Hepatocyte steatosis in HCV patients promotes fibrosis by enhancing TGF-beta liver expression.

Aim: The objective of this study was to examine the relationship between TGF-beta expression in steatotic liver and the stage and yearly progression rate of fibrosis in chronic hepatitis C (CHC) patients. Methods: We examined 44 CHC fatty liver patients, using 76 non-steatotic CHC patients as controls. The stage of hepatic fibrosis was assessed on a score scale. TGF-beta expression was determined with the use of monoclonal serum and the ABC three-step method. Results: We demonstrated a positive correlation of steatosis with the stage of fibrosis (P < 0.05). No relationship of thiskind was found with the yearly progression rate of fibrosis (P > 0.09). In steatotic biopsies, TGF-beta expression index in portal spaces and lobules was found to be higher as compared to TGF-beta expression in biopsies without steatosis (P < 0.05). Conclusion: In CHC patients steatosis induces the development of fibrosis by elevating the hepatic expression of TGF-beta.     

Enhanced Dopamine-Dependent Hippocampal Plasticity after Single MK-801 Application

Dopaminergic hyperfunction and N-methyl-D-aspartate receptor (NMDAR) hypofunction have both been implicated in psychosis. Dopamine-releasing drugs and NMDAR antagonists replicate symptoms associated with psychosis in healthy humans and exacerbate symptoms in patients with schizophrenia. Though hippocampal dysfunction contributes to psychosis, the impact of NMDAR hypofunction on hippocampal plasticity remains poorly understood. Here, we used an NMDAR antagonist rodent model of psychosis to investigate hippocampal long-term potentiation (LTP). We found that single systemic NMDAR antagonism results in a region-specific, presynaptic LTP at hippocampal CA1-subiculum synapses that is induced by activation of D1/D5 dopamine receptors and modulated by L-type voltage-gated Ca²⁺ channels. Thereby, our findings may provide a cellular mechanism how NMDAR antagonism can lead to an enhanced hippocampal output causing activation of the hippocampus-ventral tegmental area-loop and overdrive of the dopamine system.     

A case of acute monocytic leukemia with lysozyme-positive leukemic monocytes and normal serum lysozyme levels

We report a case of acute monocytic leukemia with normal serum lysozyme but with immunoperoxidase positivity for lysozyme in the leukemic blasts. The diagnosis of acute monocytic leukemia was made on the basis of cellular morphology, immunocytochemistry and cytochemistry. Discrepancy between serum lysozyme and intracytoplasmic lysozyme has not previously been reported in the literature. Levels of serum lysozyme may be misleading in cases of acute monocytic leukemia (FAB classification M5).     

DOES VISUAL SUBORDINATE-LEVEL CATEGORISATION ENGAGE THE FUNCTIONALLY DEFINED FUSIFORM FACE AREA?

Functional magnetic resonance imaging was used to compare brain activation associated with basic-level (e.g. bird) and subordinate-level (e.g. eagle) processing for both visual and semantic judgements. We localised the putative face area for 11 subjects, who also performed visual matching judgements for pictures and aurally presented words. The middle fusiform and occipital gyri were recruited for subordinate minus basic visual judgements, reflecting additional perceptual processing. When the face area was localised individually for each subject, analyses in the middle fusiform gyri revealed that subordinate-level processing activated the individuals face area. We propose that what is unique about the way faces engage this region is the focal spatial distribution of the activation rather than the recruitment of the face per se. Eight subjects also performed semantic judgements on aurally presented basic- and subordinate-level words. The parahippocampal gyri were more activated for subordinate-level than basic-level semantic judgements. Finally, the left posterior inferior temporal gyrus was activated for subordinate-level judgements, both visual and semantic, as well as during passive viewing of faces.     

Impairment of the septal cholinergic neurons in MPTP-treated A30P α-synuclein mice

Dementia in Parkinson's disease (PDD) and dementia with Lewy bodies (DLB) are characterized by loss of acetylcholine (ACh) from cortical areas. Clinical studies report positive effects of acetylcholine esterase (AChE) inhibitors in PDD and dementia with Lewy bodies. We here report that the number of neurons expressing a cholinergic marker in the medial septum-diagonal band of Broca complex decreases in A30P α-synuclein-expressing mice during aging, paralleled by a lower AChE fiber density in the dentate gyrus and in the hippocampal CA1 field. After inducing dopamine depletion by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP), no acute but a delayed loss of cholinergic neurons and AChE-positive fibers was observed, which was attenuated by L-3,4-dihydroxyphenylalanine (DOPA) treatment. Expression of nerve growth factor (NGF) and tyrosine receptor kinase A (TrkA) genes was upregulated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride-treated wild type mice, but not in A30P α-synuclein expressing animals. In contrast, upregulation of sortilin and p75^NTR genes was found in the A30P α-synuclein-expressing mice. These results suggest that dopamine deficiency may contribute to the impairment of the septohippocampal system in patients with PDD and that L-3,4-dihydroxyphenylalanine may not only result in symptomatic treatment of the akinetic-rigid syndrome but may also alleviate the degeneration of basal forebrain cholinergic system and the cognitive decline.     

Amyloid beta and the longest-lived rodent: the naked mole-rat as a model for natural protection from Alzheimer's disease

Amyloid beta (Aβ) is implicated in Alzheimer's disease (AD) as an integral component of both neural toxicity and plaque formation. Brains of the longest-lived rodents, naked mole-rats (NMRs) approximately 32 years of age, had levels of Aβ similar to those of the 3xTg-AD mouse model of AD. Interestingly, there was no evidence of extracellular plaques, nor was there an age-related increase in Aβ levels in the individuals examined (2–20+ years). The NMR Aβ peptide showed greater homology to the human sequence than to the mouse sequence, differing by only 1 amino acid from the former. This subtle difference led to interspecies differences in aggregation propensity but not neurotoxicity; NMR Aβ was less prone to aggregation than human Aβ. Nevertheless, both NMR and human Aβ were equally toxic to mouse hippocampal neurons, suggesting that Aβ neurotoxicity and aggregation properties were not coupled. Understanding how NMRs acquire and tolerate high levels of Aβ with no plaque formation could provide useful insights into AD, and may elucidate protective mechanisms that delay AD progression.     

A familial case of alveolar capillary dysplasia with misalignment of pulmonary veins supports paternal imprinting of FOXF1 in human

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare developmental lung disorder that is uniformly lethal. Affected infants die within the first few weeks of their life despite aggressive treatment, although a few cases of late manifestation and longer survival have been reported. We have shown previously that mutations and deletions in FOXF1 are a cause of this disorder. Although most of the cases of ACD/MPV are sporadic, there have been infrequent reports of familial cases. We present a family with five out of six children affected with ACD/MPV. DNA analysis identified a missense mutation (c.416G>T; p.Arg139Leu) in the FOXF1 gene that segregated in the three affected siblings tested. The same variant is also present as a de novo mutation in the mother and arose on her paternally derived chromosome 16. The two tested affected siblings share the same chromosome 16 haplotype inherited from their maternal grandfather. Their single healthy sibling has a different chromosome 16 haplotype inherited from the maternal grandmother. The results are consistent with paternal imprinting of FOXF1 in human.