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Biomedical subjects

M G Ward

Publications and source records attributed to M G Ward.

14 recordsLinked to original sources
PubMed2003

Suppression of human papillomavirus gene expression in vitro and in vivo by herpes simplex virus type 2 infection.

Recent epidemiological studies have found that women infected with both herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) type 16 or HPV-18 are at greater risk of developing cervical carcinoma compared to women infected with only one virus. However, it remains unclear if HSV-2 is a cofactor for cervical cancer or if HPV and HSV-2 interact in any way. We have studied the effect of HSV-2 infection on HPV-11 gene expression in an in vitro double-infection assay. HPV transcripts were down-regulated in response to HSV-2 infection. Two HSV-2 vhs mutants failed to reduce HPV-16 E1;E4 transcripts. We also studied the effect of HSV-2 infection on preexisting experimental papillomas in a vaginal epithelial xenograft model. Doubly infected grafts demonstrated papillomatous transformation and the classical cytopathic effect from HSV-2 infection. HPV and HSV DNA signals were mutually exclusive. These studies may have therapeutic applications for HPV infections and related neoplasms.

Animals↗
PubMed1999

A broad-spectrum microbicide with virucidal activity against sexually transmitted viruses.

Sodium dodecyl sulfate (SDS), an alkyl sulfate surfactant derived from an organic alcohol, possesses surfactant properties but also denatures and unfolds both monomeric and subunit proteins. In preliminary experiments, we demonstrated that SDS is a potent inactivator of herpes simplex virus type 2 and human immunodeficiency virus type 1 at concentrations comparable to those used for the surfactant nonoxynol-9. We hypothesized that SDS might be capable of denaturing the capsid proteins of nonenveloped viruses. In this report, we demonstrate inactivation of rabbit, bovine, and human papillomaviruses after brief treatment with dilute solutions of SDS. Effective concentrations were nontoxic to rabbit skin and to split-thickness grafts of human foreskin epithelium. This is the first report of a microbicidal surfactant that will inactivate papillomaviruses. We propose that SDS is now a candidate microbicide for formulation and testing with humans.

Animals↗
PubMed1997

Intrasplenic hepatocyte allotransplantation in dalmation dogs with and without cyclosporine immunosuppression.

Hepatocyte allotransplantation has been performed successfully in several small animal models for the amelioration of inborn metabolic errors. Before a human clinical trial of hepatocyte allotransplantation can be attempted, preliminary experience in a large animal model is needed. We transplanted isolated mongrel hepatocytes into the spleen of dalmatians in the attempt to cure their inborn error of uric acid metabolism. Of 10 dalmatian recipients, two that received 9-10 x 10(9) mongrel hepatocytes died early after surgery of acute portal hypertension and hemorrhage. The eight long-term survivors received 5-6 x 10(9) hepatocytes and were randomized either to no treatment or to oral cyclosporine (CsA). Levels of CsA were adjusted to maintain trough levels between 400 and 800 ng/ml. In the four nonimmunosuppressed dalmatians, a reproducible average reduction in urinary uric acid excretion (UUAEx) of 23.7% was achieved; values returned to baseline within 14 days. In the CsA-immunosuppressed dalmatians, the average decline in UUAEx was 30%. The partial correction of the metabolic defect persisted for an average of 25 days in three immunosuppressed dogs, whereas in one dog, the partial correction lasted for over 90 days. No change in UUAEx was observed in two dalmatians that underwent sham laparotomy and intrasplenic injection of saline solution; CsA given alone to dalmatians did not modify UUAEx. We conclude that the dalmatian dog is a valuable large animal model for studies of the role of hepatocyte transplantation in the cure of inborn hepatic metabolic errors.

Animals↗
PubMed1996

Conus medullaris injury following both tetracaine and lidocaine spinal anesthesia.

Multiple reports of cauda equina syndrome and transient radicular nerve root irritation have suggested that lidocaine spinal anesthesia may be responsible. In this case report, a patient with a preexisting diabetic neuropathy received a partial block following a tetracaine spinal, which was followed by a lidocaine spinal. Following block resolution, a new conus medullaris syndrome was diagnosed. Because of the close proximity of the cauda equina and the conus medullaris, differentiation between these syndromes can be difficult. The preexisting diabetic neuropathy may have predisposed this patient to neurologic injury. The choice of a different local anesthetic drug with less neurotoxic potential such as bupivacaine may have prevented this injury.

Anesthesia, Spinal↗
PubMed1989

Grazing selectivity and in vivo digestibility of switchgrass strains selected for differing digestibility.

Animal selectivity and digestibility differences among switchgrass strains selected for different in vitro dry matter digestibilities (IVDMD) were measured in a grazing trial with esophageally fistulated steers and a sheep digestion trial. Extrusa selected by esophageally fistulated steers grazing high-IVDMD (Trailblazer), Pathfinder and low-IVDMD strains of switchgrass were compared, as were top and whole plant hand-clipped samples from each strain. Trailblazer extrusa had higher (P less than .1) in vitro organic matter disappearance (IVOMD) and lower (P less than .1) NDF and ADF than Pathfinder extrusa. Extrusa from all three strains appeared to be of higher quality than top or whole plant hand-clipped samples. In vitro organic matter disappearance tended to be highest for Trailblazer top hand-clipped samples. Composition of hand-clipped samples among strains was not significantly different. Mature crossbred wethers were used to compare Trailblazer and Pathfinder switchgrass hay in a digestion trial. No differences (P greater than .1) were detected between strains for DMI or apparent digestibility of DM, NDF, ADF and CP. Extrusa from Trailblazer switchgrass that had been selected for whole plant IVDMD had higher IVOMD; however, there was no indication that steers selected a differentially higher IVOMD for one strain than another.

Animal Feed↗
PubMed1979

Complications of antifibrinolysis therapy after prostatectomy.

As part of a trial to compare the effectiveness of various agents which have been claimed to reduce blood loss after prostatectomy, tranexamic acid (AMCA) was given pre-operatively and post-operatively to 6 patients having routine transurethral resections. Three of these developed indissoluble intravesical blood clots which persisted until they were evacuated surgically 5 to 17 days after cessation of AMCA therapy. AMCA cannot be recommended for routine use after prostatectomy.

Cyclohexanecarboxylic Acids↗
PubMedDate not supplied

Transplantation of hepatocytes: an in-vitro and in-vivo study in canines.

We isolated and transplanted hepatocytes in the canine, large animal model to evaluate hepatocyte yield and purity as well as the optimal site for hepatocyte engraftment (i.e., the spleen or the portal bed). We obtained viable, pure, single hepatocyte suspensions that were readily preserved at 4 degrees C in University of Wisconsin (UW) solution for up to 3 days. Both intrasplenic and portal vein injection were well tolerated, with minimal recipient morbidity and mortality when 1-2 x 10(9) hepatocytes were injected into immunosuppressed allogeneic hosts. We noted the embolization of hepatocytes into the parenchyma of the native liver within 7 days of intrasplenic transplantation that produced a mild reversible derangement of liver function and histology. These results warrant consideration prior to clinical trials of hepatocyte transplantation in man.

Adenosine↗
PubMedDate not supplied

Correlation of TGF beta 1 overexpression with down-regulation of proliferation-inducing molecules in HPV-11 transformed human tissue xenografts.

The epidemiologic association of human papillomavirus (HPV) infection with dysplasia and cervical cancer is well established. Transforming growth factor beta 1 (TGF beta 1) has regulatory effects on a broad spectrum of cell types and is a growth inhibitory protein for epithelial cells. To examine the phenotype of experimentally generated, HPV-11 transformed human tissues, we looked at expression of TGF beta 1 and a number of proliferation-enhancing molecules which are known to be regulated by TGF beta 1, including bcl-2, c-myc, c-Ha-ras, c-jun and NFkB. HPV-11 transformed xenografts showed up-regulation of TGF beta 1 expression and down-regulation of the expression levels of bcl-2, c-myc, c-Ha-ras, c-jun and NFkB. These results suggest that TGF beta 1 may exert antiproliferative effects on HPV-11 transformed papillomas by down-regulating different proliferation-enhancing molecules.

Base Sequence↗
PubMedDate not supplied

Transforming growth factor beta 1 (TGF beta 1) down-regulates expression and function of proliferation-inducing molecules in HPV-transformed cells.

The epidemiologic association of human papillomavirus (HPV) infection with dysplasia and cervical cancer is well established. Transforming growth factor beta 1 (TGF beta 1) is a growth inhibitory protein for epithelial cells. To examine the phenotype of HPV-transformed cells, we examined expression of TGF beta 1 and a number of cellular proliferation-enhancing molecules which are known to be regulated by TGF beta 1, including bcl-2, c-jun and NFkB. Previous studies had identified significant induction of TGF beta 1 and concomitant down-regulation of other growth stimulatory molecules in experimental papillomas. We used HPV-16 and -18 transformed cell lines. The HPV-16 transformed cells showed down-regulation of bcl-2 and NFkB as well as NFkB function upon TGF beta 1 treatment. The results suggest that TGF beta 1 may exert antiproliferative effects on some HPV-transformed cells by down-regulating expression and function of different proliferation-enhancing molecules. It is uncertain if this function is virus type specific and/or related to state of tumor cell progression.

Base Sequence↗