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Biomedical subjects

R A White

Publications and source records attributed to R A White.

At least 73 records · Page 4Linked to original sources
PubMed1998

Use of omental pedicle grafts in the management of non-healing axillary wounds in 10 cats.

A retrospective analysis of the clinical case histories of 10 domestic shorthaired cats that underwent omentalisation, using a vascular pedicle of greater omentum, of chronic non-healing axillary wounds was carried out. Wounds were debrided and closed in a primary fashion following omentalisation. The cats had undergone a modal number of three previous repair attempts over a three- to 18-month period (mean 11 months) before referral. Further dehiscence occurred in eight cases, requiring a modal number of one further attempt at closure of the wound. Other complications included incisional herniation (two cats), serous exudate from the axillary wound (two cats) and paracostal abscessation (one cat). Long-term cure was achieved in seven of the 10 cases, with wounds finally having healed at a mean of 24 days post-omentalisation. Chronic axillary wounds are particularly difficult to treat and there are no reports of consistently successful techniques for their repair. This report suggests that omentalisation of these wounds may be a step towards such a repair procedure.

Animals↗
PubMed1998

Rhabdomyosarcoma of the tongue in a dog.

A lingual rhabdomyosarcoma was diagnosed in a six-year-old Staffordshire bull terrier with clinical signs of dysphagia. The unsuccessful response to initial chemotherapy, to surgical resection and subsequent surgical resection and radiation therapy is documented. The accurate diagnosis and prognosis of such tumours is also discussed. Lingual rhabdomyosarcoma has not previously been reported in the dog.

Animals↗
PubMed1998

A human forkhead/winged-helix transcription factor expressed in developing pulmonary and renal epithelium.

Members of the forkhead/winged-helix transcription factor family play crucial roles during vertebrate development. A human hepatocyte nuclear factor/forkhead homolog (HFH)-4 cDNA encoding a 421-amino acid protein was isolated from a human fetal lung cDNA library. By Southern blot analysis of human-rodent somatic cell hybrid genomic DNA, the human HFH-4 gene localizes to chromosome 17q23-qter. This is the locus of another forkhead/winged-helix gene, the interleukin enhancer binding factor gene. RNA blot analysis revealed a 2.5-kilobase human HFH-4 transcript in fetal lung, kidney, and brain as well as in adult reproductive tissues, lung, and brain. By in situ hybridization, HFH-4 expression is associated with differentiation of the proximal pulmonary epithelium, starting during the pseudoglandular stage of human lung development. During human renal morphogenesis, HFH-4 is expressed in the developing epithelial cells of the ureteric duct, glomerulus, and epithelial vesicles. The unique pattern of HFH-4 expression during human fetal development suggests a role for this forkhead/winged-helix factor during pulmonary and renal epithelial development.

Amino Acid Sequence↗
PubMed1998

A new member of the mouse prolactin (PRL)-like protein-C subfamily, PRL-like protein-C alpha: structure and expression.

In this study, we establish the presence of a unique member of the PRL-like protein-C (PLP-C) subfamily in the mouse, PLP-C alpha, characterize its complementary DNA and gene, and map its chromosomal location and pattern of expression during pregnancy. Mouse PLP-C alpha encodes for a 239 amino acid protein and possesses from 69-71% identity with rat PLP-C, PLP-Cv, PLP-D, and PLP-H. Another feature characteristic of PLP-C subfamily members that is also present in mouse PLP-C alpha is a 6-exon/5-intron gene structure including an aromatic domain encoded by exon 3. Southern analysis with mouse and rat PLP-C subfamily probes suggested the existence of a single mouse PLP-C alpha gene. Mouse PLP-C alpha maps to chromosome 13 along with other members of the mouse PRL family. Expression of mouse PLP-C alpha increases dramatically as gestation advances and is restricted to spongiotrophoblast and trophoblast giant cells of the junctional zone. In summary, we have established the presence of a new PLP-C subfamily member in the mouse and demonstrated its similarity in structure and expression to rat PLP-C subfamily members. This level of conservation between species expands the biological significance of the PLP-C subfamily and provides additional opportunities for genetically evaluating its function.

Amino Acid Sequence↗
PubMed1998

The effect of angulation on intravascular ultrasound imaging observed in vascular phantoms.

PURPOSE: To quantify the error introduced by noncoaxial intravascular ultrasound (IVUS) imaging and to evaluate the use of a balloon-tipped catheter in compensating for intraluminal angulation and subsequent dimensional inaccuracy. METHODS: The effect of noncoaxial IVUS imaging was investigated in both a polyvinyl chloride phantom and an in vitro canine aorta using a calibrated setup to measure angulation off axis. Imaging was performed at increasing angulation (creating an elliptical image) in both phantoms, with the transducer centered and off center. Diameters were compared to the original coaxial diameter, as well as calculated diameters based on specific angles off axis. The percentage change (error) was also calculated at these angles. The measurements were repeated using a balloon-tipped catheter to center the transducer. RESULTS: The measured diameters and percentage changes compared closely with their calculated counterpart. Up to 25 degrees off axis, the apparent increase in diameter measurement was nearly 10%. Angulation from 30 degrees to 70 degrees resulted in an increase of 15% to 192%. Use of the centering balloon reduced the amount of error by 70% to 85% but was limited to angles < or = 25 degrees due to the design of the test apparatus. CONCLUSIONS: The error introduced by noncoaxial IVUS imaging can be significant and may be partially corrected by the use of a centering balloon. Further studies in the clinical application of a centering device are warranted.

Animals↗
PubMed1998

From selectors to realizators.

In 1975 Antonio Garcia-Bellido proposed a framework for understanding the morphogenetic function of homeotic genes in terms of selector genes and realizator genes. Since then, much has been learnt of the molecular nature and expression patterns of the Hox selector genes. Our identification of realizator genes, and our understanding of how specific sets of realizators are activated in different segments, is still far from complete, however. Here we discuss the nature of the Hox target genes identified so far and the basis of the target specificity of Hox gene products.

Animals↗
PubMed1998

Wallgraft endoprosthesis: initial canine evaluation.

This study evaluated the in vivo deployment and the healing characteristics of a self-expanding endoluminal graft [Wallgraft (WG) Endoprosthesis] in a canine (n = 22) aorta. The WG consisted of a 10 or 12 mm x 7.5 cm Wallstents (Schneider, Inc.) covered with polyethylene terephthalate (Dacron) graft material. Twenty-two WGs were deployed using fluoroscopic guidance. Devices were oversized approximately 10 per cent. Intravascular ultrasound (IVUS) was repeated, and balloon expansion along the length of the WG was performed to assure maximum expansion. WGs were evaluated with IVUS, angiography, and histology at 14 (n = 4), 30 (n = 4), 90 (n = 4), 180 (n = 5), and 365 (n = 5) days. Predeployment aortic diameters were 9.9 +/- 1 mm. Mid-WG diameters were 9.0 +/- 0.8 mm before balloon dilation and 9.2 +/- 0.5 mm after dilation with 8- (n = 1), 10- (n = 16), and 12- (n = 5) mm balloons. Twenty-two of 23 devices were deployed accurately with good apposition and aortic flow after deployment. On explant, all of the covered grafts were widely patent on IVUS and angiogram. Four explants demonstrated gaps (due to WG taper) between the proximal or distal ends of the graft on IVUS. The device length (9.1 + 0.5 cm) did not change significantly after deployment. Histologically at 6 months and 1 year the lumens were cell-lined. Scanning electron micrography demonstrated endothelial-like cells. This study demonstrates the ability of a WG to be accurately deployed and maintain excellent patency. Balloon expansion after deployment did not significantly increase the diameter. Clinical evaluation of this device is in progress.

Animals↗
PubMed1997

Characterization and chromosomal localization of PTPRO, a novel receptor protein tyrosine phosphatase, expressed in hematopoietic stem cells.

Hematopoietic stem cells (HSCs) support blood cells throughout life by utilizing their self-renewing and multilineage differentiating capabilities. Hematopoietic growth factors mediate their effects on stem cells by the tyrosine phosphorylation of proteins. Regulation of tyrosine phosphorylation is partially mediated by protein tyrosine phosphatases (PTPases). A possible mechanism by which hematopoietic stem cells maintain their self-renewing capacity and undifferentiated state is by controlling the balanced and opposing actions of protein tyrosine kinases (PTKs), receptors for growth factors, and PTPases. We have characterized the expression of PTPases in 5-fluorouracil (5-FU)-treated murine bone marrow cells, which represent a very primitive population of progenitors enriched for reconstituting stem cells, by using a consensus polymerase chain reaction (PCR) method. Several PTPases were expressed abundantly in the 5-FU-treated bone marrow stem cells. A novel PTP, termed protein tyrosine phosphatase receptor omicron (PTPRO), which is related to the homotypically adhering kappa, mu and PCP-2 receptor-type tyrosine phosphatases, was identified and characterized. We have cloned the murine and full-length human PTPRO cDNAs which share 89% homology, indicating that PTPRO is highly conserved between these species. The human PTPRO cDNA clone encodes a polypeptide of 1439 amino acids (aa) and has a calculated molecular mass of approximately 162 kDa. PTPRO consists of an extracellular segment containing a MAM domain, an immunoglobulin (Ig) domain, four fibronectin-type III (FN-III) repeats, a transmembrane segment, and two tandem intracellular PTP domains. The human PTPRO gene was assigned to human chromosome 1p35-pter using Southern blot analyses of genomic DNAs from rodent/human somatic hybrid cell lines containing human chromosome 1 or the p35-pter region of the chromosome. The mouse Ptpro gene was mapped to chromosome 4, closely linked to D4Mit16 and Elp1 (elliptocytosis-1), by using genomic DNAs from a (C57BL/6J x Mus spretus)F1 x Mus spretus backcross. In fetal tissues, PTPRO expression was observed in the brain and lung, whereas lower levels were observed in the kidney. In adult tissues, PTPRO was less restricted and was observed in the lung, heart, skeletal muscle, prostate, testis, and in various areas of the brain, indicating that PTPRO expression is developmentally regulated. Expression of PTPRO was also observed in human CD34+ bone marrow cells and 5-FU-treated murine primitive stem cells. These results suggest a potential role for PTPRO in stem cell adhesion and in mediating homophilic cell-cell interactions in other cell types.

Amino Acid Sequence↗
PubMed1997

Structural characterization of the mouse Hfh4 gene, a developmentally regulated forkhead family member.

Hepatocyte nuclear factor-3/forkhead homologue 4 (HFH-4) is a forkhead/winged-helix transcription factor family member that has a unique temporal and spatial pattern of gene expression in the developing and adult lung, choroid plexus, testis, and oviduct. To characterize HFH-4 further, mouse genomic clones were isolated and analyzed. The Hfh4 gene is encoded on a 5.5-kb region located on the distal end of mouse chromosome 11 and consists of two exons and one intron. Unlike most forkhead genes, the DNA binding domain is divided between two exons, and the intron position corresponds precisely to the site of gene translocations involving two known human forkhead homologues. Multiple putative transcription start sites are identified in a G+C-rich sequence that does not contain TATA or CAAT boxes. Within 2.1 kb of 5' flanking sequence are three identical E boxes and multiple putative transcription factor binding sites. Transfection of plasmids containing Hfh4 5' flanking sequence linked to a reporter gene results in promoter activity in lung epithelial cells but not in epithelial-like fibrosarcoma cells, suggesting that this 5' flanking sequence can function as a promoter with the proper cell-type specificity.

Amino Acid Sequence↗
PubMed1997

Quiescence in R3327-G rat prostate tumors after androgen ablation.

Androgen ablation is frequently used in conjunction with radiotherapy in the treatment of high-risk prostate cancer. Androgen ablation-induced cell kinetic changes could result in sub-additive (increased quiescence) or supra-additive (reduction in repopulation) interactions with radiotherapy. The cell kinetic changes were studied in R3327-G Dunning rat prostate tumors grown in vivo using double thymidine analogue labeling and flow cytometry, the terminal deoxynucleotidyl transferase-mediated nick end labeling assay for apoptosis, and measurements of tumor cell numbers. Tumors grown in intact and castrate male rats were continuously labeled for various periods of time with chlorodeoxyuridine and pulse-labeled with iododeoxyuridine 8 h before tumor removal. Androgen ablation resulted in a maximal reduction in labeling index (10 to 1.6%) and an increase in potential doubling time (Tpot; 6-42 days) within 3 days, which was related to a reduction in growth fraction (65% to <10%). In contrast, the length of S-phase was minimally altered (19 to 23 h). The response to androgen ablation involved little apoptosis and no necrosis, and Tpot was approximately the same as the tumor volume doubling time. Hence, the increase in Tpot was mainly the result of a shift to quiescence, and this shift occurred with minimal cell loss. Because quiescence is usually associated with radioresistance, these cell kinetic changes suggest that a sub-additive interaction may occur for some prostate cancers when androgen ablation and irradiation are given together.

Animals↗
PubMed1997

Expression of a gene encoding a tRNA synthetase-like protein is enhanced in tumorigenic human myeloid leukemia cells and is cell cycle stage- and differentiation-dependent.

We cloned a tumorigenic phenotype-associated cDNA encoding a tRNA synthetase-like protein from an acute-phase human myeloid leukemia cell line. The cDNA was isolated by reiterative subtraction of cDNAs synthesized from tumor-generating parental leukemia cells versus those from a nontumorigenic variant of the same cells. The selected cDNA encodes a protein that is a close homolog of one subunit of prokaryote and yeast phenylalanyl-tRNA synthetase (PheRS). The expressed protein reacts specificially with polyclonal antibodies raised against mammalian phenylalanyl-tRNA synthetase. Expression of the gene (designated CML33) was directly confirmed by Northern blot hybridization to be substantially enhanced in the tumorigenic cells compared with the nontumorigenic variant. In addition, expression of CML33 in myeloid leukemia cells was sensitive to the stage of the cell cycle and to induction of differentiation. Although the relationship between these observations and the tumorigenic state of the human myeloid leukemia cell line used in these studies is unknown, to our knowledge, this is the first demonstration in mammalian cells of tumor-selective and cell cycle stage- and differentiation-dependent expression of a member of the tRNA synthetase gene family.

Amino Acid Sequence↗
PubMed1997

A putative serine/threonine kinase encoding gene BTAK on chromosome 20q13 is amplified and overexpressed in human breast cancer cell lines.

DNA amplification on chromosome 20q13 is commonly detected in breast cancer and correlates with poor prognosis. Definitive critical target genes on this amplicon have however, not yet been identified. We describe in this paper isolation of a novel gene named BTAK, encoding a putative member of protein serine/threonine kinase family localized on chromosome 20q13 that is amplified and overexpressed in breast tumor cell lines. BTAK maps close to the critical region of amplification defined earlier on this amplicon. Deduced amino acid sequence shows conservation of all the subdomains predicted in protein kinase super family. Translated BTAK peptide shows significant homology with previously cloned protein serine/threonine kinase encoding genes Ip11 from S cerevisae and aurora from Drosophila, both shown to be functionally involved in normal chromosome segregation process. Our findings suggest that amplification and overexpression of BTAK may be playing a critical role in oncogenic transformation of breast tumor cells.

Amino Acid Sequence↗
PubMed1997

Positive cross-regulation and enhancer sharing: two mechanisms for specifying overlapping Hox expression patterns.

Vertebrate Hox genes display nested and overlapping patterns of expression. During mouse hindbrain development, Hoxb3 and Hoxb4 share an expression domain caudal to the boundary between rhombomeres 6 and 7. Transgenic analysis reveals that an enhancer (CR3) is shared between both genes and specifies this domain of overlap. Both the position of CR3 within the complex and its sequence are conserved from fish to mammals, suggesting it has a common role in regulating the vertebrate HoxB complex. CR3 mediates transcriptional activation by multiple Hox genes, including Hoxb4, Hoxd4, and Hoxb5 but not Hoxb1. It also functions as a selective HOX response element in Drosophila, where activation depends on Deformed, Sex combs reduced, and Antennapedia but not labial. Taken together, these data show that a Deformed/Hoxb4 autoregulatory loop has been conserved between mouse and Drosophila. In addition, these studies reveal the existence of positive cross-regulation and enhancer sharing as two mechanisms for reinforcing the overlapping expression domains of vertebrate Hox genes. In contrast, Drosophila Hox genes do not appear to share enhancers and where they overlap in expression, negative cross-regulatory interactions are observed. Therefore, despite many well documented aspects of Hox structural and functional conservation, there are mechanistic differences in Hox complex regulation between arthropods and vertebrates.

Animals↗
PubMed1997

Oesophageal injury associated with the administration of an anthelmintic bolus to calves.

Six of 18 calves from a suckler herd which were dosed with a sustained-release anthelmintic bolus, using appropriate equipment, developed clinical signs related to oesophageal perforation. Two died as a direct result of the injuries sustained, one required surgical removal of the paraoesophageal bolus and the remaining three were managed medically. The calves were in the approximate weight range advised by the manufacturers as suitable for dosing, but some were younger than the minimum recommended age. These animals were of a fractious nature having been relatively little handed.

Animals↗
PubMed1997

Chromosomal localization of the human gene encoding c-myc promoter-binding protein (MPB1) to chromosome 1p35-pter.

We report the mapping of the human gene MPB1 (c-myc promoter binding protein), a recently identified gene regulatory protein. MPB1 binds to the c-myc P2 promoter and exerts a negative regulatory role on c-myc transcription. Since exogenous expression from transfection of the MPB1 gene suppresses the tumorigenic property of breast cancer cells, there was interest in determining the chromosomal location of this gene. The human MPB1 gene was assigned to human chromosome 1p35-pter using Southern blot analyses of genomic DNAs from rodent-human somatic hybrid cell lines. A specific human genomic fragment was observed only in the somatic cell lines containing human chromosome 1 or the p35-pter region of the chromosome.

Animals↗
PubMed1997

Deployment and healing of an ePTFE encapsulated stent endograft in the canine aorta.

This study evaluated deployment mechanics and long-term healing of an endoluminally placed stent/graft in normal canine aortas. The endoluminal graft (ELG) consisted of a 8.5 cm segment of expanded polytetrafluoroethylene (ePTFE) graft material (Impra, Inc., Tempe, AZ) encapsulating a series of six Palmaz P-128 stents (Johnson & Johnson Interventional Incorporated, New Brunswick, NJ) along the length of the graft. The prostheses were deployed via the femoral artery using a 14Fr delivery system that contained a balloon catheter to expand the ELG in the infrarenal aorta. Twenty-one prostheses were deployed and evaluated at 1 week (n = 3), 1 month (n = 3), 3 months (n = 3), 6 months (n = 9), and 1 year (n = 3). Dimensions of the infrarenal aorta were determined with intravascular ultrasound (IVUS) and angiography prior to deployment of devices. Real-time fluoroscopy and IVUS were used to monitor device deployment with both imaging modalities repeated following implantation. Gross inspection and microscopic evaluation was performed on the explanted specimens following in vivo evaluation by CT scan, IVUS, and angiography prior to retrieval of the specimens. The prostheses were easily deployed from the femoral access site. Oversizing of the deployment balloon compared to the aortic diameter was necessary to accommodate the 10% device recoil observed following balloon deflation, however, all devices were seated against the aortic wall as evidenced by IVUS. At explant, all devices ware widely patent with limited luminal thrombosis observed in four specimens (19%). Devices were well-incorporated by cellular ingrowth into the ePTFE with the formation of neointima. No device migration or postdeployment recoil was observed. ePTFE graft material between stents protruded slightly into the vessel lumen accounting for a 10% luminal reduction. Fully supported ELG's consisting of balloon expandable stents encapsulated in ePTFE are easily deployed using a low-profile delivery system. Specimens demonstrated uniform long-term patency and healing up to 1 year in a canine aortic model. Those preliminary findings support further study of this fully supported prosthesis in the treatment of arterial disease.

Angioplasty, Balloon↗