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J A Zimmerman

Publications and source records attributed to J A Zimmerman.

17 recordsLinked to original sources

Altered cellular responses to chemical carcinogens in aged animals.

The well-known increase in cancer incidence during aging is examined with a view toward establishing a cellular basis for the changes that might contribute to age-dependent carcinogenesis. It is hypothesized that during aging some tissues may enter into an altered state of growth regulation resembling that of tumor promotion. Entry into this state could be an event that precipitates cancer development in cells that already have been initiated.

Aging

Taking risks.

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Humans

Protective effect of glucose on the anoxic myocardium of old and young mice.

To compare the function of old and young hearts contracting under identical conditions, isolated hearts of young and old C57BL/6J mice were perfused using a Langendorff preparation. During a 3-min period of anoxia some hearts showed a decrease in systolic pressure, while other hearts developed contracture. The incidence and magnitude of contracture was greater in the old hearts and they also showed a significantly larger decline in contractility. Increasing the glucose concentration improved the performance of both age groups but the performance of the old hearts was still inferior to that of the young. The glycogen content and utilization were virtually the same in the two age groups. When iodoacetate was added, all hearts developed contracture and the magnitude of the contracture was greater than in the absence of iodoacetate; during the period of reoxygenation, the young hearts recovered but, the old hearts developed a second contracture. A brief period of anoxia is more debilitating to old C57BL/6J hearts than to young ones.

Aging

Isolation and characterization of chemically transformed pancreatic acinar cell lines from young and old mice.

To evaluate the role of animal age in chemically induced transformation, pancreatic cells were grown in culture 6 to 8 wk after injecting mice at either 6 or 22 mo. of age with a single dose of N-methyl-N-nitrosourea (NMU). The cell type and the frequency with which lines were obtained from aged animals paralleled the frequency and pattern of tumor induction by NMU in vivo. Outgrowth of pancreatic explants from young animals required the presence of the tumor promoter 12-otetradecanoyl-phorbol-13-acetate to establish continuously growing cell lines. Whereas NMU alone produced lines from aged mice, the promoter did not increase the frequency with which continuous lines were recovered from the aged animals. Of eight cloned cell lines (four young and four old), all had characteristics of transformed mouse pancreatic acinar cells when tested for lectin binding, lactate dehydrogenase isozyme pattern, chromosome number, and anchorage-independent growth. Cell lines derived from aged animals were slower growing and had higher chromosome numbers than lines derived from their younger counterparts.

Acetylglucosamine

Age-dependent changes in myocardial ultrastructure during anoxia.

We have examined left ventricular function and structure of male C57BL/6J mice at 3 and 24 months of age prior to, during and 5 min following a 3-min exposure to anoxia. During anoxia young hearts were characterized structurally by the presence of clear, abnormal non-membrane bound lipid-like vacuoles closely associated to mitochondria. Myelin figures were also present, and mitochondrial ATPase was considerably reduced. By the end of the 3-min period of anoxia hearts in young mice had irreversibly failed, and upon reoxygenation mitochondria underwent further degradation, including loss of internal structure. While continuing to function throughout anoxia, hearts of old mice had normal appearing myofibrillar, mitochondrial and sarcoplasmic structures. During reoxygenation occasional myelin figures were seen in senescent myocardium, although mitochondrial ATPase was not affected. At all times of anoxia and recovery pathological changes were more extensive in young mice than in their aged counterparts.

Adenosine Triphosphatases

A brief argument in opposition to the Orgel hypothesis.

The Orgel hypothesis receives considerable attention as a possible explanation for the phenomenon of senescence. Experimental observations which argue in favor of the Orgel hypothesis are discussed, and critized in part. This is followed by a presentation of experimental data which argue in opposition to the notion. On the basis of the considerable body of data which argue in opposition to the Orgel theory, a call for reappraisal of the applicability of this theory to the phenomenon of senescence is suggested.

Aging