Search PubMed⌕ Search

Biomedical subjects

R G Cutler

Publications and source records attributed to R G Cutler.

At least 55 records · Page 3Linked to original sources
PubMed1988

MDA content increases in fast- and slow-twitch skeletal muscle with intensity of exercise in a rat.

Previous work has shown that high-intensity (HI) exercise results in total body increased production of lipid peroxidation. These results suggest that exercise induces a higher level of oxidative stress in muscles leading to the production of various peroxides and aldehydes that are potentially toxic to cells. However, these past studies were carried out only with subjects that were exercised to exhaustion or at a very high intensity. In this paper, we report how a moderate-intensity (MI) exercise, which is more normally experienced, as well as a HI acute bout of exercise influenced oxidative stress-related reactions by measuring malonaldehyde (MDA) and lipid hydroperoxides (LH) in red vastus, white vastus, and soleus muscle. The muscles from untrained male Sprague-Dawley rats were removed immediately after either a HI 1-min run at 45 m/min (n = 8) or a 20-min MI run at 20 m/min (n = 8) and compared with a control group that did not run. MI exercise resulted in a 90% increase in MDA in white vastus and a 62% increase in red vastus muscle (P less than 0.05). HI exercise resulted in a 157, 167, and 83% increase in MDA in white vastus, red vastus, and soleus muscle, respectively. LH values in red and white vastus after HI exercise increased an average of 33%, but this proved not to be statistically significant. These results confirm earlier studies that HI exercise does increase MDA in skeletal muscle, and when intensity of exercise is considerably lowered, elevated MDA is still found but at a relatively lesser amount.

Animals↗
PubMed1987

Genomic 5-methyldeoxycytidine decreases with age.

Significant losses of DNA 5-methyldeoxycytidine residues in old age could disrupt cellular gene expression and contribute to the physiological decline of the animal. Thus, the 5-methyldeoxycytidine content of DNAs, isolated from the tissues of two rodent species of various ages, were determined. Mus musculus lost DNA methylation sites at a rate of about 4.7 X 10(4) (approximately 0.012% of the newborn level)/month. Peromyscus leucopus lost DNA 5-methyldeoxycytidine residues at a rate of only 2.3 X 10(4) (approximately 0.006% of the newborn level)/month. Since P. leucopus generally live twice as long as M. musculus, the rate of loss of DNA 5-methyldeoxycytidine residues appears to be inversely related to life span. Similar losses in genomic 5-methyldeoxycytidine content were also observed to correlate with donor age in cultured normal human bronchial epithelial cells.

Aging↗
PubMed1987

Accelerated wound repair in old deer mice (Peromyscus maniculatus) and white-footed mice (Peromyscus leucopus).

The closure of bilateral full thickness cutaneous wounds, made over the back with a sharp paper punch, was measured and assessed histologically in outbred deer mice (Peromyscus maniculatus) and white-footed mice (Peromyscus leucopus). In contrast to inbred C57BL/6J laboratory mice (Mus musculus), in which the rate of wound repair was more rapid in young than in mature or aged mice (Cohen et al., 1987), wound repair in Peromyscus was most rapid in aged animals. Aged Peromyscus (45 to 70 months) achieved 50% closure of cutaneous wounds within 3 to 4 days, whereas mature (23 or 24 months) and young Peromyscus required 5 to 7.7 days to reach the 50% closure level. Histologic indices were compatible with the more rapid rate of closure of the cutaneous wounds in aged Peromyscus. The reasons for the unexpected increase in the rate of wound repair with increasing age in Peromyscus are not clear but stress-related hormonal and cellular factors may play an important role.

Aging↗
PubMed1986

Absence of deoxyuridine and 5-hydroxymethyldeoxyuridine in the DNA from three tissues of mice of various ages.

Mutational damage to DNA may modulate the aging process as well as contribute to the high incidence of cancer in older animals. Uracil (Ura) is the deamination product of cytosine and hydroxymethyluracil (HMU) is an oxidation product of thymine. Ura, when generated from cytosine, induces mutations by mispairing with adenine. Both HMU and Ura are known to be excised from DNA by glycosylases that cleave the respective N-glycosidic bonds. This hydrolysis leaves apyrimidinic sites which are subsequently repaired by excision repair. In this report a sensitive method to detect these altered bases of HPLC separation of the components of DNA hydrolysates is described. Neither deoxyuridine (dU) nor 5-hydroxymethyldeoxyuridine (dHMU) were found in hydrolysates of DNA samples from brain, liver or small intestinal mucosa of mice of different ages.

Aging↗
PubMed1985

Dysdifferentiative nature of aging: age-dependent expression of mouse mammary tumor virus and casein genes in brain and liver tissues of the C57BL/6J mouse strain.

Many aspects of the aging process could be the result of cells slowly drifting away from their proper state of differentiation. This possibility has been studied by searching for an age-dependent increase in the expression of specific genes in tissues where expression of these genes would not normally be expected. In these studies, cDNA probes of specific genes are used in a DNA X NA hybridization assay to detect possible complementary RNA sequences in tissues of different-aged animals. Using this technique in past experiments, a qualitative increase in the RNA sequence complexity of mouse leukemia virus (MuLV) and a quantitative increase in the amount of alpha- and beta-globin RNA were found with increasing age in the brain and liver of the C57BL/6J mouse strain. We report here a similar age-dependent qualitative increase in the RNA sequence complexity for mouse mammary tumor virus (MMTV) but no quantitative or qualitative age-dependent change in casein RNA sequences for the same tissues and mouse strain.

Aging↗
PubMed1985

Peroxide-producing potential of tissues: inverse correlation with longevity of mammalian species.

Peroxidation reactions may cause many of the dysfunctions associated with aging. Accordingly, the 30-fold differences in aging rate among the mammalian species could be determined in part by peroxidation defense processes. This possibility was tested by measuring the spontaneous autoxidation of aerobically incubated brain and kidney tissue homogenates of 24 different mammalian species as a function of their maximum lifespan potential. Results show a statistically significant inverse correlation between both the rate of autoxidation and the amount of peroxidizable substrate with maximum lifespan potential. Kinetic analysis of the data indicates that the amount of peroxidizable substrate was the major factor determining the rate of autoxidation. For human tissues, antioxidants also appear to contribute to their unusually low sensitivity to peroxidation. These results support the hypothesis that aging may be caused in part by oxygen radicals initiating peroxidation reactions and that peroxidation defense processes are involved in governing the longevity of mammalian species.

Animals↗
PubMed1985

Dysdifferentiative nature of aging: passage number dependency of globin gene expression in normal human diploid cells grown in tissue culture.

Aging may be a result of cells drifting away from their proper state of differentiation. This process has been called dysdifferentiation. Normal diploid cells grown in tissue culture conditions undergo numerous biochemical and morphological changes and have a finite division potential. These changes could be a result of such a dysdifferentiation process. Changes in the differentiated state of a cell are frequently manifested by the expression of genes that are normally repressed. Previous studies have shown about a two-fold age-dependent increase of alpha and beta globin-like RNA in mouse brain and liver tissues. Therefore, the possible presence and increase of globin RNA was investigated in the nonerythroid human diploid strain WI-38 grown in tissue culture as a function of population doublings. A DNA X RNA hybridization technique using specific complementary DNA (cDNA) to alpha and beta human globin was used to detect possible complementary RNA sequences in total cellular RNA preparations extracted from cells at population doublings of 26.4 and 46. No globin-like RNA sequences could be detected above background noise levels for either of these two passage numbers. Thus, the globin RNA genes appear to be highly repressed and this degree of repression maintained as the culture approaches its characteristic population doubling limit.

Aging↗
PubMed1985

Dysdifferentiative nature of aging: age-dependent expression of MuLV and globin genes in thymus, liver and brain in the AKR mouse strain.

The amount and sequence complexity of RNA transcribed by the murine leukemia virus (MuLV) genome and to the alpha- and beta-globin genes in thymus, brain and liver were measured throughout the life span of AKR mice using a cDNA X RNA hybridization technique. RNA complementary to the complete sequence of specific cDNA probes for both MuLV and globin was found in nuclei and cytoplasm of thymus, brain and liver at all ages studied. No significant age-dependent change in the amount or sequence complexity of globin RNA was detected. The amount of MuLV RNA in both nuclei and cytoplasm of thymus increased about five times from 2 to 5 months of age, but no significant change was observed over this age range in MuLV RNA from liver and brain. By the age of 10 months, most of the mice had developed leukemia and the thymus showed a further increase in the amount of MuLV RNA. Nuclear RNA from liver and brain then showed a significant increase in the amount of MuLV, but no change in the amount of MuLV was found in the cytoplasm. No qualitative age-dependent changes in the MuLV RNA sequence complexity in thymus, liver and brain were detected. These results suggest that in the AKR mouse strain for the three tissues studied, an age-dependent relaxation occurs in the repression of the MuLV genome but not for alpha- and beta-globin genes. The rate of the depression of MuLV genes in the short-lived AKR mouse strain appears similar to that of the long-lived C57BL/6J mouse strain. This age-dependent relaxation of MuLV genes appears to be limited to the nuclei. Thus, the presence of a specific regulatory system for the transport of MuLV RNA through the nuclear membrane which does not deteriorate with age is indicated.

Aging↗
PubMed1984

Urate and ascorbate: their possible roles as antioxidants in determining longevity of mammalian species.

Urate has been shown to be a major antioxidant in human serum and was postulated to have a biological role in protecting tissues against the toxic effects of oxygen radicals and in determining the longevity of primates. This possibility has been tested by determining if the maximum lifespan potentials of 22 primate and 17 non-primate mammalian species are positively correlated with the concentration of urate in serum and brain per specific metabolic rate. This analysis is based on the concept that the degree of protection a tissue has against oxygen radicals is proportional to antioxidant concentration per rate of oxygen metabolism of that tissue. Ascorbate, another potentially important antioxidant in determining longevity of mammalian species, was also investigated using this method. The results show a highly significant positive correlation of maximum lifespan potential with the concentration of urate in serum and brain per specific metabolic rate. No significant correlation was found for ascorbate. These results support the hypothesis that urate is biologically active as an antioxidant and is involved in determining the longevity of primate species, particularly for humans and the great apes. Ascorbate appears to have played little or no role as a longevity determinant in mammalian species.

Aging↗
PubMed1984

Carotenoids and retinol: their possible importance in determining longevity of primate species.

Aging and cancer share a number of characteristics. This has led to the hypothesis that species' differences in longevity may be governed in part by the same mechanisms as those processes governing species' differences in their age-dependent probability of developing cancer. Much evidence has indicated that beta-carotene and retinol may be important natural anticarcinogens. Accordingly, they also may be important antiaging agents. This possibility has been tested by determining if a positive correlation exists between the concentration of carotenoids and retinol in serum and brain tissue with the maximal life-span potential of mammalian species. The results show a significant positive correlation for the carotenoids but not for retinol. These results suggest that the carotenoids may be biologically active as protective agents against cancer and as longevity determinants. Retinol appears to be less important in these functions.

Aging↗
PubMed1983

Superoxide dismutase, longevity and specific metabolic rate. A reply.

Sullivan [1982] has stated without reservation that our paper [Tolmasoff et al., 1980] did not present data supporting the possibility that superoxide dismutase has a role in determining longevity in mammalian species. He states that the data instead support the hypothesis that there is no association between superoxide dismutase and lifespan. On reading his arguments, I find no errors in our data analysis or in the conclusion made. Instead, I find he has failed to recognize the critical components of our data and has consequently misinterpreted the results. Because similar oversight might be made by other readers of this paper, I have included a brief review of the rationale underlying our investigation of longevity determinants in mammalian species along with the reply to Sullivan's criticisms.

Animals↗
PubMed1982

Aesthetic refinements in prophylactic subcutaneous mastectomy with submuscular reconstruction.

We present a series of 267 patients who have had bilateral prophylactic subcutaneous mastectomies with immediate submuscular reconstruction. Seventy-one of these patients had a simultaneous surgical skin reduction (mastopexy). All 276 patients have both of their implants currently in place and have achieved very satisfactory functional and aesthetic results, as judged by both the patient and the surgeon. We believe the essentials to obtaining a satisfactory result are thorough preoperative evaluation, creation of adequate muscle cover to include always a large triangle of the serratus anterior with the pectoralis and rectus abdominis muscles, proper use of skin taping in patients not undergoing a surgical mastopexy to allow adhesion of the nipple-areola complex in the proper position and shape, and careful postoperative muscle therapy.

Abdominal Muscles↗
PubMed1980

Effects of hypophysectomy on age-related changes in the rat kidney glomerulus: observations by scanning and transmission electron microscopy.

The kidney glomeruli of 9-month-old intact, 23-month-old intact, and 23-month-old hypophysectomized female rats were examined by scanning and transmission electron microscopy. With increasing age, the glomeruli increased in diameter and more podocyte microvilli were found. Hypophysectomy (4 months before sacrifice) reduced these values to levels approaching values seen in the 9-month intact controls. Transmission electron microscopy revealed that increased numbers of podocytes and endothelial cells had cytoplasmic dense bodies with advancing age. Granular cytoplasmic material, seen in podocytes, did not alter in frequency with age. Hypophysectomy reduced the number of cells containing the dense bodies as well as the number of podocytes containing granular material. Basal laminar thickness, while increasing with age, was unaffected by hypophysectomy. The results show that hypophysectomy can return some structural age-related changes to values seen in younger subjects. The effects are similar in some respects to the effects of dietary restriction.

Aging↗
PubMed1980

Superoxide dismutase: correlation with life-span and specific metabolic rate in primate species.

Much evidence now suggests that superoxide dismutase (superoxide:superoxide oxidoreductase, EC 1.15.1.1) may be a major intracellular protective enzyme against oxygen toxicity by catalyzing the removal of the superoxide radical. We examined the possible role this enzyme may have in determining the life-span of primate species. Superoxide dismutase specific activity levels were measured in cytoplasmic fractions of liver, brain, and heart of 2 rodent and 12 primate species. These species had maximum life-span potentials ranging from 3.5 to 95 years. Liver, brain, and heart had similar specific activity levels for a given species, but the levels for different species varied over 2-fold, with man having the highest level. No general correlation was found in the levels with life-span. However, the ratio of superoxide dismutase specific activity to specific metabolic rate of the tissue or of the whole adult organism was found to increase with increasing maximum lifespan potential for all the species. This correlation suggests that longer-lived species have a higher degree of protection against by-products of oxygen metabolism.

Animals↗
PubMed1980

Regulation of endogenous murine leukemia virus-related nuclear and cytoplasmic RNA complexity in C57BL/6J mice of increasing age.

The nucleotide sequence complexity of murine leukemia virus *MuLV)-related RNA has been measured by RNA-complementary DNA hybridization analysis in nuclear and cytoplasmic RNA isolated from liver and brain of low-leukemia-strain C57BL/6J mice of different ages. In these two tissues, an approximate 1.5- to 2-fold increase in the complexity of steadystate nuclear MuLV-related RNA sequences was observed as a function of age. Maximum complexity was observed with nuclear RNA extracts from old mice and corresponded to roughly 70 to 75% of the total MuLV genome. In contrast to the age-related increase in complexity of nuclear MuLV genome was detected in liver and brain steady-state cytoplasmic RNA, irrespective of animal age. These data suggest that control mechanisms regulating the transcription and/or stabilization of nuclear RNA transcripts of endogenous mouse MuLV-related genomes become less stringent with animal age even in low-tumor mouse strains. The data also support the existence of independent posttranscriptional mechanisms which prevent accumulation of these MuLV-related transcripts in steady-state cytoplasmic RNA and which do not seem to be as subject to the relaxation of stringency as a function of age.

Aging↗