Role of thrombogenic factors in the development of atherosclerosis

Hemostatic factors play a crucial role in generating thrombotic plugs at sites of vascular damage (atherothrombosis). However, whether hemostatic factors contribute directly or indirectly to the pathogenesis of atherosclerosis remains uncertain. Autopsy studies have revealed that intimal thickening represents the first stage of atherosclerosis and that lipid-rich plaque arises from such lesions. Several factors contribute to the start of intimal thickening. Platelets release several growth factors and bioactive agents that play a central role in development of not only thrombus but also of intimal thickening. We have been investigating which coagulation factors simultaneously, or subsequently with platelet aggregation, participate in thrombus formation. Tissue factor (TF) is an essential initiator of blood coagulation that is expressed in various stages of atherosclerotic lesions in humans and other animals. Factors including thrombin and fibrin, which are downstream of the coagulation cascade activated by TF, also contribute to atherosclerosis. TF is involved in cell migration, embryogenesis and angiogenesis. Thus TF, in addition to factors downstream of the coagulation cascade and the protease-activated receptor 2 activation system, would be a multifactorial regulator of atherogenesis.     

Electron beam CT versus 16-MDCT on the variability of repeated coronary artery calcium measurements in a variable heart rate phantom

OBJECTIVE: High reproducibility of coronary artery calcium (CAC) scoring is a key requirement for monitoring the progression of coronary atherosclerosis. The purposes of this study were to compare electron beam CT and 16-MDCT scanners in the variability of repeated CAC measurements and to assess the factors influencing this variability. MATERIALS AND METHODS: CAC models of different sizes attached to a cardiac phantom with a programmable variable heart rate were scanned three times, and interscan variability of the CAC measurement was calculated each time. For helical CT, different slice-thickness images of either retrospective ECG-gated or prospective ECG-triggering reconstruction were obtained. The detection of small amounts of calcium, variability of the Agatston score, and CAC measurement algorithms (Agatston, volume, and mass scores) were compared between CT scanners and protocols. RESULTS: All 1-mm-sized calcium models were detected on 0.625- and 1.25-mm helical CT, whereas some were missed on electron beam CT and 2.5-mm helical CT. Retrospective ECG-gated thin-slice helical CT showed the lowest variability. Reduction of variability by volume and mass scoring algorithms was less effective on 0.625- and 1.25-mm-thickness CT. CONCLUSION: Retrospective ECG-gated thin-slice helical CT has the potential to be a useful tool for monitoring coronary atherosclerosis.     

Expression of fasciculation and elongation protein zeta-1 (FEZ1) in the developing rat brain

Fasciculation and elongation protein zeta-1 (FEZ1) is a mammalian homologue of the Caenorhabditis elegans UNC-76 protein involved in axonal outgrowth and fasciculation. Recently, we reported that FEZ1 interacts with Disrupted-In-Schizophrenia 1 (DISC1), a product of the candidate gene for schizophrenia, and that the interaction between these proteins has a role in neurite outgrowth. This time, we investigated the expression of FEZ1 and DISC1 in the developing rat brain using in situ hybridization. Both FEZ1 and DISC1 showed high levels of expression, especially in developing hippocampal neurons. These findings suggest the potential involvement of FEZ1 and DISC1 in the formation of hippocampal neural circuits.     

Profile of gene expression in the subventricular zone after traumatic brain injury

Neural stem cells, which reside in the subventricular zone (SVZ) and dentate gyrus (DG) of adult mammals, give rise to new neurons throughout life. However, these neural stem cells do not appear to contribute to regeneration in the damaged central nervous system. Following traumatic brain injury (TBI) in adult rats, the number of proliferating cells labeled with bromodeoxyuridine (BrdU) is significantly increased in the bilateral SVZ and DG; however, these proliferating cells do not contribute to effective regeneration in the damaged area. To gain insight into the molecular mechanisms of these biological actions, changes in gene expression in the SVZ after brain trauma were examined by cDNA microarray. Of 9,596 genes screened, 97 were upregulated and 204 were downregulated. Classifying these genes according to their function suggests that TBI affects a broad range of cellular functions. The validity of the data was confirmed by RT-PCR. The expression of some genes localized in the SVZ was confirmed by in situ hybridization. This combined strategy is effective for comprehensive analysis of the pathophysiological changes in the SVZ after brain injury and should contribute to the understanding of the molecular events that occur after injury. In the future, this may enable regeneration of the damaged central nervous system.     

Evaluation of lesions of malignant lymphoma using histograms of regional SUV

We designed new evaluation method using histogram of regional standardized uptake value (SUV) of every pixels of box shape volume of interest (VOI) on 18F-FDG PET. We evaluate lung and liver of normal volunteers and also the lesions of 4 cases of patients with non Hodgikin's malignant lymphoma using this method. SUV of pixels of pretreatment lesions shows log-normal distribution, whereas SUV of lung and liver show normal shape distribution. The next day of chemotherapy, 2 cases of them showed changes of distribution pattern from long-normal to normal with decrease of component of higher SUV values. No remarkable changes of distribution pattern were observed on other 2 cases, whereas decrease of regional mean values and max values of SUV were observed. And these findings were continued to 3 weeks later. These findings suggest that regional evaluation using histograms of SUV gives additional and predictive information for tumor therapies soon after the end of course.