The effect of age and of dietary restriction on vascular beta-receptor sensitivity was investigated using cultured smooth muscle cells from rat aortas. The growth rate was slower in cells obtained from 36-month-old rats than in cells obtained from 24-month-old rats and the cells from older animals achieved lower densities. The dietary restriction did not affect growth of cells from 24-month-old rats but increased cell numbers in 36-month-old rats. The elevation of the cyclic AMP level in response to epinephrine was decreased with age. Cells from dietary restricted animals responded more to epinephrine than cells from animals of the same age fed ad libitum.

Aging↗

PubMedDate not supplied

The effect of increased longevity, produced by dietary restriction, on the neuronal population of area 17 in rat cerebral cortex.

Area 17 of the brains of Sprague-Dawley derived rats, maintained on a limited ration of food to maintain their weights at the levels attained by two months of age, was compared with area 17 in control groups of rats fed ad lib. The oldest rats in the diet restricted group were sacrificed at 46 and 48 months of age, by which time their life spans had been extended about 12 months beyond the oldest age that rats fed ad lib achieve, for only few of the latter live as long as 33 months. In this study, the rats which were compared consisted of two groups of ad lib fed rats, one 3 and 6 months of age, and the other 33 months old, and two groups of diet restricted rats, one 26 months old and the other 46 to 48 month old rats (designated as 47 month old rats). Two indices were used to assess whether age affects the volume of area 17. One, the number of clusters of apical dendrites of layer V pyramidal cells per unit area of tangential sections, was the same in all groups, indicating that the lateral spread of area 17 did not alter with age. However, the other index, the thickness of area 17, did change with age, for area 17 was significantly thinner in the 47 month old diet restricted rats than in the other three groups. It was also found that the number of neuronal profiles in strips of sections passing through the entire depth of area 17 is decreased in the 47 month old rats, indicating that neurons had been lost from their cortices. This decrease in the number of neuronal profiles in the 47 month old rats was not due to nuclear shrinkage since the sizes of neuronal nuclei were not significantly different in the older ad lib and diet restricted rats. Determinations of neuronal packing densities in layers II/III, IV, V and VIa suggest that neurons are most frequently lost from the deeper cortical layers of the 47 month old rats, and in these layers large vacuolated spaces, the sizes of neuronal cell bodies, have been encountered. It is suggested that these spaces represent places from which neurons have been lost. It is concluded, therefore, that neurons are lost from area 17 in rats whose longevity is increased by diet restriction.

Animals↗

PubMedDate not supplied

Complement activation in renal disease.

Perturbation of the serum complement system in glomerulonephritis can be the result of classical pathway activation by immune complexes or of C3 activation by the C3-C5 convertase stabilized by the C3 nephritic factor. Low C3 levels can also be the result of diminished C3 synthesis and possibly, in certain circumstances, of C3 convertases deposited on capillary walls. In glomerulonephritis the complement profile is helpful in diagnosis, in following the course of therapy and in providing insights into pathogenesis. Complement profiles must be interpreted recognizing that a pattern resembling classical pathway activation can be produced by idiopathic nephrotic syndrome, that hypogammaglobulinemia can reduce Clq levels, and that a primary deficiency of factor H or I or both, will secondarily produce subnormal levels of C3 and factor B. With these caveats, the complement profiles typical of systemic lupus erythematosus, membranoproliferative glomerulonephritis, acute glomerulonephritis, acquired Cl inhibitor deficiency, and hypocomplementemic vasculitis syndrome are described.

Antigen-Antibody Complex↗

PubMedDate not supplied

Major histocompatibility complex extended haplotypes in systemic lupus erythematosus.

In a study of 32 white patients with systemic lupus erythematosus from 28 families, 60 unique chromosome 6 haplotypes were defined. The MHC extended haplotype HLA-B8, -DR3, SC01, GL02 was strongly disease-associated (0.09 patients, 0.02 controls, RR = 4.5, C.I. = 1.6-12.4, P less than 0.05), while the corresponding haplotype with the GL01 specificity was not increased in frequency (0.05 in both patients and controls). In the present data, the increase in the haplotype bearing GL02 accounted entirely for the association between HLA-DR3 and SLE. Furthermore, the phenotype of complete C4A deficiency was also strongly disease-associated (patients 0.14, controls 0.02, RR = 8.5, C.I. = 1.8-37.0, P less than 0.05). The only other MHC association in these patients was an increased occurrence of the HLA-B17, -DR7, SC61 haplotype (patients 0.07, controls 0.01, RR = 6.0, C.I. = 1.8-20.6, P corr. less than 0.05). The relationship between MHC markers and autoimmune disease appears to be a result of an association with MHC extended haplotypes and complete complement component deficiencies rather than with individual alleles. It is important that future studies include family members so that such haplotypes can be defined.

Adolescent↗