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Biomedical subjects

C Peterson

Publications and source records attributed to C Peterson.

At least 343 records · Page 19Linked to original sources
PubMed1981

Neurotransmitter and carbohydrate metabolism during aging and mild hypoxia.

Alterations in the metabolism of the glucose derived neurotransmitters may underlie some of the deficits in brain function that can accompany aging. We examined the whole brain syntheses of acetylcholine (ACh), alanine, aspartate, glutamate, gamma-aminobutyrate (GABA), glutamine and serine in two strains (C57BL and BALB/c) of aged mice (3, 10 and 30 months). ACh synthesis in C57BL and BALB/c mice declined 41 and 44% at 10 months and 64 and 75% by 30 months. Incorporation of [U-14C]glucose into amino acids generally decreased with aging, but it was not depressed as much as ACh formation. The only significant reductions in the amino acids in the 30 month old mice of both strains were in the syntheses of GABA (46 and 32%) and glutamine (44 and 55%). These changes may make the aged brain more vulnerable to metabolic insults, since mild anemic hypoxia decreased the syntheses of all the neurotransmitters at all ages even further. ACh synthesis in hypoxic 30 month old mice was only 9-11% of the 3 month old nonhypoxic mice, whereas amino acid formation ranged from 18-55% of the 3 month old nonhypoxic mice. Carbohydrate metabolism and its response to metabolic insults was also altered by age in both strains. The 30 month old mice had higher brain lactate concentrations than the 3 month old mice. The combination of hypoxia and aging further depressed oxidative metabolism, since a greater increase in brain lactates occurred in the aged hypoxilism and its response to metabolic insults was also altered by age in both strains. The 30 month old mice had higher brain lactate concentrations than the 3 month old mice. The combination of hypoxia and aging further depressed oxidative metabolism, since a greater increase in brain lactates occurred in the aged hypoxilism and its response to metabolic insults was also altered by age in both strains. The 30 month old mice had higher brain lactate concentrations than the 3 month old mice. The combination of hypoxia and aging further depressed oxidative metabolism, since a greater increase in brain lactates occurred in the aged hypoxic mice than in young hypoxic mice. Thus, aging may reduce the ability of the brain to adapt to metabolic insults.

Acetylcholine↗
PubMed1981

Self-blame and depressive symptoms.

Are internal attributions for bad events always associated with depression? The depressive symptoms of 87 female undergraduates correlated with blame directed at their own characters. In contrast, blame directed at their own behaviors correlated with lack of depressive symptoms. Behaviorally attributed bad events were seen as more controllable and their causes less stable and less global than were characterologically attributed bad events and their causes. Characterological blame increased with more negative life events during the last year, implying that individuals who blame their character may arrive at this attributional style by a covariation analysis. Finally, characterological blame did not precede the onset of depressive symptoms 6 or 12 weeks later. Thus, characterological blame may be a strong concomitant of depression, but not a cause.

Adult↗
PubMed1981

Aging decreases oxidative metabolism and the release and synthesis of acetylcholine.

Acetylcholine (ACh) synthesis in vivo is known to decrease during the aging process (senescence). To elucidate the molecular mechanism(s) of this age-related decline, we studied brain slices from 3-, 10-, and 30-month-old mice of two strains (C57B1 and Balb/c). In low K+ media, oxidative metabolism as measured by 14CO2 production decreased with aging from 100% (3 months) to 85% (10 months) or 71% (30 months) whether [U-14C]glucose, [3,4-14C]glucose, or [1-14C]pyruvate was the substrate. In the aged brain (30 months) the increase in 14CO2 production with K+ stimulation was about twofold higher than in the young brain (3 months). Thus, in high K+ media, only slight decreases (less than 10%) in oxidative metabolism occurred with aging. Changes in ACh synthesis paralleled the decreases in 14CO2 production. Synthesis of [14C]ACh from [U-14C]glucose in low K+ media declined from 100% (3 months) to 85% (10 months) or 66% (30 months), while in high K+ media only slight decreases (less than 10.5%) occurred with aging. The Ca2+-dependent, K+-stimulated release of [14C]ACh declined from 100% (3 months) to 58% (10 months) or 25% (30 months). Only the decrease in he release of ACh declined to the same extent as the reduced in vivo synthesis of ACh with aging. The results suggest that decreases in oxidative metabolism, ACh synthesis, and in the release of ACh contribute to a reduction in cholinergic function in senescent brain.

Acetylcholine↗
PubMed1981

Decreases in amino acids and acetylcholine metabolism during hypoxia.

Hypoxia impairs brain function by incompletely defined mechanisms. Mild hypoxia, which impairs memory and judgment, decreases acetylcholine (ACh) synthesis, but not the levels of ATP or the adenylate energy charge. However, the effects of mild hypoxia on the synthesis of the glucose-derived amino acids [alanine, aspartate, gamma-amino butyric acid (GABA), glutamate, glutamine, and serine] have not been characterized. Thus, we examined the incorporation of [U-14C]glucose into these amino acids and ACh during anemic hypoxia (injection of NaNO2), hypoxic hypoxia (15 or 10% O2), and hypoxic hypoxia plus hypercarbia (15 or 10% O2 with 5% CO2). In general, the synthesis of the amino acids and of ACh declined in parallel with each type of hypoxia we studied. For example, anemic hypoxia (75 mg/kg of NaNO2) decreased the incorporation of [U-14C]glucose into the amino acids and into ACh similarly. [Percent inhibition: ACh (57.4), alanine (34.4), aspartate (49.2), GABA (61.9), glutamine (59.2), glutamate (51.0), and serine (36.7)]. A comparison of several levels (37.5, 75, 150, 225 mg/kg of NaNO2) of anemic hypoxia showed a parallel decreased in the flux of glucose into ACh and into the amino acids whose synthesis depends on mitochondrial oxidation: GABA (r = 0.98), glutamate (r = 0.99), aspartate (r = 0.96), and glutamine (r = 0.97). The synthesis of the amino acids not dependent on mitochondrial oxidation did not correlate as well with changes in ACh metabolism: serine (r = 0.68) and alanine (r = 0.76). The decreases in glucose incorporation into ACh and into the amino acids with hypoxic hypoxia (15% or 10% O2) or hypoxic hypoxia with 5% CO2 were very similar to those with the two lowest levels of anemic hypoxic. Thus, and explanation of the brain's sensitivity to a decrease in oxygen availability must include the alterations in the metabolism of the amino acid neurotransmitters as well as ACh.

Acetylcholine↗
PubMed1981

Differences in the plasma kinetics of daunorubicin in normal and leukemic rats.

The plasma pharmacokinetics of the anthracycline drug daunorubicin in doses of 1 and 10 mg/kg body weight were compared in normal and leukemic inbred Sutton-August rats (50-70 x 10(9) leukemic cells/1 blood). The area under the plasma concentration versus time curve was about 25 times larger in the leukemic rats at both dose levels. The data indicate that daunorubicin has a lower volume of distribution in leukemic rats as compared with normals. The large reduction in plasma clearance of daunorubicin in the leukemic rats can to some extent be explained by impairment of hepatic and renal functions but the results indicate that the leukemic state per se was of importance for the observed pharmacokinetic differences. This finding may be of importance for the treatment of patients with a high leukemic cell load, since higher retention of the drug in the central compartment leads to lower concentrations in poorly vascularized tissues, which favours the development of resistant leukemic cell clones.

Animals↗
PubMed1980

Determination of daunorubicin and its main metabolites in plasma, urine and leukaemic cells in patients with acute myeloblastic leukaemia.

The pharmacokinetics of daunorubicin were studied in 3 previously untreated patients with acute myeloblastic leukaemia by simultaneous monitoring of daunorubicin (DNR), daunorubicinol (DOL) and their aglycones in plasma, urine and leukaemic cells. The drug was given as an i.v. infusion in a dose of 1.5 mg/kg body wt. The plasma concentration of daunorubicin declined rapidly after the infusion. The concentration of daunorubicinol exceeded that of the parent compound only 5 min after the end of the infusion. Daunorubicin accumulated extensively in the leukaemic cells and reached concentrations there which exceeded the plasma concentration 400-4000 times. As compared to what was found in plasma, daunorubicinol appeared much slower in the leukaemic cells and the concentration ratio only reached 30-200. The concentration of aglycones was low in the leukaemic cells as well as in plasma. Only about 15% of the administered dose of daunorubicin could be recovered in the urine within 4 days, most of it as daunorubicinol. The results demonstrate that the plasma concentration of daunorubicin and its metabolites provides little information on the drug concentration in the leukaemic cells. Direct determinations of drug concentrations in the leukaemic cells might be of clinical value for optimization of the therapy in acute leukaemia.

Adult↗
PubMed1979

Steroids and immunosuppression. Effect on anastomotic intimal hyperplasia in femoral arterial dacron bypass grafts.

The effects of steroids and immunosuppression on 6-cm long bilateral femoral arterial Dacron bypass grafts were studied in 30 adult mongrel dogs. The dogs were serially placed into one of the following three groups: control, steroid, and immunosuppression. The control and steroid groups each had a 70% graft patency rate, whereas the immunosuppression group had a 100% eight-week graft patency rate. The results in the steroid group were not statistically different from the control group, whereas the results in the immunosuppression group were statistically different from the control. The decrease in internal diameter was secondary to a localized accumulation of tissue at the anastomotic site, which histologically appeared to be a hyperplastic intima morphologically different in each group. There is a substantial decrease in intimal hyperplasia at anastomotic sites and a higher graft patency rate in dogs treated with low-dose azathioprine as compared with control of steroid-treated animals. The mechanism seems to be a slower and more orderly intimalization rather than suppression of any specific intimal cellular elements.

Animals↗
PubMed1979

Uptake of the daunorubicin-DNA complex in cultured fibroblasts.

The uptake and fate of the daunorubicin-DNA complex have been studied in cultured rat embryo fibroblasts. 125I-DNA was digested by the cells and appeared as low molecular weight fragments in the incubation medium. Subcellular fractionation of fibroblasts, previously incubated with the complex, showed that daunorubicin was localized to nuclei and lysosomes. At a high incubation concentration (17.5 microM), the accumulation of the free drug exceeded that of the complex. However, at a lower concentration (1.75 microM), the accumulation of the complex was as high as that of the free drug. The results are consistent with an uptake of the complex into cultured rat embryo fibroblasts by endocytosis. However, it cannot be excluded that the complex partly dissociates in the incubation medium, and that daunorubicin and DNA thereafter enter the cells separately.

Animals↗
PubMed1979

Uptake of free and DNA-bound daunorubicin and doxorubicin into human leukemic cells.

Leukemic cells from seven patients with acute nonlymphoblastic leukemia and granulocytes, and mononuclear cells from three healthy controls were isolated by centrifugation on metrozoate-dextran. The intracellular accumulation of both the free and DNA-bound forms of daunorubicin and doxorubicin was studied in vitro. The uptake of unbound daunorubicin was higher than that of doxorubicin. At drug concentrations of 1.75 microM and higher the uptake of the free drugs was greater than that of the bound forms, but at lower drug concentrations the uptake was about the same. This could at least partly be explained by a greater dissociation of the DNA-drug complexes at lower drug concentrations. The uptake into normal leukocytes was of the same order of magnitude as that into leukemic cells. There was a great interindividual variation in the accumulation of both free and DNA-bound drugs in the cells from leukemic patients. This variation might be of importance for the prediction of individual sensitivity to the different drugs.

Bone Marrow Cells↗
PubMed1979

Treatment of acute nonlymphoblastic leukemia in adults with daunorubicin-DNA complex: a preliminary report.

Forty-four adult patients under 60 years of age with acute nonlymphoblastic leukemia were randomized for induction treatment with one of the following three regimens: R 1 = courses of daunorubicin on day 1 + ARA-C on days 1--5; R 2 = courses of daunorubicin on days 1 and 2 + ARA-C on days 4--8; R 3 = courses of daunorubicin-DNA complex on days 1--2 + ARA-C on days 4--8. Out of 14 patients, 9 went into remission on R 1, 6 out of 14 on R 2, and 8 out of 16 on R 3. The preliminary results suggest that daunorubicin-DNA complex has the same efficacy for inducing remission as daunorubicin alone, if the same time intervals and dosages are used.

Acute Disease↗
PubMed1977

Quantitation of the beta-elimination reaction as used on glycoproteins.

The carbohydrate side chains of mucus-type glycoproteins are O-glycosidic bonds between N-acetylgalactosamine to the hydroxyl groups of serine and threonine in the protein core. The alkaline catalyzed beta-elimination reaction, in the presence of sodium borohydride, is used for determining the number of side chains. The present paper presents a study of the quantitativeness of the alkaline borohydride procedure, using four parameters: the loss of seryl and threonyl residues, the formation of alanine and 2-aminobutanoic acid; the decrease in N-acetylhexosamine and the recovery of the amino sugar alcohols. Bovine, ovine and porcine submandibular glycoproteins were studied. Evidence is presented for the existence of N-acetylglucosamine involvement in O-glycosidic linkages to serine and threonine. Results for the relative rates of beta-elimination indicate that serine-linked glycosides are released more rapidly than threonine-linked glycosides.

Alanine↗