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E J Moerman

Publications and source records attributed to E J Moerman.

At least 37 records · Page 2Linked to original sources
PubMed1984

High-voltage electron microscopy of human diploid fibroblasts during ageing in vitro. Morphometric analysis of mitochondria.

Since recent studies have suggested a diminished mitochondrial functional capacity in late-passage ('old') compared to early-passage ('young') normal fibroblasts and fibroblasts from the Hutchinson-Gilford (progeria) syndrome of premature ageing, we analysed whole-cell preparations on the high voltage electron microscope to look for mitochondrial and related defects. All strains examined showed considerable heterogeneity in cell size and intracellular morphology. Mitochondria were readily seen in all cells, predominantly as long slender rods with frequent branching, but occasional circular and saccular forms were also evident. Various parameters of mitochondrial mass including mean number, weight, and total length of mitochondria per cell weight tended to increase in old and progeria cells, but only the former attained statistical significance due to the heterogeneity and consequent variance. A significant finding was the decreased width of mitochondria in old and progeria cells. Cystic blebs were evident in mitochondria of some cells with an apparent increase in old and progeria fibroblasts. These blebs appeared to be due to weakening of the inner membrane, allowing dilatation of the outer membrane which otherwise appeared intact. The number of osmiophilic inclusions per cell weight, particularly lipofuscin granules and autophagic vacuoles, was significantly increased in old and progeria cells. In conclusion, despite some morphological changes, mitochondria of old and progeria cells maintain a structurally and bioenergetically adequate mass compatible with continued cellular viability.

Aging↗
PubMed1984

Role of prejunctional alpha 2-adrenergic receptors in the regulation of myocardial performance during exercise in conscious dogs.

We examined, in conscious dogs, the potential role of prejunctional alpha 2-adrenergic receptors for the regulation of heart rate and contractility response to exercise through modulation of the neurotransmitter release. Changes in heart rate and left ventricular pressure with time during comparable exercise levels, together with changes in norepinephrine concentration in the coronary sinus, were compared before and after the intravenous administration of: prazosin (0.5 mg/kg), a preferential postjunctional alpha 1-adrenergic receptor blocking agent; phentolamine (1 mg/kg), a nonselective alpha-adrenergic blocking agent; and yohimbine (0.3 mg/kg), a preferential prejunctional alpha 2-adrenergic receptor blocking agent. During exercise after phentolamine or yohimbine, changes in heart rate and left ventricular dP/dt were markedly potentiated compared to the control exercise, as well as to exercise after prazosin, whereas the norepinephrine concentration in the coronary sinus was substantially elevated. After intracoronary administration of phentolamine (0.1 mg/kg) or yohimbine (0.03 mg/kg), heart rate and contractility response to exercise were also potentiated, compared to the control exercise. These observations indicate that, in the intact conscious animal, prejunctional alpha 2-adrenoreceptors are stimulated during exercise, thereby modulating the norepinephrine release through a negative feedback inhibitory mechanism. Blocking these receptors by phentolamine or yohimbine results in an uncontrolled norepinephrine release during exercise associated with an augmented beta-adrenergic receptor-mediated end organ response, i.e., a potentiation in heart rate and contractility response.

Adrenergic alpha-Antagonists↗
PubMed1983

Some aspects of cellular aging.

Studies were carried out on cultured human fibroblasts in order to elucidate the biology of aging and the origins of age-dependent diseases. The replicative life span of cultures was inversely proportional to the chronological age of the tissue donor, and cultures derived from subjects with two inherited disorders of premature aging, progeria and Werner syndrome, had more severely impaired growth capacity. Studies on circular outgrowths whereby cell division is restricted to a circumferential rim of cells indicated that the replicative life span is controlled by a mitotic counter to a critical limit. The response of progeria cells to a hormone preparation with insulin-like activity was decreased, while in normal cells this decrease occurred as a function of passage level with a "shift to the right" of the dose-response curve. Cyclic AMP content of fibroblasts at late passage fell in response to PGE1 stimulation but rose in response to epinephrine, likely due to altered expression of genes for the receptors for each of these two hormones. This system of cultured human fibroblasts is useful in explaining various concomitants of biological aging including decreased tissue cellularity and impaired hormone and drug responsiveness.

Aging↗
PubMed1982

Energy metabolism in cultured human fibroblasts during aging in vitro.

To explore the relationship between energy metabolism and the limited replicative life span of cultured human fibroblasts, we studied several bioenergetic parameters in normal fibroblasts at early passage (young cells) and at late passage (old cells) and early passage cells from a subject with the Hutchinson-Gilford (progeria) syndrome. Old cells consumed more glucose and produced more lactate during growth, but O2 consumption, both basal and following maximum uncoupling of oxidative phosphorylation by SF-6847, was the same as in young cells. Progeria cells produced the most lactate but did not consume more glucose, while their basal and uncoupled O2 consumption was similar to that of young and old cells during both log and confluent states. Consumption of glutamine, a source of both oxidative energy and lactate, was approximately the same in all three cell types as was 14CO2 production from 2- 14C-pyruvate and 5- 14C-glutamate. ATP and ADP concentrations were similar in all cell types with a rise in the ATP/ADP ratio during growth from log to confluent state. Thus, old and progeria cells, in contrast to young cells, produce more lactate during growth consistent with a rise in energy demand and/or inefficiency of oxidative phosphorylation. Although limitations in total energy output do not appear to be causal to the loss of replicative capacity in normal cells after serial passage, they could play a role in the curtailed replicative capacity of progeria cells.

Adenosine Diphosphate↗
PubMed1979

The effects of beta-adrenoceptor blockade on renin, angiotensin, aldosterone and catecholamines at rest and during exercise.

1 beta-adrenoceptor blockade with metoprolol provoked, both at rest and during exercise, a decrease of 'active' renin and angiotensin II together with an increase of 'inactive' renin and unchanged 'total' renin. The significant exercise-provoked increases in angiotensin II, plasma renin activity and 'active', 'inactive' and 'total' renin when on placebo, were reduced by metoprolol. 2 No significant change in serum sodium and potassium and in plasma aldosterone was found during beta-adrenoceptor blockade at rest. During exercise plasma aldosterone dropped significantly without any change in serum sodium or potassium. 3 Plasma noradrenaline increased significantly at rest on metoprolol. The increase in plasma noradrenaline and adrenaline during exercise was similar on placebo and on metoprolol.

Adult↗
PubMed1979

Diabetes mellitus and genetic prediabetes. Decreased replicative capacity of cultured skin fibroblasts.

The idea that the gene(s) that cause diabetes mellitus can be expressed in extrapancreatic cells has been examined by tissue culture techniques. Skin biopsies were obtained from 25 normal subjects (N), 26 overt diabetics (D), 16 of juvenile onset (JOD) and 9 of maturity onset (MOD), and 21 subjects genetically predisposed to diabetes (P) on the basis of maturity-onset diabetes in both parents. Each biopsy was subdivided, multiple skin fragments were explanted in vitro, and several parameters of cellular outgrowth were monitored in primary and secondary cultures until cell division ceased because of senescence. In general, the rank order of growth vigor was N greater than P greater than D although differences were often marginal and statistically significant between N and JOD and(or) MOD. Outgrowth of epithelial cells was more vigorous in N explants in early stages, but later, JOD and MOD cells grew better than those of N. Outgrowth of fibroblast cells from N explants was more vigorous both at early and later stages and required less time to achieve maximum percent outgrowth. In secondary cultures, N cells grew faster than the other three groups so that fewer days elapsed between subcultures but significant differences were only seen between N and one or two of the other groups over some of the first seven subcultures. The onset of cellular senescence occurred earlier in P and JOD cultures both in mean population doublings and calendar time. N cultures had a higher percent surviving clones after picking than MOD, and a shorter recloning time than clones of JOD. The replicative life-spans of cultures (mean population doublings +/- SE) were N = 52.54 +/- 2.24, P = 47.84 +/- 2.43, JOD = 47.12 +/- 2.99, and MOD = 46.40 +/- 4.04, but differences did not reach significance for N vs the other three groups. The data demonstrate that cellular growth is impaired in both JOD and MOD types of cultures and to a generally lesser extent in P cultures. This is consistent with intrinsic genetic defects but the possibility that persistent deleterious effects of in vivo pathophysiology contribute alone or in combination cannot be ruled out. Therefore, the diabetic defect(s) can be expressed in extrapancreatic cells of mesenchymal origin. This system should prove useful in exploring the interplay between genetic and environmental factors in diabetes, the mechanisms(s) of hyperglycemia and other metabolic derangements, and the propensity that affected individuals have to develop degenerative diseases.

Adolescent↗
PubMed1978

Simultaneous quantitation of catecholamines and metabolites in urine.

A semi-automated fluorimetric method for the quantitation of urinary catecholamines (dopamine, noradrenaline and adrenaline) combined with manual methods for the quantitation of their metabolites (homovanillic acid, normetanephrine, metanephrine and vanillylmandelic acid) is described. It provides a sensitive and reproducible analytical technique for routine use. Values obtained in healthy adults are given.

Adult↗
PubMed1978

Chronologic and physiologic age affect replicative life-span of fibroblasts from diabetic, prediabetic, and normal donors.

Cultured skin fibroblasts from subjects with clinically apparent diabetes mellitus and from subjects genetically predisposed to diabetes have a replicative lifespan that is inversely related to donor age. Fibroblasts from carefully defined normal subjects not predisposed to diabetes fail to show this correlation. The data support the idea that physiologic status of the tissue donor is a more precise determinant of fibroblast replicative lifespan than chronologic age.

Adolescent↗
PubMed1978

Heat-labile enzymes in circulating erythrocytes of a progeria family.

Cultured skin fibroblasts from subjects with progeria contain an increased fraction of heat-labile enzymes and other altered proteins. To determine whether freshly obtained cells are similarly affected, erythrocytes from a progeric female and her clinically normal parents were analyzed for heat-lability of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. Hemolysates of the child's whole erythrocyte populations and young erythrocytes isolated by equilibrium density centrifugation contained significantly higher heat-labile fractions of both enzymes compared to control hemolysates. Values in both parents were intermediate to those of their daughter and controls, consistent with autosomal recessive inheritance in this family. The primary source of these multiple protein defects is unknown but may reside in a mutant gene producing abnormal protein turnover or defective DNA repair. An increased fraction of thermolabile enzymes in circulating erythrocytes should be useful in identifying persons at risk for progeria and other disorders of premature aging.

Adult↗