In vitro and ex vivo delivery of short hairpin RNAs for control of hepatitis C viral transcript expression.

Recurrent hepatitis C virus (HCV) infection is the most common cause of graft loss and patient death after transplantation for HCV cirrhosis. Transplant surgeons have access to uninfected explanted livers before transplantation and an opportunity to deliver RNA interference-based protective gene therapy to uninfected grafts. Conserved HCV sequences were used to design short interfering RNAs and test their ability to knockdown HCV transcript expression in an in vitro model, both by transfection and when delivered via an adeno-associated viral vector.

Additional triggers of endothelial disfunction modulate antiphospholipid-mediated microangiopathy in a central nervous system-cutaneous syndrome.

It is now recognised that the spectrum of antiphospholipid (aPL)-mediated syndromes includes end-organ injury due to microangiopathic manifestations. In the central nervous system (CNS), the clinical and radiographic appearance of microangiopathic lesions can be notoriously difficult to distinguish from multiple sclerosis (MS). A patient is presented who developed white-matter lesions in the brain and spinal-cord, shortly after receiving toxic doses of radiation for an arterio-venous malformation.

Air-medical transport experience in emergency medicine residencies: then and now.

Objective: The appropriate activation and effective utilization of air-medical transport (AMT) services is an important skill for emergency medicine physicians in the United States. Previous studies have demonstrated variability with regards to emergency medical services (EMS) experience during residency training. This study was designed to evaluate the nature and extent of AMT training of the emergency medicine residency programs in the United States.

Absence of deleterious palladin mutations in patients with familial pancreatic cancer.

It has been reported that germline mutations in the palladin gene (PALLD) cause the familial aggregation of pancreatic cancer, but the evidence is weak and controversial. We sequenced the coding regions of PALLD in 48 individuals with familial pancreatic cancer. We did not find any deleterious mutations and find no evidence to implicate mutations in PALLD as a cause of familial pancreatic cancer.

Basic science and neurobiological research: potential relevance to sexual compulsivity.

A unique challenge posed by advancing scientific knowledge about the biology of human behavior is how to integrate that understanding with the desire to hold ourselves--and one another--morally accountable. As human beings, we are something more than just passive agents whose behavior is the sum product of biologic determinism. Because of the existence of the mind, we are also active agents with the capacity to influence, at least to some extent, our own destinies.

Idiopathic infantile arterial calcification: the spectrum of clinical presentations.

Idiopathic infantile arterial calcification (IIAC) is a rare disorder characterized by extensive calcification of medium and large arteries. We report the case of a 32-week-old infant with hydrops fetalis and heart failure who died at 4 days of age. At autopsy the infant was found to have cardiomegaly, myocardial infarctions and multifocal calcifications of the aorta and arteries in the lungs, heart, thyroid, spleen, and testis.

Age-60 Rule: the end is in sight.

Recent implementation of the International Civil Aviation Organization (ICAO) amendment 167 to Annex 1 allows pilots from ICAO contracting states to fly until 65 yr old. In response to the new ICAO standard, the Federal Aviation Administration (FAA) commissioned an Aviation Rulemaking Committee (ARC) to make recommendations on whether the FAA should retain or amend the Age-60 Rule. Unable to reach a consensus, the ARC formed two working groups and submitted two position papers with opposing views.

Striatal dopamine release and family history of alcoholism.

Background: The offspring of alcohol-dependent individuals are at increased risk for alcoholism. The present study was designed to determine whether mesolimbic dopamine binding potential (BP), dopamine release, stress hormones, and subjective responses to intravenous amphetamine are different in nonalcoholic offspring from families with a history of alcohol dependence [family history positive (FHP)] than in nonalcoholic offspring without a family history of alcohol dependence [family history negative (FHN)].

Methods: Participants were 41 healthy men and women (11 FHP, 30 FHN; age range 18-29).

Genetic alterations and histopathologic findings in familial renal cell carcinoma.

Renal cell carcinoma is increasing in frequency in the United States and is often detected late in the course of disease due to nonspecific symptoms. A subset of renal cell carcinoma is attributable to familial or hereditary syndromes, including von Hippel-Lindau and Birt-Hogg-Dubé syndromes, among others. Understanding of the molecular alterations in patients with familial syndromes may provide some insight into the underlying mechanisms of disease initiation and progression.

Head and neck cancer cell lines exhibit differential mitochondrial repair deficiency in response to 4NQO.

Constituents of tobacco can cause DNA adduct formation and are implicated in head and neck squamous cell cancer (HNSC) development. We investigated the capacity of HNSC cell lines to repair mitochondrial DNA (mtDNA) damage induced by a DNA adduct-forming agent. HNSC cell lines underwent 4-nitroquinoline 1-oxide (4NQO) exposure with subsequent rescue with normal media.

Vascular endothelial growth factor receptor-2: counter-regulation by the transcription factors, TFII-I and TFII-IRD1.

The vascular endothelial growth factor receptor-2 (VEGFR-2/KDR/flk-1) functions as the primary mediator of vascular endothelial growth factor activation in endothelial cells. Regulation of VEGFR-2 expression appears critical in mitogenesis, differentiation, and angiogenesis. Transcriptional regulation of the VEGFR-2 is complex and may involve multiple putative upstream regulatory elements including E boxes.

Commentary: botulinum toxin in clinical medicine.

The recent introduction of botulinum toxin (BTX) into clinical medicine has revolutionized the practice of medicine and surgery forever. Who would have ever thought that the world's most deadly of all toxins would be used for therapeutic purposes? The discovery of the beneficial effects of BTX has transformed the lives of many unfortunate individuals who have suffered from a variety of unrelated disorders, which have been virtually impossible to treat. With the help of BTX, these and hopefully many other ailments will be easily managed with a few simple injections.

The afferent synapse of cochlear hair cells.

Mechanosensory hair cells of the cochlea must serve as both transducers and presynaptic terminals, precisely releasing neurotransmitter to encode acoustic signals for the postsynaptic afferent neuron. Remarkably, each inner hair cell serves as the sole input for 10-30 individual afferent neurons, which requires extraordinary precision and reliability from the synaptic ribbons that marshal vesicular release onto each afferent. Recent studies of hair cell membrane capacitance and postsynaptic currents suggest that the synaptic ribbon may operate by simultaneous multi-vesicular release.

Prevalence of venous thromboembolism in acute hemorrhagic and thromboembolic stroke.

Objective: Deep venous thromboembolism (DVT) is an important health issue in the hospitalized geriatric population that leads to increased length of stay, morbidity, and mortality. Patients with hemorrhagic strokes are usually not placed on prophylactic therapy because of the risk of hemorrhagic extension of the stroke. The purpose of this study was to evaluate the prevalence of DVTs in hospitalized patients with hemorrhagic vs.

Diagnosis of Wihipple disease by immunohistochemical analysis: a sensitive and specific method for the detection of Tropheryma whipplei (the Whipple bacillus) in paraffin-embedded tissue.

Whipple disease is a rare infection characterized clinically by diarrhea, fever, weight loss, arthralgia, malabsorption, and other systemic manifestations. The etiologic agent, Tropheryma whipplei, has been cultured only rarely. By using a polyclonal rabbit antibody produced against a cultured strain of T whipplei, tissue sections from 18 patients with Whipple disease were studied.

Metabolic abnormalities in HIV disease and injection drug use.

HIV infection is associated with a number of adverse consequences, including metabolic disorders. This article reviews disorders such as wasting, lipid metabolism disorders (including fat redistribution or dyslipidemia), glucose abnormalities, bone disease, and endocrine disorders such as hypogonadism in the presence of HIV infection and/or drug abuse. The issues covered are current estimations of prevalence, risk factors, underlying pathophysiology, diagnosis, and interventions (prevention and treatment) for metabolic complications of HIV and drug abuse.

Review article: genetic testing and counselling for hereditary colorectal cancer.

Colorectal cancer is the second leading cause of cancer death, after lung cancer, in the USA. The great majority (80%) of patients with colorectal cancer have sporadic disease with no evidence of having inherited the disorder. In the remaining 20%, a potentially definable genetic component exists.

Percutaneous vertebroplasty in benign and malignant disease.

Based on experience, published data, and published series, the authors recommend the use of vertebroplasty for painful destructive vertebral lesions. In the authors' opinion, the greatest difficulty lies in denying the treatment to patients with advanced metastatic disease, where other surgical or medical treatments may have greater morbidity and mortality. The few complications reported have been related to excessive PMMA injection, underlining the need for excellent imaging conditions to control the cement injection.

Aneurysmal subarachnoid hemorrhage: prognostic features and outcomes.

The prognostic features and outcomes associated with aneurysmal subarachnoid hemorrhage (SAH) are reviewed. In the first section, the epidemiology of SAH is discussed with emphasis on prevalence, incidence, risk factors, heredity, activity, and seasonal variability. In the second section, the presentation, diagnosis, and treatment of patients with aneurysmal SAH is briefly reviewed.

No allelic association of an exon 13 polymorphism of the Gsα gene to alcohol and/or drug dependence.

The adenylyl cyclase signal transduction system, a ubiquitous second messenger system, has been identified as a potential marker for genetic risk of alcohol and drug dependence. Using the polymerase chain reaction (PCR) to amplify exon 13 of the Gsα gene, two alleles were distinguished by denaturing gradient gel electrophoresis. One allele, designed A, contained the previously published C in the codon for asparagine 371, while the second allele, designated A, contains a C-T transition that conserves the asparagine residue at codon 371.

Characterization of a novel component of the peroxisomal protein import apparatus using fluorescent peroxisomal proteins.

Fluorescent peroxisomal probes were developed by fusing green fluorescent protein (GFP) to the matrix peroxisomal targeting signals PTS1 and PTS2, as well as to an integral peroxisomal membrane protein (IPMP). These proteins were used to identify and characterize novel peroxisome assembly (pas) mutants in the yeast Pichia pastoris. Mutant cells lacking the PAS10 gene mislocalized both PTS1-GFP and PTS2-GFP to the cytoplasm but did incorporate IPMP-GFP into peroxisome membranes.

High male:female ratio of germ-line mutations: an alternative explanation for postulated gestational lethality in males in X-linked dominant disorders.

In this paper I suggest that a vastly higher rate of de novo mutations in males than in females would explain some, if not most, X-linked dominant disorders associated with a low incidence of affected males. It is the inclusion of the impact of a high ratio of male:female de novo germ-line mutations that makes this model new and unique. Specifically, it is concluded that, if an X-linked disorder results in a dominant phenotype with a significant reproductive disadvantage (genetic lethality), affected females will, in virtually all cases, arise from de novo germ-line mutations inherited from their fathers rather than from their mothers.