Serial Magnetic Resonance Imagings of Multiple Brain Abscesses in a Patient with Pneumococcal Meningoencephalitis

We report a 43-yr-old man manifesting bacterial meningoencephalitis and multiple abscesses by Streptococcus pneumoniae. Serial magnetic resonance (MR) imagings and MR spectroscopy showed the evolution of multiple brain abscesses over 4 weeks: the enhanced rings became thicker and the dimension of whole lesions larger despite shrinkage of the ring-enhanced regions. These findings may be evidence of active inflammation working to sequestrate the lesion and protect the surrounding normal brain parenchyma from additional damage, even in the final stage of the brain abscess

Laparoscopic Total Mesorectal Excision in a Rectal Cancer Patient with Situs Inversus Totalis

Situs inversus totalis is a rare anomaly in which the abdominal and thoracic cavity structures are opposite their usual positions. A 41-yr-old woman, who had an ulcerating cancer on the rectum, was found as a case of situs inversus totalis. We present an overview of the operative technique for the first documented laparoscopic total mesorectal excision of a rectal cancer in the patient with situs inversus totalis. Careful consideration of the mirror-image anatomy permitted a safe operation using techniques not otherwise different from those used for the general population. Therefore, curative laparoscopic surgery for rectal cancer in this patient is feasible and safe

The Evolutionarily Conserved LIM Homeodomain Protein LIM-4/LHX6 Specifies the Terminal Identity of a Cholinergic and Peptidergic C. elegans Sensory/Inter/Motor Neuron-Type

The expression of specific transcription factors determines the differentiated features of postmitotic neurons. However, the mechanism by which specific molecules determine neuronal cell fate and the extent to which the functions of transcription factors are conserved in evolution are not fully understood. In C. elegans, the cholinergic and peptidergic SMB sensory/inter/motor neurons innervate muscle quadrants in the head and control the amplitude of sinusoidal movement. Here we show that the LIM homeobox protein LIM-4 determines neuronal characteristics of the SMB neurons. In lim-4 mutant animals, expression of terminal differentiation genes, such as the cholinergic gene battery and the flp-12 neuropeptide gene, is completely abolished and thus the function of the SMB neurons is compromised. LIM-4 activity promotes SMB identity by directly regulating the expression of the SMB marker genes via a distinct cis-regulatory motif. Two human LIM-4 orthologs, LHX6 and LHX8, functionally substitute for LIM-4 in C. elegans. Furthermore, C. elegans LIM-4 or human LHX6 can induce cholinergic and peptidergic characteristics in the human neuronal cell lines. Our results indicate that the evolutionarily conserved LIM-4/LHX6 homeodomain proteins function in generation of precise neuronal subtypes

Disrupted intracellular calcium regulates BACE1 gene expression via nuclear factor of activated T cells 1 (NFAT 1) signaling

Beta-site APP-cleaving enzyme 1 (BACE1) expression is elevated in the brains of Alzheimer's disease (AD) patients and in aged-animal models. Because both AD and aging are associated with disrupted calcium homeostasis, we investigated the role of nuclear factor of activated T cells (NFAT) - a transcription factor regulated by the calcium- and calmodulin-dependent phosphatase calcineurin - in BACE1 expression. BACE1 expression was stimulated by a calcium ionophore in primary cortical cultures, and by SH-SY5Y neuroblastoma cells, which was both blocked by pretreatment with either cyclosporin A, an inhibitor of calcineurin, or ethyleneglycotetraacetic acid, a calcium chelator. Gel shift assays revealed direct binding of NFAT1 to specific DNA sequences within the BACE1 gene promoter region. Treatment with amyloid beta (Abeta), one of the major factors in AD pathogenesis, stimulated activation and nuclear translocation of NFAT1 following up-regulation of BACE1 expression. In addition, primary cortical cultures from Tg2576 mouse brains generated more Abeta by ionophore stimulation, which was reversed by cyclosporin A treatment. Furthermore, NFAT1 activation was observed in Tg2576 mouse brains. These results suggest that calcium ionophore- or Abeta-induced increases in intracellular calcium concentration stimulate BACE1 expression, resulting in accelerated Abeta generation, and that this process is mediated through the calcineurin-NFAT1 signaling pathway. This process may play a significant role in the pathogenesis of AD and aging