Jalil Afnan

Mast Cell Protease 5 Mediates Ischemia-Reperfusion Injury of Mouse Skeletal Muscle

Ischemia with subsequent reperfusion (IR) injury is a significant clinical problem that occurs after physical and surgical trauma, myocardial infarction, and organ transplantation. IR injury of mouse skeletal muscle depends on the presence of both natural IgM and an intact C pathway. Disruption of the skeletal muscle architecture and permeability also requires mast cell (MC) participation, as revealed by the fact that IR injury is markedly reduced in c-kit defective, MC-deficient mouse strains. In this study, we sought to identify the pathobiologic MC products expressed in IR injury using transgenic mouse strains with normal MC development, except for the lack of a particular MC-derived mediator. Histologic analysis of skeletal muscle from BALB/c and C57BL/6 mice revealed a strong positive correlation (R2 = 0.85) between the extent of IR injury and the level of MC degranulation. Linkage between C activation and MC degranulation was demonstrated in mice lacking C4, in which only limited MC degranulation and muscle injury were apparent. No reduction in injury was observed in transgenic mice lacking leukotriene C4 synthase, hemopoietic PGD2 synthase, N-deacetylase/N-sulfotransferase-2 (enzyme involved in heparin biosynthesis), or mouse MC protease (mMCP) 1. In contrast, muscle injury was significantly attenuated in mMCP-5-null mice. The MCs that reside in skeletal muscle contain abundant amounts of mMCP-5 which is the serine protease that is most similar in sequence to human MC chymase. We now report a cytotoxic activity associated with a MC-specific protease and demonstrate that mMCP-5 is critical for irreversible IR injury of skeletal muscle.

CT Findings in Adult Celiac Disease

Celiac disease is now recognized as a common disease, occurring in about one in every 200 Americans. However, less than 10% of cases are currently diagnosed, with a diagnostic delay of more than 10 years from onset of symptoms. In the past, barium examination of the small bowel demonstrated a pattern of abnormal findings caused by the pathophysiologic changes induced by malabsorption, thus leading to diagnosis of celiac disease and other diseases of malabsorption. Although not specific, that pattern prompted further patient evaluation. The number of barium examinations performed and the skill necessary to interpret their results are both in decline. Abdominal pain in celiac disease is a common early complaint that often leads to computed tomography (CT). Improved CT resolution now permits better depiction of the small bowel, colon, and mesenteric lymph nodes, all of which are affected by celiac disease. Detection of celiac disease with CT will allow treatment to be initiated to prevent the significant morbidity and increased mortality associated with a delay in diagnosis. The abnormal CT findings seen over the past decade during review of more than 200 cases of celiac disease demonstrate that CT depicts more features of celiac disease than did barium examination. Pattern recognition for the diagnosis of small bowel diseases that create structural changes in the bowel wall is well accepted. Because it demonstrates features of celiac disease not detected with barium examination, CT may be more sensitive than barium examination for diagnosis of this disease.

Update on Prostate Imaging

Successful and accurate imaging of prostate cancer is integral to its clinical management from detection and staging to subsequent monitoring. Various modalities are used including ultrasound, computed tomography, and magnetic resonance imaging, with the greatest advances seen in the field of magnetic resonance.

Inhibition of rat gut reperfusion injury with an agent developed for the mouse. Evidence that amplification of injury by innate immunity is conserved between two animal species

Murine reperfusion injury follows binding of specific IgM natural antibodies to neo-antigens exposed in ischemic tissue. Peptides that mimic the site of antibody binding in the injury prevent IgM binding when administered intravenously before reperfusion. To determine whether this pathogenic sequence is restricted to mice, we have tested the ability of the peptide to prevent reperfusion injury in a dissimilar species, the rat. Sprague-Dawley rats were subjected to 40 min of mesenteric ischemia followed by 180 min of reperfusion. The peptide mimic was administered intravenously prior to reperfusion. Gut injury was quantified using a scoring system based on the hematoxylin-and-eosin section. (125)I-labeled albumin was used to assess local (gut) and remote (lung) injury. The macroscopic appearance of bowel from peptide-treated animals was less edematous and hemorrhagic. Microscopic analysis showed a significantly reduced injury score in peptide-treated animals. Permeability data indicated a significant reduction in local and remote injury in peptide-treated animals. The data demonstrate attenuation of rat gut microvillus injury, of gut edema, and of remote injury following mesenteric ischemia-reperfusion due to administration of an intravenous peptide mimic of a murine ischemia neo-antigen, indicating a second species uses a similar ischemia neo-antigen and corresponding natural antibody specificity to amplify reperfusion injury to the point of necrosis. This mechanism of inflammation is potentially applicable to higher species.

Constructing a new bony posterior canal wall in elimination of the radical mastoid cavity. Use of pedicled temporal bone-periosteum flap.

An operation is described which was devised to reconstruct a new bony posterior canal wall using a temporal bone-periosteum pedicle flap. We feel that this is not only advantageous in the obliteration of the mastoid cavity but will also enhance subsequent functional surgery. This method was utilized in four patients with effective results. The first two patients did not have mastoid-cavities to start with. Their posterior canal walls were taken down unsparingly at time of operation for chronic disease of the tympanic cleft and a one-stage reconstruction performed. It is suggested that this addition to the technique of Rambo might significantly rehabilitate our “aural cripples”, as indicated by our present experience.ZUSAMMENFASSUNGEine Operationsmethode wurde beschrieben, die unter Ausnutzung eines Knochen-Periost-Lappens aus dem Schlafenbein einen Canalis posterior herstellt. Wir fuhlen, dass dies nicht nur von Vorteil in der Obliteration von Mastoidhohlen ist, sondern auch von Hilfe bei spaterer Wiederh...

Intracranial, intradural aneurysmal bone cyst

Aneurysmal bone cysts (ABCs) are benign, expansile, blood-filled, osteolytic lesions with internal septations that may be intraosseous or extraosseous. The cysts may cause local mass effect, and changes in the regional vascular supply necessitating intervention. A case of an intracranial, intradural ABC in a young male patient with progressively severe headaches is presented. This is only the third recorded intradural case, the majority of these rare lesions being extracranial and only a minute fraction intracranial.

Imaging of Renal Cancer

The global incidence of adult renal cancer continues to increase, with little change in the predominant cell type, renal cell carcinoma. The rise in incidence is in part due to an increasing number of imaging studies of the abdomen and pelvis performed for a variety of reasons, and therefore, incidental diagnosis. The majority of cases are localized. This has a favorable prognostic impact, since cancer may be detected at an earlier stage.