Dermatomyositis

Dermatomyositis is a rare inflammatory myopathy with characteristic skin manifestations and muscular weakness. The disease can be categorized as adult idiopathic, juvenile, or amyopathic dermatomyositis as well as that associated with a connective tissue disease or a malignancy. Immunologic factors are most likely involved in the pathogenesis of the disease; however, genetic and environmental issues may also play important roles. Treatment with immunosuppressive agents has proved successful in the majority of patients, although significant morbidity still occurs.     

Monogenic determinants of familial Alzheimer''s disease: presenilin-1 mutations

The authors describe a new simple noniterative, yet efficient method to estimate the risk ratio in studies using case-parental control design. The new method is compared with two other noniterative methods, Khoury's method and Flanders and Khoury's method, and with a maximum likelihood-based method of Schaid and Sommer. The authors found that the variance of the new estimation method is usually smaller than that of Khoury's method or Flanders and Khoury's method and that it is slightly larger than that of the maximum likelihood-based method of Schaid and Sommer. Despite the slightly large variance of the new estimator compared with that of the maximum likelihood-based method, the simplicity of the new estimator and its variance makes the new method appealing. When genotypic information for only one parent is available, the authors also describe a method to estimate the risk ratio without assuming Hardy-Weinberg equilibrium or random mating. A simple formula for the variance of the estimator is given.     

Cell-specific transcription of the smooth muscle gamma-actin gene requires both positive- and negative-acting cis elements

We recently labeled with carbon-11, a high affinity, selective, 5-HT3 receptor (5-HT3R) ligand, S21007, for potential positron emission tomography (PET) applications. To evaluate the in vivo binding properties of [11C]S21007, its brain regional distribution, tissue and plasma pharmacokinetics and plasma metabolisation were characterized. To circumvent the problem of highly discrete brain localization of the 5-HT3R (area postrema, hippocampus), we designed an original approach combining high-resolution imaging techniques (ex vivo phosphor plate autoradiography and MRI-guided coronal PET in the rat and baboon, respectively). After i.v. injection of trace amounts of [11C]S21007 to rats, phosphorimager autoradiography failed to reveal in vivo specific binding to, nor selectivity for 5-HT3R-rich areas. PET studies in the baboon showed consistent results, i.e., there was no selective accumulation of [11C]S21007 in the area postrema or hippocampus, and neither displacement nor presaturation with cold S21007 resulted in significant changes in tissue distribution or kinetics of [11C]S21007.     

Double-blind comparison of lansoprazole 15 mg, lansoprazole 30 mg, and placebo in the maintenance of healed gastric ulcer

Traditionally health care outcomes have been evaluated by measuring immediate and long-term survival. This paper demonstrates the importance of quality of life as an alternative outcome indicator by considering two dimensions of quality of life and how they affect patients following liver transplantation. These two dimensions are physical recovery and functional recovery and they are considered by analysing the literature exploring quality of life following liver transplantation. Physical recovery is be subdivided into sleep, pain and mobility and functional recovery is subdivided into occupational rehabilitation and domestic rehabilitation.     

Fluorescent microsatellite analysis reveals duplication of specific chromosomal regions in papillary renal cell tumors

The traditional approach in epidemiology of relating exposure to an environmental agent such as a drug or infective agent has been to measure an overall risk (i.e., average and then "adjust risk for demographic variables and other confounders"). An attempt is sometimes made to define a "susceptible" subgroup. The analyses are usually based on good statistical methodology rather than an understanding of the interaction of body of host and agent. A twofold risk for 1000 exposed versus nonexposed people could be an average twofold risk for all 1000 exposed or a 20-fold risk for 100 exposed individuals (i.e., a drug-host interaction). Clearly, finding the 100 individuals with a 20-fold risk has much greater clinical importance than a twofold risk for 1000 people. The world of epidemiology may be changing-we may soon be able to define risk based on genetic susceptibility, at least sometimes.     

Evidence that C1q binds specifically to CH2-like immunoglobulin gamma motifs present in the autoantigen calreticulin and interferes with complement activation

Calreticulin (CRT) is located predominantly in the endoplasmic reticulum (ER) of cells, where it functions as a quality control controller of protein folding. However, CRT is also a prevalent autoantigen in patients with systemic lupus erythematosus (SLE), where its release from the cell may arise as a results of dysfunctional apoptosis and inefficient removal of ER vesicles, which are an abundant source of CRT and other autoantigens. Indicative of this is the presence of autoantibodies against CRT in the sera of 40-60% of all SLE patients. Once released into the circulation, CRT might bind directly to C1q and we have suggested that this association may result in a defect in C1q-mediated clearance of antigen-antibody complexes. It has been previously shown that CRT under physiological salt conditions binds to the globular head of C1q. It is known that the globular head region of C1q binds to the CH2 domain in the Fc portion of immunoglobulin gamma (IgG). The N-terminal half of CRT contains a number of short regions of 7-10 amino acids that show sequence similarity to the putative C1q binding region in the CH2 domain of IgG. By use of a series of 92 overlapping CRT synthetic peptides, a number of C1q binding sites on the CRT molecule have been identified, including several containing a CH2-like motif similar to the ExKxKx C1q binding motif found in the CH2 domain of IgG. A number of these peptides were shown to inhibit binding of C1q to IgG and reduce binding of native CRT to C1q. Moreover, several of the peptides were capable of inhibiting the classical pathway of complement activation. These studies have identified specific binding sites on the CRT molecule for C1q and lend support to the hypothesis that interaction of CRT with C1q may interfere with the ability of C1q to associate with immune complexes in autoimmune-related disorders.     

Resonant two-photon ionization mass spectrometry of jet-cooled phenolic acids and polyphenols

A method for analyzing phenolic acids and polyphenols by means of resonant two-photon ionization (R2PI) mass spectrometry coupled with laser desorption and supersonic jet cooling is described. The R2PI spectra of gallic acid, 3-O-methylgallic acid, protocatechuic acid, syringic acid, vanillic acid, and trans-resveratrol are vibronically resolved and distinct to allow for unambiguous identification. For vanillic acid, its R2PI spectrum can be separated into contributions of two rotational isomers based on UV-UV and IR-UV double-resonance spectroscopy. Since R2PI spectra display sharp and well-resolved peaks, the laser wavelength can be tuned for selective ionization of targeted molecules. The mass spectrum recorded under jet-cooled conditions and at the resonant wavelength displays only the molecular ion peak with no fragmentation or background peaks. Picogram sensitivity and linear response over a nanogram range allows trace quantitative measurements of target molecules in complex matrixes. These techniques were applied to detect syringic acid in a model archaeological wine vessel.     

What is psychotherapy?

The membership of APA's Division of Psychotherapy (29) is increasingly engaged in an enormously important and growing debate about the essential nature of our calling. The very term "psychotherapy"—with its connotations as "mind healing"—contains within itself the seeds of our discontent. In this paper, these debates concerning psychotherapy will be discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A composite silent corticotroph pituitary adenoma with interspersed adrenocortical cells: case report

Recently, perfusion imaging has been of increasing interest in MRI. We applied this method for semiquantitative evaluation of hepatic parenchymal portal blood flow in patients with diffuse liver damage. Twenty patients with diffuse hepatic damage were divided according to the Child's Classification and studied. Gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) was administered into the superior mesenteric artery (SMA), and a dynamic series of T2*-weighted fast low angle shot (FLASH) images was obtained. We evaluated relative regional portal blood volume (rrPBV), mean transit time (MTT), and relative regional portal blood flow (rrPBF). The relationship between the rrPBV, rrPBF, and plasma indocyanine green retention rate test at 15 minutes (ICGR15 was also evaluated in 12 patients. Both rrPBF and rrPBV are significantly decreased in Child B & C patients compared with Child A patients. On the other hand, the MTT is significantly prolonged in Child B & C patients compared with Child A patients. Significant correlations were also noted between rrPBV and ICGR15 and between rrPBF and ICGR15. By means of selective catheterization into the SMA, we were able to estimate rrPBV, rrPBF, and MTT. This method may play a clinical role for assessment of regional portal perfusion in various diseases with diffuse liver damage.     

Behavioral factors affecting exposure potential for household cleaning products

Variation in repeated nucleotide sequences (RNSs) at the level of entire families assayed by Southern blot hybridization is remarkably low within species and is a powerful tool for scrutinizing the origin of allopolyploid taxa. Thirty-one clones from RNSs isolated from different Triticeae genera were used to investigate the genome constitution of South American Elymus. One of these clones, pHch2, preferentially hybridized with the diploid H genome Hordeum species. Hybridization of this clone with a worldwide collection of Elymus species with known genome formulas showed that pHch2 clearly discriminates Elymus species with the H genome (StH, StHH, StStH, and StHY) from those with other genome combinations (StY, StStY, StPY, and StP). Hybridization with pHch2 indicates the presence of the H genome in all South American Elymus species except Elymus erianthus and Elymus mendocinus. Hybridization with additional clones that revealed differential restriction fragments (marker bands) for the H genome confirmed the absence of the H genome in these species. Differential restriction fragments for the Ns genome of Psathyrostachys were detected in E. erianthus and E. mendocinus and three species of Leymus. Based on genome constitution, morphology, and habitat, E. erianthus and E. mendocinus were transferred to the genus Leymus.