Physiological consequences of the TRα1 aporeceptor state

Many patients have been characterized harboring a mutation in thyroid hormone receptor (TR) β. Surprisingly none has yet been identified carrying a mutation in TRα1. To facilitate the identification of such patients, several animal models with a mutant TRα1 have been generated. While some phenotypic characteristics, such as an adult euthyroidism, are similar in the mutant mice, other aspects such as metabolism are quite variable. This review summarizes the most important consequences of a mutation in TRα1 in mice focusing on the TRα1-R384C mutation, and projects the insights from the animal models to a putative phenotype of patients with a mutated TRα1.     

Comparing the Clinical and Economic Impact of Laparoscopic Versus Open Liver Resection

Background  

Laparoscopic liver resection has thus far not gained widespread acceptance among liver surgeons. Valid questions remain regarding the relative clinical superiority of the laparoscopic approach as well as whether laparoscopic hepatectomy carries any economic benefit compared with open liver surgery.     

Interactions between mannose-binding lectin and MASPs during complement activation by the lectin pathway

The lectin pathway of complement performs a key role within the immune system by recognising pathogens through patterns of sugar moieties displayed on their cell surfaces and neutralising them via an antibody-independent reaction cascade. While particularly important during early childhood before the adaptive immune system is established, or when adaptive immunity is compromised, it has a protective function throughout life, neutralising invading pathogens directly and helping to stimulate and direct an effective immune response. Complement activation is initiated when complexes comprising mannose-binding lectin (MBL) or serum ficolins and MBL-associated serine protease-2 (MASP-2) bind to pathogens. Binding induces conformational changes in these complexes, leading to autoactivation of the MASPs, which in turn activate the downstream reaction cascade. A major goal in complement research is to understand the molecular events that trigger complement activation. Over the last few years, structure-function studies have improved our knowledge of the way in which MBL binds to MASPs by defining the portions of these proteins that interact and by solving the structures of key protein fragments. In this review, I will summarise the main findings of these studies and describe current theories to explain how the components combine to initiate the reaction cascade.     

Sex determination in platypus and echidna: autosomal location of <Emphasis Type="Italic">SOX3</Emphasis> confirms the absence of <Emphasis Type="Italic">SRY</Emphasis> from monotremes

In eutherian ('placental') mammals, sex is determined by the presence or absence of the Y chromosome-borne gene SRY, which triggers testis determination. Marsupials also have a Y-borne SRY gene, implying that this mechanism is ancestral to therians, the SRY gene having diverged from its X-borne homologue SOX3 at least 180 million years ago. The rare exceptions have clearly lost and replaced the SRY mechanism recently. Other vertebrate classes have a variety of sex-determining mechanisms, but none shares the therian SRY-driven XX female:XY male system. In monotreme mammals (platypus and echidna), which branched from the therian lineage 210 million years ago, no orthologue of SRY has been found. In this study we show that its partner SOX3 is autosomal in platypus and echidna, mapping among human X chromosome orthologues to platypus chromosome 6, and to the homologous chromosome 16 in echidna. The autosomal localization of SOX3 in monotreme mammals, as well as non-mammal vertebrates, implies that SRY is absent in Prototheria and evolved later in the therian lineage 210-180 million years ago. Sex determination in platypus and echidna must therefore depend on another male-determining gene(s) on the Y chromosomes, or on the different dosage of a gene(s) on the X chromosomes.     

Is the outcome of in-vitro fertilization and embryo transfer treatment improved by spontaneous or surgical drainage of a hydrosalpinx?

A pilot study was designed to examine whether the outcome of embryo transfer in women with a hydrosalpinx might be improved by surgical drainage of the hydrosalpinx at the time of oocyte collection for in- vitro fertilization treatment. A comparative, controlled but retrospective analysis of the results was performed of all women with infective tubal damage aged <40 years old, who had ovulatory cycles, a normal uterus and a partner with normal spermatozoa. A standardized treatment regimen was used. A maximum of three embryos were transferred. Hydrosalpinx was defined by prior hysterosalpingography and/or laparoscopy with transcervical dye injection. A total of 237 embryo transfer cycles in women with hydrosalpinges (tubal distension not visible in 151, visible but not drained in 30 and drained in 56) were compared with 705 embryo transfer cycles in women with tubal disease but no hydrosalpinx. Results were analysed in the first three cycles but also separately in the first cycle to check for bias. Success rates were higher in the first cycle, but did not significantly influence overall differences. Implantation rates were significantly reduced overall in the hydrosalpinx group (8.0 versus 13.2% for controls; P < 0.001), being 8.3% (P < 0.01) in the subgroup without evident tubal distension and 7.5% (not significant) in the drained hydrosalpinx group. This study shows that tubal damage with distal occlusion is associated with a marked reduction in embryo implantation, even in the absence of obvious fluid distension. Surgical drainage of distended hydrosalpinges appears to offer no benefit.      

The neuroendocrine stress hormone norepinephrine augments Escherichia coli O157:H7-induced enteritis and adherence in a bovine ligated ileal loop model of infection

The role of the neuroendocrine environment in the pathogenesis of enteric bacterial infections is increasingly being recognized. Here we report that norepinephrine augments Escherichia coli O157:H7-induced intestinal inflammatory and secretory responses as well as bacterial adherence to intestinal mucosa in a bovine ligated ileal loop model of infection. Norepinephrine modulation of enteritis and adherence was dependent on the ability of E. coli O157:H7 to form attaching and effacing lesions.     

Characterization of the human jumonji gene

While constructing a cDNA library of human embryos, we have isolated a clone homologous to jumonji, a mouse gene required for neural tube formation. We have determined the complete coding sequence of the human homologue (JMJ) and deduced the amino acid sequence of the putative protein. We show here that human and mouse jumonji putative proteins are homologous and present 90% identity. During human embryogenesis, JMJ mRNAs are predominantly expressed in neurons and particularly in dorsal root ganglion cells. They are also expressed in neurons of human adult cerebral cortex. In view of these observations, we propose JMJ as a candidate gene for developmental defects of the central nervous system in the human. The human JMJ gene maps at position 6p24-6p23.