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D Cosgrove

Publications and source records attributed to D Cosgrove.

At least 19 recordsLinked to original sources
PubMed2004

Liver tumors: evaluation with contrast-enhanced ultrasound.

The development and clinical introduction of microbubble contrast agents has had a particular impact on the detection and differential diagnosis of liver tumors. The first approach widely employed made use of high-transmission power ultrasound, which destroyed the microbubbles in the process of imaging them. It is particularly successful for those agents that have a liver-specific post-vascular phase because, like liver-specific agents used in other imaging modalities such as magnetic resonance imaging and nuclear medicine, malignancies do not retain the contrast, so they stand out with very high conspicuity. Used this way with color Doppler or variants of it, more subcentimeter lesions can be demonstrated with ultrasound than with computed tomography. However, the destructive nature of this approach meant that continuous real-time scanning was impossible. Two developments allowed this to be redressed: new classes of microbubbles with perfluoro gasses instead of air and the invention of multipulse scanning modes that are sensitive to the nonlinear (harmonic) responses of the microbubbles and suppresses tissue signals. This low-power approach is now used almost exclusively, and it has the advantage of displaying the arterial phase of blood supply to a mass and a later phase when the bubbles are trapped in the sinusoids so that the vascular volume of the tissue is depicted. Malignancies typically show a low signal intensity in this phase, regardless of whether they are hyper- or hypovascular in terms of their arterial supply. This allows them to be detected with high sensitivity and much more easily than the destructive modes allowed. In addition, the arterial supply that can be now depicted in real time has characteristics that allow most benign masses to be distinguished from each other and from malignancies, thus improving specificity. Microbubbles also can be used as tracers to provide functional information that can detect occult metastases and cirrhosis noninvasively.

Acoustics↗
PubMed2001

Global gene expression analysis reveals a role for the alpha 1 integrin in renal pathogenesis.

Kidney fibrosis is the hallmark of most types of progressive kidney disease, including the genetic disorder Alport's syndrome. We undertook gene expression analysis in Alport's syndrome mouse kidneys using microchip arrays to characterize the development of fibrosis. In addition to matrix and matrix-remodeling genes, consistent with interstitial fibrosis, macrophage-related genes show elevated expression levels in Alport's syndrome kidneys. Immunohistochemical analysis of kidney sections illustrated that macrophages as well as myofibroblasts accumulate in the tubular interstitium. Deletion of alpha(1) integrin results in decreased accumulation of both myofibroblasts and macrophages in the tubular interstitium in Alport's syndrome mice and delays disease progression. Transforming growth factor beta antagonism, although reducing interstitial fibrosis, does not limit macrophage accumulation in the tubular interstitium and disease progression. In this study, we identified previously overlooked inflammatory events that occur in the tubulointerstitial region. We propose that in addition to the previously suggested role for the alpha(1)beta(1) integrin in mesangial expansion and abnormal laminin deposition, this integrin may be critical for monocyte accumulation that, in turn, may lead directly to renal failure. Our gene expression and immunohistochemical data indicate that macrophage accumulation is dependent on alpha(1) integrin expression on the macrophage cell surface and that anti-alpha(1) integrin strategies may be employed as therapeutics in the treatment of chronic inflammatory and fibrotic diseases.

Animals↗
PubMed2001

Quantification of blood flow.

Traditionally, Doppler ultrasound has been used to estimate blood flow as the mean velocity multiplied by the vessel area, but this is subject to significant errors and may be difficult to perform accurately. Microbubbles, developed as contrast agents for ultrasound, were initially envisaged as useful for increasing the intensity of echoes and thus rescuing Doppler studies that were technical failures because of attenuated signals or very slow flow. However, they can act as tracers and, by analogy with isotope techniques, can be used to measure blood flow with transit-time methods which exploit both arterial and venous time-intensity data. An acceptable compromise is to acquire both a tissue intensity curve and one from the feeding artery. The transit of microbubbles across an organ or tissue can be used to estimate haemodynamic alterations, e.g. the arterialisation of the supply to the liver in malignancies and cirrhosis and the delayed arterio-venous transit in the transplant kidney during rejection. The fragility of microbubbles can be turned to advantage by being exploited to create a negative bolus by exposing a tissue slice to a high power beam. The rate of refilling of this slice by circulating microbubbles can then be followed with a low-intensity monitoring beam and the resulting rising exponential curve analysed to extract indices of both the reperfusion rate (the slope) and the fractional vascular volume (the asymptote). The product of these is a measure of true tissue perfusion.

Blood Flow Velocity↗
PubMed2001

The laminins in the murine inner ear: developmental transitions and expression in cochlear basement membranes.

The laminins are a family of heterotrimeric extracellular matrix molecules that form suprastructural networks in basement membranes and elsewhere. They interact with integrin receptors, playing key roles in modulating programs of cytodifferentiation and maintaining tissue homeostasis in animals. Earlier studies have demonstrated an extensive laminin network in both the developing and adult cochlea, primarily associated with the basement membranes. These studies, however, did not address the laminin chain composition of these networks. In this study, we used antibodies specific for the known laminin chains to examine the composition of laminins in both the developing and adult murine cochlea. The results illustrate a complex and dynamic postnatal developmental regulation pattern for most of these chains, and suggest that an unusually large number of laminin heterotrimers are present in both the developing and adult cochlea. The laminin composition at postnatal day 2 is relatively simple. By postnatal day 7, however, activation of several laminin chains results in a very complex laminin composition. In the basement membrane underlying the region of the basilar membrane under the developing organ of Corti, eight of the 11 known basement membrane laminins are possible by co-localization inference. Dynamic changes in expression continue through day 14, but simplify by adulthood. Thus, the most dynamic period for laminin expression in the mouse cochlea coincides with terminal cytodifferentiation of the cochlear epithelial structures. Considering the well established role of laminins in regulating both embryonic and organ development in other systems, these data suggest a closer look at the role of the laminins in cochlear development and function may be warranted.

Aging↗
PubMed2001

Freehand three-dimensional Doppler demonstration of monochorionic vascular anastomoses in vivo: a preliminary report.

OBJECTIVES: To demonstrate the three-dimensional vascular anatomy of monochorionic placental anastomoses in vivo, both arterioarterial and arteriovenous. DESIGN: Two-dimensional placental mapping techniques were used to locate arterioarterial and arteriovenous anastomoses. A freehand sweep was performed across the anastomotic site, and multiple images were stored to disk, at 17 Hz. These were then segmented to show only color information (vascular flow) using purpose-designed software (CQ analysis) and the files reconstructed into a three-dimensional volume, for multidirectional viewing and movie generation. RESULTS: Both arterioarterial and arteriovenous anastomoses could be visualized in detail. Reconstruction of a dual volume of gray-scale and segmented color images allowed recreation of the vascular anatomy within the placental substance, as well as retention of the original directional flow information. CONCLUSIONS: Detailed anastomotic anatomy can be demonstrated three dimensionally in vivo. Given the increasing evidence implicating various anastomotic configurations in pathological intertwin transfusion, this technique may prove useful in the antenatal assessment and treatment of monochorionic twin pregnancies.

Arterio-Arterial Fistula↗
PubMed2000

Assembly of type IV collagen. Insights from alpha3(IV) collagen-deficient mice.

Type IV collagen includes six genetically distinct polypeptides named alpha1(IV) through alpha6(IV). These isoforms are speculated to organize themselves into unique networks providing mammalian basement membranes specificity and inequality. Recent studies using bovine and human glomerular and testis basement membranes have shown that unique networks of collagen comprising either alpha1 and alpha2 chains or alpha3, alpha4, and alpha5 chains can be identified. These studies have suggested that assembly of alpha5 chain into type IV collagen network is dependent on alpha3 expression where both chains are normally present in the tissue. In the present study, we show that in the lens and inner ear of normal mice, expression of alpha1, alpha2, alpha3, alpha4, and alpha5 chains of type IV collagen can be detected using alpha chain-specific antibodies. In the alpha3(IV) collagen-deficient mice, only the expression of alpha1, alpha2, and alpha5 chains of type IV collagen was detectable. The non-collagenous 1 domain of alpha5 chain was associated with alpha1 in the non-collagenous 1 domain hexamer structure, suggesting that network incorporation of alpha5 is possible in the absence of the alpha3 chain in these tissues. The present study proves that expression of alpha5 is not dependent on the expression of alpha3 chain in these tissues and that alpha5 chain can assemble into basement membranes in the absence of alpha3 chain. These findings support the notion that type IV collagen assembly may be regulated by tissue-specific factors.

Animals↗
PubMed2000

Modular retro-vectors for transgenic and therapeutic use.

Retroviruses have been used for many years as vectors for human gene therapy as well as for making transgenic animals. However, the efficient insertion of genes by retroviruses is often complicated by transcriptional inactivation of the retroviral long terminal repeats (LTRs) and by the production of replication-competent retroviruses (RCR). Solutions to these and other difficulties are being found in modular vectors, in which the desirable features of different vector systems are combined. Examples of synergistic vectors include virosomes (liposome/virus delivery), adeno-retro vectors, and MLV/VL30 chimeras. As gene delivery systems become increasingly complex, methodology is also needed for precise assembly of modular vectors. Gene self-assembly (GENSA) technology permits seamless vector construction and simultaneous, multifragment assembly.

Animals↗
PubMed2000

Integrin alpha1beta1 and transforming growth factor-beta1 play distinct roles in alport glomerular pathogenesis and serve as dual targets for metabolic therapy.

Alport syndrome is a genetic disorder resulting from mutations in type IV collagen genes. The defect results in pathological changes in kidney glomerular and inner-ear basement membranes. In the kidney, progressive glomerulonephritis culminates in tubulointerstitial fibrosis and death. Using gene knockout-mouse models, we demonstrate that two different pathways, one mediated by transforming growth factor (TGF)-beta1 and the other by integrin alpha1beta1, affect Alport glomerular pathogenesis in distinct ways. In Alport mice that are also null for integrin alpha1 expression, expansion of the mesangial matrix and podocyte foot process effacement are attenuated. The novel observation of nonnative laminin isoforms (laminin-2 and/or laminin-4) accumulating in the glomerular basement membrane of Alport mice is markedly reduced in the double knockouts. The second pathway, mediated by TGF-beta1, was blocked using a soluble fusion protein comprising the extracellular domain of the TGF-beta1 type II receptor. This inhibitor prevents focal thickening of the glomerular basement membrane, but does not prevent effacement of the podocyte foot processes. If both integrin alpha1beta1 and TGF-beta1 pathways are functionally inhibited, glomerular foot process and glomerular basement membrane morphology are primarily restored and renal function is markedly improved. These data suggest that integrin alpha1beta1 and TGF-beta1 may provide useful targets for a dual therapy aimed at slowing disease progression in Alport glomerulonephritis.

Animals↗
PubMed2000

The Cox-Maze procedure: the Cleveland Clinic experience.

The Cox-Maze procedure was designed to address the consequences of atrial fibrillation, tachycardia, hemodynamic impairment, and thromboembolism. From 1991 until June 1999, 100 patients underwent the Maze operation at the Cleveland Clinic Foundation. The group included 72 men with a mean age of 58 +/- 11 years (range, 23 to 78 years). Initially, the Maze-I procedure was performed primarily for patients with lone atrial fibrillation. However, since 1995, the Maze-III procedure has been performed exclusively, and it is typically combined with mitral valve repair. Twenty-three patients had only a Maze procedure, 60 patients had the Maze procedure/mitral valve repair, 10 patients had Maze procedure/coronary artery bypass, 6 had Maze procedure/mitral valve replacement, and 1 had Maze procedure/atrial septal defect repair. Chronic atrial fibrillation was present in 78% of patients for a mean of 8 +/- 9 years. There was a 1% perioperative mortality and 5% late mortality rate. Median hospital stay was 9 +/- 5 days. Six patients required new early permanent pacemaker insertion. With a mean follow-up of 3 years, 90.4% of patients are in sinus rhythm (or atrial pacing). Preoperative symptoms were reduced: 24% had preoperative syncope; none had syncope in follow-up; 14% of patients preoperatively had cerebral or systemic emboli; and there were no perioperative or late embolic events. The Maze procedure effectively addressed the major complications of atrial fibrillation and was associated with low perioperative and late morbidity rates.

Adult↗
PubMed1999

Liver-specific imaging with SHU 563A: diagnostic potential of a new class of ultrasound contrast media.

The purpose of this study was to evaluate the imaging properties and diagnostic potential of the novel polymeric ultrasound contrast agent SHU 563 A. After i. v. injection, the agent circulates in the blood pool for about 10 min and is then subsequently sequestered by the RES cells predominantly in the liver. The acoustic emission capabilities enable a very sensitive detection during the blood pool phase and after uptake in the RES cells, contributing to differential diagnosis as well as detection of liver lesions. During a multicenter study, 28 patients with liver lesions were examined. In all patients the results were compared to baseline ultrasound and Contrast enhanced Spiral CT. With respect to lesion size and location, very good agreement between SHU 563 A ultrasound and Spiral CT was achieved. Additional lesions could be shown in the RES phase by SHU 563 A enhanced ultrasound. 26 further patients were examined in other indications. The results in all 54 patients indicate good safety and tolerance of SHU 563 without limitations for diagnostic use. SHU 563 A enhanced ultrasound adds significantly to the detection and delineation of focal liver lesions by improving conspicuity due to RES based contrast after uptake.

Adenocarcinoma↗
PubMed1999

The breast.

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Blood Flow Velocity↗