Motion‐compensated b‐tensor encoding for in vivo cardiac diffusion‐weighted imaging

Motion is a major confound in diffusion‐weighted imaging (DWI) in the body, and it is a common cause of image artefacts. The effects are particularly severe in cardiac applications, due to the nonrigid cyclical deformation of the myocardium. Spin echo‐based DWI commonly employs gradient moment‐nulling techniques to desensitise the acquisition to velocity and acceleration, ie, nulling gradient moments up to the 2nd order (M2‐nulled). However, current M2‐nulled DWI scans are limited to encode diffusion along a single direction at a time. We propose a method for designing b‐tensors of arbitrary shapes, including planar, spherical, prolate and oblate tensors, while nulling gradient moments up to the 2nd order and beyond. The design strategy comprises initialising the diffusion encoding gradients in two encoding blocks about the refocusing pulse, followed by appropriate scaling and rotation, which further enables nulling undesired effects of concomitant gradients. Proof‐of‐concept assessment of in vivo mean diffusivity (MD) was performed using linear and spherical tensor encoding (LTE and STE, respectively) in the hearts of five healthy volunteers. The results of the M2‐nulled STE showed that (a) the sequence was robust to cardiac motion, and (b) MD was higher than that acquired using standard M2‐nulled LTE, where diffusion‐weighting was applied in three orthogonal directions, which may be attributed to the presence of restricted diffusion and microscopic diffusion anisotropy. Provided adequate signal‐to‐noise ratio, STE could significantly shorten estimation of MD compared with the conventional LTE approach. Importantly, our theoretical analysis and the proposed gradient waveform design may be useful in microstructure imaging beyond diffusion tensor imaging where the effects of motion must be suppressed.     

In vivo intrarater and interrater precision of measuring apparent bone mineral density in vertebral subregions using supine lateral dual-energy x-ray absorptiometry.

Analysis of apparent bone mineral density (BMD) in the lumbar spine is commonly based on anteroposterior (AP) scanning using dual-energy X-ray absorptiometry (DXA). Although not widely used, clinically important information can also be derived from lateral scanning. Vertebral bone density, and therefore strength, can may vary in different subregions of the vertebral body. Therefore, subregional BMD measurements might be informative about fracture risk. However, the intrarater and interrater precision of in vivo subregional BMD assessments from lateral DXA remains unknown. Ten normal, young (mean: 24 yr) and 10 older (mean: 63 yr) individuals with low BMD were scanned on one occasion using an AP/lateral sequence. Each lateral scan was reanalyzed six times at L2 by three raters to determine the intrarater and interrater precision in selecting seven regions of interest (subregions). Precision was expressed using percentage coefficients of variation (% CV) and intraclass correlation coefficients (ICC). Intrarater precision ranged from ICC(1,1) 0.971 to 0.996 (% CV: 0.50-3.68) for the young cohort and ICC(1,1) 0.934 to 0.993 (% CV: 1.46-5.30) for the older cohort. Interrater precision ranged from ICC(2,1) 0.804 to 0.915 (% CV: 1.11-2.35) for the young cohort and ICC(2,1) 0.912 to 0.984 (% CV: 1.85-4.32) for the older cohort. Scanning a subgroup of participants twice with repositioning was used to assess short-term in vivo precision. At L2, short-term in vivo precision ranged from ICC(1,1) 0.867 to 0.962 (% CV: 3.38-9.61), at L3 from ICC(1,1) 0.961 to 0.988 (% CV: 2.02-5.57) and using an L2/L3 combination from ICC(1,1) 0.942 to 0.980 (% CV: 2.04-4.61). This study demonstrated moderate to high precision for subregional analysis of apparent BMD in the lumbar spine using lateral DXA in vivo.     

SELECTIVE IgA DEFICIENCY PRESENTING WITH HYPERSPLENISM

SUMMARY A young patient presenting with splenomegaly and hypersplenism was inadvertently found to have selective IgA deficiency. There were no symptoms of immunodeficiency and the patient responded well to splenectomy, with return of blood counts to normal without adverse effects. No other cause for the hypersplenism was found. We postulate selective IgA deficiency as a cause of splenomegaly and hypersplenism.     

A rare polymorphism affects a mitogen-activated protein kinase site in synapsin III: possible relationship to schizophrenia.

BACKGROUND: Synapsin III plays a role in neuronal plasticity and maps to chromosome 22q12-13, a region suggested to be linked to schizophrenia. To determine if synapsin III plays a role in this disease, we searched for polymorphisms in this gene in patients with schizophrenia and controls. METHODS: The synapsin III gene was initially sequenced from 10 individuals with schizophrenia to identify polymorphisms. Association analysis was then performed using 118 individuals with schizophrenia and 330 population controls. Synapsin III expression was studied by immunoblot analyses, and phosphorylation sites were mapped by sequencing trypsin-digested synapsin III fragments phosphorylated with phosphorus-32. RESULTS: A rare, missense polymorphism, S470N, was identified in the synapsin III gene and appeared more frequently in individuals with schizophrenia than in controls (p =.0048). The site affected by the polymorphism, Ser470, was determined to be a substrate for mitogen-activated protein kinase, a downstream effector of neurotrophin action. Phosphorylation at Ser470 was increased during neonatal development and in response to neurotrophin-3 in cultured hippocampal neurons. CONCLUSIONS: Our observations suggest an association of a rare polymorphism in synapsin III with schizophrenia, but further studies will be required to clarify its role in this disease.     

Lectin histochemistry of ovarian mucinous cystadenomas.

The lectin histochemistry of ovarian mucinous cystadenoma was studied using a panel of lectins comprising Triticum vulgaris, Lotus tetragonolobus, Arachis hypogaea, Griffonia simplicifolia I, concanavalin A, and Dolichus biflorus. All 23 cases examined in this study stained extensively with T. vulgaris. Of all the lectins, D. biflorus was the least reactive. Concanavalin A stained mainly the perinuclear zone, whereas the other lectins frequently stained the cytoplasm, glycocalyx, and extracellular luminal mucin. This pattern of lectin reactivity resembles endocervical more than intestinal epithelium and suggests that ovarian mucinous cystadenomas are of müllerian nature. The lack of difference in lectin reactivity between cystadenomas with and without goblet/Paneth cells supports a common histogenetic origin of both groups.     

CDX2 expression is progressively decreased in human gastric intestinal metaplasia, dysplasia and cancer.

Intestinal metaplasia is a key event in multistep gastric carcinogenesis. CDX2, a master regulator of intestinal phenotype, was shown to play a tumor-suppressive role in colon cancer. However, it was reported to be expressed in nearly all gastric intestinal metaplasia and many gastric cancers. As CDX2 is differentially expressed in normal stomach and intestine, we sought to relate the CDX2 expression to gastrointestinal differentiation along gastric carcinogenesis. The expression of CDX2 protein in gastric intestinal metaplasia, dysplasia and cancer was examined and related to their gastrointestinal differentiation. CDX2 expression was significantly decreased in incomplete intestinal metaplasia, which expresses both gastric mucins (MUC5AC and MUC6) and intestinal mucin (MUC2), compared with complete intestinal metaplasia, which expresses intestinal mucin (MUC2) only. Although incomplete intestinal metaplasia morphologically resembles colon, its CDX2 expression was apparently lower than that in the normal colon. Moreover, CDX2 expression was progressively reduced in gastric dysplasia and cancer. The CDX2 expression in gastric cancer was also inversely correlated with the expression of gastric mucins. As incomplete intestinal metaplasia is associated with higher risk of gastric cancer, its lower CDX2 expression compared with that in complete intestinal metaplasia and normal colon epithelium resolved the current contradiction between the tumor-suppressive role of CDX2 in the colon and the high prevalence of CDX2 in intestinal metaplasia. Further decrease of CDX2 expression in gastric dysplasia and cancer suggests that CDX2 plays a similar anticarcinogenic role in intestinal metaplasia as it does in colon. Intestinal metaplasia or dysplasia with low expression of CDX2 may serve as predictive markers for gastric cancer.     

Tumor necrosis factor receptor II (TNFRII) exon 6 polymorphism in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a complex autoimmune disease that exhibits extensive clinical heterogeneity. Several studies have suggested a role for tumor necrosis factor alpha (TNFalpha) in SLE and recently, the locus encompassing the TNF receptor II (TNFRII), which is a mediator of TNF effect, was amongst the candidate loci suggested by genetic linkage studies of multi-case SLE families. Komata et al. reported an association between a polymorphism at position 196 (R allele) of TNFR II and SLE in Japanese patients. We have typed SLE patients from two different ethnic populations, Spanish and UK Caucasoids, for this polymorphism using a polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP)-based technique. No significant differences in allele or genotype frequencies were found between cases and matched controls in either population. The TNFRII 196R allele does not appear to be associated with SLE susceptibility in either Spanish or UK populations.     

CD8 is needed for positive selection but differentially required for negative selection of T cells during thymic ontogeny

During thymic development, immature thymocytes expressing major histocompatibility complex (MHC) class I-restricted T cell receptors (TcR) differentiate into CD8⁺ T cells with cytolytic functions. To evaluate the role of CD8 in positive and negative selection during thymic ontogeny, mice rendered CD8-null by gene targeting were bred with three lines of transgenic mice expressing unique MHC class I-restricted TcR. In all three instances CD8 was required for positive selection of MHC class I-restricted transgenic T cells. The efficiency of positive selection decreased in accordance with a reduced level of CD8 expression on thymocytes. Surprisingly, there was a differential requirement for CD8 expression in negative selection of MHC class I-restricted thymocytes, depending on the antigen specificity of TcR. These observations show that CD8 is essential for positive selection but is differentially required for negative selection of MHC class I-restricted T cells. Thus thymic selection, at least for negative selection, can occur in the absence of the CD8 accessory molecule.