Toll-like receptor signaling inhibits structural development of the distal fetal mouse lung.

We tested the hypothesis that innate immune signaling in utero could disrupt the structural development of the fetal lung, contributing to the pathogenesis of bronchopulmonary dysplasia. Injection of Escherichia coli lipopolysaccharide (LPS) into the amniotic fluid of E15 BALB/cJ mice increased the luminal volume density of fetal mouse lungs at embryonic day (E) 17 and E18. LPS also increased luminal volume and decreased distal lung branching in fetal mouse lung explants. This effect required NF-kappaB activation and functional Toll-Like Receptor 4. Airway branching may require fibronectin-dependent epithelial-mesenchymal interactions, representing a potential target for innate immune signaling. Anti-fibronectin antibodies and LPS both blocked distal lung branching. By immunofluorescence, fibronectin localized to the clefts between newly formed airways but was restricted to peripheral mesenchymal cells in LPS-exposed explants. These data suggest that LPS may alter the expression pattern of mesenchymal fibronectin, potentially disrupting epithelial-mesenchymal interactions and inhibiting distal airway branching and alveolarization. This mechanism may link innate immune signaling with defects in structural development of the fetal lung.     

Educational level as a modulator of cognitive performance and neuropsychyatric features in Parkinson disease.

OBJECTIVES: To test a possible association between the educational level (EL), cognitive performance, and neuropsychiatric features in Parkinson disease (PD). BACKGROUND: An inverse association has been reported between EL and cognitive dysfunction in patients with senile dementia of Alzheimer type but it is yet unsettled whether education has a similar effect on cognition in PD. METHODS: Seventy-two PD patients (45 males, mean age 68.7+/-11.6 y) underwent a detailed neurologic examination, a battery of neuropsychologic tests, and questionnaires for the evaluation of psychosis, sleep disturbances, and depression. According to the number of educational years, patients were divided into 3 groups: low EL (0 to 8 y), (15 patients), intermediate EL (9 to 12 y) (28 patients), and high EL (>/=13 y) (29 patients). RESULTS: Patients with a higher EL had a better cognitive function and an association was found between the patients' EL and their scores in various neuropsychologic tests mainly those sensitive to frontal lobe dysfunction. Low education was associated with an increased risk for hallucinations and a trend for more depression, delusions, and sleep disturbances. CONCLUSIONS: The association between high educational attainment and the lower risk of cognitive dysfunction suggest that education might modulate cognitive performance in PD.     

Human leukocyte antigen and adult living-donor liver transplantation outcomes: an analysis of the organ procurement and transplantation network database.

Human leukocyte antigen (HLA) compatibility has no clinically significant impact in cadaveric liver transplantation. Less is known regarding living-donor liver transplantation (LDLT). Our prior analysis of the Organ Procurement and Transplantation Network (OPTN) database suggested a higher graft failure rate in patients who underwent LDLT from donors with close HLA match. We further investigated the effect of HLA-A, -B, and -DR matching on 5-yr graft survival in adult LDLT by analyzing OPTN data regarding adult LDLT performed between 1998 and 2005. We evaluated associations between 5-yr graft survival and total, locus-specific, and haplotype match levels. Separate analyses were conducted for recipients with autoimmune (fulminant autoimmune hepatitis, cirrhosis secondary to autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis) or nonautoimmune liver disease. Multivariable Cox proportional hazard models were used to evaluate interactions and adjust for potential confounders. Among 631 patients with available donor/recipient HLA data, the degree of HLA match had no significant effect on 5-yr graft survival, even when analyzed separately in recipients with autoimmune vs. nonautoimmune liver disease. To be able to include all 1,838 adult LDLTs, we considered a first-degree related donor as substitute for a close HLA match. We found no difference in graft survival in related vs. unrelated pairs. In conclusion, our results show no detrimental impact of close HLA matching on graft survival in adult LDLT, including in recipients with underlying autoimmune liver disease.     

Motor and non-motor sequence learning in children and adolescents with cerebellar damage.

Cerebellar involvement in motor and non-motor sequence learning was examined with serial reaction time tasks (SRT). Our sample consisted of 8 children and adolescents who had undergone surgical removal of a benign posterior fossa tumor (PFT) during childhood. None of them had undergone chemotherapy or cranial radiation therapy (CRT). Ages ranged from 1-11 years at surgery and 9-17 years at testing. The children were tested not earlier than 2.5 years after surgery (M = 5.9 years), enabling brain plasticity and recovery of functions. Their performance was compared with a matched control sample. The PFT group was not impaired in the implicit learning of sequences, as reflected in their performance in blocks with a repeated sequence, both before and after a random block. However, in the perceptual task, their performance deteriorated more than that of the control group when a random block was introduced, suggesting that it was more difficult for the patients to respond flexibly or change their response set when encountering changing task demands. These results are in line with another study by our group on task switching with the same patients.     

Comparison between true and partial hemifacial hypertrophy.

Hemifacial hypertrophy (HFH) is rare and characterized by unilateral enlargement of the head and teeth. Hemifacial hypertrophy is classified as true HFH (THFH) with unilateral enlargement of the viscerocranium, and partial HFH (PHFH) in which not all structures are enlarged. We present a case of THFH and compare and contrast it with a case of PHFH. Hemifacial hypertrophy may cover a wide spectrum of defects or may involve only muscle or bone. Myohyperplasia, reported previously as a separate syndrome, may actually represent a forme fruste of PHFH or THFH. The PHFH patient lead a healthy, normal life without significant psychosocial problems and was reluctant to accept his deformity. Contrastingly, the THFH patient had significant social stigma and compromised health together with major aesthetic morbidity. Treatment planning in THFH is arduous and involves multiple modalities. Therefore, it is imperative to differentiate THFH and PHFH for better understanding and management of the condition.     

Effects of the novel antidepressant S-adenosyl-methionine on alpha 1- and beta-adrenoceptors in rat brain

alpha 1- and beta-adrenoceptors were studied ex vivo in the brains of rats receiving repeated daily treatment with the standard antidepressant imipramine or the atypical antidepressant S-adenosyl-L-methionine (SAM), which has minimal effects on monoamine reuptake or turnover. Consistent with past studies, a decrease in the density of beta receptors at three weeks and an increase in the affinity of alpha 1 receptors for the agonist phenylephrine at one week of treatment was observed with imipramine. By comparison, an increase in the density of beta receptors and a decrease in the affinity of alpha 1 receptors for phenylephrine was observed at one week of treatment with SAM. These changes were no longer apparent at three weeks of treatment. The results suggest that treatment with SAM does lead to changes in adrenergic neurotransmission, but that down regulation of beta receptors or increased agonist affinity of alpha 1 receptors may not be necessary for the production of antidepressant effects.