Heterogeneity in the pyramidal network of the medial prefrontal cortex.

The prefrontal cortex is specially adapted to generate persistent activity that outlasts stimuli and is resistant to distractors, presumed to be the basis of working memory. The pyramidal network that supports this activity is unknown. Multineuron patch-clamp recordings in the ferret medial prefrontal cortex showed a heterogeneity of synapses interconnecting distinct subnetworks of different pyramidal cells.

Parkin protects against mitochondrial toxins and beta-amyloid accumulation in skeletal muscle cells.

Mutations in the ubiquitin ligase-encoding Parkin gene have been implicated in the pathogenesis of autosomal recessive Parkinson disease. Outside of the central nervous system, Parkin is prominently expressed in skeletal muscle. We have found accumulations of Parkin protein in skeletal muscle biopsies taken from patients with inclusion body myositis, a degenerative disorder in which intramyofiber accumulations of the beta-amyloid peptide are pathognomonic.

Emp is a component of the nuclear matrix of mammalian cells and undergoes dynamic rearrangements during cell division.

Emp, originally detected in erythroblastic islands, is expressed in numerous cell types and tissues suggesting a functionality not limited to hematopoiesis. To study the function of Emp in non-hematopoietic cells, an epitope-tagged recombinant human Emp was expressed in HEK cells. Preliminary studies revealed that Emp partitioned into both the nuclear and Triton X-100-insoluble cytoskeletal fractions in approximately a 4:1 ratio.

Synergistic effect of combined intramyocardial CD34+ cells and VEGF2 gene therapy after MI.

Previous studies have shown that local angiogenic gene therapy acts, in part, by recruiting endothelial progenitor cells (EPCs) to ischemic tissue. Recent data indicate that patients with the most severe vascular disease may have insufficient or deficient EPCs and the poorest response to angiogenic therapy. Accordingly, we hypothesized that combining human CD34(+) cell implantation with local vascular endothelial growth factor 2 (phVEGF2) gene therapy might overcome these deficiencies.

Endothelial progenitor thrombospondin-1 mediates diabetes-induced delay in reendothelialization following arterial injury.

Delayed reendothelialization contributes to restenosis after angioplasty and stenting in diabetes. Prior data have shown that bone marrow (BM)-derived endothelial progenitor cells (EPCs) contribute to endothelial recovery after arterial injury. We investigated the hypothesis that the EPC contribution to reendothelialization may be impaired in diabetes, resulting in delayed reendothelialization.

Posttraumatic stress disorder after occupational HIV exposure: two cases and a literature review.

Two healthcare workers developed disabling chronic posttraumatic stress disorder after needlestick exposures to blood from a patient infected with human immunodeficiency virus (HIV), even though both continue to test negative for HIV antibody more than 22 months after their exposures. We describe these 2 cases and review the relevant literature. Prospective studies of psychological morbidity after occupational needlestick injuries are required to determine the role of long-term psychological follow-up, counseling, and support.

Combined data from two phase III trials of the NK1 antagonist aprepitant plus a 5HT 3 antagonist and a corticosteroid for prevention of chemotherapy-induced nausea and vomiting: effect of gender on treatment response.

Goals Of Work: Prevention of chemotherapy-induced nausea and vomiting (CINV) with standard antiemetics has been more difficult to achieve in female patients. Data from two phase III trials of the NK1 antagonist aprepitant were assessed for potential effect of gender on treatment response.

Patients And Methods: 1,044 patients receiving cisplatin (> or = 70 mg/m2) were randomly assigned to control regimen [ondansetron (O) 32 mg i.

Dissociation of ERK and Akt signaling in endothelial cell angiogenic responses to beta-amyloid.

Cerebrovascular deposits of beta-amyloid (Abeta) peptides are found in Alzheimer's disease and cerebral amyloid angiopathy with stroke or dementia. Dysregulations of angiogenesis, the blood-brain barrier and other critical endothelial cell (EC) functions have been implicated in aggravating chronic hypoperfusion in AD brain. We have used cultured ECs to model the effects of beta-amyloid on the activated phosphorylation states of multifunctional serine/threonine kinases since these are differentially involved in the survival, proliferation and migration aspects of angiogenesis.

Functional disruption of alpha4 integrin mobilizes bone marrow-derived endothelial progenitors and augments ischemic neovascularization.

The cell surface receptor alpha4 integrin plays a critical role in the homing, engraftment, and maintenance of hematopoietic progenitor cells (HPCs) in the bone marrow (BM). Down-regulation or functional blockade of alpha4 integrin or its ligand vascular cell adhesion molecule-1 mobilizes long-term HPCs. We investigated the role of alpha4 integrin in the mobilization and homing of BM endothelial progenitor cells (EPCs).

Airway obstruction in never smokers: results from the Third National Health and Nutrition Examination Survey.

Purpose: Chronic obstructive pulmonary disease (COPD) is usually described as a disease of cigarette smoking. COPD is rarely considered in persons with no smoking history except in the context of another exposure. Accordingly, the disease has not been well characterized in these "never smokers.

Progression of chronic kidney disease: can it be prevented or arrested?

Chronic kidney disease constitutes a highly prevalent health problem worldwide. Left untreated, it progresses inexorably to greater levels of severity at variable rates. The morbid impact of chronic kidney disease is heightened by its role as risk factor for cardiovascular disease.

High septal osteotomy in rhinoplasty for the deviated nose.

When attempting to straighten a patient's healed, deviated bony nasal dorsum, deviation of the central structure (high dorsal septum and medial nasal bones) must be addressed following the completion of medial and lateral osteotomies. When hump resection is not performed, blunt fracture (digitally or with forceps) of the deviated central structure is not a reliable method of mobilization, often leading to postoperative nasal drift. An intranasal osteotomy technique to mobilize the central structure of the nose is described, called "high septal osteotomy.

The acute phase reactant, fibrinogen, as a guide to plasma exchange therapy for acute Guillain-Barré syndrome.

The Guillian Barré syndrome is an acute inflammatory disorder for which plasma exchange is effective treatment. Up to 10% relapse after plasma exchange suggesting that treatment sometimes finishes before disease activity has resolved. We studied whether plasma fibrinogen, an inflammatory marker, might be used to determine when to discontinue plasma exchange in patients with acute Guillain-Barré syndrome.

Massachusetts cardiac surgery report card: implications of statistical methodology.

Background: Choice of statistical methodology may significantly impact the results of provider profiling, including cardiac surgery report cards. Because of sample size and clustering issues, logistic regression may overestimate systematic interprovider variability, leading to false outlier classification. Theoretically, the use of hierarchical models should result in more accurate representation of provider performance.

Comparison of the effectiveness of two liquid-based Papanicolaou systems in the handling of adverse limiting factors, such as excessive blood.

Background: Excessive blood may compromise gynecologic Papanicolaou (Pap) smears. Liquid-based cytologic techniques have been developed in part to address this problem. In the current study, conditions of excessive blood were simulated to compare the ability of two liquid-based systems, ThinPrep and SurePath, to satisfactorily process specimens in the presence of this potentially limiting factor.

Two Plasmodium falciparum merozoite proteins binding to erythrocyte band 3 form a direct complex.

Erythrocyte invasion by malaria parasites requires multiple protein interactions. Our earlier studies showed that erythrocyte band 3 is an invasion receptor binding Plasmodium falciparum merozoite surface protein 1 and 9 (MSP1, MSP9) existing as a co-ligand complex. In this study, we have used biochemical approaches to identify the binding sites within MSP1 and MSP9 involved in the co-ligand complex formation.

Host receptors in malaria merozoite invasion.

The clinical manifestations of Plasmodium falciparum malaria are directly linked to the blood stage of the parasite life cycle. At the blood stage, the circulating merozoites invade erythrocytes via a specific invasion pathway often identified with its dependence or independence on sialic acid residues of the host receptor. The invasion process involves multiple receptor-ligand interactions that mediate a complex series of events in a period of approximately 1 min.

Drug insight: New antiemetics in the management of chemotherapy-induced nausea and vomiting.

Nausea and vomiting remain among the most feared side effects of chemotherapy for cancer patients. Significant progress has been made in the last 15 years in developing more effective and better-tolerated measures to minimize chemotherapy-induced nausea and vomiting (CINV). During the 1990s, the selective 5-hydroxytryptamine receptor antagonists were first introduced for the treatment of CINV, and resulted in more effective and better tolerated treatment of CINV.

Future perspectives in COPD.

The pathophysiology of chronic obstructive pulmonary disease (COPD) is complex. The development of a multidimensional index--such as the BODE index--provides a means of classifying patients with COPD that also correlates with their prognosis. The individual components of the BODE index--body mass index (B), airflow obstruction (O) dyspnoea (D) and exercise capacity (E)--incorporate the pulmonary as well as the systemic effects seen in patients with COPD.

Therapeutic plasma exchange performed in tandem with hemodialysis for patients with M-protein disorders.

M-proteins are monoclonal immunoglobulins or immunoglobulin fragments that aberrantly accumulate in the plasma. Hemodialysis (HD) patients with M-proteins may, under certain circumstances, also need therapeutic plasma exchange (TPE). We employed a protocol for tandem TPE/HD in patients with M-protein disorders.

Topical anesthetics for dermal instrumentation: a systematic review of randomized, controlled trials.

Study Objective: We compare the analgesic efficacy of topical anesthetics for dermal instrumentation with conventional infiltrated local anesthesia and also compare topically available amide and ester agents with a eutectic mixture of local anesthetics (EMLA).

Methods: We conducted a systematic review of randomized, controlled trials. Relevant literature was identified through searches of MEDLINE, Cochrane Central Register of Controlled Trials, and the Excerpta Medica Database Drugs and Pharmacology.

N-acetyldopamine inhibits rat brain lipid peroxidation induced by lipopolysaccharide.

The effects of N-acetyldopamine, a sepiapterin reductase inhibitor, on lipopolysaccharide-induced lipid peroxidation were examined in rat brain homogenates in vitro. Lipid peroxidation in the form of malondialdehyde (MDA) was evaluated by the measurement of thiobarbituric acid (TBA) reactive substances. N-Acetyldopamine inhibited the formation of MDA in a concentration-dependent manner.

Immune-modulating effects of melatonin, N-acetylserotonin, and N-acetyldopamine.

Melatonin and N-acetylserotonin (NAS) have antioxidant properties. In the present study, we examined whether melatonin, NAS, and N-acetyldopamine (NAD) have a modulatory effect on tumor necrosis factor-alpha (TNF-alpha) synthesis and superoxide production. Differentiated THP-1-derived human monocytes were coincubated with Escherichia coli lipopolysaccharide (LPS) and rising concentrations of melatonin, NAS, or NAD.