Peripheral blood gene expression signature differentiates children with autism from unaffected siblings.

Autism spectrum disorder (ASD) is one of the most prevalent neurodevelopmental disorders with high heritability, yet a majority of genetic contribution to pathophysiology is not known. Siblings of individuals with ASD are at increased risk for ASD and autistic traits, but the genetic contribution for simplex families is estimated to be less when compared to multiplex families. To explore the genomic (dis-) similarity between proband and unaffected sibling in simplex families, we used genome-wide gene expression profiles of blood from 20 proband-unaffected sibling pairs and 18 unrelated control individuals. The global gene expression profiles of unaffected siblings were more similar to those from probands as they shared genetic and environmental background. A total of 189 genes were significantly differentially expressed between proband-sib pairs (nominal p < 0.01) after controlling for age, sex, and family effects. Probands and siblings were distinguished into two groups by cluster analysis with these genes. Overall, unaffected siblings were equally distant from the centroid of probands and from that of unrelated controls with the differentially expressed genes. Interestingly, five of 20 siblings had gene expression profiles that were more similar to unrelated controls than to their matched probands. In summary, we found a set of genes that distinguished probands from the unaffected siblings, and a subgroup of unaffected siblings who were more similar to probands. The pathways that characterized probands compared to siblings using peripheral blood gene expression profiles were the up-regulation of ribosomal, spliceosomal, and mitochondrial pathways, and the down-regulation of neuroreceptor-ligand, immune response and calcium signaling pathways. Further integrative study with structural genetic variations such as de novo mutations, rare variants, and copy number variations would clarify whether these transcriptomic changes are structural or environmental in origin.

Three-dimensional color Doppler sonography before and after fibroid embolization.

Three-dimensional color Doppler sonography was performed within 1 hour, 1 day, 3 months, and 6 months of fibroid embolization in 20 patients who had a total of 31 fibroids greater than 2 cm in average dimension. The greatest decrease in vascularity occurred 1 day after the procedure, whereas the greatest volume change was found at the 3 month follow-up examination. In about one half of the patients scanned, depiction of fibroid vascularity by color Doppler sonography was found to improve the delineation of the size, location, and extent of myometrial involvement. Hypervascular fibroids (12 of 31) tended to decrease in size after treatment more than isovascular (10 of 31) or hypovascular ones (9 of 31). Additional investigations that are similar to this one will be needed to determine if three-dimensional color Doppler sonography can be used to predict those who will be responders, partial responders, or nonresponders to embolotherapy.

Positron emission tomography to stage suspected metastatic colorectal carcinoma to the liver.

BACKGROUND: Accurate detection of recurrent colorectal carcinoma remains a clinical challenge. Positron emission tomography (PET) using 18F-fluorodeoxyglucose (18FDG) is an imaging technique that allows direct evaluation of cellular metabolism. 18F-fluorodeoxyglucose PET was compared to computed tomography (CT) and CT portography for staging metastatic colorectal carcinoma. PATIENTS AND METHODS: Twenty-four patients previously treated for colorectal carcinoma who had suspected recurrence to the liver underwent an 18FDG PET scan of the entire body. All patients had either a CT scan of the abdomen (n = 17), a CT portogram (n = 18), or both (n = 11). The final diagnosis was obtained by tissue pathology in 19 patients and clinical follow-up in 5 patients. RESULTS: A total of 60 suspicious lesions were identified. Of the 55 intrahepatic lesions, 39 were malignant and 16 were benign. Of the 5 extra-hepatic lesions, 4 were malignant. The 18FDG PET imaging had a higher accuracy (93%) than CT and CT portography (both 76%) in detecting metastatic disease to the liver, and detected unsuspected extrahepatic recurrence in 4 patients. Although the sensitivity of 18FDG PET (90%) was slightly lower than that of CT portography (97%), the specificity was much higher (100% versus 9%), including postsurgical sites. 18FDG PET altered surgical plans in 6 (25%) of 24 patients. CONCLUSIONS: 18FDG PET is extremely useful in staging patients with suspected metastatic colorectal carcinoma to the liver.

Rest myocardial perfusion/metabolism imaging using simultaneous dual-isotope acquisition SPECT with technetium-99m-MIBI/fluorine-18-FDG.

UNLABELLED: The purpose of this study was to develop a dual-isotope simultaneous acquisition (DISA) protocol using a multihead SPECT camera equipped with an ultrahigh-energy (UHE) collimator to evaluate simultaneously rest cardiac perfusion and metabolism with 99mTc-MIBI/18FDG. METHODS: Physical measurements were first performed with phantoms to develop the acquisition protocol. Fifteen patients underwent DISA-SPECT with 99mTc-MIBI/18FDG to validate the protocol. To evaluate the quality of the 99mTc-MIBI images acquired with the UHE collimator, four patients underwent a resting 99mTc-MIBI scan acquired with a high-resolution, low-energy collimator prior to DISA-SPECT. RESULTS: With a window of 20% for both photopeaks and a 99mTc/18F concentration ratio of 3.2:1, the spillover from 18F into the 99mTc window is 6% of the counts in the window for normal subjects. Phantom images clearly demonstrated defects measuring 2 x 1 and 2 x 0.5 cm. Technetium-99m-MIBI images obtained with the UHE and high-resolution collimators provided similar diagnostic information. Using a stenosis of > 70% as criteria to diagnose coronary artery disease, DISA-SPECT had a sensitivity of 100% and a positive predictive value of 93%. CONCLUSION: Simultaneous evaluation of rest myocardial perfusion/metabolism with a multihead SPECT camera equipped with an UHE collimator is possible using 99mTc-MIBI/18FDG with a dual-isotope simultaneous acquisition protocol.

Pheromone components and active spaces: what do moths smell and where do they smell it?

The pheromone-mediated flight behavior of male Oriental fruit moths was observed in the field to test the hypothesis that male activation far downwind of a female is initiated by the major, or most abundant, component of the pheromone blend. Males responded at significantly greater distances to the three-component pheromone blend produced by females than to the major component alone or to either binary mixture containing the major component and one minor component. These results support the alternative hypothesis that the active space of a multicomponent pheromone is a function of male perception of the female-released blend of components, rather than of the major component alone, and that so-called minor components have a greater impact on male behavior farther downwind of a female than previously thought.

Male moth sensitivity to multicomponent pheromones: Critical role of female-released blend in determining the functional role of components and active space of the pheromone.

In the present study male redbanded leafroller (Argyrotaenia velutinana), cabbage looper (Trichoplusia ni), and Oriental fruit moths, (Grapholita molesta), were tested in a flight tunnel to (1) the major pheromone component, (2) theZ/E pheromone component mixtures for Oriental fruit moth and redbanded leafroller, (3) and the female-released blends, over a series of dosages. Experiments were designed to test the hypothesis that male response downwind of a female is initiated by the major component and that minor components function only to elicit behaviors close to the female during close-range approach and courtship. The results did not support this hypothesis, but rather showed that males initiated upwind flight in significantly higher percentages to the complete blends of components, at all dosages, compared to single components or partial blends. Addition of minor components also signficantly enhanced male perception of the major component at lower dosages, resulting in completed flights to dosages of the major component that alone did not elicit any upwind flight. Our results support the concept that minor components function to enhance male sensitivity to the pheromone, and the specificity of the signal. Our results also support the hypothesis that the active space of the pheromone is a function of the upper and lower concentration thresholds for the blend of components, and not simply for the major component.

A comparison of normal limits arising in nerve conduction studies.

A detailed study has been carried out on the influence of various factors, including sex of the patient and side examined, on normal values in peripheral nerve conduction studied. Patients were selected from three clinics, thereby enabling comparisons not only to be made within clinics but also between clinics.

A complete response in metastatic malignant thymoma to cis-platinum, doxorubicin and cyclophosphamide: a case report.

Systemic chemotherapy as a mode of therapy in metastatic malignant thymoma has never been systematically evaluated. Chemotherapeutic agents, including doxorubicin, cyclophosphamide, cis-platinum, nitrogen mustard, prednisone or combination of agents like MOPP have produced tumor remission. A case report of complete remission of malignant thymoma in which the combination of cyclophosphamide, doxorubicin and cis-platinum (CAP) was used is reported.