Objective. To describe liver histopathologic features and ultrastructural changes in a prospectively studied cohort of rheumatoid arthritis (RA) patients receiving long-term methotrexate (MTX) therapy, and to seek correlations between these changes and simultaneously measured laboratory indices of liver function.Methods. This was a long-term, prospective, open observational study. Twenty-seven outpatients with RA who began therapy with MTX and continued treatment for extended periods underwent baseline and followup liver biopsies. One hundred seventy liver biopsy specimens were analyzed by light microscopy (LM) and assessed according to a modified Roenigk score and a newly devised numerical grading system. Ninety-three biopsy specimens were also analyzed by electron microscopy (EM). Blood samples were obtained at 4-6-week intervals for determination of bilirubin, alkaline phosphatase, aspartate aminotransferase (AST), and albumin levels, and the weekly dosage of MTX was adjusted if there were abnormalities in the AST or albumin level. A mean of 6.3 liver biopsies per patient were obtained over a mean followup period of 8.2 years (range 2-13 years).Results. cantly different from baseline at year 3, when it increased from a mean of 1.8 to 2.3 (P = 0.05) and at year 6, when it increased to 2.4 (P = 0.04), but this was not considered clinically meaningful. No other significant changes from baseline were observed by either LM grading system. No significant progression was observed by EM over the course of the investigation. Increases in serial measurements of AST correlated with both the modified Roenigk score (r = 0.21, P = 0.016) and the numerical rating score (r = 0.19, P = 0.027).
Conclusion.Patients with RA who are receiving weekly single-dose oral MTX therapy exhibit little deterioration in hepatic architecture by LM or EM when the dosage of the drug is adjusted for abnormalities in AST and serum albumin, monitored at frequent intervals.
alpha A2-crystallin is one of the major water-soluble proteins of the mammalian lens. Using a cloned cDNA probe coding for mouse alpha A2-crystallin and Southern blot hybridization, DNA isolated from a panel of somatic cell hybrids prepared from mouse fibroblasts or mouse spleen cells fused with Chinese hamster fibroblasts was probed to determine the chromosomal localization of the alpha A2-crystallin structural gene. We have located this gene on mouse chromosome 17.
ELETERIOUS mutations are produced in the germ plasm when animals are exposed to total body radiation. The ovaries of most higher animals contain germ cells a t different stages of development, and these cells may be expected to be affected to different degrees by ionizing radiation. I t is, therefore, of both practical and theoretical interest to study the mutation frequency in successive batches of germ cells produced by females subsequent to radiation exposure, since it is important to know whether or not mutated cells are eliminated from the germ line and if mutant-free eggs are eventually produced.
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