Limbic progesterone receptor activity enhances neuronal excitability and seizures.

Objective: Emerging evidence raises the possibility that progesterone receptor (PR) signaling may contribute to the reproductive hormone fluctuation-linked seizure precipitation, called catamenial epilepsy. Therefore, we studied PR isoform expression in limbic regions involved in temporal lobe epilepsy and the effect of PR activation on neuronal activity and seizures.

Methods: We evaluated PR expression in the limbic regions, entorhinal cortex (EC), hippocampus, and amygdala in female rats using quantitative real-time polymerase chain reaction (qRT-PCR).

Progesterone modulates neuronal excitability bidirectionally.

Progesterone acts on neurons directly by activating its receptor and through metabolic conversion to neurosteroids. There is emerging evidence that progesterone exerts excitatory effects by activating its cognate receptors (progesterone receptors, PRs) through enhanced expression of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs). Progesterone metabolite 5α,3α-tetrahydro-progesterone (allopregnanolone, THP) mediates its anxiolytic and sedative actions through the potentiation of synaptic and extrasynaptic γ-aminobutyric acid type-A receptors (GABARs).

N-methyl-D-aspartic acid receptor activation downregulates expression of δ subunit-containing GABAA receptors in cultured hippocampal neurons.

Neurosteroids are endogenous allosteric modulators of GABAA receptors (GABARs), and they enhance GABAR-mediated inhibition. However, GABARs expressed on hippocampal dentate granule neurons of epileptic animals are modified such that their neurosteroid sensitivity is reduced and δ subunit expression is diminished. We explored the molecular mechanisms triggering this GABAR plasticity.

M-type potassium channels modulate Schaffer collateral-CA1 glutamatergic synaptic transmission.

Previous studies have suggested that muscarinic receptor activation modulates glutamatergic transmission. M-type potassium channels mediate the effects of muscarinic activation in the hippocampus, and it has been proposed that they modulate glutamatergic synaptic transmission. We tested whether M1 muscarinic receptor activation enhances glutamatergic synaptic transmission via the inhibition of the M-type potassium channels that are present in Schaffer collateral axons and terminals.

Central cholinesterase inhibition enhances glutamatergic synaptic transmission.

Central cholinergic overstimulation results in prolonged seizures of status epilepticus in humans and experimental animals. Cellular mechanisms of underlying seizures caused by cholinergic stimulation remain uncertain, but enhanced glutamatergic transmission is a potential mechanism. Paraoxon, an organophosphate cholinesterase inhibitor, enhanced glutamatergic transmission on hippocampal granule cells synapses by increasing the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) in a concentration-dependent fashion.

Hemodialysis for the non-nephrologist.

Hemodialysis is now routinely provided to more than 300,000 patients in the United States. An epidemic of end-stage renal disease will nearly double this number by 2010. Patients undergoing chronic hemodialysis have high morbidity and mortality rates.

Modulation of histone deposition by the karyopherin kap114.

The nuclear import of histones is a prerequisite for the downstream deposition of histones to form chromatin. However, the coordinate regulation of these processes remains poorly understood. Here we demonstrate that Kap114p, the primary karyopherin/importin responsible for the nuclear import of histones H2A and H2B, modulates the deposition of histones H2A and H2B by the histone chaperone Nap1p.

Cultured Hippocampal Pyramidal Neurons Express Two Kinds of GABAA Receptors.

We combined a study of the subcellular distribution of the alpha1, alpha2, alpha4, beta1, beta2/3, gamma2, and delta subunits of the GABAA receptor with an electrophysiological analysis of GABAA receptor currents determine the to types of receptors expressed on cultured hippocampal pyramidal neurons. The immunocytochemistry study demonstrated that alpha1, alpha2, beta2/3, and gamma2 subunits formed distinct clusters of various sizes, which were colocalized with clusters of glutamate decarboxylase (GAD) immunoreactivity at rates ranging from 22 to 58%. In contrast, alpha4, beta1, and delta subunits were distributed diffusely over the cell soma and neuronal processes of cultured neurons and did not colocalize with the synaptic marker GAD.

Aneurysm growth, elastinolysis, and attempted doxycycline inhibition of elastase-induced aneurysms in rabbits.

Purpose: To establish the relationship between elastin degradation and aneurysm growth in New Zealand white rabbit model aneurysms, and to explore the potential for pharmacologic inhibition of elastinolysis and aneurysm growth with use of the matrix metalloproteinase (MMP) inhibitor doxycycline.

Materials And Methods: Elastase-induced, saccular aneurysms created in the right common carotid artery in 30 animals randomly divided into controls (n = 16) and doxycycline treated (n = 14) were studied. Aneurysm growth was determined by angiography and aneurysm specimens were collected at 7 and 14 days for histologic and immunohistochemical analysis.

A presynaptic action of the neurosteroid pregnenolone sulfate on GABAergic synaptic transmission.

The endogenous neurosteroid pregnenolone sulfate (PS) is known to enhance memory and cognitive function at nanomolar concentrations. However, the effect of these low concentrations on synaptic transmission has not been previously studied. The effects of PS on GABAA receptor-mediated inhibitory postsynaptic currents were studied in cultured hippocampal pyramidal neurons.

Evaluation of peptide vaccine immunogenicity in draining lymph nodes and peripheral blood of melanoma patients.

Many peptide epitopes for cytotoxic T lymphocytes (CTLs) have been identified from melanocytic differentiation proteins. Vaccine trials with these peptides have been limited mostly to those associated with HLA-A2, and immune responses have been detected inconsistently. Cases of clinical regression have been observed after peptide vaccination in some trials, but melanoma regressions have not correlated well with T-cell responses measured in peripheral blood lymphocytes (PBLs).

The spindle checkpoint: two transitions, two pathways.

The spindle checkpoint is an evolutionarily conserved mitotic regulatory mechanism that ensures that anaphase is not attempted until chromosomes are properly aligned on the spindle. Two different cell-cycle transitions must be inhibited by the spindle checkpoint to arrest cells at metaphase and prevent mitotic exit. The checkpoint proteins interact in ways that are more complex than was originally envisioned.

Secondary gain influences the outcome of lumbar but not cervical disc surgery.

Background: The expectation of monetary compensation has been associated with poor outcomes in lumbar discectomy, fueling a reluctance among surgeons to treat worker's compensation cases. This issue, however, has not been investigated in patients undergoing cervical disc surgery. This study analyzes the relationship between economic forms of secondary gain and surgical outcome in a group of patients with common pay scales, retirement plans, and disability programs.

Virulence factors of Entamoeba histolytica.

Recent studies have increased our knowledge of Entamoeba histolytica cell biology and gene regulation. In the ameba, dominant-negative mutations in the Gal/GalNAc lectin affect adhesion and cytolysis, whereas mutations in meromyosin affect cytoskeletal function. Studying these mutant proteins has improved our understanding of the role of these proteins in E.

Increased early morbidity and mortality with acceptable long-term function in severely obese patients undergoing liver transplantation.

The effect of obesity on outcomes following liver transplantation remains unclear. We reviewed our experience with 302 liver transplants in 277 patients from September 1989 to September 1996 to determine the effect of body mass on outcome. Two-hundred and seventeen transplants were performed in patients with a body mass index (BMI) < 30 kg/m2, 55 in patients with a BMI of 30-34 kg/m2 (obese), and 30 in patients with a BMI > 35 kg/m2 (severely obese).

Reversible posterior leukoencephalopathy following organ transplantation. Description of two cases.

Although neurologic changes after organ transplantation are often secondary to opportunistic infections or vascular insults, new pathological entities are emerging. We have recently encountered two patients who, a few days after liver and heart transplant, respectively, developed neurological signs and symptoms. Head computerized tomography (CT) scan showed nonenhancing areas of low attenuation, and magnetic resonance imaging (MRI) demonstrated multiple areas of increased signal intensity in the subcortical white matter on T2-weighted images.

Intravascular catheter colonization in critically ill children.

In a prospective study, cultures were obtained of all intravascular catheters removed from children in an intensive care unit. Of 366 catheters removed from 217 children, 110 (30%) were found to be colonized, most commonly with coagulase-negative staphylococci. Despite the high rate of colonization, there were only nine instances (2%) of catheter-related bacteremia.

Spiral waves and intracellular calcium signalling.

Confocal imaging of intracellular Ca2+ brings a new level of resolution to the study of hormonal control of intracellular Ca2+ release. This approach has demonstrated the existence of pulsatile circular and spiral waves of Ca+ release induced by receptor activation. The data obtained by confocal imaging support a new framework for understanding intracellular Ca2+ signalling.