Publications by authors named "Kevin Carnevale"

Pathology education is taught using different curricula in the United States (USA) and abroad. We evaluate and compare the hours spent in different forms of pathology teaching such as lectures, team-based learning (TBL), problem-based learning (PBL), and other methods taught in general and systemic pathology amongst different medical schools within the USA and outside the USA. The total number of lecture hours taught in general and systemic pathology combined was greater in outside schools than within the USA (141 h vs 97.

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MCP-1-induced monocyte chemotaxis is a crucial event in inflammation and atherogenesis. Identifying the important signal transduction pathways that control monocyte chemotaxis can unravel potential targets for preventive therapies in inflammatory disease conditions. Previous studies have shown that the focal adhesion kinase Pyk2 plays a critical role in monocyte motility.

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Objective: microRNA-155 (miR155) plays a critical role in immunity and macrophage inflammation. We aim to investigate the role of miR155 in atherogenesis.

Approach And Results: Quantitative real-time polymerase chain reaction showed that miR155 was expressed in mouse and human atherosclerotic lesions.

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Deoxycorticosterone salt (DOC-salt) hypertension-induced renal damage is enhanced in α-calcitonin gene-related peptide (α-CGRP) knockout (KO) compared with wild-type (WT) mice. However, since the α-CGRP KO mice have a 15-20 mmHg higher baseline mean arterial pressure (MAP) than WT mice, they also have a higher MAP than WT mice throughout the course of DOC-salt hypertension. To determine the mechanism by which the absence of α-CGRP enhances hypertension-induced renal damage, DOC-salt hypertension was induced in telemetry probe implanted α-CGRP KO and WT mice.

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Monocyte chemoattractant protein-1 (MCP-1)-induced monocyte chemotaxis is a major event in inflammatory disease. Our prior studies have demonstrated that MCP-1-dependent chemotaxis requires release of arachidonic acid (AA) by activated cytosolic phospholipase A(2) (cPLA(2)). Here we investigated the involvement of AA metabolites in chemotaxis.

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We examined the effects of three high-fat diets (HFD), differing in the percentage of total calories from saturated fat (SF) (6%, 12%, and 24%) but identical in total fat (40%), on body composition, macrophage behavior, inflammation, and metabolic dysfunction in mice. Diets were administered for 16 weeks. Body composition and metabolism [glucose, insulin, triglycerides, LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), total cholesterol (TC)] were examined monthly.

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Tumor-associated macrophages are associated with poor prognosis in certain cancers. Monocyte chemoattractant protein 1 (MCP-1) is thought to be the most important chemokine for recruitment of macrophages to the tumor microenvironment. However, its role on tumorigenesis in a genetic mouse model of colon cancer has not been explored.

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Article Synopsis
  • The development and implementation of a 4-year integrated ultrasound curriculum for medical students is reviewed, highlighting various teaching methods and assessment strategies.
  • Results from testing and student surveys indicate that ultrasound is a valuable and well-received tool for enhancing medical education throughout all four years.
  • Key lessons learned during the establishment of the curriculum emphasize the positive impact of ultrasound training on students' learning experiences.
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Lung cancer is the leading cause of cancer-related deaths with current chemotherapies lacking adequate specificity and efficacy. Beta-lapachone (beta-lap) is a novel anticancer drug that is bioactivated by NAD(P)H:quinone oxidoreductase 1, an enzyme found specifically overexpressed in non-small cell lung cancer (NSCLC). Herein, we report a nanotherapeutic strategy that targets NSCLC tumors in two ways: (a) pharmacodynamically through the use of a bioactivatable agent, beta-lap, and (b) pharmacokinetically by using a biocompatible nanocarrier, polymeric micelles, to achieve drug stability, bioavailability, and targeted delivery.

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Background: The role of vascularized bone allografting is not established in plastic and reconstructive surgery. The authors evaluated the contribution by osteopontin to fibrosis of allografted bone in a vascularized bone marrow transplantation model across a major histocompatibility complex barrier.

Methods: Thirty-six transplantations were performed between Brown Norway (RT1 n) donors and Lewis (RT1 l) recipients divided into three groups: group 1, isografts between Lewis rats (n = 12); group 2, allografts without treatment (n = 8); and group 3, allografts under a 7-day alphabeta-T-cell receptor/cyclosporine protocol (n = 16).

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Colorectal cancer risk is increased in shift workers with presumed circadian disruption. Intestinal epithelial cell proliferation is gated throughout each day by the circadian clock. Period 2 (Per2) is a key circadian clock gene.

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Monocyte chemoattractant protein-1 (MCP-1) directs migration of blood monocytes to inflamed tissues. Despite the central role of chemotaxis in immune responses, the regulation of chemotaxis by signal transduction pathways and their in vivo significance remain to be thoroughly deciphered. In this study, we examined the intracellular location and functions of two recently identified regulators of chemotaxis, Ca(2+)-independent phospholipase (iPLA(2)beta) and cytosolic phospholipase (cPLA(2)alpha), and substantiate their in vivo importance.

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We developed a rat model to test the effects of vascularized maxilla allotransplantation on composite maxillary substructures. Allograft maxilla transplantations were performed across the major histocompatibility barrier between 10 Lewis-Brown-Norway (RT1(n+l)) and 10 Lewis (RT1(l)) recipient rats under cyclosporin A monotherapy. Grafts were dissected along Le-Fort II osteotomy lines based on the common carotid artery and external jugular vein and transplanted to the anterior abdominal wall via microvascular anastomosis.

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Bilateral vascularized bone marrow transplant (VBMT) model was designed to induce chimerism across the major histocompatibility (MHC) barrier under combined alphabeta T-cell receptor monoclonal antibody and cyclosporine A (alphabeta-TCRmAb/CsA) protocol. Seventeen transplants were performed between BN(RT1) donors and Lewis(RTI) recipients. Group I, isograft controls; Group II, allografts rejection controls; Group III, allografts under 7-day protocol of alphabeta-TCRmAb/CsA.

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We present a new model of vascularized bone marrow transplantation-bilateral vascularized femoral bone (BVFB) isograft transplant based on abdominal aorta and inferior vena cava. A total of 7 BVFB isograft transplants were performed between Lewis (RT1) rats. In the donor, both femoral bones were harvested based on the abdominal aorta and inferior vena cava.

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Purpose: To describe the in vivo results of a promising new stent-graft lined with peritoneum.

Methods: Eighteen dogs underwent balloon angioplasty injury to the bilateral iliac arteries followed by placement of either an 8-mm x 5-cm glutaraldehyde-fixed bovine peritoneum- lined balloon-expandable stent (PLS) or a similarly sized, commercially prepared, polyester-lined self-expanding stent (DLS) as a control. Animals were sacrificed at 1 and 6 months.

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Objective: This study evaluates the efficacy of bovine peritoneum/fascia as an arterial substitute.

Methods And Outcome Measures: Twelve dogs underwent bilateral femoral artery patch angioplasty with a glutaraldehyde-fixed bovine peritoneal/fascial patch (PFA patch) on one side and polyester patch on the contralateral side. Arteriograms were performed just before vessel harvest at 1 and 6 months, and vessels were evaluated for aneurysms and inflammation.

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Phagocyte NADPH oxidase is critical for defense against pathogens and contributes to inflammatory tissue injury. One component of the NADPH oxidase complex is the small GTP-binding protein Rac. There are two isoforms of Rac, and Rac2 is the predominant isoform in neutrophils and has been shown to be essential for NADPH oxidase activity.

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Monocyte chemoattractant protein 1 (MCP-1) is important in attracting monocytes to sites of inflammation. Using predominantly pharmacological approaches, prior studies have indicated that serine/threonine kinases are involved in the MCP-1-induced signaling pathways. We report here that there is substantial inhibition of MCP-1-stimulated chemotaxis of human monocytes treated with inhibitors selective for the subset of serine/threonine kinases, protein kinase C (PKC).

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An experimental study was conducted to investigate the effect of time of adenovirus-mediated vascular endothelial growth factor (VEGF) gene therapy on the viability of epigastric skin flaps. Eighty-four male Sprague-Dawley rats were used. Skin flaps measuring 8 x 8 cm were marked on the ventral abdominal wall.

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Background: The ubiquitous plasma membrane transcobalamin II receptor (TC II-R) mediates uptake of cobalamin (Cbl; vitamin B12), an essential micronutrient. Tumors often require more Cbl than normal tissue, and increased Cbl uptake may result from increased TC II-R expression. To examine whether Cbl could therefore be used as a carrier molecule to target a chemotherapy drug, we tested an analogue of Cbl with nitric oxide as a ligand, nitrosylcobalamin (NO-Cbl).

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An experimental study was conducted to investigate the potential use of intravascular gene therapy with adenovirus-mediated (Ad) vascular endothelial growth factor (VEGF) or angiopoietin-1 (Ang-1) for the enhancement of muscle flap perfusion and to evaluate the effect of therapy on microcirculatory hemodynamics and microvascular permeability in vivo by using a cremaster muscle flap model in the rat. The cremaster tube flap was left intact after isolation of the pudo-epigastric pedicle. A total of 90 male Sprague-Dawley rats were divided into five groups of 18 each, according to the type of intraarterial treatment.

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Angiopoietin-1 (Ang-1) constitutes a novel family of endothelial cell-specific angiogenic factors. Ang-1 functions mainly in remodeling, maturation, and stabilization of blood vessels. Its direct role in the process of angiogenesis remains unknown.

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The capacity of an adenovirus encoding the mature form of vascular endothelial growth factor (VEGF)-D, VEGF-D Delta N Delta C, to induce angiogenesis, lymphangiogenesis, or both was analyzed in 2 distinct in vivo models. We first demonstrated in vitro that VEGF-D Delta N Delta C encoded by the adenovirus (Ad-VEGF-D Delta N Delta C) is capable of inducing endothelial cell proliferation and migration and that the latter response is primarily mediated by VEGF receptor-2 (VEGFR-2). Second, we characterized a new in vivo model for assessing experimental angiogenesis, the rat cremaster muscle, which permits live videomicroscopy and quantitation of functional blood vessels.

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