Blockade of thrombospondin-1-CD47 interactions prevents necrosis of full thickness skin grafts.

Background: Skin graft survival and healing requires rapid restoration of blood flow to the avascular graft. Failure or delay in the process of graft vascularization is a significant source of morbidity and mortality. One of the primary regulators of blood flow and vessel growth is nitric oxide (NO).

Detection and localization of the hydrophobic surfactant proteins B and C in human tear fluid and the human lacrimal system.

Purpose: To evaluate the expression and presence of the surfactant proteins (SP) B and C in the lacrimal apparatus at the ocular surface and in tear fluid.

Methods: Expression of SP-B and SP-C was analyzed by RT-PCR in healthy lacrimal gland, conjunctiva, meibomian gland, accessory lacrimal glands, cornea, and nasolacrimal ducts. The deposition of the hydrophobic proteins SP-B and SP-C was determined by Western blot and immunohistochemistry in healthy tissues, tear fluid, and aqueous humor.

[Death on a sauna stove].

A 67-year-old woman noticed a strange smell from the cellar of her house. When she followed the smell, she found her 64-year-old husband with the face and upper part of his body lying on the stove of the private sauna. He was dead when the emergency doctor arrived.

Blocking thrombospondin-1/CD47 signaling alleviates deleterious effects of aging on tissue responses to ischemia.

Objective: Decreased blood flow secondary to peripheral vascular disease underlies a significant number of chronic diseases that account for the majority of morbidity and mortality among the elderly. Blood vessel diameter and blood flow are limited by the matricellular protein thrombospondin-1 (TSP1) through its ability to block responses to the endogenous vasodilator nitric oxide (NO). In this study we investigate the role TSP1 plays in regulating blood flow in the presence of advanced age and atherosclerotic vascular disease.

Nelfinavir, A lead HIV protease inhibitor, is a broad-spectrum, anticancer agent that induces endoplasmic reticulum stress, autophagy, and apoptosis in vitro and in vivo.

Purpose: The development of new cancer drugs is slow and costly. HIV protease inhibitors are Food and Drug Administration approved for HIV patients. Because these drugs cause toxicities that can be associated with inhibition of Akt, an emerging target in cancer, we assessed the potential of HIV protease inhibitors as anticancer agents.

Acute pancreatitis presenting as sudden, unexpected death: an autopsy-based study of 27 cases.

Acute pancreatitis represents a spectrum of disease, ranging from a mild, transitory illness to a severe, rapidly progressive hemorrhagic form, with massive necrosis and mortality rates of up to 24%. The reported incidence of acute pancreatitis diagnosed first at clinicopathologic autopsy ranges between 30% and 42%. To better describe outpatient fatalities due to acute pancreatitis that present as sudden, unexpected death, we retrospectively reviewed the autopsy files at the Institute of Legal Medicine, University of Hamburg, Germany, from 2000-2004.

Symmetrical "mirror-image" injuries and the "chessboard" pattern: useful markers of self-mutilation.

The evaluation of injuries due to self-mutilation may be complicated by atypical lesions and fabricated histories of the causative events. Four cases are described where one of the most striking findings was the presence of "mirror-image" injuries and/or a "chessboard" pattern of intersecting parallel lines from self-inflicted incised wounds. Case 1: A 32-year-old man was dead in his burnt-out car, with symmetrical, "mirror-image", circular burns from the car cigarette lighter over his forehead, cheeks, ears, upper and lower arms, the dorsal and palmar aspects of the hands, the anterior chest wall including the nipples, the anterior abdomen, thighs, lower legs, and the back of his neck.

Vertebral column kyphoscoliosis and unexpected death.

A case of spontaneous gastric perforation is reported in a 75-year-old woman due to massive hemorrhaging from a benign gastric ulcer. Blood was prevented from leaving the stomach due to posterior displacement and rotation of the stomach associated with marked underlying vertebral column kyphoscoliosis. Significant deformity of the spine had caused malpositioning of the stomach as a result of the abnormal shape of the peritoneal and chest cavities.

Laparoscopic cholecystectomy associated lethal hemorrhage.

Background And Objectives: Blood oozing after cholecystectomy is a rare but potentially life-threatening complication. Recently, 2 patients died from this cause. The deaths resulted in criminal proceedings and medical experts were called in.

Forensic issues in cases of Diogenes syndrome.

Diogenes syndrome is a syndrome described in the clinical literature in elderly individuals characterized by social isolation and extreme squalor. A number of typical features are found in the forensic evaluation of these deaths as the cases usually initiate medicolegal investigations due to the circumstances and the lack of recorded medical histories. Examinations of the death scenes are often difficult as victim's houses are in a state of disrepair, with filth and clutter, and pet dogs may resent the intrusion of strangers.

Extensive and mutilating craniofacial trauma involving defleshing and decapitation: unusual features of fatal dog attacks in the young.

Four cases of fatal dog attacks are reported in 3 children aged 6, 10, and 11 years and in an infant aged 3 weeks. The cases were all characterized by extensive and mutilative stripping of soft tissues from the face and scalp, progressing to decapitation in the infant. The attacks were highly focused, involving 2 dogs in all but 1 case, with the area of trauma localized to the craniofacial region.

Interferon-gamma sensitizes resistant Ewing's sarcoma cells to tumor necrosis factor apoptosis-inducing ligand-induced apoptosis by up-regulation of caspase-8 without altering chemosensitivity.

Ewing's sarcoma cells are highly susceptible to apoptosis via tumor necrosis factor apoptosis-inducing ligand (TRAIL). Resistance to TRAIL has been linked to deficient expression of caspase-8 in vitro. Here, we report on the status of caspase-8 expression in tumors from patients with Ewing's sarcoma, the effect of interferon-gamma on caspase-8 expression and apoptosis, and the role of caspase-8 for TRAIL- and chemotherapy-mediated apoptosis in Ewing's sarcoma.

Adenoviral gene transfer in bovine adrenomedullary and murine pheochromocytoma cells: potential clinical and therapeutic relevance.

Recombinant adenoviruses (rAd) have been widely used as gene transfer vectors both in the laboratory and in human clinical trials. In the present study, we investigated the effects of adenoviral-mediated gene transfer in primary bovine adrenal chromaffin cells (BACC) and a murine pheochromocytoma cell line (MPC). Cells were infected with one of three nonreplicating E1/E3-deleted (E1(-)/E3(-)) rAd vectors: Ad.

Sinonasal rhabdomyosarcoma in children and young adults.

Rhabdomyosarcoma is an aggressive malignant tumor often developing in the head and neck in children. In the sinonasal region, rhabdomyosarcoma constitutes a clinically important group because of the difficulty of surgical resection and its generally poor prognosis. We reviewed the archival pathology materials of 39 cases of rhabdomyosarcoma of the head and neck in children and young adults.

Phosphoprotein pathway mapping: Akt/mammalian target of rapamycin activation is negatively associated with childhood rhabdomyosarcoma survival.

Mapping of protein signaling networks within tumors can identify new targets for therapy and provide a means to stratify patients for individualized therapy. Despite advances in combination chemotherapy, the overall survival for childhood rhabdomyosarcoma remains approximately 60%. A critical goal is to identify functionally important protein signaling defects associated with treatment failure for the 40% nonresponder cohort.

[Atypical injury pattern of a pedestrian run over by an unimog in the epigastric region].

Strongly intoxicated, a 37-year-old man fell in front of the right back wheel of an emergency vehicle (MB Unimog) and was run over according to eye witnesses. He died in hospital shortly afterwards. The autopsy revealed that he bled to death from a traumatic liver rupture (bursting of the right hepatic lobe and severing of a piece of tissue measuring 17 x 8 x 4 cm).

Pathology of fatal traumatic and nontraumatic clostridial gas gangrene: a histopathological, immunohistochemical, and ultrastructural study of six autopsy cases.

We prospectively investigated six fatal cases of clostridial gas gangrene using autopsy, histology, immunohistochemistry, microbiology, and scanning electron microscopy. The causative pathogen was Clostridium perfringens in four cases, C. sordellii in one case, and a mixed infection with both C.

High-frequency ultrasound confirmation of positional plagiocephaly.

Object: Positional plagiocephaly has become an increasing problem for pediatricians and craniofacial specialists. Diagnosis is commonly based on history and clinical features, but may be difficult in some cases when characteristic features are missing and radiographic studies seem to be necessary. Near-field high-frequency ultrasound has been used to evaluate the sonographic findings of suture anatomy and confirm the diagnosis of positional plagiocephaly as well as provide information of prognostic value.

Massive, fatal aspiration of blood: not necessarily a result of trauma.

We report the rare pathologic finding of massive, fatal aspiration of blood in an 82-year-old woman, originating from a ruptured atherosclerotic aneurysm of the ascending part of the thoracic aorta eroding into the left lung. This case demonstrates that lethal bilateral hemoaspiration does not necessarily have to be the result of trauma and that in such cases, the bleeding site does not have to be situated above the trachea.

Sialylated core 1 O-glycans influence the sorting of Pmel17/gp100 and determine its capacity to form fibrils.

Pmel17 is a melanocyte/melanoma-specific protein that is essential for the maturation of melanosomes to form mature, fibrillar, and pigmented organelles. Recently, we reported that the less glycosylated form of Pmel17 (termed iPmel17) is sorted via the plasma membrane in a manner distinct from mature Pmel17 (termed mPmel17), which is sorted directly to melanosomes. To clarify the mechanism(s) underlying the distinct processing and sorting of Pmel17, we generated a highly specific antibody (termed alphaPEP25h) against an epitope within the repeat domain of Pmel17 that is sensitive to changes in O-glycosylation.

Increasing survival of ischemic tissue by targeting CD47.

Thrombospondin-1 (TSP1) limits the angiogenic and vasodilator activities of NO. This activity of TSP1 can be beneficial in some disease states, but endogenous TSP1 limits recovery of tissue perfusion following fixed ischemic injury in dorsal skin flaps in mice. Using mice lacking the TSP1 receptors CD36 or CD47, we now show that CD47 is the necessary receptor for limiting NO-mediated vascular smooth muscle relaxation and tissue survival following ischemic injury in skin flaps and hindlimbs.

Increased tumor localization and reduced immune response to adenoviral vector formulated with the liposome DDAB/DOPE.

Unlabelled: We aimed to increase the efficiency of adenoviral vectors by limiting adenoviral spread from the target site and reducing unwanted host immune responses to the vector. We complexed adenoviral vectors with DDAB-DOPE liposomes to form adenovirus-liposomal (AL) complexes. AL complexes were delivered by intratumoral injection in an immunocompetent subcutaneous rat tumor model and the immunogenicity of the AL complexes and the expression efficiency in the tumor and other organs was examined.

Fatal bleeding from major femoral vessels: three case reports.

We present three unusual cases of fatal bleeding from eroded femoral blood vessels. Erosion was due to tumor metastases in one and abscess formation in two cases. Bleeding occurred from the femoral vein in two cases and from the femoral artery in one case.