Fast implementation of the single scatter simulation algorithm and its use in iterative image reconstruction of PET data

In positron emission tomography (PET), scatter correction is usually performed prior to image reconstruction using a more or less exact model of the scatter processes. These models require estimates of the true activity and object density distributions of the imaged object. The problem is that these estimates are computed from measured data and, therefore, already contain scattered events. The purpose of this work was to overcome this problem by incorporating scatter characteristics directly into the process of iterative image reconstruction. This could be achieved by an optimized implementation of the single scatter simulation (SSS) algorithm, which results in a significant speed-up of the scatter estimation procedure. The scatter simulation was then included in the forward projection step of maximum likelihood image reconstruction. The results demonstrate that this approach leads to a more exact estimation of the scatter component which cannot be obtained by a simple sequential data processing strategy.     

4E-binding protein phosphorylation and eukaryotic initiation factor-4E release are required for airway smooth muscle hypertrophy

The molecular mechanisms of airway smooth muscle hypertrophy, a feature of severe asthma, are poorly understood. We previously established a conditionally immortalized human bronchial smooth muscle cell line with a temperature-sensitive SV40 large T antigen. Temperature shift and loss of large T cause G1-phase cell cycle arrest that is accompanied by increased airway smooth muscle cell size. In the present study, we hypothesized that phosphorylation of eukaryotic initiation factor-4E (eIF4E)-binding protein (4E-BP), which subsequently releases eIF4E and initiates cap-dependent mRNA translation, was required for airway smooth muscle hypertrophy. Treatment of cells with chemical inhibitors of PI 3-kinase and mammalian target of rapamycin blocked protein synthesis and cell growth while decreasing the phosphorylation of 4E-BP and increasing the binding of 4E-BP to eIF4E, consistent with the notion that 4E-BP1 phosphorylation and eIF4E function are required for hypertrophy. To test this directly, we infected cells with a retrovirus encoding a phosphorylation site mutant of 4E-BP1 (AA-4E-BP-1) that dominantly inhibits eIF4E. Upon temperature shift, cells infected with AA-4E-BP-1, but not empty vector, failed to undergo hypertrophic growth. We conclude that phosphorylation of 4E-BP, eIF4E release, and cap-dependent protein synthesis are required for hypertrophy of human airway smooth muscle cells.     

Diffuse optical tomography of breast cancer during neoadjuvant chemotherapy: a case study with comparison to MRI

We employ diffuse optical tomography (DOT) to track treatment progress in a female subject presenting with locally advanced invasive carcinoma of the breast during neoadjuvant chemotherapy. Three-dimensional images of total hemoglobin concentration and scattering identified the tumor. Our measurements reveal tumor shrinkage during the course of chemotherapy, in reasonable agreement with magnetic resonance images of the same subject. A decrease in total hemoglobin concentration contrast between tumor and normal tissue was also observed over time. The results demonstrate the potential of DOT for measuring physiological parameters of breast lesions during chemotherapy.     

Metastatic potential of human CX-1 colon adenocarcinoma cells is dependent on the expression of sialosyl Le a antigen

Several lines of evidence indicate that sialosyl Le a , tumor-associated carbohydrate antigen present on human colon carcinoma cells, is involved in formation of metastases. To study the role of this carbohydrate structure in development of metastases, we have used the clone of human colon carcinoma CX-1 cells transfected with antisense expression vector containing fragment of cDNA for a1,3/4-fucosyltransferase (FT III), which is involved in synthesis of sialosyl Le a tetrasaccharide. It has been reported previously that, in contrast to the parental cells, the antisense-transfected CX-1.1AS5 cells do not express sialosyl Le a and do not adhere to E-selectin-expressing CHO cells. In the present work we have studied the formation of liver metastases by CX-1.1AS5 cells after their orthotopic or intrasplenic implantation into athymic nu/nu mice. After orthotopic implantation of sialosyl Le a -negative colon carcinoma CX-1.1AS5 cells, the number of mice with liver metas-tases was markedly lower (21% of mice) in comparison with their number after implantation of the parental CX-1.1 cells (86% of mice). However, no differences in ability to form colonies in liver were observed between parental CX-1.1 cells and antisense-transfected CX-1.1AS5 cells after intrasplenic inoculation. The liver metastases were formed in 89% and 84% of mice, respectively. Our data support the thesis on the importance of sialosyl Le a antigen expression in the development of liver metastases by colon cancer cells, and indicate the role of transplantation route and primary tumor localization in formation of metastases.© Kluwer Academic Publishers 1998     

Systemic activity of ivermectin on the human body louse (Anoplura: Pediculidae)

Eighty-one to 100% of nymphs and females of the human body louse (Pediculus humanus humanus) that fed artificially on blood containing 2.5-10 ng ivermectin/ml died. The mortality of nymphs and female lice fed on rabbits treated with 200 micrograms/kg ivermectin was very high during the first two to three days, then declined sharply, reaching the level of the controls on day six. Nymphs were more sensitive than females. The average number of eggs laid by surviving females and the percentage that hatched from those eggs were lower than in controls.     

Effects of stimulant medications on the EEG of children with Attention-Deficit/Hyperactivity Disorder Predominantly Inattentive type.

Stimulant medications are the most commonly-used treatments for Attention-Deficit/Hyperactivity Disorder (ADHD) in North America and Australia, although it is still not entirely known how these medications work. This study investigated the effects of stimulant medications on the EEG of children with the Inattentive type of ADHD. An initial EEG was recorded during an eyes-closed resting condition and Fourier transformed to provide absolute and relative power estimates for the delta, theta, alpha and beta bands. Theta/alpha and theta/beta ratios were also calculated. Subjects were placed on a 6-month trial of a stimulant and a second EEG was recorded at the end of the trial. Subjects were included in this study only if they showed a good clinical response during the trial. The unmedicated ADHD group had significantly greater absolute and relative theta, less relative alpha, and higher theta/alpha and theta/beta ratios than the control group. The stimulant medications resulted in a normalisation of the EEG, with changes in the theta, alpha and beta bands being most evident. These results suggest that stimulants act to increase cortical arousal in children with ADHD, normalising their EEG.     

Acute lymphocytic leukemia manifesting as splenic rupture.

Pathologic rupture of the spleen is a rare phenomenon in acute lymphocytic leukemia, and its mechanism is unknown. This complication has been seen almost exclusively in men, and at ages much older than those of the majority of patients who have this leukemia; these unusual features are also unexplained. A case of acute lymphoctyic leukemia with pathologic rupture of the spleen in which the pathologic findings suggest that the splenic rupture was due to infiltration and destruction of the splenic capsule by leukemic cells is reported.     

TGFbeta1 enhances formation of cellular Abeta/apoE deposits in vascular myocytes

Brain injury increases the risk of Alzheimer's disease (AD) through unknown mechanisms. We studied deposition of amyloid-beta protein (Abeta) in cells exposed to transforming growth factor beta1 (TGFbeta1), a cytokine that regulates cell metabolism during brain injury, and apolipoproteinE (apoE), the major lipid transporter in the brain. The studies were conducted by using brain vascular smooth muscle cells that are engaged in beta-amyloidosis in vivo and produce Abeta in cell culture. We found that cell treatment with TGFbeta1 together with apoE4 strongly increased the amount of cellular Abeta. The intracellular Abeta co-localized with apoE but not with TGFbeta, similarly as in vascular beta-amyloid. Some cellular Abeta/apoE deposits increased in size and persisted in culture even after the TGFbeta1 and apoE4 were removed. The appearance of cellular deposits of Abeta was associated with increased production of the amyloid-beta precursor protein and cellular retention of its mature form. The results suggest that the concomitant presence of apoE and TGFbeta1 can trigger vascular beta-amyloidosis by inducing intracellular formation of stable Abeta/apoE deposits.     

Consensus statement on the bio-safety of urinary-derived gonadotrophins with respect to Creutzfeldt-Jakob disease

Human transmissible spongiform encephalopathies (TSE) encompass a group of rare neurodegenerative diseases. In April 2004, a group of international experts and regulators met in Buenos Aires, Argentina, to review the safety and to reach consensus on the use of urinary-derived gonadotrophins with respect to TSE. Iatrogenic transmission of Creutzfeldt-Jakob Disease (CJD) from pituitary-derived gonadotrophins has been reported, no infectivity in urine has been demonstrated, and no definite cases of transmission via urine have been reported. It is currently not possible to monitor donor urine or finished product for the presence of prions. Therefore the assessment of risk has to be based on the likelihood of infection in urine, the source of the urine, and the capacity of the manufacturing process to remove any adventitious infection. Urine for the production of medicinal products should be obtained from sources that minimize the possible presence of materials derived from subjects suffering from human TSE. As no strong evidence for TSE infectivity in urine exists, it can be concluded that the risk of disease-generating prions and TSE infectivity being present in donor urine is low. Current evidence indicates that, with respect to the risk of TSE infection, urinary-derived gonadotrophins appear to be safe.