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PubMed1988

Lipid fluidity directly modulates the overall protein rotational mobility of the Ca-ATPase in sarcoplasmic reticulum.

We have developed a quantitative and relatively model-independent measure of lipid fluidity using EPR and have applied this method to compare the temperature dependence of lipid hydrocarbon chain fluidity, overall protein rotational mobility, and the calcium-dependent enzymatic activity of the Ca-ATPase in sarcoplasmic reticulum. We define membrane lipid fluidity to be T/eta, where eta is the viscosity of a long chain hydrocarbon reference solvent in which a fatty acid spin label gives the same EPR spectrum (quantitated by the order parameter S) as observed for the same probe in the membrane. This measure is independent of the reference solvent used as long as the spectral line shapes in the membrane and the solvent match precisely, indicating that the same type of anisotropic probe motion occurs in the two systems. We argue that this empirical measurement of fluidity, defined in analogy to the macroscopic fluidity (T/eta) of a bulk solvent, should be more directly related to protein rotational mobility (and thus to protein function) than are more conventional measures of fluidity, such as the rate or amplitude of rotational motion of the lipid hydrocarbon chains themselves. This new definition thus offers a fluidity measure that is more directly relevant to the protein's behavior. The direct relationship between this measure of membrane fluidity and protein rotational mobility is supported by measurements in sarcoplasmic reticulum. The overall rotational motion of the spin-labeled Ca-ATPase protein was measured by saturation-transfer EPR. The Arrhenius activation energy for protein rotational mobility (11-12 kcal/mol/degree) agrees well with the activation energy for lipid fluidity, if defined as in this study, but not if more conventional definitions of lipid fluidity are used. This agreement, which extends over the entire temperature range from 0 to 40 degrees C, suggests that protein mobility depends directly on lipid fluidity in this system, as predicted from hydrodynamic theory. The same activation energy is observed for the calcium-dependent ATPase activity under physiological conditions, suggesting that protein rotational mobility (dependent on lipid fluidity) is involved in the rate-limiting step of active calcium transport.

Animals↗
PubMed1988

The effect of HMOs on overall hospital expenses: is anything left after correcting for simultaneity and selectivity?

Policymakers are interested in the effect health maintenance organizations (HMOs) have had not only on the hospital expenditures of their enrollees, but also on the expenditures of non-HMO consumers. Previous studies of the "HMO effect" have focused on the comparison between hospital expenditures of HMO enrollees and those of non-HMO groups within the same market area. To the extent that the expenditures of non-HMO groups are affected by the presence of HMOs, this comparison will not give an accurate measure of the change in expenditures due to HMOs for either group. Using SMSAs without any HMOs as the comparison group can provide an accurate measure of the HMO effect on overall hospital expenses, if any nonrandom selection process of HMOs into SMSAs is controlled. In this article, the effect of prepaid group practices (PGPs) on overall hospital expenses is estimated using a simultaneous-equation model and all 283 standard metropolitan statistical areas (SMSAs) in 1980, controlling for any nonrandom selection process. The results indicate that while a significant selectivity bias exists that must be corrected, there is no significant PGP effect on hospital expenses. Controlling for other factors, hospital expenses per capita, per admission, and per day do not change as the PGP market share increases. While hospital expenses per capita for PGP enrollees may be falling, those of non-PGP groups in those SMSAs must be increasing by offsetting amounts.

Catchment Area, Health↗
PubMed1985

Effect of cis-diamminedichloroplatinum (II), cyclophosphamide and tumor age on the rate of mitochondrial and overall cellular protein synthesis in Zajdela hepatoma.

The effect of in vivo treatment with cis-Pt(II) and/or cyclophosphamide on overall cellular and mitochondrial protein synthesis in Zajdela hepatoma was examined. The rate of the overall cellular protein synthesis decreased by about 60-80%, whereas the rate of the process in mitochondria was affected only marginally upon the treatment. Qualitatively similar changes in the relative rates of the two processes were found in Zajdela hepatoma cells during the ageing of the tumor.

Animals↗
PubMed1982

Effect of interferons on protein synthesis in human lymphocytes: enhanced synthesis of eight specific peptides in T cells and activation-dependent inhibition of overall protein synthesis.

Lymphoblastoid and fibroblast IFN inhibited PHA stimulation of overall protein synthesis in human lymphocytes by ca. 30%. Inhibition occurred within the first 6 hr of PHA treatment and was not progressive. DNA synthesis at 48 hr was inhibited to the same extent. Overall protein synthesis in resting lymphocytes was not detectably inhibited by IFN concentrations up to 1000 U/ml. Thus, inhibition of protein synthesis and subsequent reduction of cell proliferation by IFN require certain early events in mitogen activation. Resting lymphocytes were not unresponsive to IFN treatment, however. Two-dimensional electrophoretic analysis of newly synthesized proteins after IFN treatment showed enhanced synthesis of a specific set of eight peptides (I-peptides), which were shown to be synthesized in T lymphocytes. This enhancement was produced by both IFN-alpha and IFN-beta after 4 to 6 hr of exposure and was identical for all lymphocyte donors studied. After growth stimulation, IFN treatment produced no enhancements of additional peptides, although the original eight I-peptides were enhanced as usual. It is concluded that the biochemical activities of the I-peptides, which remain to be determined, cannot inhibit protein synthesis in resting lymphocytes, but may do so after mitogen activation, when the major physiologic restriction of lymphocyte protein synthesis is released. Alternatively, the I-peptides may be unrelated to regulation of protein synthesis but may be involved in viral protection or enhancement of NK activity.

Blood Proteins↗
PubMed1983

Role of splanchnic venous system in overall cardiovascular homeostasis.

A blood reservoir is an organ or region containing a significant portion of the blood volume that can be mobilized by the sympathetic nervous system to subserve overall cardiovascular homeostasis. To be effective, the reservoir must be as insensitive as possible to the passive effects of changes in flows or external pressures. Evidence is presented that the splanchnic venous bed fulfills these criteria. Hepatic venous resistance maintains portal pressure and intrinsic hepatic arterial mechanisms maintain total hepatic flow. These mechanisms minimize passive effects of portal flow changes on splanchnic blood volume, whereas enclosure of the liver in the peritoneal cavity minimizes effects of external pressures. Up to 27% of total blood volume can be mobilized from the splanchnic venous bed by sympathetic stimulation. Maintenance of cardiac preload depends on the ability of the central nervous system to control venous compliance and hence to redistribute blood volume between peripheral organs and the cardiopulmonary compartment. Three examples of the role of the splanchnic blood reservoir in overall homeostasis are discussed: hemorrhage, splanchnic nerve stimulation, and responses to epinephrine. Reflex and central control of the splanchnic blood reservoir are discussed but available information is fragmentary.

Animals↗
PubMed1983

Determinants of the overall response to furosemide: pharmacokinetics and pharmacodynamics.

After an oral or i.v. dose of furosemide, there is considerable interindividual variability in the amount of unchanged drug delivered into the urine. On the average, approximately half as much reaches the intraluminal site of action with an oral compared with an i.v. dose. However, the natriuretic response to the same dose administered by either route is virtually the same. Similarly, after pretreatment with probenecid, the same total amount of furosemide in urine causes a greater overall response. It has been presumed that this paradox is accounted for by differences in rate of delivery of furosemide to the active site such that after an oral dose or after pretreatment with probenecid, amounts of drug are at the "steep" portion of the dose-response curve for longer periods of time. Our analysis shows that this is not the case. For furosemide, the amount of diuretic delivered into the urine that is maximally efficient (21.5 micrograms/min) is considerably less than the amount causing half-maximal response (69.8 micrograms/min). Oral administration or pretreatment with probenecid maintains drug close to this maximally efficient amount more persistently than does i.v. administration. By so doing, total response to an oral dose approaches that of i.v. dosing despite delivering half the amount of drug to the active site, and after probenecid an i.v. dose causes a greater response than i.v. dosing alone despite delivering the same amount of drug to the active site. These data emphasize the importance of the time course of delivery of drug to the active site as an independent determinant of overall response.

Dose-Response Relationship, Drug↗
PubMed1980

[Angiographic frame-by-frame computerized evaluation of overall and regional left ventricular wall motion (author's transl)].

This paper describes a semi-automated quantitative method to evaluate left ventricular overall and regional wall motion. Left ventricular (LV) outlines are digitized on a frame-by-frame basis using a sonic graf/pen interfaced with a 9845 HP minicomputer. A high fidelity simultaneous LV pressure recording is also digitized. The overall myocardial pump and muscle function are expressed by the projections of the pressure-volume-flow and of the mid-wall equatorial stress-length-velocity relationships. The dynamic regional wall motion is quantitated using a radial coordinate method. The centers of mass of serial frames are superimposed, and the apical anti-clockwise rotation is corrected. The regional wall motion (RWM) and the rate of change of the RWM are calculated with this method, and the results plotted as a single hard copy output. This method permits evaluation of the effect of segmental wall dysfunction on total cardiac performance during different portions of the cardiac cycle. The relationships between the time course of LV pressure and stress and the dynamic RWM can also be studied in subjects with segmental contraction abnormalities.

Biomechanical Phenomena↗
PubMed1994

The overall and temporal association of cancer with polymyositis and dermatomyositis.

OBJECTIVE: To summarize the association of cancer with adult polymyositis (PM) and dermatomyositis (DM) and to test whether myositis precedes or follows cancer diagnosis, with the latter suggesting that myositis is paraneoplastic. METHODS: Using primary patient data, we performed an analysis of all published case control and cohort studies evaluating the association of myositis and malignancy. We evaluated the overall association of cancer within 10 years of myositis diagnosis and separately assessed cancer occurrence in periods 5 years before and 5 years after myositis diagnosis. RESULTS: Four case control or cohort studies met inclusion criteria providing 1078 myositis cases (565 PM and 513 DM) with a comparable number of controls. One hundred fifty-three myositis patients had cancer within 10 years of diagnosis. Despite reports of no myositis association with cancer, each study's data suggested an association of both PM and DM with cancer. Overall odds ratio (OR) for the association of cancer with DM = 4.4 (9.5% CI 3.0, 6.6) and for PM, OR = 2.1 (95% CI 1.4, 3.3). Cancer risk was high both before and after DM diagnosis, but for PM, cancer risk was increased only after myositis diagnosis. CONCLUSION: DM is associated with cancer, and our results suggest that DM is often paraneoplastic. The high rate of malignancy only after PM diagnosis is consistent with cancer detection bias, but may suggest joint susceptibility of affected individuals to both cancer and myositis.

Case-Control Studies↗
PubMed1994

Measurement of overall and cause-specific mortality in infants and children: memorandum from a WHO/UNICEF meeting.

A joint WHO/UNICEF informal consultation on the "Measurement of overall and cause-specific mortality in infants and children" was held in Geneva on 15-17 December 1992. The participants included physicians, demographers, statisticians and programme personnel from different regions. The recommendations were aimed at helping countries and international organizations to produce more frequent and more reliable data on overall child mortality and to estimate broad patterns of child mortality by cause of death, especially for ranking the major causes of death and monitoring progress towards the achievement of mortality reduction goals of the World Summit for Children. The verbal autopsy method was reviewed to assess its potential for use in different situations--surveys, longitudinal surveillance, health services and civil registration--and its capacity to provide national estimates of cause of death. Documented national and international experiences and validation studies were examined together with other methods already being used. The potential of the preceding birth technique and other indirect methods to estimate mortality in childhood--for use by countries and programmes more frequently and with as much disaggregation as possible--was evaluated.

Autopsy↗
PubMedDate not supplied

Immunodetection of HER-2/neu protein in frozen sections evaluated by image analysis: correlation with overall and disease-free survival in breast carcinomas.

The immunodetection of HER-2/neu oncogene product was performed in 108 breast carcinomas using immunoperoxidase technique. Monoclonal anti HER-2/neu protein was applied on frozen sections. Immunoprecipitates were evaluated by a computerized system of image analysis (SAMBA). The percentage of the immunostained tissue surfaces and mean optical densities were correlated with the 5 year overall and disease-free survival rates. It was shown that in optimal conditions of antigen preservation and standardized method of immunoprecipitates evaluation, 67% of breast carcinomas were more than 20% pHER-2/neu positive. The pHER-2/neu overexpression was not significantly correlated with the overall 5 year survival. However large positive anti pHER-2/neu surfaces were correlated with higher risk of recurrence (p = 0.0013) and of metastases (p = 0.035).

Adult↗
PubMed1994

The COOH terminus of suppressor of stem loop (SSL2/RAD25) in yeast is essential for overall genomic excision repair and transcription-coupled repair.

We examined several yeast strains with different mutations in the essential SSL2 (Suppressor of Stem Loop, also called RAD25) gene for their ability to remove cyclobutane pyrimidine dimers from expressed genes, and from the genome overall. The SSL2 protein has a high degree of amino acid sequence identity to the protein encoded by the human ERCC3 gene (Gulyas, K. D., and Donahue, T. F. (1992) Cell 69, 1031-0142). The mutant allele SSL2-XP encodes a protein resembling the mutated ERCC3 protein from UV-sensitive human cells belonging to xeroderma pigmentosum complementation group B and Cockayne's syndrome (CS) complementation group C (Weeda, G., van Ham, R. C. A., Vermeulen, W., Bootsma, D., van der Eb, A. J., and Hoeijmakers, J. H. J. (1990) Cell 62, 777-791; Gulyas and Donahue, 1992). The SSL2-XP allele confers UV sensitivity on yeast strain KG119. We found that the biochemical basis for the UV sensitivity of KG119 is a complete deficiency in the removal of cyclobutane pyrimidine dimers from the overall genome as well as a deficiency in transcription-coupled repair. This is the first analysis of the DNA repair defect responsible for the UV sensitivity of cells carrying the SSL2-XP allele, and it documents the similarity of the defect to that associated with XP-B/CS-C, and the difference between this defect and that in cells belonging to CS complementation groups A and B.

Alleles↗
PubMed1995

Integration of the overall response to exercise.

Physical activity ellicits major perturbations in metabolism during the period of exertion and continues to influence metabolism afterwards as well. The overall effect of these intermittent and extended effects on the balance between energy expenditure and food intake regulation can best be judged by the impact of exercise on the fat mass. Expansion of the adipose tissue mass promotes fat oxidation more than glucose oxidation, but excessive fat accumulation is often necessary to reach the state where fat oxidation becomes commensurate with fat intake. Since the steady-state of weight maintenance is achieved with less body fat in physically active individuals, exercise is a substitute for an enlarged fat mass in bringing about rates of fat oxidation commensurate with fat intake. The increases in energy expenditure induced by expansion of the adipose tissue mass or by physical activity are quantitatively very different. The fact that they are substitutes for each other in relation to body weight maintenance indicates that the critical issue, under conditions where food availability is not a limiting factor, is not overall energy turnover. It appears therefore that it is the effect of exercise on the 24-h RQ that allows the organism to operate with an average RQ as low as the diet's FQ in the presence of less body fat. This also explains why the diet's carbohydrate-to-fat ratio can be an important parameter in shaping the interactions between physical activity and body weight maintenance.

Animals↗
PubMed1996

[The effect of local control on overall survival after the breast-conserving therapy of breast carcinoma].

BACKGROUND: The impact of local control on survival in breast carcinoma has been controversially discussed depending upon the specific view of disease as being systemic from the initial onset or locally confined with spread sequentially from the primary tumor to the regional lymph nodes and then to distant sites. Results of recent studies provide a good example of why controversy persists over the benefit of local control on survival. PATIENTS AND METHODS. There are 4 recently updated randomised trials that compare conservation surgery alone or with radiation: Milan III (follow-up 3.5 years), Canada (follow-up 5 years), Uppsala/Orebro (follow-up 5 years), and NSABP-B06 (follow-up 10 to 12 years). In addition, the reanalysis of NSABP-B06-protocol reported by the EMMES Corporation has become available. Of further importance is the meta-analysis of Levitt et al. [7], which has used special statistical tools, the BAYESIAN-technique. RESULTS: All 4 trials report statistically significant increased local control and improved survival for the irradiated patients. Based on p-values and confidence intervals, survival was statistically improved in long-term follow-up of the NSABP-B06 trial, but not in the other trials, probably because of small sample sizes and short follow-up. At 10 years, the overall survival rates for the NSABP-B06 were 65 +/- 2.1% and 71 +/- 2.0% for lumpectomy alone or with radiation respectively (p = 0.04), the distant-disease-free survival 55 +/- 2.3% vs. 62 +/- 2.2% (p = 0.03), and the disease-free survival 48 +/- 2.2% vs. 56 +/- 2.2% (p < 0.01). Within the Bayesian framework, the expected advantage in 10 year survival was 6% (the mean of NSABP-B06 10 year survival) with an 83% probability that the 10-year-survival difference ranges between 2% and 10%. CONCLUSIONS: The careful analysis of these randomized trials comparing lumpectomy with or without radiation clearly indicate an improvement in overall survival for the irradiated patients which is associated with increased local control. Combination of this survival trend with the reduced psychological and economic costs associated with local recurrence provides excellent arguments for radiation therapy as the standard treatment concept in breast conservation therapy.

Bayes Theorem↗
PubMed1996

Leptin concentrations in relation to overall adiposity and regional body fat distribution in Mexican Americans.

OBJECTIVE: Leptin, the product of the human OB gene is increased in obese individuals suggesting resistance to its effect. However, there is variability in leptin levels at each level of body mass index suggesting that genetic and environmental factors other than overall adiposity may regulate leptin concentrations. Moreover, the relation of leptin to various adipose depots may differ. Upper body (or central adiposity) is more metabolically active than peripheral adiposity. METHODS: We examined the relation of serum leptin levels to body fat distribution in 147 non-diabetic subjects from the San Antonio Heart Study. RESULTS: Leptin concentrations in men were significantly correlated with body mass index (BMI) (r = 0.741), waist-to-hip ratio (WHR) (r = 0.567), waist circumference (r = 0.840), hips circumference (r = 0.842) triceps skinfold (r = 0.520) and subscapular skinfold (r = 0.668) but not with subscapular to triceps skinfold (r = 0.185). Leptin concentrations in women were significantly correlated with BMI (r = 0.814), WHR (r = 0.377), waist circumference (r = 0.718), hips circumference (r = 0.779), subscapular skinfolds (r = 0.636) and triceps skinfolds (r = 0.587) but not with the ratio of subscapular to triceps skinfolds (r = 0.184) in women. CONCLUSIONS: Since the associations of leptin with body mass index (a surrogate for overall adiposity), waist circumference (a surrogate for upper body) and hips circumference (a surrogate for lower body adiposity) are similar, we conclude that leptin concentrations are associated with all adipose tissue depots and not disproportionately with upper body or central adiposity.

Adipose Tissue↗
PubMed1996

Blood vessel and lymphatic vessel invasion in resected nonsmall cell lung carcinoma. Correlation with TNM stage and disease free and overall survival.

BACKGROUND: The objective of this prospective study was to assess in 96 patients with resected nonsmall cell lung carcinoma (NSCLC) the prevalence of both blood and lymphatic vessel invasion (BVI and LVI) according to stage, as well as their prognostic value for disease free and overall survival. METHODS: BVI and LVI were evaluated by hematoxylin and eosin stains on surgical specimens after resection. Associations among variables were tested by Fisher's exact test or the chi-square test; prognostic values on time-failure data were analyzed by the log rank test and the multivariate Cox model. RESULTS: BVI was present in 52% of NSCLC cases and LVI in 59%. Venous but not arterial vascular invasion correlated with the T factor and pTNM, whereas LVI correlated with the N factor and pTNM. In univariate analysis, LVI but not BVI was associated with a short disease free interval (P = 0.0007) and poor survival (P = 0.0001). The estimated relative risk of death in patients with LVI was 3.2 compared with patients without LVI. In multivariate analysis, LVI and pTNM were additional predictors for poor disease free and overall survival. In this series, BVI had no prognostic value. CONCLUSIONS: The prevalence of BVI and LVI appeared high in patients with NSCLC, especially those with advanced pTNM stages. LVI was predictive of poor outcome, both time to recurrence and death.

Adenocarcinoma↗
PubMedDate not supplied

Empirical decompositions of overall AIDS epidemics in local epidemics using generalized neural networks.

A generalized neural network was adapted for the simulation of processes strongly dependent upon the history, imposed by the inner own history of an individual neuronal activation. This involves the dependence of the neural network parameters upon the cumulated values of the corresponding neuron activations. When in the neural network weakly coupled blocks with strong inner couplings can be identified, the activation wave on the entire network (associated with the overall epidemic) can be decomposed into quasi-independent intra-block local activation waves, with characteristic delays between them (corresponding to the simultaneous and successive local epidemics). Special simulations on strongly connex neural network determine the typical local activation waves for various block parameters and the mentioned delays between two such successive activation waves in two coupled blocks. Another type of neural network is used to achieve the empirical decomposition of the overall epidemic into simultaneous (corresponding to a layer) and successive local epidemics (corresponding to the various epidemic waves, associated with different layers). A simpler approximative algorithm for the estimation of the number of the mentioned simultaneous local typical epidemics is also presented.

Acquired Immunodeficiency Syndrome↗
PubMed1976

Dissociation of beta-hydroxy-beta-methylglutaryl-CoA reductase activity from the overall rate of cholesterol synthesis in the liver following the intravenous administration of lipid.

After the intravenous administration to the intact rat of triglyceride carried in either intestinal lipoproteins or in an artificial fat emulsion, the enzymatic activities of microsomal beta-hydroxy-beta-methylglutaryl-CoA reductase activity in the liver assayed in vitro became markedly elevated. This elevation of enzyme activity was not associated with a corresponding change in the overall rate of cholesterol synthesis in the rat liver slice as measured by the incorporation of either [3H]water or [1-14C]octanoate into nonsaponifiable lipids or into digitonin-precipitable sterols. The degree of dissociation of hydroxymethylglutaryl-CoA reductase activity from the overall rate of cholesterol synthesis correlated closely with the amount of lipid administered to the animal, the level of circulating lipids, and the level of ketone synthesis manifest in the liver cell suggesting that this phenomenon might be the consequence of a detergent effect of elevated cellular levels of fatty acids. In any event, under these experimental circumstances hydroxymethylglutaryl-CoA redutase activity no longer reflects the rate at which the liver cell is synthesizing cholesterol.

Acetates↗
PubMed1998

Evaluating overall usage of a digital health sciences library.

BACKGROUND: Digital health sciences library (DHSL) evaluation involves studying the usage of the DHSL by individuals as well as populations. The purpose of this study was to evaluate trends in overall usage of a DHSL as part of a process of continuous quality improvement in order to learn how to enhance a DHSL in order to meet its users' needs better. METHODS: Web server log file analysis was performed on a prototype DHSL, the Virtual Hospital, using two log file analysis programs on data from the month of February over four consecutive years, 1995 to 1998. RESULTS: Overall DHSL usage increased between 1995 and 1997 and leveled off in 1998. Fifteen percent of usage came from countries outside the United States. A broad spectrum of medical information for health care providers and patients was accessed and centered around specialty medical information. CONCLUSIONS: To be of optimal assistance to users, DHSLs should (1) contain a broad base of information on common and uncommon medical problems, (2) accommodate the needs of the significant percentage of users that are international through content translation and mirroring, and (3) ensure they are indexed and catalogued in the major Web search engines and Web general and medical indices so they can be easily found by users.

Evaluation Studies as Topic↗