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J A Zimmerman

Publications and source records attributed to J A Zimmerman.

At least 19 recordsLinked to original sources
PubMed2002

Dislocation emission around nanoindentations on a (001) fcc metal surface studied by scanning tunneling microscopy and atomistic simulations.

We present a combined study by scanning tunneling microscopy and atomistic simulations of the emission of dissociated dislocation loops by nanoindentation on a (001) fcc surface. The latter consist of two stacking-fault ribbons bounded by Shockley partials and a stair-rod dislocation. These dissociated loops, which intersect the surface, are shown to originate from loops of interstitial character emitted along the <110> directions and are usually located at hundreds of angstroms away from the indentation point. Simulations reproduce the nucleation and glide of these dislocation loops.

Journal Article↗
PubMed2001

Surface step effects on nanoindentation.

Atomistic simulation is used to examine nanoindentation of a Au(111) crystal both near and far from a surface step. While the load needed to nucleate dislocations decreases significantly when indenting close to the step, the extent of the step's influence is not as great as seen experimentally. This behavior is explained by measuring the contact area from the simulation data. A new metric, the slip vector, shows material slip coinciding with the <112> directions of a lowest unstable stacking fault barrier. The slip vector is used to calculate an atomic critical resolved shear stress, which is shown to be a good dislocation nucleation criterion.

Journal Article↗
PubMed1996

Characterization of a solid state reaction product from a lyophilized formulation of a cyclic heptapeptide. A novel example of an excipient-induced oxidation.

PURPOSE: To elucidate the structure of a degradation product arising from a lyophilized formulation of a cyclic heptapeptide, and to provide a mechanism to account for its formation. METHODS: Preparative HPLC was used to isolate the degradate in quantities sufficient for structural studies. A structure assignment was made on the basis of the compounds spectroscopic properties (UV, MS, NMR) and the results of amino acid analysis. RESULTS: The degradate was identified as a benzaldehyde derivative arising from the oxidative deamination of an aminomethyl phenylalanine moiety. The extent of formation of this product is influenced by the amount of mannitol used as an excipient in the formulation. A mechanism is proposed whereby reducing sugar impurities in mannitol act as an oxidizing agent via the intermediacy of Schiff base adducts which subsequently undergo tautomerization and hydrolysis. CONCLUSIONS: Reducing sugar impurities in mannitol are responsible for the oxidative degradation of the peptide via a mechanism that involves Schiff base intermediates. This mechanism may be a potential route of degradation of other arylmethyl amines in mannitol-based formulations.

Benzaldehydes↗
PubMed1994

Methionine restriction increases blood glutathione and longevity in F344 rats.

Little is known about the biochemical mechanisms responsible for the biological aging process. Our previous results and those of others suggest that one possible mechanism is based on the loss of glutathione (GSH), a multifunctional tripeptide present in high concentrations in nearly all living cells. The recent finding that life-long dietary restriction of the GSH precursor methionine (Met) resulted in increased longevity in rats led us to hypothesize that adaptive changes in Met and GSH metabolism had occurred, leading to enhanced GSH status. To test this, blood and tissue GSH levels were measured at different ages throughout the life span in F344 rats on control or Met-restricted diets. Met restriction resulted in a 42% increase in mean and 44% increase in maximum life span, and in 43% lower body weight compared to controls (P < 0.001). Increases in blood GSH levels of 81% and 164% were observed in mature and old Met-restricted animals, respectively (P < 0.001). Liver was apparently the source for this increase as hepatic GSH levels decreased to 40% of controls. Except for a 25% decrease in kidney, GSH was unchanged in other tissues. All changes in GSH occurred as early as 2 months after the start of the diet. Altogether, these results suggest that dramatic adaptations in sulfur amino acid metabolism occur as a result of chronic Met restriction, leading to increases in blood GSH levels and conservation of tissue GSH during aging.

Animals↗
PubMed1993

Low methionine ingestion by rats extends life span.

Dietary energy restriction has been a widely used means of experimentally extending mammalian life span. We report here that lifelong reduction in the concentration of a single dietary component, the essential amino acid L-methionine, from 0.86 to 0.17% of the diet results in a 30% longer life span of male Fischer 344 rats. Methionine restriction completely abolished growth, although food intake was actually greater on a body weight basis. Studies of energy consumption in early life indicated that the energy intake of 0.17% methionine-fed animals was near normal for animals of their size, although consumption per animal was below that of the much larger 0.86% methionine-fed rats. Increasing the energy intake of rats fed 0.17% methionine failed to increase their rate of growth, whereas restricting 0.85% methionine-fed rats to the food intake of 0.17% methionine-fed animals did not materially reduce growth, indicating that food restriction was not a factor in life span extension in these experiments. The biochemically well-defined pathways of methionine metabolism and utilization offer the potential for uncovering the precise mechanism(s) underlying this specific dietary restriction-related extension of life span.

Animals↗
PubMed1989

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↗
PubMed1988

Taking risks.

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Humans↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1982

Pancreatic carcinoma induced by N-methyl-N'-nitrosourea in aged mice.

We have studied the ability of N-methyl-N'-nitrosourea to induce pancreatic carcinoma within 5 months when single doses were administered to C57BL/6J male mice at 3, 12 and 24 months of age. Pancreatic tumors were not observed in the young and middle-aged animals, but 3/15 of the surviving aged mice showed gross evidence of carcinoma. Ultrastructural analysis revealed in each tumor the presence of two populations of undifferentiated cells, both cell types possibly being of acinar cell origin. The observation of pancreatic carcinoma only in aged animals treated with an environmental carcinogen may be a model paralleling the human condition, which also shows a strong age dependency.

Age Factors↗