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Biomedical subjects

K Hillan

Publications and source records attributed to K Hillan.

7 recordsLinked to original sources

Unlocking the archive--gene expression in paraffin-embedded tissue.

The histopathology archive represents a vast, well-characterized source of specimens covering virtually every disease and is available for molecular biological investigation. The archive has in recent years become widely used for molecular genetic analysis and DNA can be routinely extracted from formalin-fixed, paraffin-embedded tissue. More recently, archival specimens have become a source of material for extensive analysis of mRNA expression utilizing DNA microarrays, real-time quantitative reverse transcriptase polymerase chain reaction (PCR), and in situ hybridization and amplification techniques. These techniques will enable a greater understanding of the changes that occur in gene function during every stage of the development of disease and will lead to better diagnosis, better evaluation of prognosis, and better treatment through targeted therapeutic regimes.

Biological Specimen Banks↗

FGF-19, a novel fibroblast growth factor with unique specificity for FGFR4.

We have identified a novel fibroblast growth factor, FGF-19, the most distant member of the FGF family described to date. FGF-19 is a high affinity, heparin dependent ligand for FGFR4 and is the first member of the FGF family to show exclusive binding to FGFR4. Human FGF-19 maps to chromosome 11 q13.1, a region associated with an osteoporosis-pseudoglioma syndrome of skeletal and retinal defects. FGF-19 message is expressed in several tissues including fetal cartilage, skin, and retina, as well as adult gall bladder and is overexpressed in a colon adenocarcinoma cell line.

Adenocarcinoma↗

Gene expression analysis by transcript profiling coupled to a gene database query.

We describe an mRNA profiling technique for determining differential gene expression that utilizes, but does not require, prior knowledge of gene sequences. This method permits high-throughput reproducible detection of most expressed sequences with a sensitivity of greater than 1 part in 100,000. Gene identification by database query of a restriction endonuclease fingerprint, confirmed by competitive PCR using gene-specific oligonucleotides, facilitates gene discovery by minimizing isolation procedures. This process, called GeneCalling, was validated by analysis of the gene expression profiles of normal and hypertrophic rat hearts following in vivo pressure overload.

Animals↗

Neuregulin-3 (NRG3): a novel neural tissue-enriched protein that binds and activates ErbB4.

We describe the identification of Neuregulin-3 (NRG3), a novel protein that is structurally related to the neuregulins (NRG1). The NRG1/neuregulins are a diverse family of proteins that arise by alternative splicing from a single gene. These proteins play an important role in controlling the growth and differentiation of glial, epithelial, and muscle cells. The biological effects of NRG1 are mediated by receptor tyrosine kinases ErbB2, ErbB3, and ErbB4. However, genetic studies have suggested that the activity of ErbB4 may also be regulated in the central nervous system by a ligand distinct from NRG1. NRG3 is predicted to contain an extracellular domain with an epidermal growth factor (EGF) motif, a transmembrane domain, and a large cytoplasmic domain. We show that the EGF-like domain of NRG3 binds to the extracellular domain of ErbB4 in vitro. Moreover, NRG3 binds to ErbB4 expressed on cells and stimulates tyrosine phosphorylation of this receptor. The expression of NRG3 is highly restricted to the developing and adult nervous system. These data suggest that NRG3 is a novel, neural-enriched ligand for ErbB4.

Amino Acid Sequence↗

The healing of colonic anastomoses after early intraperitoneal chemotherapy: an experimental study in rats.

Early postoperative intraperitoneal administration of 5-fluorouracil (5-Fu) is a logical adjuvant treatment of patients with resectable colonic cancers. It is easier and less invasive than the intraportal administration of the drug. However, before applying the procedure to humans it must be demonstrated than it does not disturb the healing of recent colonic anastomoses. Colonic sutures were performed in 78 male Wistar rats. The animals then either served as controls or received intraperitoneal 5-Fu during 5 days starting on the first, third, or seventh postoperative day. No statistical difference was observed between treated and control groups when observing the incidence of anastomotic spontaneous disruptures, anastomotic healing strength, or the weight of the animals. It is concluded that early intraperitoneal 5-Fu administration does not impair the healing of recent colonic anastomoses in rats.

Anastomosis, Surgical↗

Can hepatocytes proliferate when transplanted into the spleen? Demonstration by autohistoradiography in the rat.

The aim of this work was to study hepatocyte multiplication after transplantation into the spleen, in order to apply this technique to the treatment of chronic liver disease. Hepatocytes isolated by an in situ collagenase perfusion technique in Wistar Furth rats were injected into the splenic parenchyma of three groups of syngeneic rats: controls with normal liver (group 1), 75% hepatectomies (group 2), and end-to-side portacaval shunts (group 3). The proliferation of transplanted hepatocytes was studied by autohistoradiography after the intraperitoneal administration of 0.6 microCi/g body weight of [3H]-thymidine, at 1, 3, 7 and 15 days after transplantation of hepatocytes. Significant incorporation of [3H]-thymidine by the transplanted hepatocytes during the study period was observed mostly in groups 2 and 3. The incorporation, although delayed was sustained and of greatest magnitude in the portacaval-shunted animals. The ability of transplanted hepatocytes to proliferate in the spleen, particularly after a portacaval shunt, indicates that this procedure may have therapeutic applications in the treatment of chronic liver disease.

Animals↗