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Biomedical subjects

H M White

Publications and source records attributed to H M White.

At least 19 recordsLinked to original sources
PubMed1999

The effect of ursodeoxycholic acid on the florid duct lesion of primary biliary cirrhosis.

The frequency with which florid duct lesions are seen in needle-biopsy specimens of the liver was assessed in patients with primary biliary cirrhosis (PBC) enrolled in a 2-year randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid (UDCA) versus placebo. Paired biopsy specimens obtained at entry and after 2 years on medication were reviewed blindly and mostly simultaneously by a panel of 5 hepatopathologists who, earlier, had characterized the florid duct lesion, which has been well described in the pathology literature. Florid duct lesions at entry were identified in approximately 36%. Patients with earlier disease showed florid duct lesions much more frequently than those with more advanced disease. The prevalence of florid duct lesions in 60 patients receiving placebo medication fell from 38.3% to 21.7%, P =. 025, over the period of 2 years. The prevalence of florid duct lesions also decreased in the 55 patients receiving UDCA, from 32.7% to 18.2%, P =.046. The prevalences of these lesions in the placebo and UDCA patients at entry and at 2 years were not significantly different from each other. The findings suggest that UDCA does not prevent ongoing bile duct destruction in patients with PBC. Instead, they support the impression that UDCA exerts its beneficial effects by protecting against the consequences of bile duct destruction.

Bile Ducts↗
PubMed1997

Optimal filter combinations for photographing SYPRO orange or SYPRO red dye-stained gels.

Photography or electronic image acquisition is required to document results obtained from staining protein gels with the fluorescent SYPRO dyes. We found that, when using Polaroid type 667 or 57 instant films, the choice of optical filter combination and photographic exposure time strongly influences protein detection sensitivity limits. Ultraviolet light-blocking Kodak Wratten No. 2A and 2B gelatin filters autofluorescence when illuminated at 300 nm. The use of these filters in combination with Wratten No. 22 or 25 filters or SYPRO gel photographic filters gives rise to increased background signals, which for long photographic exposures can obscure signals due to protein bands. Surprisingly, the use of these same ultraviolet lightblocking filters enhanced the protein detection sensitivity obtained with short photographic exposures. Under the conditions tested, we found minimal differences in performance for Polaroid type 667 and 57 films.

Electrophoresis, Polyacrylamide Gel↗
PubMed1995

Serological evidence of past hepatitis B infection in liver donor and hepatitis B infection in liver allograft.

The presence of hepatitis B surface and core antibodies (anti-HBs and anti-HBc) in a liver donor without hepatitis B surface antigen is taken to indicate resolution of hepatitis B and is not considered to contraindicate donation. We report a liver transplant recipient who developed hepatitis B after such a donation. It seems that hepatitis B virus can reside in the liver of a patient who has seemingly recovered from his disease. We recommend avoidance of liver transplants from donors who are positive for anti-HBs and anti-HBc.

Female↗
PubMed1995

FK 506 rescue therapy for hepatic allograft rejection: experience with an aggressive approach.

Although initial experiences with FK 506 rescue therapy for acute hepatic allograft rejection have provided promising results, analysis of available data indicates that inferior results are obtained when FK 506 rescue therapy is initiated in the latter stages of rejection. Since its initial availability, we have applied an aggressive approach towards FK 506 rescue therapy based on early conversion and assiduous dosing. We have reviewed our experience with this approach in patients with refractory hepatic allograft rejection to provide an assessment of this approach. Sixteen patients were treated for corticosteroid and OKT3-resistant acute hepatic allograft rejection. Fourteen patients were treated for cellular rejection and 2 for humorally-mediated rejection. Median follow-up was 7.3 months posttransplant and 6.0 months post-initiation of FK 506 therapy. Median time to first rejection was 8 days and median time to FK 506 therapy was 29 days. Laboratory values at the time of initiation of FK 506 therapy included: mean serum bilirubin, 4.0 +/- 3.1 mg/dl and SGPT 136 +/- 105 U/l. Prior to FK 506 therapy, patients received an average of 35.5 +/- 19.1 mg/kg of bolus/taper corticosteroids (prednisone equivalent) and 11.25 +/- 4.8 days of OKT3 therapy. FK 506 therapy was successful in reversing all episodes of rejection. Median time to rejection reversal with FK 506 rescue therapy was 23 days (mean +/- SD, 27.6 +/- 16.7 days) in patients with cellular rejection. Time to rejection reversal was 26 and 28 days in the 2 patients with humoral rejection. Patient and graft survival at 6 months were 100%/100%, and 94%/94% at 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Expression cloning of a functional glycoprotein ligand for P-selectin.

The initial adhesive interactions between circulating leukocytes and endothelia are mediated, in part, by P-selectin. We now report the expression cloning of a functional ligand for P-selectin from an HL-60 cDNA library. The predicted amino acid sequence reveals a novel mucin-like transmembrane protein. Significant binding of transfected COS cells to P-selectin requires coexpression of both the protein ligand and a fucosyltransferase. This binding is calcium dependent and can be inhibited by a neutralizing monoclonal antibody to P-selectin. Cotransfected COS cells express the ligand as a homodimer of 220 kd. A soluble ligand construct, when coexpressed with fucosyltransferase in COS cells, also mediates P-selectin binding and is immunocrossreactive with the major HL-60 glycoprotein that specifically binds P-selectin.

Amino Acid Sequence↗
PubMed1993

Increased hepatocyte expression of hepatitis B virus transcription in patients with features of fibrosing cholestatic hepatitis.

BACKGROUND: Recurrent hepatitis B after liver transplantation may be complicated by fibrosing cholestatic hepatitis. This syndrome is associated with rapid graft failure and is characterized by ballooning degeneration of hepatocytes and abundant viral antigen expression. METHODS: To study this disorder further, in situ hybridization studies were performed on 36 liver biopsy specimens from 14 transplanted patients with recurrent hepatitis B and 18 nontransplanted controls with chronic hepatitis B. Biopsy specimens were scored for histological features and intensity of riboprobe hybridization signal to hepatitis B virus (HBV) DNA and RNA. RESULTS: HBV DNA hybridization signals of 2+ to 3+ intensity were observed in 53% of the posttransplant biopsies but none of the nontransplanted samples (P < 0.001). HBV RNA signals of this intensity were found in 42% of the transplant biopsy specimens compared with 17% of the nontransplant specimens (P < 0.07). Features of fibrosing cholestatic hepatitis were noted in 12 biopsies; 11 of these displayed RNA signals of 2+ to 3+ intensity (92%) compared with 4 of 24 (17%) biopsy specimens without this diagnosis (P < 0.001). The level of hepatocyte RNA correlated with the extent of hepatocellular ballooning (P < 0.007). CONCLUSIONS: These data suggest that fibrosing cholestatic hepatitis is associated with enhanced hepatitis B virus transcription and support a cytopathic role for the virus in the development of this syndrome.

Adult↗
PubMed1993

Intrahepatic portosystemic vascular stents: a bridge to hepatic transplantation.

Refractory esophageal variceal hemorrhage (EVH) remains a formidable problem in patients awaiting liver transplantations. Transjugular intrahepatic portosystemic shunts (TIPS) have provided an alternative approach for managing EVH that may obviate the need for portosystemic shunt surgery. Experience with TIPS placement and subsequent successful hepatic transplantation in patients without previous portosystemic shunt surgery has not been previously reported. Two patients are reported who underwent TIPS placement and subsequent successful hepatic transplantation without previous portosystemic shunt surgery. This experience indicates that (1) TIPS can provide effective control of EVH for at least several weeks, (2) TIPS placement decreases portal hypertension, thus facilitating technical performance of the transplant procedure and minimizing blood loss, (3) TIPS may undergo vascular incorporation, thus requiring that they be accurately positioned so that the lengths of suprahepatic inferior vena cava and portal vein are not compromised at the time of transplantation, (4) TIPS thrombosis can be effectively treated and prolonged patency may be observed, and (5) deterioration in hepatic function and exacerbation of hepatic encephalopathy were not observed after TIPS placement. In summary, TIPS provide an attractive, effective means for managing refractory EVH in patients awaiting liver transplantation.

Esophageal and Gastric Varices↗
PubMed1992

Immunosuppressants.

The role and pharmacology of a variety of immunosuppressant agents in the gastrointestinal tract and liver are reviewed in this article. Immunosuppressants covered include cyclosporine, corticosteroids, OKT3, antithymocyte globulin, azathioprine, methotrexate, and FK506. Guidelines for the use and complications of immunosuppressants in liver, pancreas, and small bowel transplantations are presented. Controlled and uncontrolled data for use of immunosuppressants in the management of gastrointestinal and hepatic disorders are also described.

Autoimmune Diseases↗
PubMed1983

Reendothelialization and maintenance of endothelial integrity in longitudinal denuded tracks in the thoracic aorta of rats.

Endothelial repair was studied during, and up to 26 weeks following reendothelialization of longitudinal tracks denuded of endothelium. Deendothelialized tracks were produced on the ventral aspect of the thoracic aortas of rats. A standardized denudation procedure was used in conjunction with continuous intravenous infusion of [3H]thymidine to obtain quantitative evaluations of replication, migration, and cell density. The method of denudation was relatively gentle, selective, and reproducible. Reendothelialization was completed in less than 66 h. During reendothelialization, cell migration and replication proceeded simultaneously until confluence was reached. Following confluence, as migration ceased, cell density returned toward control levels. It continued to rise, associated with continued, though attenuated, nuclear incorporation of [3H]thymidine, until it reached 1 1/2 - 2 1/2 times that of adjacent uninjured control endothelium. The boundaries, or margins, of the tracks were well demarcated as judged by the pattern of labeled cells within and unlabeled cells adjacent to reendothelialized tracks. Widths of deendothelialized and reendotheliazed tracks were similar. Thus, endothelial cells in uninjured regions surrounding denuded tracks were not observed to contribute to reendothelialization by proliferation. During reendothelialization, unlabeled cells were observed within reendothelializing tracks. Thus, some cells migrated relatively long distances (0.3-0.4 mm) before either replicating or sloughing from the luminal surface. Endothelial cell density within reendothelialized tracks remained elevated at 12 and 26 weeks following denudation. At 12 weeks there was little intermingling of cells inside tracks (labeled during reendothelialization) with unlabeled cells in adjacent uninjured areas. At 26 weeks, after a terminal 12-day continuous labeling period in previously unlabeled animals, replication of cells inside tracks was far less than that in adjacent uninjured endothelium. Thus, the newly regenerated cell population in tracks remained synchronously quiescent and physically segregated for long periods of time, despite normally occurring hemodynamic and remodeling factors which might be expected to favor continuous cell turnover and migration. Our findings relating to endothelial cell migration and replication during reendothelialization vary somewhat from those reported using other methods of deendothelialization.

Animals↗