Sonographic diagnosis of neuritis ossificans of the median nerve

We report the sonographic appearance of a rare case of neuritis ossificans of the median nerve at the wrist, which appeared as a hyperechoic lesion around the nerve. Diagnosis was confirmed with magnetic resonance imaging (MRI).     

Hemodynamic Instability during Carotid Angioplasty and Stenting-Relationship of Calcified Plaque and Its Characteristics

Purpose

During carotid angioplasty and stenting (CAS), hemodynamic instability (HDI) can occur, possibly causing post-procedural ischemic complications. The goal of this study was to investigate the risk factors of HDI focusing on characteristics of plaque.

Materials and Methods

Thirty nine CAS patients were retrospectively evaluated for HDI. Prolonged HDI that lasted over 30 minutes was analyzed in relation to characteristics of calcified plaque.

Results

Nineteen (48.7%) patients had HDI. Ten of the 19 had both bradycardia and hypotension, and nine had only bradycardia. All bradycardia was treated well with a transcutaneous temporary cardiac pacemaker. But eight patients presented with prolonged hypotension in spite of recovery of bradycardia. Calcified plaque was a related factor associated with HDI (odds ratio, 8.571; 95% confidence interval, 1.321-55.62; p=0.024). Extensive and eccentric type calcified plaques were associated with prolonged hypotension (p=0.04, and p=0.028, respectively).

Conclusion

The calcification of plaque is a predictable factor of HDI during CAS, and its extensive and eccentric calcified plaques may be related to prolonged HDI.     

Brain activation and connectivity in anorexia nervosa and body dysmorphic disorder when viewing bodies: relationships to clinical symptoms and perception of appearance

Brain Imaging and Behavior - Anorexia nervosa (AN) and body dysmorphic disorder (BDD) are characterized by distorted perception of appearance, yet no studies have directly compared the neurobiology...     

Changes of serum hepatitis B virus DNA in two types of clinical events preceding spontaneous hepatitis B e antigen seroconversion in chronic type B hepatitis

Two types of clinical events, acute exacerbation and uneventful course, precede spontaneous HBeAg seroconversion to its antibody (anti-HBe) in chronic type B hepatitis. To examine the possible mechanism responsible for these two types of clinical events, serial serum specimens from 75 patients who underwent spontaneous HBeAg seroconversion were assayed for hepatitis B virus DNA by slot blot hybridization with 32P-labeled cloned hepatitis B virus DNA as probe. Of these 75 patients, 47 (62.7%) had episodes of acute exacerbation (ALT greater than 300 IU per liter) within 3 months prior to HBeAg seroconversion. All of these 47 patients had high hepatitis B virus DNA levels (greater than 1,000 pg per ml) at the onset of acute exacerbation. Their serum hepatitis B virus DNA disappears shortly before or simultaneously with the HBeAg clearance in 27 patients (57.4%) and persisted but with decreasing levels for 2 to 40 months in 20 patients. Most of these patients had high alpha-fetoprotein levels or evidence of bridging hepatic necrosis. In contrast, the serum hepatitis B virus DNA was undetectable for a minimum of 3 (3-17) months in the 28 patients who had an uneventful course before HBeAg seroconversion. Twenty of these 28 patients had well-documented episodes of acute exacerbation with high hepatitis B virus DNA levels, but with normal alpha-fetoprotein and little evidence of extensive necrosis as far back as 6 to 27 months before HBeAg seroconversion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Association of granulocyte-macrophage colony-stimulating factor with the crystalloid granules of human eosinophils

We have previously shown that normal-density human peripheral blood eosinophils transcribe and translate mRNA for granulocyte-macrophage colony-stimulating factor (GM-CSF) and that the intracellular distribution was granular as assessed by light microscopy immunocytochemistry. The present study was conducted to confirm this apparent association between GM-CSF and the crystalloid granule using a subcellular fractionation method for human eosinophils and immunogold electron microscopy (EM). Highly purified (> 99%, by negative selection using anti-CD16 immunomagnetic microbeads) human peripheral blood eosinophils were obtained from four asthmatic subjects (not taking systemic medication), homogenized and density fractionated (5 x 10(7) cells/subject) on linear Nycodenz gradients. Twenty-four fractions were collected from each cell preparation and analyzed for marker enzyme activities as well as total protein. Dot blot analysis with specific monoclonal antibodies (MoAbs) was used to detect the eosinophil granule proteins major basic protein (MBP) and eosinophil cationic protein (ECP). An anti-CD9 MoAb was used as an eosinophil plasma membrane marker. Lactate dehydrogenase (LDH) was used as a cytosolic marker. Immunoreactivity for GM-CSF was detected by a specific enzyme-linked immunosorbent assay using a polyclonal antihuman GM-CSF antibody and confirmed by dot blot. GM-CSF coeluted with the cellular fractions containing granule markers (MBP, ECP, eosinophil peroxidase, hexosaminidase, and arylsulphatase), but not those containing cytoplasm (LDH+) or membrane (CD9+) markers. EM examination of pooled fractions associated with the peak of GM-CSF immunoreactivity confirmed that they contained crystalloid and small granules, but not plasma membrane. In addition, quantification, using immunogold labeling with an anti/GM-CSF MoAb, indicated preferential localization of gold particles over the eosinophil granule cores of intact cells. Thus, our results indicate that GM-CSF resides as a granule-associated, stored mediator in unstimulated human eosinophils.     

Gene Therapy of Patient-Derived T Lymphocytes to Target and Eradicate Colorectal Hepatic Metastases

PURPOSE: The overall aim of this study was to develop a novel treatment for colorectal cancer based on the use of gene therapy. Genetic modification of T lymphocytes has been used to specifically target and kill tumor cell lines directly. To test the efficacy of this method with clinically relevant materials, this study investigated the potential of T lymphocytes derived from patients with advanced colorectal disease to target autologous primary tumor material. METHODS: T lymphocytes isolated preoperatively were modified genetically with recombinant retroviruses encoding CD3-based chimeric immune receptors and were tested for functional activity against freshly isolated autologous tumor cells harvested from hepatic colorectal metastases. RESULTS: Patient-derived T cells were successfully transduced, and chimeric immune receptor expression was confirmed. Carcinoembryonic antigen expression on freshly isolated colorectal tumor cells was also demonstrated by molecular and immunohistochemical techniques. T cells expressing the anticarcinoembryonic antigen receptor were specifically activated by coculture with disaggregated or intact, diced tumor, whereas control non-carcinoembryonic antigen-targeted T-cell populations failed to activate. CONCLUSIONS: These results indicate that gene-targeted primary T lymphocytes depict specific functional activity against autologous colorectal tumor cells. This evidence indicates that chimeric immune receptor-expressing T cells may be able to circumvent the mechanisms used by tumor cells to avoid immune cell activity in vivo. This study emphasizes the potential of this approach as a therapy for carcinoembryonic antigen-expressing primary colorectal tumor and its metastases.     

Targeting Notch signaling in autoimmune and lymphoproliferative disease

Patients with autoimmune lymphoproliferative syndrome (ALPS) and systemic lupus erythematosis (SLE) have T-cell dysregulation and produce abnormal, activated T lymphocytes and an atypical peripheral T-cell population, termed double negative T cells (DNTs). T-cell functions, including DNT transition in T-cell development and T-cell activation, are critically dependent on Notch signaling. We hypothesized that inhibiting Notch signaling would be effective in ALPS and SLE by reducing the production of abnormal DNTs and by blocking aberrant T-cell activation. We tested this hypothesis using murine models of ALPS and SLE. Mice were randomized to treatment with the notch pathway inhibitor (gamma-secretase inhibitor), N-S-phenyl-glycine-t-butyl ester (DAPT), or vehicle control. Response to treatment was assessed by measurement of DNTs in blood and lymphoid tissue, by monitoring lymph node and spleen size with ultrasound, by quantifying cytokines by bead-array, by ELISA for total IgG and anti-double-stranded DNA (dsDNA) specific antibodies, and by histopathologic assessment for nephritis. We found a profound and statistically significant decrease in all disease parameters, comparing DAPT-treated mice to controls. Using a novel dosing schema, we avoided the reported toxicities of gamma-secretase inhibitors. Inhibiting the Notch signaling pathway may thus present an effective, novel, and well-tolerated treatment for autoimmune and lymphoproliferative diseases.