John F. Townsend

Aging-related decrease in hepatic cytochrome oxidase of the Fischer 344 rat.

Abstract The effect of aging on the hepatic mitochondrial population has been determined using a rigorously defined group of Fischer 344 rats with known survivorship data. The age groups studied included mature adult controls (8.5 months; 100% survivorship), an intermediate aged group (17.5 months; 90% survivorship), and an aged group (29 months; 20% survivorship). Cytochrome oxidase activity and content were determined in homogenates and mitochondrial fractions. The mitochondrial fractions were characterized by determination of respiratory activity, and monoamine oxidase activity as well as evaluation of the polypeptide composition by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and two-dimensional electrophoresis. The yield of protein in the isolated mitochondrial fraction as well as the mitochondrial specific content decreased significantly as a function of aging. Mitochondrial specific content was determined from the specific activities of cytochrome oxidase in the homogenate (per gram liver) and in the isolated mitochondrial fraction (per mg protein). Specific activity of hepatic cytochrome oxidase decreased approximately 15% (P = 0.035) in homogenates from the 17.5-month animals with a further, highly significant (P = 0.0002) decrease (29%) in the 29-month animals. In contrast, there was no statistically significant difference among the age groups in the cytochrome oxidase specific activity in the isolated hepatic mitochondrial fractions. However, the percentage of the total homogenate cytochrome oxidase activity recovered in the isolated mitochondrial fraction decreased significantly in the 29-month animals (P = 0.0063 vs the 8.5-month controls; P = 0.022 vs the 17.5-month group). Cytochrome aa3 content of total liver homogenates from aged animals decreased (P = 0.00064) which is in agreement with the decline in cytochrome oxidase specific activity in this age group. In the mitochondrial fraction from the aged animals, cytochrome aa3 content was essentially unchanged which is consistent with the lack of aging-related change in mitochondrial cytochrome oxidase specific activity. In freshly isolated mitochondrial fractions, no aging-related alterations were observed in respiratory control and ADP O ratios. The addition of exogenous NADH and cytochrome c did not change significantly the respiratory rate of hepatic mitochondria from control or aged animals. These results demonstrate the integrity of freshly isolated mitochondrial preparations from both control and aged Fischer 344 rats. In addition, there was no aging-related alteration in either monoamine oxidase specific activity or polypeptide composition. The similarities observed in the specific activities of cytochrome oxidase and monoamine oxidase, as well as in the cytochrome aa3 content and polypeptide composition of the isolated mitochondrial fraction, suggest a generalized decrease in hepatic mitochondrial content as a function of aging rather than a selective loss of mitochondrial components.

The sex chromatin count in pregnancy

Abstract The role of specific hormones in activation of the second X chromosome in women is studied by relating changes in sex chromatin count during pregnancy and the menstrual cycle to well-known hormone fluctuations of these periods.

Computerized 3-dimensional analysis of mitochondrial structure

A computer program has been written to calculate surface area and volume of subcellular organelles. Sophisticated and extremely accurate point sampling routines and volume computational techniques have been developed. This program has been used to study mitochondrial 3-dimensional structure when stereological estimates have proven inadequate.

Uterine peroxidase activity in abnormal human endometrium

Abstract Peroxidase activity in endometrial tissue from women taking an oral progestogen and from women with histories of atypical premenopausal uterine bleeding has been investigated. Enzyme activity throughout the progestogen-induced cycle is similar to that found in normal endometrium. Peroxidase activity is distinctly abnormal in the majority of women with premenopausal bleeding disorders. These observations are discussed in light of their possible significance as another parameter for assessment of endometrial dysfunction.

Uterine peroxidase activity in malignant, hyperplastic, and atrophic endometrium

Abstract Uterine peroxidase activity in endometrial adenocarcinoma, hyperplasia, and atrophy has been studied. This investigation supplements previous studies which have defined uterine peroxidase activity in the normal menstrual cycle, in women receiving an oral progestogen, and in women with premenopausal dysfunctional uterine bleeding. The potential significance of uterine peroxidase activity as an index of the relationship between estrogen and the endometrium is discussed.