Rodney S. Markin

Reliability and predictive value of the national institute of diabetes and digestive and kidney diseases liver transplantation database nomenclature and grading system for cellular rejection of liver allografts

Pathologists participating in the National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplant Database (LTD) created a histopathological grading system for acute liver allograft rejection, and tested it first for inter- and intra-rater reliability among a group of five pathologists experienced in liver and transplantation pathology. Specimens from post-transplantation biopsies from 48 patients with rejection, hepatitis, or other diagnosis(es) were reviewed. There was moderate to good (kappa = 0.40 to 0.55) inter-rater and good (kappa = 0.55 to 0.58) intrarater agreement for the diagnosis and exact grading of mild, moderate, or severe acute rejection, which improved when a short clinical history was provided. Thus, the scheme was reproducible, and few of the disagreements among the pathologists would have affected treatment decisions. Secondly, the ability of the grading system to predict an unfavorable short- or long-term outcome from the initial histopathological diagnosis of cellular rejection was tested on groups of 168 and 133 patients, respectively, from the three LTD clinical centers, who were followed up for at least 6 months after the first onset of rejection. This analysis showed that a higher histopathological grade of acute rejection on first biopsy diagnosis was significantly associated (P < or = .006) with both an unfavorable short-term outcome, defined by failure of the episode to resolve within 21 days or the need for aggressive immunosuppressive treatment, and a long-term outcome defined by death or retransplantation from rejection within 6 months of onset. Lastly, an analysis was performed to determine whether subjective rejection grading by the pathologist or certain objective histopathological features identified by logistic regression modeling were more accurate in predicting an unfavorable outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

A graph-theoretic approach to quantitative structure—activity/reactivity studies

Abstract Characterization of molecular species based on the use of suitable graph invariants (graph paths, in particular) can provide a quantitative means of encoding structure; the technique is complementary to commoner approaches to studies of quantitative structure— activity relationships. Graph path encoding is here applied to quantitative studies of relationships between molecular structures and biological activity; the examples are the rates of various substrate reactions with hexoldnase, and the potential opiate-like activity of enkephalin analogs.

The effects of dietary amino acids on hepatic l-asparagine synthetase

Rats were fed Rogers synthetic amino acid diets, complete or without asparagine, aspartate, or glutamate, for 2 weeks. Hepatic and serum amino acid content and hepatic asparagine synthetase were assayed before and after the test diets were administered. Special attention was paid to the multiple forms of asparagine synthetase present. Rats fed the test diet without asparagine exhibited high molecular weight (110,000) alpha-form and intermediate molecular weight (57,000) beta-form of asparagine synthetase. Rats fed the complete test diet and the test diet without asparatate exhibited only the beta-form of the enzyme. Rats fed the test diet without glutamate exhibited no enzyme activity. These data are related to the hepatic amino acid levels and to the role of asparagine and asparagine synthetase in amino acid homeostasis.