High Cell Turnover Research Articles

Sister chromatid exchange and growth kinetics in untreated acute leukemia.

Sister chromatid exchange (SCE) frequency has been analyses after short-term culture of leukemic bone marrow cells of eight untreated patients with acute leukemia. Compared to normal bone marrow, results show a statistically significant decrease of SCE (p less than 0.001) in euploid as well as in aneuploid leukemias, ranging from 2.11 to 2.97 SCE per metaphase. The different SCE values were not related to contraction status of chromosomes and could not be explained by the age of patients. Therefore, low SCE may be a typical feature of leukemic cells. An examination of growth rates by the SCE technique revealed a high turnover of normal bone marrow cells. About 80% of the cells did not need more than 50 h to run two or three cell cycles. Leukemic cells, however, apparently divided more slowly, which is in good agreement with data obtained by autoradiographic methods.

Biological effects in rodents exposed to 10-8 pulses of electromagnetic radiation.

Rodents were exposed to electromagnetic pulse (EMP) radiation to test the hypothesis that rapid changes in electric and magnetic fields would induce injuries in biological systems with high cell turnover rates. The AFRRI EMP generator provided five pulses per second with a peak electric field intensity of 447 kV/m with a 5 nsec rise time and 550 nsec 1/e fall time. Exposures, totalling 108 pulses, were continuous except for approximately 2 hr, 5 days per week for biological sampling and animal care during 38 weeks. Biological assays were periodically conducted in exposed and nonexposed animals at appropriate intervals. It was observed that the reticulocyte count in exposed rats was nearly always greater than in nonexposed rats. However, there were no concomitant differences in peripheral erythrocyte counts beriveen the two groups, nor did radio active iron in corporation indicate increased cellular production in the irradiated group. Platelet counts in exposed rats were decreased about 10% below those in the nonexposed group most of the time. Levels or relative counts of circulating leukocytes did not differ between the two groups. Bone marrow cellularity was not different between the two groups. Analysis of chromosomes from bone marrow cells showed no detectable increases of aberrations in EMP exposed rats. Routine chemical analysis of blood demonstrated similar values in the two groups. Histological studies indicated no effect of EMP. Observations of fetuses from pregnant rats showed no abnormalities. No incidence of mammary tumors was observed in the female Sprague-Dawley rats. In leukemia prone AKR/J male mice, leukemia did not occur earlier in EMP exposed animals, nor was the fraction of leukemic mice greater in this group when compared with the nonirradiated control mice. The present experiment utilizing the above-described physical parameters represented a condition exceeding by several orders of magnitude that normally encountered by humans who operate EMP facilities. Exposures of rodents under these conditions indicated no apparent acute injuries.

Protein synthesis by human intestinal mucosa: Variations with diseases of the gut

Studies of protein synthesis by human intestinal mucosa were performed by determining the in vitro incorporation of l-leucine-U- 14C into the total proteins of peroral mucosal biopsy specimens. The mean value for normal mucosa was 1483 dpm/mg/30 min ± 402. In mucosa from patients with sprue the mean value for mucosal protein synthesis was 3056, a significant elevation which might reflect abnormally high cell turnover in this disease. In mucosa from patients with abetalipoproteinemia the mean value for protein synthesis was 535. This value, which is significantly lower than normal, may be related to diminished or absent synthesis of betalipoproteins by the intestine in this disease. The mean value for mucosal protein synthesis among patients with treated Whipple's disease in remission was normal. Measurement of protein synthesis by intestinal mucosa, obtained by peroral biopsy, appears to be useful in assessing metabolic aberrations and adaptations of the gut.

Small-intestinal cell turnover in patients with parasitic infections.

Small-intestinal deoxyribonucleic acid (DNA) loss rates were measured in six patients with Strongyloides stercoralis hyperinfestation, in four patients with hookworm disease, and in eight normal controls. In the four patients with strongyloidiasis having weight loss, hypoproteinaemia, and oedema the mean DNA loss rates were 73.9, 51.6, 58.0, and 62.2 ng atoms DNA-P/min respectively, which was significantly higher than that of patients with hookworm disease (mean 17.3, S.D. 6.6) or in eight control subjects (mean 14.5, S.D. 7.5). In two of three patients with strongyloidiasis the high DNA loss rates fell to normal after treatment, and in two others investigated only after treatment the rates were normal. It is suggested that the high epithelial cell turnover in these patients may result in excessive loss of endogenous substances and that this may be an important mechanism in causing malnutrition and hypoproteinaemia in patients with S. stercoralis hyperinfestation.

Further Studies of a Thymus Nucleohistone-associated Protease

Abstract The endogenous proteolytic degradation of the histones of calf thymus nucleohistone has been followed with polyacrylamide disc gel electrophoresis and dansylation of amino-terminal amino acids. The proteolytic enzyme is tightly associated with nucleohistone, is essentially inactive below pH 7.0, is decreased in activity at lower ionic strengths, shows a rather specific bond cleavage for those histone fractions which are susceptible to its attack, and is inactivated by brief heat treatment (2 min at 90°). The susceptibility of the five histone fractions to proteolysis is critically dependent upon whether the histones form a complex or not with DNA. In the intact nucleohistone three groups of histone are almost or totally resistant to proteolytic attack while the lysine-rich histone and the sulfhydryl-containing histone fractions are rapidly attacked. If histones are freed from DNA, only the lysine-rich fraction is resistant to the protease; all other fractions are rapidly degraded. In general those tissues having a high cell turnover, e.g. thymus and intestinal mucosa, exhibit a greater rate of proteolysis of nucleohistone than is observed for other tissue. The proteolytic activity is reversibly inhibited by either the presence of sodium bisulfite or by storing the nucleohistone at low ionic strength (∼5 x 10-4).

Catechol-O-Methyl Transferase (Comt) in Skin of Patients with Psoriasis

Activity of the enzyme COMT in involved areas of skin of patients with psoriasis is much greater than in uninvolved areas of skin of the same patients, or in skill of normal individuals. The relation between activity of the enzyme, high epidermal cell turnover and the distinctive vasodilatation of the capillaries in the dermis is discussed.

DEOXYRTBONUCLEIC ACID (DNA) LOSS, CELL LOSS AND CELL TURNOVER IN EXFOLTATIVE PSORIASIS

SUMMARY. DNA was measured in the naturally exfoliated skin scales from 2 patients with generalized exfoliative psoriasis. The mean DNA values indicated that the rate of loss of cells from the skin in these 2 patients was approximately 4 million/min. No DNA was found in skin scales from 3 patients with ichthyosis vulgaris. The difference in DNA content of scales in these disorders appeared to reflect the fact that psoriatic scales were nucleated, whereas the ichthyotic ones were not. It is suggested that the DNA content of psoriatic scales is a reflection of the high turnover of epithelial cells in this condition.

DELAYED INCORPORATION OF TRITIATED THYMIDINE INTO DNA.

Delayed utilization of tritiated thymidine by regenerating mouse liver can be almost completely suppressed by a continuous infusion of nonradioactive thymidine. In addition, as shown earlier for lymphocytes, labeled granulocytes are a potential source of the tritium marker. These observations suggest that the delayed incorporation of label into DNA must be due to the transfer of labeled nucleoside, which may be derived either from the degradation of DNA or from a long-lived intracellular pool. In either case, the transferred material probably originates from all tissues that have a high rate of cell turnover.