No abstract

Summary. Background: ÔIdlingÕ or ongoing low-level activity of the tissue factor (TF) pathway is a postulated mechanism by which the coagulation process can become active without a lag period at sites of injury. Objective: To determine whether TF around cutaneous vessels has bound factor VIIa in the absence of injury, and thus could participate in the idling process. Methods: Immunostaining of mouse skin with antibodies against a 15-residue peptide from the sequence of mouse TF, and against the whole extracellular portion of TF. Results: The whole TF antibody recognized TF in squamous epithelium and around vessels in the dermis. By contrast, the monospecific antibody only recognized TF in the squamous epithelium, but not around vessels. We also found that biotinylated, active siteinhibited FVIIa (FVIIai) bound to tissue sections in the same areas in which TF was recognized by the monospecific antibody (squamous epithelium), but did not bind around vessels. Molecular modeling revealed that FVIIa and FX binding to TF masked a significant part of the surface of the target peptide. Conclusions: In the aggregate, these data are most consistent with the interpretation that TF in perivascular sites has bound FVIIa, even in the absence of any injury. The presence of endogenously bound FVIIa prevents the subsequent binding of the monospecific antibody or exogenous FVIIai to perivascular TF.

Restoring initial hemostasis can modulate some of the parameters of wound healing. However, an extended period of adequate hemostatic function is necessary to achieve normal healing, probably because the risk of hemorrhage is increased by vascular remodeling and angiogenesis during the healing process.

Healing of skin wounds is delayed in hemophilia B (HB) mice. HB mice do not bleed excessively at wounding, yet rebleed hours to days later. Tissue factor (TF) expression is up-regulated by inflammatory cytokines and has been linked to angiogenesis. We hypothesized that impaired thrombin generation in HB leads to impaired TF expression following injury. Punch biopsies were placed on wild-type (WT) and HB mice. Tissues from wound sites were immunostained for TF. Blood vessels are normally surrounded by a coat of pericytes expressing TF. Surprisingly, within a day after wounding TF disappeared from around nearby vessels; returning after 8 days in WT and 10 days in HB mice. The granulation tissue filling the wound during healing also lacked TF around angiogenic vessels. Thus, perivascular TF expression is downregulated during wound healing. This may prevent thrombosis of neovessels during angiogenesis but renders hemophiliacs vulnerable to hemorrhage during healing.

Intravenous leiomyomatosis (IVL) is an unusual uterine smooth muscle proliferation that can be associated with aggressive clinical behavior despite a histologically benign appearance. It has some overlapping molecular characteristics with both uterine leiomyoma and leiomyosarcoma based on limited genetic data. In this study, we assessed the clinical and morphological characteristics of 28 IVL and their correlation with molecular features and protein expression, using array comparative genomic hybridization (aCGH) and Cyclin D1, p16, phosphorylated-Rb, SMARCB1, SOX10, CAIX, SDHB and FH immunohistochemistry. The most common morphologies were cellular (n=15), usual (n=11) and vascular (n=5; including 3 cellular IVL showing both vascular and cellular features). Among the immunohistochemical findings, the most striking was that all IVL showed differential expression of either p16 or Cyclin D1 in comparison to surrounding non-neoplastic tissue. Cytoplasmic phosphorylated-Rb was present in all but one IVL with hyalinization. SMARCB1, FH and SDHB were retained; S0X10 and CAIX were not expressed. The most common genetic alterations involved 1p (39%), 22q (36%), 2q (29%), 1q (25%), 13q (21%) and 14q (21%). Hierarchical clustering analysis of recurrent aberrations revealed 3 molecular groups: Group 1 (29%) and 2 (18%) with associated del(22q) and group 3 (18%) with del(10q). The remaining IVL had non-specific or no alterations by aCGH. Genomic index scores were calculated for all cases and showed no significant difference between the 14 IVL associated with aggressive clinical behavior (extrauterine extension or recurrence) and those without (median scores 5.15 vs 3.5). Among the 5 IVL associated with recurrence, 4 had a vascular morphology and 3 had alterations of 8q. Recurrent chromosome alterations detected herein overlap with those observed in the spectrum of uterine smooth muscle tumors and involve genes implicated in mesenchymal tumors at different sites with distinct morphological features.

Primary liposarcomas of the uterus are extremely rare and are most likely to arise from malignant transformation of a lipoleiomyoma. These tumors should be added to the differential diagnosis of benign lipomatous tumors, myxoid mesenchymal tumors, and malignant mixed Müllerian tumors (if pleomorphic) of the uterus.

High-resolution CT coupled with histopathology provides elucidation of the morphology of the CML, a strong indicator of infant abuse. This new information may prove useful in assessing the biomechanical factors that produce this strong indicator of abusive assaults in infants.

Witnessed reports of sudden death are rare, but critical to deciphering its mechanism(s). We report such a death in a seemingly healthy 8-month-old boy in whom seizures and respiratory distress in the prone position were witnessed upon discovery during a sleep period. Following cardiopulmonary resuscitation, anoxic encephalopathy resulted in “brain death” and withdrawal of life support after 2 days. The autopsy did not reveal a primary anatomic cause of death. Metabolic evaluation failed to uncover an inborn error of ammonia, amino, organic, or fatty acid metabolism. Seizures in this case may have been secondary to cerebral hypoxia–ischemia complicating cardiorespiratory arrest of unknown etiology. Yet, they may represent the first manifestation of idiopathic epilepsy, triggering cardiopulmonary arrest, analogous to the terminal events postulated in sudden and unexplained death in epilepsy. This report alerts the forensic community to the possibility that sudden and unexplained death in infants may be due to seizures.