Showing papers by "University of Colorado Denver published in 1987"

Gene induction by gamma-irradiation leads to DNA fragmentation in lymphocytes.

Abstract: An early event in death of interphase lymphocytes exposed in vivo or in vitro to low doses of gamma-irradiation is the degradation of DNA into nucleosome-sized fragments. Induction of fragmentation required RNA and protein synthesis because actinomycin D and cycloheximide, respectively, are able to inhibit DNA fragmentation in irradiated lymphocytes. Studies adding cycloheximide and actinomycin D at various times postirradiation suggest that once the metabolic process is initiated within an individual cell it proceeds to completion. The reversible RNA synthesis inhibitor, 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole inhibits DNA fragmentation in irradiated thymocytes. When this drug is removed after 6 hr, irradiated thymocytes proceed to fragment their DNA; this suggests that an inducing "signal" that is not simply mRNA persists within the irradiated cell for at least 6 hr after irradiation. In contrast to mitogen-activated T and B lymphoblasts, resting T and B cells show significant DNA fragmentation after exposure to 100 to 500 rad. At 2000 rad, all of the splenic subpopulations die rapidly via a different mechanism. By studying the mechanism of DNA fragmentation induced during the interphase death of lymphocytes, we hope to understand better the extreme sensitivity of resting lymphocytes to radiation and what may be the common final pathway of programmed cell death.

Identification of an Amplified, Highly Expressed Gene in a Human Glioma

Abstract: A gene, termed gli, was identified that is amplified more than 50-fold in a malignant glioma. The gene is expressed at high levels in the original tumor and its derived cell line and is located at chromosome 12 position (q13 to q14.3). The gli gene is a member of a select group of cellular genes that are genetically altered in primary human tumors.

Tests of the helix dipole model for stabilization of α-helices

Abstract: Charged groups play a critical role in the stability of the helix formed by the isolated C-peptide (residues 1-13 of ribonuclease A) in aqueous solution. One charged-group effect may arise from interactions between charged residues at either end of the helix and the helix dipole. We report here that studies of C-peptide analogues support the helix dipole model, and provide further evidence for the importance of electrostatic interactions not included in the Zimm-Bragg model for alpha-helix formation.

Functional interaction between human T-cell protein CD4 and the major histocompatibility complex HLA-DR antigen

Abstract: Mature T cells segregate phenotypically into one of two classes: those that express the surface glycoprotein CD4, and those that express the glycoprotein CD8. The CD4 molecule is expressed primarily on helper T cells whereas CD8 is found on cytotoxic and suppressor cells. A more stringent association exists, however, between these T-cell subsets and the major histocompatibility complex (MHC) gene products recognized by their T-cell receptors (TCRs). CD8+ lymphocytes interact with targets expressing class I MHC gene products, whereas CD4+ cells interact with class II MHC-bearing targets. To explain this association, it has been proposed that these 'accessory' molecules bind to monomorphic regions of the MHC proteins on the target cell, CD4 to class II and CD8 to class I products. This binding could hold the T cell and its target together, thus improving the probability of the formation of the trimolecular antigen: MHC: TCR complex. Because the TCR on CD4+ cells binds antigen in association with class II MHC, it has been difficult to design experiments to detect the association of CD4 with a class II molecule. To address this issue, we devised a xenogeneic system in which human CD4 complementary DNA was transfected into the murine CD4-, CD8- T-cell hybridoma 3DT-52.5.8, the TCR of which recognizes the murine class I molecule H-2Dd. The murine H-2Dd-bearing target cell line, P815, was cotransfected with human class II HLA-DR alpha, beta and invariant chain cDNAs. Co-culture of the parental T-cell and P815 lines, or of one parental and one transfected line resulted in a low baseline response. In contrast, a substantial increase in response was observed when CD4+ 3DT-52.5.8 cells were co-cultured with HLA-DR+ P815 cells. This result strongly indicates that CD4:HLA-DR binding occurs in this system and that this interaction augments T-cell activation.

Do good or poor performers leave? A meta-analysis of the relationship between performance and turnover.

Abstract: A meta-analysis designed to estimate the direction and magnitude of the correlation between turnover and employee performance was conducted. The sample size-weighted mean correlation across 24 stud...

Operation Everest II: preservation of cardiac function at extreme altitude

Abstract: Hypoxia at high altitude could depress cardiac function and decrease exercise capacity. If so, impaired cardiac function should occur with the extreme, chronic hypoxemia of the 40-day simulated climb of Mt. Everest (8,840 m, barometric pressure of 240 Torr, inspiratory O2 pressure of 43 Torr). In the five of eight subjects having resting and exercise measurements at the barometric pressures of 760 Torr (sea level), 347 Torr (6,100 m), 282 Torr (7,620 m), and 240 Torr, heart rate for a given O2 uptake was higher with more severe hypoxia. Slight (6 beats/min) slowing of the heart rate occurred only during exercise at the lowest barometric pressure when arterial blood O2 saturations were less than 50%. O2 breathing reversed hypoxemia but never increased heart rate, suggesting that hypoxic depression of rate, if present, was slight. For a given O2 uptake, cardiac output was maintained. The decrease in stroke volume appeared to reflect decreased ventricular filling (i.e., decreased right atrial and wedge pressures). O2 breathing did not increase stroke volume for a given filling pressure. We concluded that extreme, chronic hypoxemia caused little or no impairment of cardiac rate and pump functions.

Reliable and Fictitious Accounts of Sexual Abuse to Children

Abstract: The various categories of reports of child sexual abuse were examined in Phase 1 of a two-part study. In this first phase, all the reports (N = 576) of child sexual abuse made to the Denver Department of Social Services were categorized. Most reports were reliable accounts (70%), but a small proportion appeared to be fictitious (8%). In Phase 2, fictitious (false) reports of child sexual abuse were examined in detail. Certain clinical features appeared to mark the fictitious reports: lack of emotion and an absence of coercion and threat in the child's account, absence of detail, and several of the children and some adults were suffering from preexisting posttraumatic stress disorders based upon previous experiences. In certain cases, custody or visitation disputes were in force when the allegation arose. Poor quality of interviews with children was sometimes a factor. In our current state of knowledge absolute conclusions are not possible in the absence of corroboration. Tentative conclusions are drawn co...

Risk of ulcerative colitis among former and current cigarette smokers.

Abstract: We performed a case-control study of the effect of tobacco smoking on the risk of acquiring ulcerative colitis among the 304,000 members of a health maintenance organization. Smoking histo...

Severe pulmonary hypertension and arterial adventitial changes in newborn calves at 4,300 m.

Abstract: Some human newborns have a syndrome characterized by irreversible pulmonary hypertension and severe hypoxemia and by medial hypertrophy and adventitial thickening of pulmonary arteries. We considered that newborn calves made severely hypoxic might reproduce features of the human disease. When 2-day-old calves were placed at 4,300 m simulated altitude, pulmonary arterial pressure was increased and could be reversed by 100% O2. However, after 2 wk at 4,300 m, pulmonary arterial pressures were suprasystemic and there was right-to-left shunting probably through the foramen ovale and a patent but restrictive ductus arteriosus. Suprasystemic pulmonary pressure and hypoxemia persisted with 100% O2 breathing. Morphometrical examination of the lung arteries showed a markedly thickened adventitia with cellular proliferation and collagen and elastin deposition. There was increased medial thickness and distal muscularization of the pulmonary arteries associated with decreased luminal diameter. The rapid development of severe pulmonary hypertension and poor responsiveness to O2 was associated with increased arterial wall thickness, particularly involving the adventitia. Thus the pulmonary arterial circulation in these calves, which were placed at high altitude for 2 wk, exhibited features resembling persistent pulmonary hypertension in newborn infants.

DNA microextraction from dried blood spots on filter paper blotters: potential applications to newborn screening.

Abstract: Microextraction of DNA from dried blood specimens would ease specimen transport to centralized laboratory facilities for recombinant DNA diagnosis in the same manner as use of dried blood spots allowed the broad application of screening tests to newborn populations. A method is described which reproducibly yields 0.5μg DNA from the dried equivalent of 50μl whole blood. Though DNA yields decreased with storage of dried specimens at room temperature, good-quality DNA was still obtained. Sufficient DNA was routinely obtained for Southern blot analysis using repetitive and unique sequences. This microextraction procedure will allow immediate application of molecular genetic technology to direct newborn screening follow-up of disorders amenable to DNA diagnosis, such as sickle cell anemia, and may eventually permit primary DNA screening for specific mutations.

Progressive neuropsychologic impairment and hypoxemia. Relationship in chronic obstructive pulmonary disease.

Abstract: • In previous work we showed that patients with chronic obstructive pulmonary disease (COPD) suffered decrements in neuropsychologic functioning suggestive of organic mental disturbance. This study combined data from two multicenter clinical trials to explore the nature and possible determinants of such neuropsychologic change. Three groups of patients with COPD whose hypoxemia was mild (N = 86), moderate (N =155), or severe (N = 61) were compared with age- and education-matched nonpatients (N = 99). The rate of neuropsychologic deficit rose from 27% in mild hypoxemia to 61% in severe hypoxemia. Various neuropsychologic abilities declined at different rates, suggesting differential vulnerability of neuropsychologic functions to progress of COPD. Multivariate analyses revealed a consistent significant relationship between degree of hypoxemia and neuropsychologic impairment, but the amount of shared variance was small (7%). Increasing age and lower education were also associated with impairment.

Genetic resistance to mouse hepatitis virus correlates with absence of virus-binding activity on target tissues.

Abstract: The molecular mechanism of genetic resistance of inbred mouse strains to mouse hepatitis virus, a murine coronavirus, was studied by comparing virus binding to plasma membranes of intestinal epithelium or liver from susceptible BALB/c and resistant SJL/J mice with a new solid-phase assay for virus-binding activity. Virus bound to isolated membranes from susceptible mice, but not to membranes from resistant mice. F1 progeny of SJL/J X BALB/c mice had an intermediate level of virus-binding activity on their enterocyte and hepatocyte membranes. This correlated well with previous studies showing that susceptibility to mouse hepatitis virus strain A59 is controlled by a single autosomal dominant gene (M. S. Smith, R. E. Click, and P. G. W. Plagemann, J. Immunol. 133:428-432). Because virus binding was not prevented by treating membranes with sodium dodecyl sulfate, the virus-binding molecule could be identified by a virus overlay protein blot assay. Virus bound to a single broad band of Mr 100,000 to 110,000 in membranes from hepatocytes or enterocytes of susceptible BALB/c and semisusceptible C3H mice, but no virus-binding band was detected in comparable preparations of resistant SJL/J mouse membranes. Therefore, SJL/J mice may be resistant to mouse hepatitis virus A59 infection because they lack a specific virus receptor which is present on the plasma membranes of target cells from genetically susceptible BALB/c and semisusceptible C3H mice.

Lymphocyte responses to varicella zoster virus in the elderly.

Abstract: Elderly subjects (age 75–95 years) immune to varicella zoster virus (VZV) were identified by the presence of serum IgG antibody. The frequency of lymphocytes in their blood which proliferated in varicella zoster virus antigen-stimulated cultures was 1:78,000±6600. This is less than the 1:14,000±2000 frequency of VZV-responsive lymphocytes in blood from younger adult (20–43 years) donors. Elderly donors' blood mononuclear cells were less efficient than those of younger adults at lysing VZV-infected fibroblasts but not K562 target cells. The lysis of VZV target cells by elderly donors' MNC increased to control levels in the presence of 10 U/ml of interleukin-2 (IL-2). These results suggest that mononuclear cells capable of killing VZV-infected target cells persist with aging but that reduced numbers of antigenresponsive and lymphokine-releasing T cells may limit their function.

Left-handedness and immune disorders in familial dyslexics.

Abstract: We examined the frequency of left-handedness, various immune disorders, and comparison disorders in 87 dyslexics and 86 nondyslexics from 14 extended dyslexic families. These families were participants in our genetic linkage studies of dyslexia, which found linkage to chromosome 15 in some families but not others. In the present study, we found a significant elevation of both autoimmune and allergic disorders in the dyslexics only, but no elevation in mixed- or left-handedness in either group. Moreover, the frequency of immune disorders was not higher in the mixed- or left-handed subjects. There was also no elevation in the comparison disorders, which argues against an overreporting bias. The elevation of immune disorders did not vary with linkage status, arguing against a common cause for dyslexia and immune disorders. These findings are discussed in light of Geschwind's hypothesis of a testosterone-mediated association within families between left-handedness, immune disorders, and dyslexia.

Multi-center study of Parkinson mortality with early versus later dopa treatment.

Abstract: Four geographically diverse centers provided data on mortality in 359 patients with Parkinson's disease, the majority of whom began dopa treatment during the early experimental trials of 1968 to 1970. Patients were classified into three groups based on the duration of symptoms prior to starting dopa treatment: Group 1, 1 to 3 years; Group 2, 4 to 6 years; Group 3, 7 to 9 years. After 15 years of treatment and 3,689 person-years of observation, Group 1 had an observed-to-expected mortality ratio of 1.43; Group 2, 2.44; and Group 3, 2.95 (p less than 0.05). This result confirmed that increased duration of disease was associated with increased mortality risk. To examine the effect of the time of initiation of dopa treatment, duration of disease was held constant at 17 years for all three groups. Observed-to-expected mortality ratios were 1.43 for Group 1; 2.66 for Group 2; 2.63 for Group 3. This statistically significant advantage for Group 1 (p less than 0.0001) led to the conclusion that early treatment with dopa has a beneficial effect on life expectancy. After 17 years of disease, causes of death in Group 1 were less likely (p = 0.027) to be due to Parkinson's disease than was found in the other groups.