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Biomedical subjects

R C Bailey

Publications and source records attributed to R C Bailey.

At least 37 records · Page 2Linked to original sources

IGF-I does not mediate T-lymphoblast colony formation in response to estradiol, testosterone, 1,25(OH)2 vitamin D3, and triiodothyronine: studies in control and pygmy T-cell lines.

The mechanism by which estradiol, testosterone, 1,25(OH)2 vitamin D3, and triiodothyronine promote tissue growth is unknown, although, in some tissues, a role for local IGF-I has been suggested. We previously showed that HTLV-II-transformed T-cell lines from healthy adults augmented basal colony formation in response to peptide (growth hormone, parathormone, and adrenocorticotrophin) and glycoprotein (thyroid-stimulating hormone) hormones through stimulation of local IGF-I. T-cell lines from African Efe Pygmies, however, were resistant to the direct growth-promoting action of IGF-I, as well as to the growth-promoting action of growth hormone, parathormone, adrenocorticotrophin, and thyroid-stimulating hormone. We, therefore, used these cell lines to determine the mechanism of T-cell growth in response to steroid and thyroid hormones. We quantified colony formation of American control T-cell lines in the presence and absence of alpha IR-3 antibody against the type 1 IGF receptor and Pygmy T-cell lines in response to estradiol (36.7-1835 pmol/ liter), testosterone (34.7-17,350 pmol/liter), 1,25(OH)2 vitamin D3 (2.4-24,000 pmol/liter), and triiodothyronine (1536-192,000 pmol/liter). There were no statistically significant differences by ANOVA in overall response curves for any of the four hormones comparing control clonal responses in the presence or absence of alpha IR-3 and no statistically significant difference in overall responsiveness between control and Pygmy T-cell lines. From these data, we conclude that (i) normal T-cell lines grow in response to estradiol, testosterone, 1,25(OH)2 vitamin D3, and triiodothyronine; (ii) these responses are not mediated through local IGF-I since they are not blocked by pretreatment with antibody to the type 1 IGF receptor; and (iii) Pygmy T-cell lines, which are genetically resistant to IGF-I, grow equivalently to control T-cell lines in response to estradiol, testosterone, 1,25(OH)2 vitamin D3, and triiodothyronine, further underscoring the IGF-I independence of this stimulation in our system.

Analysis of Variance↗

Design and application of a low-temperature Peltier-cooling microscope stage.

A light microscopy system has been designed for freezing and lyophilization studies of protein pharmaceuticals. The system consists of a cascade of four Peltier thermoelectric modules in the lyophilization cell to freeze samples to -60 degrees C, controllers to regulate temperature and pressure conditions, and a video camera to record the events under study. Specific demonstration of the system was conducted using recombinant CD4-IgG and human growth hormone (hGH) as model proteins. Observations of recrystallization during warming of frozen CD4-IgG solution and lyophilization of hGH solution are discussed. These examples demonstrate that the system is a useful tool for the fundamental understanding of freezing and lyophilization of protein pharmaceuticals.

CD4 Antigens↗

Decreased insulin-like growth factor I receptor expression and function in immortalized African Pygmy T cells.

Efe Pygmies of northeast Zaire have the shortest mean adult stature of any population on earth. Although various alterations in the GH/insulin-like growth factor I (IGF-I) axis have been suggested, the basis for short stature in the Pygmy is unknown. We previously described IGF-I unresponsiveness in a T lymphoblast cell line derived from an Efe Pygmy, and studies in five additional lines have confirmed severe IGF-I resistance in these cells. We have now performed experiments to determine the molecular basis for the IGF-I resistance in these cells. We found markedly decreased cell surface expression of IGF-I receptors with normal ligand binding affinity. The Pygmy IGF-I receptors were not autophosphorylated and did not transmit a signal in response to physiological concentrations of IGF-I. There was a substantially decreased level of IGF-I receptor messenger ribonucleic acid in the Pygmy cells with a normal messenger ribonucleic acid half-life. The nucleotide sequence of the full-length IGF receptor complementary DNA in Pygmy 1 showed no significant variation. These results indicate decreased IGF-I receptor gene transcription and IGF-I receptor signaling as the primary variation in the Pygmy cell lines. The findings point to the IGF-I receptor as the locus governing short stature in the African Pygmy and suggest that human stature may be genetically controlled by expression of the IGF-I receptor.

Base Sequence↗

Adequacy of national mortality data for internal hospital use: a case study.

OBJECTIVE: The study investigated the value of using national or regional data bases to examine care in a specific hospital. DATA SOURCES: The following data sources were included: (1) the results of the 1992 HCFA analysis of the index hospital for patients hospitalized in fiscal year 1990; (2) the 1989 Medicare Provider Analysis and Review (MEDPAR) file; and (3) clinical information from bypass surgery patients in Wisconsin and from the index hospital. PRINCIPAL FINDINGS: The assessment of the mortality rates in the index hospital for all conditions combined and for CABG patients differed depending on what data base was used and how the data were analysed. The national data were most useful in establishing that the coding practices for all patients and the mortality rate for intra-aortic balloon patients differed between the index hospital and other hospitals. The regional clinical data base for bypass surgery patients was used to establish that the high mortality rates for intra-aortic balloon patients were due to patient selection. CONCLUSIONS: National claims data must be analysed carefully before applying results to an individual hospital. Even a careful analysis is more for raising questions about care at a specific hospital rather than for reaching definitive conclusions.

Aged↗

Growth-promoting actions of parathyroid hormone, adrenocorticotrophic hormone, and thyroid-stimulating hormone: in vitro studies in normal and pygmy T-lymphoblast cell lines.

We used an in vitro T-lymphoblast clonal proliferation assay to quantify human IGF-I (hIGF-I)-, human PTH (hPTH)-, human ACTH (hACTH)-, and human TSH (hTSH)-stimulated growth of human T-cell leukemia virus-II-transformed T-lymphoblast cell lines from normal individuals and to elucidate the role of IGF-I as the mediator of hPTH-, hACTH-, and hTSH-induced T-cell growth. Normal T-lymphoblast cell lines respond to hIGF-I in a bimodal fashion. The mean first peak response was 143 +/- 9.8% above baseline (defined as 100%) occurring at 8 micrograms/L, and the mean second peak response was 154 +/- 14.4% occurring at 100 micrograms/L. Both responses were completely blocked after incubation with alpha IR-3, an MAb to the IGF-I receptor (by analysis of variance, p = 0.015 between full response curves). After stimulation with hPTH, the mean peak clonal response of normal T-lymphoblast cell lines was 189 +/- 7.0%; after incubation with alpha IR-3, the mean peak clonal response was 108 +/- 7.9% (p = 0.0015 between full response curves). The mean peak clonal response of normal T-lymphoblast cell lines after hACTH stimulation was 192 +/- 8.6%; preincubation with alpha IR-3 reduced the mean peak clonal response to 94 +/- 1.2% (p < 0.0001 between full response curves). With hTSH stimulation, the mean peak clonal response of normal T-lymphoblast cell lines was 167 +/- 7.0%; after incubation with alpha IR-3, the mean peak clonal response was 94 +/- 8.2% (p = 0.003 between full response curves).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

Insulin-like growth factor I resistance in immortalized T cell lines from African Efe Pygmies.

Previous investigations suggested that resistance to GH was the cause of short stature of African Pygmies. Because many of the actions of GH are mediated by insulin-like growth factor I (IGF-I), we sought to determine whether Pygmy tissue was responsive to IGF-I. An initial effort to obtain HTLV-II-transformed T lymphoblast cell lines resulted in a single cell line that showed complete resistance to both IGF-I and GH in a clonal proliferation assay as well as decreased IGF-I binding. In the current study, we examined T cell lines from seven Efe Pygmy subjects, three neighboring Lese farmers, and six American controls and quantified clonal responses to IGF-I, GH, and insulin. The T cell lines from the Efe Pygmies were all completely resistant to the growth-promoting actions of IGF-I concentrations less than 250 micrograms/L and GH concentrations less than 500 micrograms/L. The Lese population, with whom there is admixture with the Efe population, showed heights and clonal responses to IGF-I and GH intermediate between those of Pygmies and American controls. The Pygmy T cell lines showed reduced clonal proliferation in response to high insulin concentrations known to act through the IGF-I receptor. These findings indicate that genetic IGF-I resistance is present in the T cell lines of Efe Pygmies and suggest that unresponsiveness to IGF-I may be responsible for their short stature.

Adult↗

The level and tempo of children's physical activities: an observational study.

We develop an observation system that quantifies the duration, intensity, and frequency of children's physical activities. We use this system to assess the level and tempo of energy expenditure under free-ranging, natural conditions experienced by 15 children aged 6-10 yr in southern California. Observations were recorded every 3 s during 4-h time blocks from 8:00 a.m.-8:00 p.m. Agreement among observers using the coding system was 91%. Using indirect calorimetry, calibration studies in the laboratory determined VO2 (ml.min-1.min-1) during each coded activity, and activities were categorized by intensity (low, medium, or high). Subjects were found to engage in activities of low intensity 77.1% of time and activities of high intensity 3.1% of time. The median duration of low and medium intensity activities was 6 s, of high intensity activities only 3 s with 95% lasting less than 15 s. Children engaged in very short bursts of intense physical activity interspersed with varying intervals of low and moderate intensity. These findings may be important for discovering how children's activity patterns under natural conditions influence physiological processes leading to growth and development. This study demonstrates the advantages of using an observational system that captures more than the intensity and frequency of children's activities to include duration and the length of intervals between activities of varying intensity.

Child↗

Interpreting the Health Care Financing Administration's mortality statistics.

In this article, the methodology used by the Health Care Financing Administration in the 1992 release of 1990 mortality statistics is described, and the performance of one outlier hospital is evaluated as a case study. The study hospital is compared to all other hospitals, and to a smaller cohort of 200-to-299-bed minor teaching hospitals, in terms of predicted and observed mortality rates and mortality model determinants. Proportionately more patients treated in the study hospital were women and had cerebrovascular degeneration or chronic renal disease; fewer patients had cardiovascular disease. Substantially more patients from this hospital were transfers from a skilled nursing facility. Fewer patients were admitted through the emergency department. Although patients tended to be more seriously ill overall compared with other hospitals in the country, observed mortality rates were still higher than predicted. Possible explanations for the discrepancy were coding inconsistencies, inability to control adequately for the severity of illness of transfers from skilled nursing facilities, or quality of care problems.

Centers for Medicare and Medicaid Services, U.S.↗

The relationship of hospital ownership and teaching status to 30- and 180-day adjusted mortality rates.

Hospital characteristics have been shown previously to be associated with variations in the probability of death within 30 days of admission. In the current study, the authors extend the examination of the relationship between hospital type to both short-term and long-term adjusted mortality. Observed and predicted 1988 hospital mortality rates were obtained from the Health Care Financing Administration (HCFA). A total of 3,782 acute care hospitals were divided into six mutually exclusive groups on the basis of their status as osteopathic, private for-profit, public teaching, public nonteaching, private teaching, and private nonteaching hospitals. After adjusting for the HCFA predicted mortality, Medicaid admissions, and emergency visits, 30-day and 30-to-180-day patient mortality rates were compared for these hospital types. Separate comparisons also were performed after stratifying hospitals into three groups defined by community size. The risk-adjusted 30-day mortality per 1,000 patients was 91.5, ranging from 85.4 for private teaching hospitals to 95.3 for nonteaching public hospitals, and 97.4 for osteopathic hospitals. The adjusted 30-to-180-day mortality was 84.7, ranging from 82.6 for nonteaching public hospitals to 87.4 and 88.2, respectively for public teaching and osteopathic hospitals. Differences among hospital types were minimal for small communities and increased with community size. In the large communities, the types of hospitals with high 30-day mortality also had higher mortality after 30 days. There was a strong association of hospital type with adjusted 30-day mortality, which should depend on the quality of hospital care, and a much weaker association with post-30-day mortality, which may be more dependent on patient risk. There was no evidence that types of hospitals with low 30-day mortality were postponing rather than preventing mortality.

Acute Disease↗

Growth hormone induces resistance to the mitogenic action of insulin through local IGF-I. Studies in normal and Pygmy T-cell lines.

Growth hormone (GH) and insulin have both mitogenic and metabolic actions. The growth-promoting effects of GH in vivo are thought to be mediated by insulin-like growth factor-I (IGF-I), whereas the metabolic effects of GH are thought to be either direct or mediated by factors other than IGF-I. In previous studies using HTLV-II-transformed T-lymphoblast cell lines established from normal individuals, we have shown that GH preincubation induces resistance to the growth-promoting (mitogenic) action of insulin. In this study, using T-cell lines from 3 American control subjects, 1 African control subject, and 1 African Pygmy (the latter previously shown to be resistant to the growth-promoting actions of both IGF-I and GH), we examined the role of local IGF-I in the mediation of GH-induced resistance to the mitogenic action of insulin. In these studies, we quantified the stimulation of T-cell colony formation in response to insulin in the presence and absence of either GH or IGF-I.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Causal attribution and affective response as mediated by task performance and self-acceptance.

Predictions derived from cognitive consistency theories, self-esteem theories, and ego-serving-bias theory concerning how students would make attributional and affective responses to their academic performance were investigated. 202 university students completed a measure of self-acceptance of their college ability and made attributional and affective responses to an hypothetical examination performance. Analyses showed that students receiving positive feedback perceived greater internal causality and responded with greater positive affect than students receiving negative feedback. Self-acceptance did not moderate the attributions or affective reactions. The results supported the ego-serving-bias theory and provided partial support for self-esteem theory. Findings did not support predictions from cognitive-consistency theory.

Adult↗

The Behavioral and Attitudinal Modification Project (BAM): a failed experiment using a classical experimental research design in a closed institutional setting for drug addicts.

Failure in program implementation and related research within closed institutional settings has long been a source of discouragement for correctional administrators and correctional researchers. This paper describes an attempt to implement an innovative treatment program, The Experimental Behavioral and Attitudinal Modification Project, within a civil addict treatment facility to enhance treatment effectiveness. It documents the major obstacles to correctional program innovation and research which ultimately brought about disruption, complacent cooperation, and other implementation problems leading to a project shutdown. It also attempts to place in theoretical perspective the reasons behind implementation failures, particularly as they relate to innovations in treatment and the use of classical experimental designs in closed institutional settings. The article is adapted from the executive summary of the final report to the funding agency. Researchers working to facilitate the effective reintegration of drug-using offenders into society should take heed from this research project, originally implemented in 1970, as a study in FAILURE as apropos today as it was over two decades ago.

Attitude of Health Personnel↗

Insulin-like growth factor-I unresponsiveness in an Efe Pygmy.

The cause of short stature in African Pygmies is unknown, but some evidence suggests that they are GH resistant. Since IGF-I mediates many actions of GH, we sought to determine if Pygmy tissue is responsive to IGF-I. We established HTLV-II-transformed cell lines from 1 Efe Pygmy, 1 African control, and 3 American controls, and quantified in vitro colony formation in response to IGF-I, GH, and insulin, and assessed IGF-I receptor binding. The Pygmy T-cell line showed no clonal responsiveness following stimulation with physiologic concentrations of IGF-I or any concentration of GH, but responded normally to insulin. IGF-I binding studies showed no binding to the Pygmy T-cell line with normal binding to control cells. The primary abnormality in this Pygmy T-cell line is IGF-I resistance at the receptor level with secondary GH resistance.

Adult↗

Data about mortality.

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Data Interpretation, Statistical↗

The ecology of birth seasonality among agriculturalists in central Africa.

The Lese are subsistence farmers living in the Ituri Forest of north-east Zaïre. They exhibit significant birth seasonality, with lowest frequencies of conception when food production is least, nutritional status is low and ovarian function, as measured by salivary steroid hormone levels, is reduced. Efe pygmy foragers, who live in the same geographical area but are less dependent on cultivated foods and have a more flexible life style, do not exhibit frequent fluctuations in nutritional status nor significant birth seasonality. These findings support a model of birth seasonality relating climatic variables to variation in fertility through a causal chain linking rainfall to food production to energy balance to ovarian function to fertility. The model, which emphasises an ecological approach to the study of human reproduction, should have broad applicability since seasonality of food production and energy balance is widespread geographically and across a wide variety of economies and cultures.

Agriculture↗

Evaluation of the HCFA model for the analysis of mortality following hospitalization.

From 1987 through 1990, the Health Care Financing Administration (HCFA) evaluated variations in the mortality rates experienced by patients admitted to hospitals participating in the Medicare program. This study was conducted to evaluate the adequacy of the model used for that purpose. Detailed clinical data were gathered on 42,773 patients admitted to 84 statistically selected hospitals. The effect of risk adjustment using the HCFA model, which is based on claims data, was compared to a risk-adjustment model based on physiologic and clinical data. Models that include claims data were markedly superior to those containing only demographic characteristics in predicting the probability of patient death, and the addition of clinical data resulted in further improvement. The correlation of ranks of hospitals based on a model that uses only the claims data and on one that uses, in addition, clinical data, was .91. As a screen for the identification of "high (mortality) outlier" hospitals, the claims model had moderate sensitivity (81 percent) and specificity (79 percent), a high negative predictive value (90 percent), and a low positive predictive value (64 percent) when compared to the clinical model. The two mortality models gave similar results when used to determine which structural characteristics of hospitals were related to mortality rates: hospitals with a higher proportion of registered nurses or board-certified physician specialists, or with a greater level of access to high-technology equipment had lower risk-adjusted mortality rates. These data suggest that the current claims-based risk-adjustment procedure may satisfactorily be used to characterize variations in mortality rates associated with hospitalization. The procedure could also be used as a basis for further epidemiological analyses of factors that affect the probability of patient death. However, it does not positively identify outlier hospitals as providers of problematic care.

Centers for Medicare and Medicaid Services, U.S.↗

Epidemiologic oversight of the medical care provided to Medicare beneficiaries.

The Health Care Financing Administration is charged by law with the assurance of the quality of the medical care rendered to Medicare beneficiaries, a function carried out through the Peer Review Organizations. To guide and support this activity, a programme of epidemiologic surveillance of the health of such persons has been devised and is being implemented. Its focus is on the objective measures of health-mortality, morbidity, disability and expenditures for health care. Its principal components are analyses of trends in those measures over time and of their variations among geographic areas, as problem-finding techniques, and evaluations of the comparative effectiveness of strategies of management of patients, as problem-solving tools. Examples of the feasibility and utility of this strategy include an evaluation of the longitudinal impact of administrative changes undertaken in 1983-1984, the assessment of variations in patient mortality rates among hospitals, the characterization of the management of patients with ischemic heart disease, and a demonstration of a methodology for the observational evaluation of revascularization in various types of patients hospitalized for acute myocardial infarction. The objectives of the programme are the improvement of review of medical practices as carried out by the Peer Review Organizations, assistance to clinicians in the management of patients, and guidance to planners in the allocation of resources.

Aged↗