Inhibition of growth of normal murine granulocytes by cocultured acute leukemic cells.
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Biomedical subjects
Publications and source records attributed to A M Miller.
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The patterns of proliferation of C1498 mouse acute leukemic cells have been studied using the diffusion chamber technique of cell culture. These malignant cells grow to the same maximal cell concentration irrespective of initial cell input. Leukemic cells proliferate equally well with or without the stimulus of prior host irradiation. When cells cultured for several days are diluted to the original input concentration and recultured, they rapidly proliferate back to maximal cell number. All of these findings are in sharp contrast to the behavior of granulocytes from normal mouse marrow grown in the same culture system. Co-culutre of equal numbers of normal marrow cells and leukemic cells results in virtually complete inhibition of normal marrow cells and leukemic cells results in virtually complete inhibition of normal granulocyte growth. These experiments provide a means of studying malignant growth of leukemic cells, as compared to the controlled growth and differentiation of normal granulocytes, and mechanisms by which leukemic cells suppress normal granulocyte development.
Previous experiments have indicated that eosinophilopoiesis is stimulated in lymphoid cell-dependent eosinophil responses to certain antigens. In order to study if the potential for this stimulation of eosinophilopoiesis is a function of lymphoid cells and can be expressed on challenge with the eosinophilia-inducing antigen, the diffusion chamber technique for the culture in vivo of murine hemopoietic cells has been modified. A quadrachamber diffusion assembly allows for the simultaneous maintenance in the same host of four cell populations, pairs of which are separated by a cell-impermeable Millipore diffusion membrane of defined porosity. Spleen cells for chambers were from normal mice and mice primed with tetanus toxoid; secondary challenge induces eosinophilia. These spleen cells were placed transfilter from isogeneic bone marrow cells and cultured in vivo for 6 days in normal mice that received tetanus toxoidintraperitoneally following chamber-assembly implant. The marrow cell transfilter from spleen cells of primed-donor origin exhibited significantly greater eosinophilopoiesis than contiguous-chamber marrow transfilter from normal spleen cells. Such stimulated eosinophilopoiesis was independent of total chamber marrow cellularity. The data indicated that antigen-stimulated lymphoid cells may be the source of an eosinophilopoietic factor.
Normal mouse marrow cells were cultured in Millipore diffusion chambers for long periods of time and at a variety of cell concentrations. All cultures showed a pattern of granulocyte proliferation characterized by logarithmic growth followed by prolonged stabilization of cell number starting a 7 days thereafter. The height of this "plateau" varied in relationship to the level of cell input and characteristically was far lower than the maximum cell density that can be maintained in this culture system. Additional studies showed that the plateau represented a steady state of granulocyte turnover and was not due to alterations in the diffusion chambers or the host mice. Regulatory mechanisms intrinsic to the cultured cell population appeared to play a primary role in maintaining this stable plateau. Modulation of granulocyte proliferation was partly due to increasing cell density; particularly with high input concentrations. In addition, differential cell counts suggested that critical changes in the relationship between immature and mature granulocytes partially accounted for this apparent autoregulation of cell growth. The plateau period in diffusion chamber cultures in many ways resembles granulocyte proliferation in normal mouse bone marrow and is a useful model for the study of regulatory functions in granulocytopoiesis.
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Cephalopod retinas exhibit several responses to light and dark adaptation, including rhabdom size changes, photopigment movements, and pigment granule migration. Light- and dark-directed rearrangements of microfilament and microtubule cytoskeletal transport pathways could drive these changes. Recently, we localized actin-binding proteins in light-/dark-adapted octopus rhabdoms and suggested that actin cytoskeletal rearrangements bring about the formation and degradation of rhabdomere microvilli subsets. To determine if the microtubule cytoskeleton and associated motor proteins control the other light/dark changes, we used immunoblotting and immunocytochemical procedures to map the distribution of tubulin, kinesin, and dynein in dorsal and ventral halves of light- and dark-adapted octopus retinas. Immunoblots detected alpha- and beta-tubulin, dynein intermediate chain, and kinesin heavy chain in extracts of whole retinas. Epifluorescence and confocal microscopy showed that the tubulin proteins were distributed throughout the retina with more immunoreactivity in retinas exposed to light. Kinesin localization was heavy in the pigment layer of light- and dark-adapted ventral retinas but was less prominent in the dorsal region. Dynein distribution also varied in dorsal and ventral retinas with more immunoreactivity in light- and dark-adapted ventral retinas and confocal microscopy emphasized the granular nature of this labeling. We suggest that light may regulate the distribution of microtubule cytoskeletal proteins in the octopus retina and that position, dorsal versus ventral, also influences the distribution of motor proteins. The microtubule cytoskeleton is most likely involved in pigment granule migration in the light and dark and with the movement of transport vesicles from the photoreceptor inner segments to the rhabdoms.
A putative origin of DNA replication is associated with the DNA sequences necessary for the repression of silent mating type loci in yeast. These sequences lie about a kilobase away from the affected promoters, so the repression must act at a distance. We show here that DNA replication is required for the onset of repression.
The MAT alpha 2 protein of budding yeast represses a set of genes; if the MATa1 protein is also present, a further set of genes is repressed. DNA sequence comparisons reveal a 20-base pair 'operator' sequence that is present in genes repressed by a1/alpha 2. A related, but distinct, sequence is found in genes repressed by alpha 2 alone.
Several studies of workers exposed to various forms of chromium compounds have suggested an increased incidence of respiratory cancers. Lead and zinc chromates were among the chromium compounds implicated. The Department of Preventive Medicine and Community Health of the New Jersey Medical School undertook a detailed mortality study of a pigment plant in Newark which utilized both of these compounds. We compared observed deaths from each cause among 1296 white and 650 non-white males who were employed at the plant between January 1, 1940 and December 31, 1969, with expected deaths, as computed from cause-, age-, and time-specific standard death rates for the United States. A statistically significant relative risk of 1.6 for lung cancer among white male employees was found, as well as among the cohorts of white males employed 10 yr or more. A relative risk of 1.9 was noted for individuals employed at least 2 yr who were at least moderately exposed to chromates. An increased incidence of lung cancer among non-white males and stomach and pancreatic cancer among the total cohort was also evident. These data support the validity of the association between chromate pigment exposure and lung cancer, suggesting that pigment workers and other exposed to chromates be observed carefully in regard to possible risk or pancreatic and stomach cancers.
Early detection through regular mammography screening is the most effective way to decrease mortality from breast cancer. Our purpose in writing this report was to identify factors that influenced women to adhere to mammography guidelines within the year prior to the study. A sample of 581 women aged 35 years and older was used. Data were collected during in-home interviews led by graduate research assistants. Results indicated that the predisposing variables of seriousness, benefits, health motivation, control, knowledge of breast cancer and mammography guidelines, socioeconomic status, age, physician recommendation for mammography, and prior breast symptoms were significantly related to having had recent mammography.
Murray short-necked turtles were trained to walk on a motorised treadmill and to swim in a recirculating flume. Through filmed records, the frequency of limb movement and the time that thrust was directed against the substrate were measured. The animals wore masks when walking and accessed air when swimming from a ventilated capsule placed on top of the water surface. Measurement of the exhalant O(2) and CO(2) levels from these devices enabled the measurement of metabolic rates. Equivalent data were obtained from swimming and hopping cane toads, although repeatable measures of limb frequency and contact times were not obtained due to the intermittent form of locomotion in this species. Comparing the cost of transport, the energy required to transport a mass of animal over a unit distance, with other animals showed that toads do not have a cheap form of terrestrial locomotion, but turtles do; turtles use half the cost predicted from their body mass. This economy of locomotion is consistent with what is known about turtle muscle, the mechanics of their gait, and the extremely long contact time for a limb with the substrate. Swimming in toads is energetically expensive, whereas turtles, on the basis of mass, use about the same energy to transport a unit mass as an equivalent-size fish. The data were compared with the predictions of the Kram-Taylor hypothesis for locomotory scaling, and walking turtles were found to provide a numerical fit. The data show that both terrestrial and aquatic locomotory energetics in toads are generally higher than predictions on the basis of mass, whereas in turtles they are lower.
The literature on use of trimethoprim-sulfamethoxazole (TMP-SMZ) for prophylaxis in abdominal, pelvic, and prostatic surgery is meager. There is some evidence that TMP-SMZ may be effective prophylactically in biliary surgery (in patients with functioning gall bladders). Further study is needed to clarify the mixed results seen in prostatic and pelvic surgery. An evaluation was made of the effectiveness of TMP-SMZ in the prevention of endomyometritis following cesarean section in 206 women who were comparable in terms of risk factors. Among patients given a placebo, a total of 44 infections (42%) occurred, whereas among those given TMP-SMZ prophylaxis, 22 infections (22%) occurred, a statistically significant difference (P = .037, chi 2). The rate of endomyometritis among placebo recipients was 33%, as contrasted with one of 19% in those given TMP-SMZ (P = .02, chi 2). Prophylactic treatment resulted in lower rates of endomyometritis in both high- and low-risk women, but the results reached statistical significance only among high-risk patients. In essence, prophylaxis changed high-risk patients into low-risk patients.
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A survey examined self-reported mammography use in a convenience sample of 1,083 women 50 years of age and over. Relationships were examined between ever having mammography; 3-year adherence to mammography guidelines; the predisposing variables of attitudes, knowledge, health history factors, and selected demographics; and the enabling variables of income, health insurance, source of regular medical care, and type of regular physician. Logistic regression analysis for ever having a mammogram identified significant odds ratios (OR) > 1 (p < or = .05) for doctor recommendation for mammography (OR = 14.26), satisfaction with way of living (OR = 2.77), perceived benefits of mammography (OR = 1.35), and knowledge (OR = 1.21). Odds ratios < 1 were found for scaled variables of barriers and control (OR = .81 and .65, respectively). For 3-year adherence, significant odds ratios > 1 were annual Pap tests (OR = 3.36), willingness to pay > or = $50 for mammography (OR = 2.00), benefits (OR = 1.20), and knowledge (OR = 1.18). The odds ratio for control was significant at .85.