Growth hormone as an early embryonic growth and differentiation factor

In this review we consider the evidence that growth hormone (GH) acts in the embryo as a local growth, differentiation, and cell survival factor. Because both GH and its receptors are present in the early embryo before the functional differentiation of pituitary somatotrophs and before the establishment of a functioning circulatory system, the conditions are such that GH may be a member of the large battery of autocrine/paracrine growth factors that control embryonic development. It has been clearly established that GH is able to exert direct effects, independent of insulin-like growth factor-I (IGF-I), on the differentiation, proliferation, and survival of cells in a wide variety of tissues in the embryo, fetus, and adult. The signaling pathways behind these effects of GH are now beginning to be determined, establishing early extrapituitary GH as a bona fide developmental growth factor.     

MR microscopy and high resolution small animal MRI: applications in neuroscience research

The application of magnetic resonance (MR) imaging in the study of human disease using small animals has steadily evolved over the past two decades and strongly established the fields of "small animal MR imaging" and "MR microscopy." An increasing number of neuroscience related investigations now implement MR microscopy in their experiments. Research areas of growth pertaining to MR microscopy studies are focused on (1). phenotyping of genetically engineered mice models of human neurological diseases and (2). rodent brain atlases. MR microscopy can be performed in vitro on tissue specimens, ex vivo on brain slice preparations and in vivo (typically on rodents). Like most new imaging technologies, MR microscopy is technologically demanding and requires broad expertise. Uniform guidelines or "standards" of a given MR microscopy experiment are non-existent. The main focus therefore of this review will be on biological applications of MR microscopy and the experimental requirements. We also take a critical look at the biological information that small animal (rodent) MR imaging has provided in neuroscience research.     

Hormones increase mRNA of cyclic-nucleotide-gated cation channels in airway epithelia

Previous studies have shown that the mRNA of cyclic-nucleotide-gated nonselective cation (CNG) channels is expressed in rat airway epithelia and that these channels contribute to sodium-mediated short-circuit currents in cultured rat tracheal epithelia. Patch-clamp studies from human A549 cells indicate that these channels contribute to cGMP-stimulated L-cis-diltiazem- and dichlorobenzamil-inhibited whole-cell sodium currents. This study demonstrates that mRNA for primary and secondary subunits of CNG channels, halphaCNG1 and hbetaCNG1 respectively, are expressed in several human airway cell lines, including normal and cystic fibrosis bronchial airway cells, in normal and cystic fibrosis tracheal airway cell lines and nasal polyp tissue from a cystic fibrosis patient. The mRNA of ralphaCNG1 in rat lung increased in response to increased circulating glucocorticoids and decreased in animals with lowered circulating glucocorticoids after aminoglutethimide treatment. Likewise the mRNA of halphaCNG1 increased in the presence of glucocorticoids in cultured alveolar airway cells. The mRNA of alphaCNG1 in rat lung was also increased in response to a low-salt diet and lowered in animals fed a high-salt diet. Likewise the mRNA of alphaCNG1 was increased in response to increased aldosterone and decreased in animals given spironolactone. These results suggest that mRNA for alphaCNG1 increases in response to elevated glucocorticoids or mineralocorticoids. Because alphaCNG1 is a functional sodium entry channel in both rat and human airway epithelial cells, if channel protein is also elevated this channel could mediate an increase in sodium absorption across lung epithelia in response to circulating hormones.     

Involvement of tumour necrosis factor and other cytokines in immune-mediated vascular pathology

Vascular endothelial cells are actively involved in coagulation and inflammation processes and appear to represent an important element in cell-mediated immune responses. In this paper, the possible role of endothelial cells as a target for immunopathological reactions was analyzed. Experimental neurovascular lesions were studied in a model of cerebral malaria, with particular attention to the role of cytokine interactions in vivo.     

Use of pulsed field gel electrophoresis to determine the source of microbial contamination of central venous catheters

Microorganisms detected in situ on the distal tip of central venous catheters (CVC) within 90 min of insertion were investigated using pulsed-field gel electrophoresis to analyse genomic fragments obtained with theSmaI restriction enzyme. Thirty patients received a triple lumen CVC, which was inserted directly through the skin using the Seldinger technique. In a further 30 patients a triple lumen CVC was inserted through a Swan sheath, thereby avoiding direct contact of the CVC with the skin. Staphylococci were isolated from the distal tips of the catheters in 6 patients (5 who had the CVC inserted directly through the skin and 1 who had the CVC inserted via a Swan sheath.) Twenty-three staphylococcal isolates were also isolated from the insertion equipment and the skin swabs surrounding the insertion site of these six patients. All the isolates were genotyped. In one of the patients the organisms isolated from the skin were identical to those on the CVC tip. In two further patients similar organisms were isolated from the insertion equipment and the patients' skin. These results, in addition to the reduced colonisation rates observed when catheters were introduced through a Swan sheath, support the hypothesis that microorganisms from the skin are impacted onto the CVC tip and the CVC insertion equipment at catheter insertion.     

False resistance to imipenem with a microdilution susceptibility testing system.

Routine monitoring of antibiotic resistance at Children's Hospital, Boston, detected a dramatic increase in the prevalence of imipenem-resistant strains of Pseudomonas aeruginosa. Further studies documented that false resistance to imipenem was due, in part, to the loss of imipenem potency in customized MIC microdilution trays supplied by Sensititre Ltd. (West Sussex, United Kingdom). Recognition of the problem was delayed by use of the quality control standard recommended by the manufacturer, which were higher and broader than those suggested by the National Committee for Clinical Laboratory Standards.