Human studies suggest that a variety of prenatal stressors are related to high risk for cognitive and behavioral abnormalities associated with psychiatric illness (Markham and Koenig, 2011). Recently, a down-regulation in the expression of GABAergic genes (i.e., glutamic acid decarboxylase 67 and reelin) associated with DNA methyltransferase (DNMT) overexpression in GABAergic neurons has been regarded as a characteristic phenotypic component of the neuropathology of psychotic disorders (Guidotti et al., 2011). Here, we characterized mice exposed to prenatal restraint stress (PRS) in order to study neurochemical and behavioral abnormalities related to development of schizophrenia in the adult. Offspring born from non-stressed mothers (control mice) showed high levels of DNMT1 and 3a mRNA expression in the frontal cortex at birth, but these levels progressively decreased at post-natal days (PND) 7, 14, and 60. Offspring born from stressed mothers (PRS mice) showed increased levels of DNMTs compared to controls at all time-points studied including at birth and at PND 60. Using GAD67-GFP transgenic mice, we established that, in both control and PRS mice, high levels of DNMT1 and 3a were preferentially expressed in GABAergic neurons of frontal cortex and hippocampus. Importantly, the overexpression of DNMT in GABAergic neurons was associated with a decrease in reelin and GAD67 expression in PRS mice in early and adult life. PRS mice also showed an increased binding of DNMT1 and MeCP2, and an increase in 5-methylcytosine and 5-hydroxymethylcytosine in specific CpG-rich regions of the reelin and GAD67 promoters. Thus, the epigenetic changes in PRS mice are similar to changes observed in the post-mortem brains of psychiatric patients. Behaviorally, adult PRS mice showed hyperactivity and deficits in social interaction, prepulse inhibition, and fear conditioning that were corrected by administration of valproic acid (a histone deacetylase inhibitor) or clozapine (an atypical antipsychotic with DNA-demethylation activity). Taken together, these data show that prenatal stress in mice induces abnormalities in the DNA methylation network and in behaviors indicative of a schizophrenia-like phenotype. Thus, PRS mice may be a valid model for the investigation of new drugs for schizophrenia treatment targeting DNA methylation.
Perfusion nuclear medicine study has a statistically significantly lower effective and breast-absorbed dose (P<0.0001) when compared with CTPA. Similarly, the fetal-absorbed dose for pulmonary scintigraphy has a statistically lower dose (P=0.0010) when compared with CTPA, even if the ventilation component of pulmonary scintigraphy is performed, although these values are so small that they are unlikely to be clinically significant.
The time sensitivity factor reflects another kinetic parameter of tumor metabolism besides SUV when using variable dual-time FDG PET. It offers another useful diagnostic tool in optimizing choices of dual-time protocols for oncologic PET-CT and in reducing SUV variations due to time interval differences with corrections using S.
Solitary pulmonary nodules are a common finding on chest radiography and CT. We present the case of an asymptomatic 59-year-old male found to have a 13 mm left upper lobe nodule on CT scan. The patient was asymptomatic and the CT was performed to follow up mediastinal and hilar lymphadenopathy that had been stable on several previous CT scans. He had a history of emphysema and reported a 15 pack-year smoking history. PET-CT was performed which demonstrated mild 18-FDG uptake within the nodule. Given his age and smoking history, malignancy was a consideration and he underwent a wedge resection. Pathological examination revealed a necrobiotic granulomatous nodule with a central thrombosed artery containing a parasitic worm with internal longitudinal ridges and abundant somatic muscle, consistent with pulmonary dirofilariasis. Dirofilaria immitis, commonly known as the canine heartworm, rarely affects humans. On occasion it can be transmitted to a human host by a mosquito bite. There are two major clinical syndromes in humans: pulmonary dirofilariasis and subcutaneous dirofilariasis. In the pulmonary form, the injected larvae die before becoming fully mature and become lodged in the pulmonary arteries.
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