Primary gonadal failure in men selectively amplifies the mass of follicle stimulating hormone (FSH) secreted per burst and increases the disorderliness of FSH release patterns: reversibility with testosterone replacement.

The neuroendocrine mechanisms by which primary gonadal failure in men increases mean serum FSH concentrations (castration-like response) are not known. To investigate the testosterone-dependent mechanisms of the FSH castration response: (i) blood was sampled at 10-min intervals for 24 h for later FSH assay in seven normal middle-aged men and in six patients with primary testicular failure, during testosterone withdrawal and after 6 weeks of parenteral testosterone replacement; (ii) using a specific two-site IRMA, serum FSH concentrations were measured, since this assay correlates well with an in-vitro Sertoli cell bioassay; (iii) multiparameter deconvolution analysis was then applied to estimate the frequency, amplitude, duration, and mass of underlying FSH secretory bursts, and the half-life of endogenous FSH, and (iv) approximate entropy was calculated to quantify the relative orderliness of FSH release over 24 h. Mean (+/- SEM) 24-h serum FSH concentrations were 3.

RalA and RalB: antagonistic relatives in cancer cell migration.

The Ral family of small G proteins has been implicated in tumorigenesis, invasion, and metastasis. However, little emphasis has been placed on clarifying the individual roles of the two Ral proteins, RalA and RalB, in these processes in view of their high sequence homology. Here we analyze the separate contributions of RalA and RalB in regulating cell migration, a necessary component of the invasive phenotype, in two human cancer cell lines; UMUC-3, a bladder carcinoma line, and the prostate carcinoma line, DU145.

Mimicry of a host anion channel by a Helicobacter pylori pore-forming toxin.

Bacterial pore-forming toxins have traditionally been thought to function either by causing an essentially unrestricted flux of ions and molecules across a membrane or by effecting the transmembrane transport of an enzymatically active bacterial peptide. However, the Helicobacter pylori pore-forming toxin, VacA, does not appear to function by either of these mechanisms, even though at least some of its effects in cells are dependent on its pore-forming ability. Here we show that the VacA channel exhibits two of the most characteristic electrophysiological properties of a specific family of cellular channels, the ClC channels: an open probability dependent on the molar ratio of permeable ions and single channel events resolvable as two independent, voltage-dependent transitions.

The effects of leukocyte-type 12/15-lipoxygenase on Id3-mediated vascular smooth muscle cell growth.

Objective: 12/15-lipoxygenase (12/15-LO) has been implicated in the pathogenesis of vascular disease. Vascular smooth muscle cell (VSMC) proliferation is a key component of the response to injury in vascular disease. The role of 12/15-LO in regulating VSMC proliferation is poorly understood.

Training room management of medical conditions: sports dermatology.

Athletes' skin is subject to a distinct array of physical and environmental stressors. Trauma, the elements, and pathogenic organisms constantly challenge the skin's integrity. This article intends to arm the clinician with a fundamental knowledge of infections, mechanical injuries, and environmental insults common to the skin of athletes.

Pulmonary embolism: comprehensive evaluation with MR ventilation and perfusion scanning with hyperpolarized helium-3, arterial spin tagging, and contrast-enhanced MRA.

Purpose: Development of a comprehensive magnetic resonance (MR) examination consisting of MR angiography (MRA) and MR ventilation and perfusion (MR V/Q) scan for the detection of pulmonary emboli (PE) and assessment of the technique in a rabbit model.

Materials And Methods: Reversible PE was induced by inflating a non-detachable silicon balloon in the left pulmonary artery of five New Zealand White rabbits. MR V/Q scans were obtained prior to, during, and after balloon deflation.

Teaching evidence-based medicine: should we be teaching information management instead?

To encourage high-quality patient care guided by the best evidence, many medical schools and residencies are teaching techniques for critically evaluating the medical literature. While a large step forward, these skills of evidence-based medicine are necessary but not sufficient for the practice of contemporary medicine. Incorporating the best evidence into the real world of busy clinical practice requires the applied science of information management.

Selective and efficient inhibition of the alternative pathway of complement by a mAb that recognizes C3b/iC3b.

The alternative pathway (AP) of the complement system plays an important role in tissue damage and inflammation associated with certain autoimmune diseases and with ischemia-reperfusion injury. Selective inhibition of the AP could prevent such pathologies while allowing the classical and lectin pathways of complement activation to continue to provide protection. Here we present data describing selective inhibition of the AP of complement by anti-C3b/iC3b monoclonal antibody (mAb) 3E7, and by a chimeric, "deimmunized" form of this mAb, H17, which contains the human IgG1 Fc region and was further modified by substitution of amino acids in order to remove T cell epitopes.

Management of bony deficiency in revision anterior cruciate ligament reconstruction using allograft bone dowels: surgical technique.

Revision anterior cruciate ligament (ACL) reconstruction surgery has become increasingly common over the past decade and its popularity is likely to rise further as the number of primary ACL reconstructions increases each year. More than 75% of all cases of failed ACL reconstruction are the result of technical error and, of these, more than 70% are attributed specifically to malpositioned tunnels. Management of tunnel malposition in revision surgery often requires innovative approaches for dealing with the resultant bony defects.

Anterior capsulorrhaphy: an in vitro comparison of volume reduction--arthroscopic plication versus open capsular shift.

Purpose: The purpose of this study was to objectively compare volume reduction after arthroscopic plication and open lateral capsular shift.

Type Of Study: Experimental cadaver study.

Methods: Fifteen fresh-frozen human cadaver shoulders were assigned to 1 of 2 groups: arthroscopic plication (n = 7) or open lateral capsular shift (n = 8).

Status epilepticus increases the intracellular accumulation of GABAA receptors.

Status epilepticus is a neurological emergency that results in mortality and neurological morbidity. It has been postulated that the reduction of inhibitory transmission during status epilepticus results from a rapid modification of GABA(A) receptors. However, the mechanism(s) that contributes to this modification has not been elucidated.

BRCA2 BRC motifs bind RAD51-DNA filaments.

Germ-line mutations in BRCA2 account for approximately half the cases of autosomal dominant familial breast cancers. BRCA2 has been shown to interact directly with RAD51, an essential component of the cellular machinery for homologous recombination and the maintenance of genome stability. Interactions between BRCA2 and RAD51 take place by means of the conserved BRC repeat regions of BRCA2.

Ocular abnormalities associated with advanced kidney disease and hemodialysis.

Patients undergoing chronic hemodialysis (HD) are subject to the unique effects of both uremia and the dialysis procedure on multiple organ systems. Many patients on chronic HD suffer from chronic eye diseases, such as diabetic retinopathy and glaucoma, and the interaction of these diseases with the dialysis procedure can lead to worsening of vision. This review focuses on the common eye diseases seen in patients undergoing chronic HD and how the dialysis procedure and the uremic state impact the visual system.

WAVE2 signaling mediates invasion of polarized epithelial cells by Salmonella typhimurium.

The bacterial pathogen Salmonella penetrates the intestinal epithelium by inducing its own phagocytosis into epithelial cells. The dramatic reorganization of the actin cytoskeleton required for internalization is driven by bacterial manipulation of host signaling pathways, including activation of the Rho family GTPase Rac1 and subsequent activation of the Arp2/3 complex. However, the mechanisms linking these two events remain poorly understood.

Intramedullary spinal cysticercosis. Case report and review of the literature.

Cysticercosis is the most common parasitic infection of the central nervous system. It infrequently affects the spine, but when it does, it can present with symptoms similar to other more common spinal diseases. The authors present a case of isolated intramedullary cysticercosis of the cervical spine and review the literature.

Tumor control outcomes of patients treated with trimodality therapy for locally advanced prostate cancer.

Objectives: To evaluate, in a pilot study, the tumor control outcomes of our approach and define the pretreatment characteristics that predict a response to therapy. Patients with advanced clinically localized prostate cancer have a high likelihood of prostate-specific antigen (PSA) failure 3 to 5 years after initial treatment. We adopted trimodality therapy (neoadjuvant and adjuvant androgen ablation, external beam radiotherapy [RT], and a brachytherapy boost) to augment biochemical disease-free survival in this patient population.

Stress fracture of the pedicle after extensive decompression and contralateral posterior fusion for lumbar stenosis. Report of three cases.

Lumbar spinal stenosis can be effectively treated by performing an extensive ipsilateral spinal decompression, including a partial pediculotomy, and contralateral posterior bone fusion. Infrequently, complications can arise following radical decompression to alleviate symptoms of stenosis, and one such complication is a pedicle fracture. Three reports of pedicle fractures following extensive spinal decompression and contralateral posterior fusion are detailed.

Quantitative methods to analyze subnuclear protein organization in cell populations with varying degrees of protein expression.

The control of gene transcription is dependent on DNA-binding and coregulatory proteins that assemble in distinct regions of the cell nucleus. We use multispectral wide-field microscopy of cells expressing transcriptional coregulators labeled with fluorescent proteins (FP) to study the subnuclear localization and function of these factors in living cells. In coexpression studies, the glucocorticoid receptor interacting protein (GRIP) coactivator protein and the silencing mediator of retinoid and thyroid (SMRT) corepressor protein form spherical subnuclear focal bodies that are spatially distinct, suggesting that specific protein interactions concentrate these divergent proteins in separate subnuclear regions.

Toll-like receptor 2-mediated gene expression in epithelial cells during Helicobacter pylori infection.

Background: Helicobacter pylori is the major pathogen causing chronic gastritis and peptic ulcer disease and is closely linked to gastric malignancy. We have previously shown that H. pylori-induced NF-(kappa)B activation and interleukin (IL)-8 secretion are mediated by Toll-like receptor (TLR) 2 in epithelial cells.

Nuclear import of TFIIB is mediated by Kap114p, a karyopherin with multiple cargo-binding domains.

Nuclear import and export is mediated by an evolutionarily conserved family of soluble transport factors, the karyopherins (referred to as importins and exportins). The yeast karyopherin Kap114p has previously been shown to import histones H2A and H2B, Nap1p, and a component of the preinitiation complex (PIC), TBP. Using a proteomic approach, we have identified several potentially new cargoes for Kap114p.

Undetectable prostate specific antigen at 6-12 months: a new marker for early success in hormonally treated patients after prostate brachytherapy.

Background: The concept of a prostate-specific antigen (PSA) "nadir" has been used as a predictive marker for treatment success in patients treated with radiotherapy for localized prostate carcinoma. However, this approach is not applicable in patients who are concomitantly treated with short-term hormonal therapies. To address this, the authors sought to develop a new predictive marker in such patients after prostate brachytherapy (BT).

Surgical management of unruptured basilar artery bifurcation aneurysms. Technical note.

The basilar artery (BA) bifurcation is the most common site for aneurysms arising from the posterior circulation. Their inhospitable location, nested within the narrow confines of the interpeduncular fossa anterior to the brainstem, coupled with the rich network of adjacent critical thalamoperforating arteries irrigating the midbrain and thalamus, pose difficult anatomical obstacles for the surgeon. The age old adage that the only cure for intracranial aneurysms remains exclusion from circulation before rupture still holds true.