Expression of transforming growth factor-β-responsive smads in cranial suture development and closure.

The transforming growth factor-β (TGF-β) family of extracellular signaling molecules is heavily involved in developmental events, including patterning, formation, maintenance, and closure of the cranial suture. Several studies have demonstrated that TGF-βs are temporally and spatially localized to the suture and play a pivotal role in sutural state. These signals are translated into intracellular activity through a family of proteins known as smads.

Angiotensin AT₂ receptor stimulation inhibits early renal inflammation in renovascular hypertension.

Angiotensin II type 2 receptor (AT₂R) counteracts most effects of angiotensin II type 1 receptor (AT(1)R). We hypothesized that direct AT₂R stimulation reduces renal production of the inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and transforming growth factor-β1 (TGF-β1) and enhances the production of nitric oxide (NO) and cyclic guanosine 3',5'-monophosphate (cGMP) in the clipped kidney of 2-kidney, 1-clip (2K1C) hypertension rat model. We used Sprague-Dawley rats to evaluate changes in renal interstitial fluid recovery levels of TNF-α, IL-6, NO, and cGMP; renal expression of AT₁R, AT₂R, TGF-β1, TNF-α, and IL-6 in sham and 2K1C rats treated for 4 days with vehicle, AT₂R agonist compound 21 (C21), or AT₂R antagonist PD123319 (PD), alone and combined (n=6, each group).

Overhead throwing injuries of the shoulder and elbow.

Injuries to the shoulder and elbow are common in athletes involved in sporting activities that require overhead motion of the arm. An understanding of the forces involved in the throwing motion, the anatomic structures most at risk, and the magnetic resonance imaging appearances of the most common associated injuries can help to improve diagnostic accuracy when interpreting imaging studies in these patients.

Early draining vein occlusion after gamma knife surgery for arteriovenous malformations.

Background: Increased signals on T2-weighted magnetic resonance imaging usually interpreted as radiation-induced changes or brain edema is a common short- to mid-term complication after Gamma Knife surgery (GKS) for intracranial arteriovenous malformations (AVMs), although its nature remains to be clarified. Early draining vein occlusion with resultant brain edema or hemorrhage, although well established in surgical series, was not described in radiosurgical literature until recently.

Objective: To outline the incidence, clinical manifestations, and outcomes of this unusual complication in our series of 1256 AVM patients treated with GKS.

Gamma knife radiosurgery for brain metastasis of nonsmall cell lung cancer: is there a difference in outcome between morning and afternoon treatment?

Background: Circadian cell-cycle progression causes fluctuating radiosensitivity in many tissues, which could affect clinical outcomes. The purpose of this study was to determine whether outcomes of single-session gamma knife radiosurgery (GKRS) for metastatic nonsmall cell lung cancer (NSCLC) differ based on treatment time.

Methods: Fifty-eight patients received GKRS between 10:00 am and 12:30 pm and 39 patients received GKRS between 12:30 pm and 3:00 pm.

Stereotactic radiosurgery for WHO grade I meningiomas.

Meningiomas represent a common intracranial tumor in the adult population. Although extirpation to achieve a gross total resection or at least decrease mass effect has been the mainstay of treatment, stereotactic radiosurgery has come to play an increasingly important role in the management of patients with meningiomas. Radiosurgery utilizes highly focused, beams of ionizing radiation to inactivate tumor cells.

Temozolomide-induced inhibition of pituitary adenoma cells.

Object: Aggressive pituitary adenomas frequently require multimodality treatment including pituitary-suppressive medications, microsurgery, and radiation therapy or radiosurgery. The effectiveness of temozolomide in terms of growth suppression and decreased hormonal production is evaluated.

Methods: Three pituitary adenoma cell lines--MMQ, GH3, and AtT20--were used.

IgM, Fc mu Rs, and malarial immune evasion.

IgM is an ancestral Ab class found in all jawed vertebrates, from sharks to mammals. This ancient ancestry is shared by malaria parasites (genus Plasmodium) that infect all classes of terrestrial vertebrates with whom they coevolved. IgM, the least studied and most enigmatic of the vertebrate Igs, was recently shown to form an intimate relationship with the malaria parasite Plasmodium falciparum.

Adipocytes constitutively release factors that accelerate keratinocyte proliferation in vitro.

Keratinocytes grown directly on adipose tissue have greater proliferation rates than keratinocytes grown alone. It is unknown if factors released by adipose tissue into culture media could increase keratinocyte proliferation without requiring incorporation of adipose tissue into skin graft models, or serve as a substitute for the fibroblast feeder layer.Human keratinocytes were grown with and without NIH 3T3 fibroblast feeder layer in the following conditions (12 cultures per group) adipose tissue coculture (AT), cultures supplemented with medium from whole adipose tissue referred to as adipose-conditioned medium (ACM), and control.

Closed-loop artificial pancreas using subcutaneous glucose sensing and insulin delivery and a model predictive control algorithm: the Virginia experience.

Background: Recent progress in the development of clinically accurate continuous glucose monitors (CGMs), automated continuous insulin infusion pumps, and control algorithms for calculating insulin doses from CGM data have enabled the development of prototypes of subcutaneous closed-loop systems for controlling blood glucose (BG) levels in type 1 diabetes. The use of a new personalized model predictive control (MPC) algorithm to determine insulin doses to achieve and maintain BG levels between 70 and 140 mg/dl overnight and to control postprandial BG levels is presented.

Methods: Eight adults with type 1 diabetes were studied twice, once using their personal open-loop systems to control BG overnight and for 4 h following a standardized meal and once using a closed-loop system that utilizes the MPC algorithm to control BG overnight and for 4 h following a standardized meal.

A novel approach to preventing the hemolysis of paroxysmal nocturnal hemoglobinuria: both complement-mediated cytolysis and C3 deposition are blocked by a monoclonal antibody specific for the alternative pathway of complement.

The clinical hallmark of paroxysmal nocturnal hemoglobinuria (PNH) is chronic intravascular hemolysis that is a consequence of unregulated activation of the alternative pathway of complement (APC). Intravascular hemolysis can be inhibited in patients by treatment with eculizumab, a monoclonal antibody that binds complement C5 thereby preventing formation of the cytolytic membrane attack complex of complement. However, in essentially all patients treated with eculizumab, persistent anemia, reticulocytosis, and biochemical evidence of hemolysis are observed; and in a significant proportion, their PNH erythrocytes become opsonized with complement C3.

A protocadherin-cadherin-FLRT3 complex controls cell adhesion and morphogenesis.

Background: Paraxial protocadherin (PAPC) and fibronectin leucine-rich domain transmembrane protein-3 (FLRT3) are induced by TGFbeta signaling in Xenopus embryos and both regulate morphogenesis by inhibiting C-cadherin mediated cell adhesion.

Principal Findings: We have investigated the functional and physical relationships between PAPC, FLRT3, and C-cadherin. Although neither PAPC nor FLRT3 are required for each other to regulate C-cadherin adhesion, they do interact functionally and physically, and they form a complex with cadherins.

Clinical and pathological characteristics of brain metastasis resected after failed radiosurgery.

Objective: This study evaluates the tumor histopathology and clinical characteristics of patients who underwent resection of their brain metastasis after failed gamma knife radiosurgery.

Methods: This study was a retrospective review from a prospective database. A total of 1200 brain metastases in 912 patients were treated by gamma knife radiosurgery during a 7-year period.

Reducing irreducible complexity: divergence of quaternary structure and function in macromolecular assemblies.

The bacterial flagellar system is an intricate assembly (containing approximately 40 different proteins) that is involved in both protein secretion and bacterial motility. It has also become the icon of the neo-creationist movement in the United States, with the argument that it shows 'irreducible complexity' and could not have been the product of evolution. Recent studies provide new insights into the evolution of the flagellar system and lead to the suggestion that the divergence of quaternary structure in protein assemblies may be an underappreciated mechanism for rapid evolutionary divergence.

Driving mishaps among individuals with type 1 diabetes: a prospective study.

Objective: Hypoglycemia-related neuroglycopenia disrupts cognitive-motor functioning, which can impact driving safety. Retrospective studies suggest that drivers with type 1 diabetes experience more collisions and citations than their nondiabetic spouses. We present the first prospective data documenting the occurrence of apparent neuroglycopenia-related driving performance impairments.

Radiosurgery in the treatment of spinal metastases: tumor control, survival, and quality of life after helical tomotherapy.

Objective: The effectiveness and limitations of spinal radiosurgery using a helical TomoTherapy system for the treatment of spinal metastases are reviewed in this article.

Methods: This is a retrospective review of patients who underwent stereotactic radiosurgery for spinal metastases between July 2004 and December 2007. Radiographic follow-up consisted of magnetic resonance imaging to assess tumor growth control as well as pre- and posttreatment x-rays, which were used to measure changes in segmental angulation and deformity.

Nap1 and Chz1 have separate Htz1 nuclear import and assembly functions.

We analyzed the nuclear import and regulation of the yeast histone variant Htz1 (H2A.Z), and the role of histone chaperones Nap1 and Chz1 in this process. Copurification suggested that Htz1 and H2B dimerized in the cytoplasm prior to import.

Activating mutations in TOR are in similar structures as oncogenic mutations in PI3KCalpha.

TOR (Target of Rapamycin) is a highly conserved Ser/Thr kinase and a central controller of cell growth. Using the crystal structure of the related lipid kinase PI3KCgamma, we built a model of the catalytic region of TOR, from the FAT domain to near the end of the FATC domain. The model reveals that activating mutations in TOR, identified in yeast in a genetic selection for Rheb-independence, correspond to hotspots for oncogenic mutations in PI3KCalpha.

Postoperative outcomes and reliability of "sensation-sparing" sural nerve biopsy.

Sural nerve biopsy is a valuable tool for the diagnosis of neuropathic disorders. However, concerns of persisting pain and numbness resulting from traditional whole sural nerve biopsy have led to interfascicular dissection techniques with inconsistent benefits over whole nerve biopsy. In this study we describe a novel technique of atraumatic anterior fascicular sural nerve biopsy designed to preserve calcaneal sensation while maintaining diagnostic benefit, without requiring significant interfascicular dissection.

Safety profile of dexlansoprazole MR, a proton pump inhibitor with a novel dual delayed release formulation: global clinical trial experience.

Background: Dexlansoprazole MR is a dual delayed release formulation of dexlansoprazole, an enantiomer of lansoprazole.

Aim: To assess safety of dexlansoprazole MR in phase 3 clinical trials.

Methods: Data from 4270 patients receiving dexlansoprazole MR 30 mg (n = 455), 60 mg (n = 2311) or 90 mg (n = 1864); lansoprazole 30 mg (n = 1363); or placebo (n = 896) in six randomized controlled trials and a 12-month safety study were pooled.

Regulation of Lhb and Egr1 gene expression by GNRH pulses in rat pituitaries is both c-Jun N-terminal kinase (JNK)- and extracellular signal-regulated kinase (ERK)-dependent.

Pulsatile GNRH regulates the gonadotropin subunit genes in a differential manner, with faster frequencies favoring Lhb gene expression and slower frequencies favoring Fshb. Early growth response 1 (EGR1) is critical for Lhb gene transcription. We examined GNRH regulation of EGR1 and its two corepressors, Ngfi-A-binding proteins 1 and 2 (NAB1 and NAB2), both in vivo and in cultured rat pituitary cells.

The human IgM pentamer is a mushroom-shaped molecule with a flexural bias.

The textbook planar model of pentameric IgM, a potent activator of complement C1q, is based upon the crystallographic structure of IgG. Although widely accepted, key predictions of this model have not yet been directly confirmed, which is particularly important since IgG lacks a major Ig fold domain in its Fc region that is present in IgM. Here, we construct a homology-based structural model of the IgM pentamer using the recently obtained crystallographic structure of IgE Fc, which has this additional Ig domain, under the constraint that all of the cysteine residues known to form disulfide bridges both within each monomer and between monomers are bonded together.

Exercise-induced vasculitis associated with autoimmune disease.

Exercised-induced vasculitis (EIV) is an underreported and frequently misdiagnosed condition that occurs on the lower extremities shortly after exercise. Most reported cases have presented in healthy-appearing individuals, but some cases have been linked to other disease processes. A case report is presented of recurring EIV in a 65-year-old woman with a history of dermatitis herpetiformis; chronic, mildly elevated liver transaminases of unknown cause; microscopic colitis; celiac disease; multiple miscarriages; and heart block who was found to have autoimmune hepatitis upon workup of her rash.