The use of a priori knowledge to quantify short echo in vivo 1h mr spectra

In vivo ¹H MR spectra of the prefrontal cortex acquired with the stimulated echo acquisition mode (STEAM) TE = 20 ms sequence were quantified to determine relative levels of cerebral metabolites. A priori knowledge of spectra from individual metabolites in aqueous solution was incorporated into a frequency domain quantification technique. The accuracy and precision of modeling these metabolites were investigated with simulated spectra of varying signal-to-noise ratios (SNRs) and relative metabolite levels. The efficacy of modeling in vivo data was tested by quantifying 10 repeated measures of two consecutively acquired in vivo spectra (an 8?cm³ volume of interest (VOI) and a 4?cm³ VOI positioned within the 8?cm³ VOI) on the same normal subject. The differences in levels of glutamate (Glu), phosphocreatine plus creatine (PCr+Cr) and choline-containing compounds (Cho₁ between spectra from the 8? and 4?cm³ VOIs corresponded with the expected differences observed in the proportions of gray matter within the VOIs (estimated from ¹H images). Correcting for the T₁ and T₂ relaxation, the estimated concentrations of N-acetylaspartate, PCr+Cr, Cho₁, Glu, and glutamine were consistent with previous in vivo and in vitro reports.     

Longitudinal histopathologic assessment of rejection after bladder-drained canine pancreas allograft transplantation

In preparation for assessment of percutaneous biopsies in our clinical pancreas transplant program, a working knowledge of the histopathologic changes after transplantation was obtained in a longitudinal open biopsy study of 16 dogs receiving bladder-drained whole pancreas allografts. Edema, extravasation of polymorphs, and lymphocytes associated with focal parenchymal injury were early, invariable, and probably nonspecific findings. The initial feature of unmodified rejection was the appearance of capillary and small vein endothelial changes with mainly perivascular inflammatory cell infiltration. Acinar cell loss occurred early and was progressive, whereas islets and ducts were relatively preserved, indicating that acinar tissue may be more vulnerable to lytic necrosis when damaged. Functional rejection, determined by fasting urinary amylase levels, was at a stage of extensive and irreversible necrosis. Functioning grafts in immunosuppressed dogs had minor and transient endothelial changes with absence of class II antigen staining of parenchymal cells.     

The Validity of the Neale and Kendler Model-Fitting Approach in Examining the Etiology of Comorbidity

Given that knowledge regarding the etiology of comorbidity between disorders can have a significant impact on research regarding the classification, treatment, and etiology of the disorders, the ability to reject incorrect hypotheses regarding the causes of comorbidity is very important. A simulation study was conducted to assess the validity of the Neale and Kendler (1995) model-fitting approach in examining the etiology of comorbidity between two disorders. First, data were simulated under the assumptions of the 13 alternative comorbidity models described by Neale and Kendler. Second, model-fitting analyses testing the comorbidity models were conducted on the simulated datasets. Thirteen sets of data with varying model parameters were simulated to test Neale and Kendler's assertion that their model-fitting approach is appropriate across a range of potential prevalences and degrees of familiality. The validity of the model-fitting approach in examining unselected twin data and a combination of selected family data and unselected family data was explored. The model-fitting approach successfully discriminated several classes of comorbidity models, although discrimination between models within classes of related models was less accurate. Results suggest that the model-fitting approach can be a useful tool in examining the etiology of the comorbidity between disorders if the caveats of the present study's results are considered carefully. As predicted by Neale and Kendler, variations in the disorder prevalences and familial correlations did not affect the validity of their model-fitting approach, but affected the power to discriminate the correct model. As suggested by Neale and Kendler, the model-fitting approach can be applied to both unselected and selected data and to both twin and family data.     

Fatigue and fitness modelled from the effects of training on performance

Summary The purpose of this study was to compare two ways of estimating both fatigue and fitness indicators from systems model of the effects of training on performance. The model was applied to data concerning the training of a hammer thrower. The variations in performance were mathematically related to the successive amounts of training. The model equation was composed of negative (NF) and positive (PF) functions. The NF and PF were associated with the fatigue and fitness estimated in previous studies. Using another method, fatigue and fitness indicators were estimated from a combination of NF and PF. The influence of training on performance was negatively associated with fatigue (NI), and positively to fitness (PI). The changes in performance were well described by the model in the present study (r = 0.96,N = 19,P<0.001). Significant correlations were observed between NF and NI (r = 0.93,P < 0.001) on the one hand and between PF and PI (r = 0.90,P < 0.001) on the other. The absolute values and the time variations of PI and NI were closer to the change in performance than NF and PF. The NF and PF were accounted for mainly by the accumulation of amounts of training. On the other hand, NI and PI were accounted for rather by the impact of these amounts of training on performance.     

Classical Noonan syndrome is not associated with deletions of 22q11

Deletions of 22qll cause DiGeorge sequence (DGS), velo-cardio-facial syndrome (VCFS), conotruncal anomaly face syndrome, and some isolated conotruncal heart anomalies. Demonstration of a 22qll deletion in a patient with manifestations of DGS and Noonan syndrome (NS) has raised the question of whether NS is another of the chromosome 22 microdeletion syndromes. This prompted us to evaluate a cohort of patients with NS for evidence of 22qll deletions. Five of 6 NS propositi studied in our laboratory with marker N25 (D22S75) did not have a 22qll deletion. A 2-month-old infant with several findings suggestive of NS did have a 22qll deletion, suggesting that a small number of 22qll deletion propositi may present with a NS-like picture. However, most cases of NS must have another cause. © 1995 Wiley-Liss, Inc.     

Retinal dehydrogenase-2 is inhibited by compounds that induce congenital diaphragmatic hernias in rodents

Currently, the etiology of the serious developmental anomaly congenital diaphragmatic hernia (CDH) is unknown. We have used an animal model of CDH to address this issue. We characterized four separate teratogens that produced diaphragmatic defects in embryonic rats that are similar to those in infants with CDH. We then tested the hypothesis that all these agents share the common mechanism of perturbing the retinoid-signaling pathway. Specifically, inhibition of retinal dehydrogenase-2 (RALDH2), a key enzyme necessary for the production of retinoic acid and that is expressed in the developing diaphragm, was assayed by measuring retinoic acid production in cytosolic extracts from an oligodendrocyte cell line. The following compounds all induce posterolateral defects in the rat diaphragm; nitrofen, 4-biphenyl carboxylic acid, bisdiamine, and SB-210661. Importantly, we demonstrate that they all share the common mechanism of inhibiting RALDH2. These data provide an important component of mounting evidence suggesting that the retinoid system warrants consideration in future studies of the etiology of CDH.     

Frontal and non-frontal lobe neuropsychological test performance and clinical symptomatology in schizophrenia.

Schizophrenic subjects performed significantly worse on neuropsychological tests of frontal lobe function but not on tests of non-frontal lobe function when compared to a matched group of normal subjects. Correlations expected between frontal lobe neuropsychological test performance and negative symptoms were not found.     

The complete nucleotide sequence of Subterranean clover mottle virus

Summary The complete nucleotide sequence of Subterranean clover mottle virus (SCMoV) genomic RNA has been determined. The SCMoV genome is 4,258 nucleotides in length. It shares most nucleotide and amino acid sequence identity with the genome of Lucerne transient streak virus (LTSV). SCMoV RNA encodes four overlapping open reading frames and has a genome organisation similar to that of Cocksfoot mottle virus (CfMV). ORF1 and ORF4 are predicted to encode single proteins. ORF2 is predicted to encode two proteins that are derived from a –1 translational frameshift between two overlapping reading frames (ORF2a and ORF2b). A search of amino acid databases did not find a significant match for ORF1 and the function of this protein remains unclear. ORF2a contains a motif typical of chymotrypsin-like serine proteases and ORF2b has motifs characteristically present in positive-stranded RNA-dependent RNA polymerases. ORF4 is likely to be expressed from a subgenomic RNA and encodes the viral coat protein. The ORF2a/ORF2b overlapping gene expression strategy used by SCMoV and CfMV is similar to that of the poleroviruses and differ from that of other published sobemoviruses. These results suggest that the sobemoviruses could now be divided into two distinct subgroups based on those that express the RNA-dependent RNA polymerase from a single, in-frame polyprotein, and those that express it via a –1 translational frameshifting mechanism.Received December 17, 2001; accepted April 15, 2003 Published online August 7, 2003