efficacy end points included the proportion of patients who were migraine free (ie, no pain and no associated symptoms of nausea, vomiting, photophobia, or phonophobia) 2 hours postdose; the proportion reporting worsening of pain (ie, moderate or severe pain) 2 hours postdose; and the proportion with a sustained pain-free result (ie, pain free from 2-24 hours postdose with no use of a second dose of study medication or of rescue medication). Tolerability was assessed by evaluating the incidence of individual adverse events. The investigators assessed each adverse event's relationship to study medication. RESULTS: The number of patients in the intent-to-treat population was 2297 (771 sumatriptan 50 mg, 759 sumatriptan 100 mg, 767 placebo). Patients' mean age ranged from 39.4 to 39.8 years across groups, and most patients were female (90%-92%) and white (89%-90%). A pain-free result 2 hours post dose was reported by significantly more patients who took either dose of sumatriptan tablets compared with placebo and by significantly more patients who took the 100-mg dose compared with the 50-mg dose (50 mg, 49%; 100 mg, 58%; placebo, 24%; P < 0.001, both sumatriptan doses vs placebo, and 100 mg vs 50 mg). A similar pattern was observed for migraine-free results 2 hours postdose (50 mg, 42%; 100 mg, 47%; placebo, 20%; P < 0.05, both sumatriptan doses vs placebo, and 100 mg vs 50 mg), worsening of pain 2 hours postdose (50 mg, 26%; 100 mg, 21%; placebo, 46%; P < 0.05, both sumatriptan doses vs placebo, and 100 mg vs 50 mg), and sustained pain-free results from 2 through 24 hours postdose (50 mg, 30%; 100 mg, 35%; placebo, 12%; P < 0.05, both sumatriptan doses vs placebo, and 100 mg vs 50 mg). Both doses of sumatriptan were well tolerated, and no dose-related trends in the incidence of individual drug-related adverse events were observed. CONCLUSIONS: In this analysis of pooled data from 6 clinical trials, sumatriptan tablets 50 mg and 100 mg administered early in a migraine attack while the pain was mild were well tolerated and significantly more effective than placebo. The 100-mg dose of sumatriptan was significantly more effective than the 50-mg dose.

Adult↗
PubMed2004

Fibrinogen catabolism within the procoagulant VX-2 tumor of rabbit lung in vivo: Effluxing fibrin(ogen) fragments contain antiangiogenic activity.

Many types of solid tumors are known to be procoagulant environments. This is partly because a hyperpermeable vascular system within the tumor allows plasma hemostatic factors to accumulate in relatively high concentrations in the stroma, and many solid-tumor cells express tissue factor or a procoagulant factor. These circumstances appear to exist in the VX-2 lung tumor of the New Zealand White (NZW) rabbit, and they sustain a measurable turnover of stromal deposits of fibrin(ogen). We have measured the turnover of fibrinogen within tumors of the VX-2 tumor-burdened rabbit and analysed the catabolic products of fibrin(ogen) and the status of fibrinolysis in tumor-derived interpleural effusate. Using intravenously injected (125)I-labeled rabbit fibrinogen as a marker, we found that fibrinogen (approximate blood concentration 1740 microg/mL) passed from blood to VX-2 tumor stroma, saturating the tumor at a concentration of approximately 348 microg fibrinogen/g in approximately 12 hours. We measured fibrin(ogen) fragments, at a concentration of approximately 292 microg/mL, in interpleural effusates that we recovered from 13% of the VX-2-burdened rabbits. Unreduced fibrin(ogen) fragments consisted of 4 major components with a relative molecular mass of approximately 250,000 (assumed to be fragment X; approximately 9% of total fragments from densitometry of immunoblots), 200,000 (d-dimer; 41%), 110,000 (fragment D; 49%), and 50,000 to 55,000 (fragment E; 1%-2%) kD. Total fibrin(ogen) fragments immunopurified from effusates exhibited an antiangiogenic effect when subjected to a chick embryo chorioallantoic membrane procedure. Interpleural effusates were devoid of plasmin activity or active plasminogen activator inhibitor-1 but contained plasmin complexes and active urokinase-like plasminogen activator (uPA), alpha(2)-antiplasmin, and thrombin-activatable fibrinolysis inhibitor. We speculate that VX-2 cells release uPA to activate fibrinolysis within the tumor stroma. Catabolic products of hemostasis (eg, fibrinolytic fragments, angiostatin) flux from the stroma into the interpleural space, thereby providing a net antiangiogenic property to the effusate and ultimately to the lymphatic and circulatory systems.

Animals↗
PubMed2004

Quantification of anti-angiogenesis using the capillaries of the chick chorioallantoic membrane demonstrates that the effect of human angiostatin is age-dependent.

We present a method whereby en face estimation of the chorionic capillary plexus can be generated in the living chick chorioallantoic membrane (CAM) and confirmed by post-fixation cross section analysis. This value does not alter significantly with age and provides a reliable and simple method to evaluate anti-angiogenesis. Anti-angiogenesis may be induced by an intervention, such as a pharmacological agent, applied to the surface of the CAM. We describe the use of silastic rings that are associated with minimal inflammatory reaction, in this process. By estimating changes in the chorionic capillary plexus to quantify anti-angiogenesis, together with silastic rings, we examined the anti-angiogenic effect of human angiostatin and demonstrated that although there is a significant loss of capillaries en face after exposure from days 7 to 9 of incubation, in contrast there is no significant inhibition after exposure to a similar dose of angiostatin from days 11 to 13 of incubation. This not only demonstrates the important effects on neo-angiogenesis compared to mature vessels, but also illustrates the potential of the CAM to readily provide a means for such a comparison.

Age Factors↗
PubMed2003

Observations on the use of the avian chorioallantoic membrane (CAM) model in investigations into angiogenesis.

The chorioallantoic membrane (CAM) is widely used as a model to examine angiogenesis, and anti-angiogenesis. Its advantages over mammalian systems include low cost, and ease of preparation, as well as the absence of a mature immune system. Although the use of this model presents a major opportunity to compare data generated in different laboratories, thereby expediting the evaluation of new drugs, angiogenic potential of cells and tissues, and body fluids, as well as to provide meaningful information concerning the molecular mechanisms involved, the wide range of methodologies used, especially in the quantification of the response, make any comparison essentially invalid. In this review, the major methodologies for all aspects of the use of the CAM in angiogenesis-related studies have been described. These include the source of the CAM, the methods for culture, and methods for evaluation of normal growth and of the response to an intervention. Methods for applying an intervention, the age for intervention and the duration of an intervention are documented. The structure and growth characteristics, the nature of possible responses to stimulation and inhibition of angiogenesis, and the complications of non-specific reactions have been examined. The need for a standardized approach to the use of the CAM model is obvious. One set of possible parameters is suggested.

Angiogenesis Inhibitors↗
PubMed2002

Platelet and fibrinogen turnover at the exposed subendothelium measured over 1 year after a balloon catheter de-endothelializing injury to the rabbit aorta: thrombotic eruption at the late re-endothelialization stage.

Balloon catheter de-endothelialization of the rabbit aorta in vivo causes a rapid release of thrombin and a consequent hemostatic response at the surface of the exposed subendothelium. Previously, we have compared the net fluxes of several hemostatic proteins from plasma into the exposed aorta subendothelium for up to 600 days after injury. We now report the turnover of platelets, compared to fibrinogen, at the de-endothelialized aorta for up to 390 days after injury. Anesthetized NZW rabbits received either a de-endothelializing or a sham injury (controls) to their aortas. At a predetermined time (either 10 min before or up to 390 days after injury), each rabbit was infused with known quantities of rabbit (51)Cr-platelets and rabbit (125)I-fibrinogen; the radiolabels were allowed to circulate for 10 min before the rabbit was rapidly exsanguinated. Radioactivity measurements and tissue analysis revealed that at 10 min after balloon injury, approximately 165,000 platelets/mm(2) were associated with the aorta surface, and platelet turnover was 840/min/mm(2). Turnover had decreased to <200/min/mm(2) at 10-21 days but, from 65 to 390 days, had increased to approximately 1500/min/mm(2). In comparison, approximately 17 pmol of fibrinogen/cm(2) saturated the ballooned surface by 10 min after injury. Fibrinogen turnover at the aorta surface at 10 min after injury amounted to 0.2 pmol/min/cm(2), increasing to 0.7 at 10 days but decreasing to 0.25 at 21 days. Between 65 and 390 days, fibrinogen turnover increased slowly to 1.3 pmol/min/cm(2). Fibrinogen turnover at the surface of the aorta paralleled that within the intima-media over 390 days. Platelet and fibrin(ogen) deposits within the aorta wall increased over the 21-390 days interval as shown by immunostaining. The results are consistent with the re-endothelializing aorta tending to support thrombosis and ulceration in the late healing stage.

Animals↗
PubMed2002

Angiostatin II is the predominant glycoform in pleural effusates of rabbit VX-2 lung tumors.

Angiostatin (AST), a polypeptide with potent antiangiogenic properties, is released proteolytically from plasminogen in vivo. Plasminogen exists naturally in plasma as two glycoforms (PLGs), I and II. Recently it was shown with the use of a chick-embryo chorioallantoic membrane (CAM) assay that rabbit PLG-I and -II yield distinct ASTs-AST-I and -II, respectively-with different antiangiogenic activities. AST glycoforms were of similar molecular weight, approximately 30 to 32,000 kD, and probably consisted of kringles 1 to 3 only. AST has now been identified in the interpleural effusate released from VX-2 lung tumors in rabbits. Effusate was collected from six rabbits with high tumor burdens and fractionated by means of lysine-Sepharose chromatography. The epsilon-aminohexanoic acid-eluted protein of all effusates contained AST (kringles 1-3) at a mean concentration of 1.2 microg/mL of effusate; with regard to AST content, 97% was AST-II. A CAM assay revealed that the lysine-Sepharose-bound fraction from all interpleural effusates contained potent antiangiogenic activity. Blood and urine from rabbits with high burdens of VX-2 contained essentially only AST-II, at mean concentrations of 145 and 4 ng/mL, respectively. AST was absent from the blood of control rabbits. In an attempt to compare their uptake by VX-2, iodine 125-labeled AST-I and iodine 131-labeled AST-II were injected intravenously into tumor-bearing rabbits. AST-I entered the tumor 1.6 times faster than AST-II. As a means of accounting for the preponderance of AST-II in the interpleural effusate, we postulate that VX-2 cells release proteolytic activity to activate plasminogen but that of the two PLGs, PLG-II may be the preferred substrate for AST formation in vivo.

Angiostatins↗
PubMedDate not supplied

Immunolocalization of surfactant protein A and D in sinonasal mucosa.

BACKGROUND: Surfactant-associated proteins (SP) A and D are in the family of collectin proteins that play an integral part in the innate defense system. SP-A and SP-D expression and function are altered in a variety of inflammatory and infectious diseases of the lungs, such as asthma, allergies, and cystic fibrosis. Our prior studies are the first to identify the presence of these proteins in the human sinonasal cavity. The objective of this study was to immunolocalize SP-A and SP-D in human sinonasal tissue. METHODS: Sinonasal mucosal biopsies were performed in patients with various forms of chronic hyperplastic rhinosinusitis with nasal polyposis and nondiseased mucosa from patients undergoing transsphenoidal hypophysectomy. (n = 10) Immunolocalization of surfactant proteins was performed with antibodies to SP-A and SP-D using immunoperoxidase staining technique. Isotype-negative controls were performed on all specimens. RESULTS: Analyses of mucosal biopsy specimens from human sinonasal tissue reveals staining within respiratory and intermediate (metaplastic)-type surface epithelium. In addition, staining was intense in the submucosal ductal epithelium of the seromucinous glands. These properties appear to be consistent regardless of disease state and location within the sinuses. CONCLUSION: This is the first study to immunolocalize SP-A and SP-D in sinonasal human mucosa. These are secreted proteins that are intricately involved in innate immunity in the lungs. Their secretion in the upper airway indicates that future studies may allow manipulation of these proteins and development of novel treatments for sinonasal pathology.

Humans↗
PubMedDate not supplied

It's the difference between life and death.

The Heartstart UK initiative offers a coordinated approach to community resuscitation training, as there is evidence to show that survival rates following cardiac arrest almost double when cardiopulmonary resuscitation is initiated by a bystander as quickly as possible.

Health Education↗