Synchronous primary colorectal and liver metastasis: impact of operative approach on clinical outcomes and hospital charges.

Objectives: The management of patients with colorectal cancer (CRC) and synchronous colorectal liver metastasis (CLM) remains controversial. The present study was conducted in order to assess the clinical and economic impacts of managing synchronous CLM with a staged versus a simultaneous surgery approach.

Methods: A total of 224 patients treated for synchronous CLM during 1990-2012 were identified in the Johns Hopkins Hospital liver database.

Functional consequences of mutations in the Drosophila histamine receptor HCLB.

The gene hclB encodes a histamine-gated chloride channel subunit in Drosophila melanogaster. Mutations in hclB lead to defects in the visual system and altered sensitivity to the action of ivermectin. To investigate whether this member of the Cys-loop receptors is common across the Insecta, we analysed the genomes of seven other insect species (Diptera, Hymenoptera, Coleoptera) and revealed orthologues of hclB in all of them.

Altered ivermectin pharmacology and defective visual system in Drosophila mutants for histamine receptor HCLB.

The Drosophila gene hclB encodes a histamine-gated chloride channel, which can be activated by the neurotoxin ivermectin when expressed in vitro. We have identified two novel hclB mutants, carrying either a missense mutation (P293S, allele hclB (T1)) or a putative null mutation (W111*, allele hclB (T2)), as well as a novel splice form of the gene. In survival studies, hclB (T1) mutants were more sensitive to ivermectin than wild-type, whereas hclB (T2) were more resistant.

Distinct roles for two histamine receptors (hclA and hclB) at the Drosophila photoreceptor synapse.

Histamine (HA) is the photoreceptor neurotransmitter in arthropods, directly gating chloride channels on large monopolar cells (LMCs), postsynaptic to photoreceptors in the lamina. Two histamine-gated channel genes that could contribute to this channel in Drosophila are hclA (also known as ort) and hclB (also known as hisCl1), both encoding novel members of the Cys-loop receptor superfamily. Drosophila S2 cells transfected with these genes expressed both homomeric and heteromeric histamine-gated chloride channels.

Phylogenetic shadowing of a histamine-gated chloride channel involved in insect vision.

A recently identified gene, hclA (synonym: ort), codes for an ionotrophic histamine receptor subunit in Drosophila melanogaster, and known hclA mutations lead to defects in the visual system, neurologic disorders and changed responsiveness to neurotoxins. To investigate whether this novel class of receptors is common across the Insecta, we analysed the genomes of 15 other insect species (Diptera, Hymenoptera, Coleoptera, Lepidoptera) and revealed orthologs of hclA in all of them. The predicted receptor domain of HCLA is extensively conserved (86-100% of identity) among the 16 proteins.

Altered drug resistance and recovery from paralysis in Drosophila melanogaster with a deficient histamine-gated chloride channel.

The recent identification and characterization of two genes, encoding histamine-gated chloride channel subunits from Drosophila melanogaster, has confirmed that histamine is a major neurotransmitter in the fruitfly. One of the cloned genes, hclA (synonyms: HisCl-alpha1; HisCl2), corresponds to ort (ora transientless), mutationsin which affect synaptic transmission in the Drosophila visual system. We identified a mutational change (a null mutation) in the genomic and RNA copies of hclA derived from mutants carrying the ort(1) allele.

The target of Drosophila photoreceptor synaptic transmission is a histamine-gated chloride channel encoded by ort (hclA).

By screening Drosophila mutants that are potentially defective in synaptic transmission between photoreceptors and their target laminar neurons, L1/L2, (lack of electroretinogram on/off transients), we identified ort as a candidate gene encoding a histamine receptor subunit on L1/L2. We provide evidence that the ort gene corresponds to CG7411 (referred to as hclA), identified in the Drosophila genome data base, by P-element-mediated germ line rescue of the ort phenotype using cloned hclA cDNA and by showing that several ort mutants exhibit alterations in hclA regulatory or coding sequences and/or allele-dependent reductions in hclA transcript levels. Other workers have shown that hclA, when expressed in Xenopus oocytes, forms histamine-sensitive chloride channels.