PubMed Health⌕ Search

Biomedical subjects

D A Lipschitz

Publications and source records attributed to D A Lipschitz.

At least 73 records · Page 4Linked to original sources
PubMed1985

Cancer in the elderly: basic science and clinical aspects.

The incidence of cancer increases progressively with age. Rearrangements of genomes have been found to accompany cellular aging. These factors, in concert with age-dependent alterations in immune function and host defense, may help to explain the increased risk of malignant disease in aged persons. The clinical presentation and natural history of neoplasia are also affected by aging. This conference reviews recent developments in these areas, examines the effects of drug use in the elderly and implications for management, and discusses current information on how age may influence the response of cancer to therapy.

Aged↗
PubMed1984

Effect of donor age on long-term culture of bone marrow in vitro.

Previous reports suggest that 33 degrees C is the optimum temperature for the long-term culture of murine bone marrow in vitro. We found that horse serum was an important variable determining our ability to culture marrow from immature (less than 10 weeks) mice at 37 degrees C. While some batches supported growth others did not. The ability of deficient horse serum to support growth could be corrected if the culture was fed at mid-week with additional medium. Marrow from aged mice (96 weeks and older) could invariably be cultured at 37 degrees C irrespective of the horse serum batch used for culture. Adult mice (20-24 weeks) gave intermediate results between immature and aged mice. All three groups of mice studied could be cultured at 33 degrees C irrespective of the batch of horse serum used or the age of the donor. These results indicate that horse serum provides a factor(s) which varies in concentration from batch to batch and is essential for normal marrow growth in vitro. The requirement for this factor is greater at higher temperature and in younger animals. Marrow from adult and aged mice was then simultaneously cultured at 33 degrees C and 37 degrees C. For adult mice the cell recovery at 33 degrees C was initially significantly higher than at 37 degrees C but at later times became less. As a result cumulative recovery at both temperatures was equal. Cumulative cell recovery and culture survival time was significantly less in the aged than the young mice cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1984

The effect of high ascorbic acid supplementation on body iron stores.

The level of assimilation of dietary iron is believed to have an important influence on iron status. To examine the effect of enhancing the availability of dietary iron on iron balance, 17 adult volunteer subjects were given 2 g of ascorbic acid daily with meals for 16 weeks. Serum ferritin levels before and after the study averaged 46 and 43 micrograms/L, respectively, indicating a negligible effect on iron stores. When vitamin C supplementation was continued for an additional 20 months in five iron-replete and four iron-deficient subjects, serum ferritin determinations again failed to indicate any significant effect of the vitamin C on iron reserves. These findings were not explained by intestinal adaptation to the enhancing effect of the vitamin, because radioisotopic measurements of nonheme iron absorption showed no reduction in the enhancing effect of 1 g of ascorbic acid after four months of megadoses of vitamin C. It is concluded that altering the availability of nonheme dietary iron has little effect on iron status when the diet contains substantial amounts of meat.

Absorption↗
PubMed1984

Effect of age on hematopoiesis in man.

We have shown previously that the cause of anemia in healthy elderly subjects can usually not be identified. In this study, hematopoiesis was examined in 18 healthy elderly subjects with unexplained anemia and in 15 young and 15 healthy elderly individuals without anemia. No reduction in circulating testosterone was noted, making decreased androgen levels as a cause for the anemia unlikely. The 2,3 diphospho-glycerate (2,3DPG) levels in the anemic subjects were significantly higher than their corresponding controls, suggesting that the anemia was pathologic, as no increase would be expected if the low hemoglobin was a physiologic adjustment to age. The anemia was associated with a reduction in marrow normoblast and CFU-E number, but no decrease in BFU-E levels was seen. This suggests that the mechanism of the anemia is a decrease in stem cell proliferation. This could be caused by a reduction in circulating erythropoietin or a defect in end organ response. A second possibility is that a basic cellular abnormality exists. The presence of an overall reduction in hematopoiesis in anemic elderly (decreased peripheral blood counts, reduced marrow myeloid precursors, and CFU-C levels) makes this especially likely. The abnormality may be caused by a mechanism unrelated to the aging process. The fact that nonanemic elderly also have reductions in hematopoiesis suggests that age contributes to the defect.

2,3-Diphosphoglycerate↗
PubMed1984

Erythropoiesis in the aged mouse: I. Response to stimulation in vivo.

Changes in erythropoiesis with age were studied by examining the hematocrit increase in response to hypoxia in aged mice and by assessing the change in erythropoiesis following the injection of erythropoietin in young and old polycythemic mice. The increase in hematocrit after exposure to hypoxia was more variable and generally lower in old mice than in young mice. When erythropoietin was injected into polycythemic animals, the increase in differentiated erythroid cells and 59Fe incorporation into erythroid marrow and peripheral blood cells was significantly lower in old mice than in young mice. In contrast to differentiated erythroid cells, there was less evidence of a reduced response to stimulation of the more primitive erythroid progenitor cells of aged animals. The early undifferentiated erythroid progenitor, burst-forming units, did not decrease when either young or aged mice were made polycythemic, and no change following erythropoietin injection was noted. Polycythemia suppressed the late-differentiated erythroid progenitor, erythroid colony-forming units, to a greater extent in aged animals, but when erythropoietin was injected, the percent increase over the subsequent 24 hours was identical to that in young mice. These observations indicate a reduced erythropoietic capacity with age, the abnormality being most obvious in the more mature erythroid precursors.

Aging↗
PubMed1984

Erythropoiesis in the aged mouse: II. Response to stimulation in vitro.

In this study, we present in vitro evidence that erythropoietic precursors in aged mice respond less to stimulation by erythropoietin than do precursors in young mice. The effect of age on proliferation of differentiated erythroid cells from the marrow of young and old mice was examined in liquid culture to which increasing concentrations of erythropoietin were added. Cellular proliferation was measured indirectly by 59Fe incorporation into heme and directly as tritiated thymidine incorporation into DNA. The number of normoblasts remaining in culture with and without the addition of erythropoietin was also measured. In each case, cellular proliferation was significantly lower in marrow in old than in young mice. In contrast, CFU-E colonies cultured with increasing doses of erythropoietin were similar in young and old animals. These findings indicate that aging causes a reduction in the proliferative response of differentiated erythroid cells. Failure of these cells to respond to stimulation is the likely mechanism for the reduced erythropoietic proliferative capacity found in aged animals.

Aging↗
PubMed1984

A micromethod for long-term in vitro culture of bone marrow cells.

A micromethod to study long-term culture of bone marrow cells in vitro has been developed. Using Linbro wells one-fourteenth of the cells and medium usually required for culture in a flask are plated. Thus 40-50 cultures from a single mouse can be studied at any one time. Adherent-layer formation and supernatant cell recovery were very similar when Linbro -well cultures were compared with standard large-flask cultures. In the microculture system, supernatant and adherent-layer cell numbers increased following medium change reaching a maximum 3-4 days later and decreasing by day 7. Supernatant cells were in equilibrium with those of the adherent layer as cell numbers in both compartments prior to and following medium change fluctuated identically. Following medium change, a significant increase in myeloblasts occurred at 24 h and promyelocytes and myelocytes increased 48-72 h later. In contrast no discernible pattern in daily CFU-C production was detected. These findings provide insight into the cellular kinetics of long-term marrow culture and highlight the usefulness of this method to study hematopoiesis at frequent intervals.

Animals↗
PubMed1982

Absorption of controlled-release iron.

A multiple-dose double radioiron technic was used to compare absorption of iron administered as a controlled release (CR) capsule and as an elixir; both formulations contained 50 mg elemental iron as ferrous sulfate. When taken by normal subjects in the fasting state, mean absorption from the elixir and CR capsule averaged 4.92% and 4.38%, which gave a CR capsule:elixir ratio of 0.89. This difference was not significant, but when taken with meals that inhibit absorption of dietary iron by different degrees, absorption of the CR formulation was superior. CR capsule:elixir absorption ratios averaged 1.70 from a meal that is mildly inhibitory and 3.13 from a meal that causes more marked inhibition. It is concluded that CR iron formulations may offer a therapeutic advantage to patients who take oral iron with meals to avoid gastrointestinal side effects.

Adult↗
PubMed1982

The correctability of the nutritional, immune, and hematopoietic manifestations of protein calorie malnutrition in the elderly.

Protein calorie malnutrition is being recognized with greater frequency in the hospitalized patient. This report describes the clinical presentation and response to nutritional therapy in nine elderly malnourished patients ranging from 73 to 95 years. Clinical features of malnutrition include weight loss, confusion, hypoalbuminemia (mean 2.8 gm/dl), a low total iron binding capacity (TIBC) (mean 192 micrograms/dl), anergy, lymphocytopenia (mean 1 X 10(3) cells/microliter) and an anemia (mean 9.0 gm/dl). Our subjects were followed for 42 days. In two, hyperalimentation was achieved by voluntary food intake and polymeric dietary supplements. In seven, feeding for 21 days via nasogastric tube was required. After three weeks, weight gain, decreased confusion, improved appetite and mobility, and significant increases in serum albumin and TIBC were seen. At that time, no subject was anergic and lymphocyte counts increased significantly. Increase in the serum iron and percent saturation was noted, and by day 42, a significant elevation in the hemoglobin occurred. As a measure of stem cell function, the committed granulocyte/macrophage progenitor cell (CFU-C) was quantitated in four subjects prior to and following 21 days of nutritional support. A marked increase in CFU-C number from a mean of 0.1 X 10(7) cells/kg to a normal value of 0.85 X 10(7) cells/kg was seen. Thus in addition to correcting the nutritional deficit, hyperalimentation returned immune and hematopoietic abnormalities to near normal levels. While improvement could reflect recovery from an associated disease, it is just as likely that correction of malnutrition, a well-recognized cause of these immunologic and hematopoietic abnormalities, accounted for the response. These observations emphasize the importance of recognizing malnutrition in the elderly and highlight the need for a careful nutritional assessment prior to ascribing hematologic and immunologic abnormalities to the aging process.

Aged↗
PubMed1982

Detection of protein-calorie malnutrition in the elderly.

The geriatric population is an ever-increasing segment of our society. A careful review of the physical, anatomic, and biochemical changes which occur with aging indicates that measurements traditionally made to detect the presence of protein-calorie malnutrition may be inappropriate for the elderly due to a lack of specific norms for comparison. Changes that are normally seen with age may appear to be representative of a nutritional deficit if the observer is unfamiliar with the aging process. Methods of extrapolating existing nutritional assessment data for use in the geriatric population, development of norms specific for the aged, and study of nontraditional methods of evaluation should all be considered in an effort to improve nutritional assessment techniques for this population.

Aged↗
PubMed1982

Endotoxin-induced suppression of erythropoiesis: the role of erythropoietin and a heme synthesis stimulating factor.

The regulation of erythropoiesis is primarily controlled by erythropoietin (Ep). Recently, however, other factors that both stimulate and inhibit erythropoiesis have been reported. Using an in vitro liquid culture of bone marrow cells, a factor in normal mouse serum was demonstrated that markedly stimulated heme synthesis by marrow erythroid cells. In this study, the role of this heme synthesis stimulating factor (HSF) and Ep in the erythropoietic suppression caused by endotoxin administration to mice was examined. Although HSF levels did not alter appreciably after endotoxin injection, marrow erythroid cells from these animals became unresponsive to the factor. This could be reversed if Ep was added to the culture in vitro or if the hormone was injected into the mice 18 hr prior to harvesting the marrow. This marrow erythroid cell response is identical to that seen in animals in whom Ep levels are markedly reduced, such as that found in exhypoxic polycythemia, and suggest a decrease in the hormone following endotoxin administration. Additional studies demonstrated that when Ep was injected into mice 6 hr after endotoxin administration, an increase in femoral erythroid colony-forming units (CFU-E), proerythroblast number, and 59 Fe incorporation into femoral marrow cells could be demonstrated. These findings, together with the marrow erythroid cell response to the hormone, suggest that the mechanism for suppression of erythropoiesis after endotoxin injection is a reduction in the level of circulating Ep.

Animals↗
PubMed1981

The anemia of senescence.

A study of 196 healthy geriatric females and 26 males confirmed the high prevalence of anemia in this population. Forty-two females (21.4%) had a hematocrit of less than 36% and nine (34%) of the males had a value of less than 40%. A careful evaluation, including a therapeutic trial of oral iron in some subjects, made a diagnosis of iron deficiency anemia in only three and the anemia of chronic disease could be diagnosed in two. No subject had folate or B12 deficiency and hemolytic anemia was not present. Thus, in most of these subjects, the lower hematocrit was not due to commonly recognized causes. Further evaluation revealed a high prevalence of leukopenia in this population; 30% having counts less than 5 X 10(3)/microliter and 10% having values less than 4 X 10(-3)/microliter. Of most importance, leukocyte counts were significantly lower in anemic subjects in whom a high incidence of neutropenia was also demonstrated. This suggests that the mechanisms of the unexplained anemia and neutropenia is an overall reduction in hematopoietic cell numbers. This conclusion is consistent with the observation that many aged subjects have a decreased ability to mount an adequate leukocyte response to infection. These findings suggest that the presence of anemia marks an overall reduction in hematopoietic reserve and provides a clue to those aged subjects of greatest risk of an inadequate response to stress.

Aged↗
PubMed1981

Precision and accuracy of serum ferritin measurements.

For the epidemiological evaluation of iron stores the precision of serum ferritin measurement in the low range are important for the accurate determination of the prevalence of iron deficiency and the detection of subtle changes in serum ferritin levels after food iron manipulation. In addition the recognition of iron overload and the evaluation of its severity are important. In this study samples with low serum ferritin values were repetitively measured in a classic radioimmunoassay (RIA) and in two "2-site" immunoradiometric assays (IRMA), one of which used a polystyrene bead and the other a polystyrene tube fas the solid phase. Variability was significantly less with the IRMA using a bead than that using a tube. Optimum precision was noted when samples were run at the lowest possible dilution (1:10) with relatively long reaction times. The bead IRMA was also more precise that the RIA which had a standard curve with 50% radioactive binding (maximum precision) of 40 ng/ml. Within the normal serum ferritin range (12 to 300 ng/ml) extremely similar results were obtained with an RIA and IRMA. However, when iron overload samples (serum ferritin values greater than 2000 ng/ml) were examined the RIA gave values significantly lower than those obtained by IRMA. The lower values by RIA may be related to the immunological heterogeneity of serum ferritin which is maximized by an assay performed in antigen excess (RIA) and minimized by one performed in antibody excess (IRMA). These observations indicate a need for the development of specific serum ferritin assays for epidemiological studies. By manipulating the components of the standard curve the RIA and IRMA can be optimized to provide maximum precision when low serum ferritin values are being measured. in choosing an assay the ability of the method to determine the severity of iron overload must also be taken into consideration.

Ferritins↗
PubMed1981

The quantitation of the granulocytic/macrophage committed progenitor cell (CFUc) in man and the mouse.

A method has been developed to quantitate the morphologically unrecognizable granulocytic/macrophage committed progenitor cell (CFUc). In man this is done by relating CFUc colonies cultured in vitro to marrow normoblast number determined by ferrokinetic measurements. In the mouse total hematopoietic precursors are determined by a radioiron dilution technique and CFUc are quantitated by calculating the percentage of colonies contained in the known number of nucleated cells plated. Like other hematopoietic precursors, CFUc numbers in 14 normal men and 10 normal mice were not significantly different, the mean being 0.85 and 1.4 x 10(7) CFUc/kg body weight, respectively. The validity of these values was substantiated by demonstrating an excellent correlation in the mouse between CFUc/kg body weight and CFUc/femur. In subsequent studies CFUc were quantitated in patients with lung cancer prior to and following aggressive combination chemotherapy when hematopoietic suppression was at a maximum. Compared to a mean value of 39 CFU/10(5) cells plated from chemotherapy the value 10 days later was significantly higher, the mean being 125/10(5) cells. That this reflected a relative change in the proportion of CFUc was suggested by the finding that 10 days after chemotherapy the mean value for CFUc/kg was 1.94 x 10(7) which was not significantly greater than a mean of 1.53 x 10(7) before treatment. These studies illustrate the advantages of expressing CFUc/kg body weight and indicate the usefulness of the approach in the evaluation of CFUc growth in a wide range of physiologic and pathologic conditions. In addition to better comparisons of results obtained in groups of individuals, multiple studies in single persons in whom hematopoiesis is not in a steady state will also be possible.

Adult↗