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At least 109 records · Page 6Linked to original sources

PubMed1988

Relationship of lung function loss to level of initial function: correcting for measurement error using the reliability coefficient.

The regression of lung function change on the initial lung function level is biased when the initial level is measured with random error. Several methods have been proposed to obtain unbiased estimates of regression coefficients in such circumstances. We apply these methods to examine the relationship between lung function loss over 11 years and its initial level in 433 men aged about 20 when first seen. On theoretical and practical grounds the best method is the correction of the regression coefficient using the reliability coefficient. This is defined as the ratio of the error free variance to the variance of the variable measured with error, and is easily estimated as the correlation between repeat measurements of the underlying level. In young men the loss of some lung functions (forced vital capacity [FVC], forced expiratory volume in one second [FEV1], forced expiratory flow in the middle half of expiration, and the ratio FEV1/FVC) do not appear to be related to initial level.

Adult↗

PubMed1985

Deficiency of the adhesive protein complex lymphocyte function antigen 1, complement receptor type 3, glycoprotein p150,95 in a girl with recurrent bacterial infections. Effects on phagocytic cells and lymphocyte functions.

A patient presenting delayed umbilical cord detachment, severe recurrent bacterial infections, and inability to form pus exhibited a profound defect in the expression of alpha- and beta-chains of the receptor for the C3bi fragment of C3 (CR3), lymphocyte function antigen 1 (LFA-1) molecule, and the p150,95 molecule found on neutrophils, monocytes, and lymphocyte membranes. This was shown by immunofluorescence studies using specific monoclonal antibodies, rosette formation with C3bi-coated erythrocytes, and immunoprecipitation for the LFA-1 complex. These membrane defects were responsible for abnormal phagocytic cell functions including adherence to nylon wool, cell movement, phagocytosis, and opsonized particle-induced oxidative response and for defective natural killer cell activity. In addition, lymphocyte function deficiencies previously unobserved in this disease were found. Cytolytic T lymphocyte activity was profoundly reduced; alpha- and gamma-interferon production were impaired. Finally, there was no antibody production to vaccinal antigens whereas the antibody responses to polysaccharides and to cytomegalovirus were found to be normal. The cytotoxic T cell deficiency could be expected from previous blocking experiments of this function with monoclonal antibodies to LFA-1 and is probably related to an extremely severe deficiency in LFA-1 expression in this patient. Anomalies in interferon and in antibody production suggest additional role(s) of the LFA-1 complex in monocyte/T lymphocyte/B lymphocyte cell interactions that have not yet been envisaged.

Antibodies, Monoclonal↗

PubMed1977

Clinical significance of pulmonary function tests. Pulmonary function after uncomplicated myocardial infarction.

Derangement of pulmonary function following myocardial infarction is related to the severity of hemodynamic dysfunction. Abnormalities of pulmonary function appear even in patients without clinical or radiologic evidence of congestive failure. There is a reduction in vital capacity and rates of air flow. There is evidence for dysfunction of "small airways" and diminished ventilation to dependent parts of the lung. Total lung capacity may be normal or reduced, and residual volume may be increased slightly in uncomplicated myocardial infarction. Residual volume falls with more pronounced pulmonary congestion and edema. Distribution of pulmonary perfusion is altered after myocardial infarction, with a shift of perfusion away from the dependent parts of the lung (bases) towards the apices. Pulmonary gas exchange is impaired, with hypoxemia (due to both ventilation-perfusion inequality and increased shunting); and the diffusing capacity for carbon monoxide is diminished. Dead space is increased. The basic pathophysiologic mechanism responsible for abnormalities of pulmonary function is increased pulmonary water, which may be very minimal with uncomplicated myocardial infarction and stay primarily in the pulmonary interstitial space, but becomes progressively more severe with eventual alveolar flooding and marked impairment of pulmonary function.

Humans↗

PubMedDate not supplied

Long-term deficits of goal-directed vestibulo-ocular function following total unilateral loss of peripheral vestibular function.

Brief whole-body movements (+/- 5 to 170 degrees/s peak velocity; approximately equal to 0.5 s duration), applied during 1.44-s intervals of total darkness while subjects "looked" at a just-viewed target, were used to examine vestibulo-ocular function in 3 patients who had compensated to total unilateral loss of peripheral vestibular function. We found that the combined effects of slow-phase and saccadic eye movements both tended to keep the eyes stabilized on the unseen target. Compensatory slow-phases elicited during rapid head movements ipsilateral to (i.e., towards) the lesion were only about 60% as effective as those elicited during rapid contralateral movements. Compensatory gaze-correcting saccades tended to supplement deficient slow-phase movements, especially during rapid ipsilateral head movement. However, the gaze-correcting effect of saccades was only about half of the required for perfect stabilization. Thus, two functional vestibular deficits were observed during rapid ipsilateral head movements: (1) reduced slow-phase stabilization, and (2) reduced saccadic ability to adequately supplement the deficient slow phases. However, overall vestibular functional capability, as assessed by observation of the net effect of both slow phases and saccades, was much better than would be indicated by conventional observation of slow-phase movements alone.

Adult↗

PubMed1991

The relation between motor function development and vestibular function tests in four children with inner ear anomaly.

It is well known that the development of motor function is frequently retarded in children with congenital deafness, particularly in cases of inner ear anomaly. The relation between the results of vestibular function tests and the development of motor function in 4 children with inner ear anomaly is studied. CT scan obtained from these cases revealed the absence of lateral semicircular canals in both ears. There were no responses to caloric stimulation using 40 ml ice-water. However, damped rotation test elicited per-rotatory nystagmus in all cases. In contrast to this result, the same nystagmus was provoked only in 2 cases in Barany rotation test. Early development of motor functions, especially that of first walk, was more retarded in the 2 cases showing no per-rotatory nystagmus in Barany rotation test than in the other 2 positive cases.

Child↗

PubMed1987

Regional time-based functional imaging of hepatocyte function.

Hepatocyte function was analyzed following the injection of 5 mCi of Tc-99m disofenin by the computer generation of three kinds of functional images designed to portray regional rates of hepatic uptake. Nineteen patients were analyzed, of whom eight had no overt liver disease, five had active hepatitis, five had cirrhosis, and one had acute cholecystitis. Functional images were graded according to lack of regional homogeneity of accumulation. Uptake kinetics were found to be significantly more homogeneous in normal subjects, becoming increasingly heterogeneous in hepatitis and cirrhosis patients, respectively. Thus functional imaging may provide a tool for the quantitative analysis of parenchymal disruption in liver disease.

Adult↗

PubMed1977

Kinetics of hepatocellular proliferation as a function of the microvascular structure and functional state of the liver.

An analysis of hepatocellular proliferation in regenerating rat liver reveals a dependence of kinetic parameters on the microvascular structure of the liver. Influx kinetics of hepatocytes into DNA synthesis as well as cell cycle phases vary in different parts of the liver lobule between the afferent and efferent vascular poles. Heterogeneity of the proliferative response and size limitations on cell cycle compartments appear to be intimately related to the actual functional state of the individual liver cell. Modifications of liver cell functions result in variations of the proliferative activity. Phenobarbital-induced hypertrophy of hepatocytes reveals a permissive action on G1- S influx. Selective destruction of the subpopulations, by allyl formate, leads to a new functional determination of the residual liver and to a change in proliferative compartments. Maximum modulation of cell cycle compartments is obtained by hydroxyurea-induced synchronization of hepatocytes after partial liver resection. During hydroxyurea treatment, the regenerating liver shows a pronounced cellular hypertrophy. After release from hydroxyurea block, cells embark on DNA synthesis simultaneously. The DNA synthesizing compartment comprises almost the entire liver cell population. Heptotrophic factors might play a part in regulating or modifying hepatocellular function and proliferative response after cell loss.

Allyl Compounds↗

PubMed1989

Longitudinal study of leukocyte functions in homosexual men seroconverted for HIV: rapid and persistent loss of B cell function after HIV infection.

The early effects of infection with human immunodeficiency virus (HIV) were investigated in homosexual men who had seroconverted for anti-HIV antibodies. Leukocyte functional activities were determined in longitudinally collected peripheral blood mononuclear cell samples. During the first 10 months following seroconversion, anti-CD3 monoclonal antibody-induced T cell proliferation, monocyte accessory function and T helper activity on B cell differentiation in a pokeweed mitogen-driven system were not affected. In contrast, from the moment of seroconversion on, B cells of seroconverted men failed to produce immunoglobulin in the pokeweed mitogen-driven system. This defect was not restored by addition of normal CD4+ T cells. Immunoglobulin synthesis induced by Staphylococcus aureus and interleukin 2 decreased gradually, until it was completely lost 10 months after seroconversion. In addition, proliferation in response to anti-IgM or Staphylococcus aureus by B cells from HIV seroconverted men was decreased. The lack of inducible in vitro B cell activity was not accompanied by elevated spontaneous Ig synthesis by B cells of the seroconverted men. In the second group of men studied during the 2nd year following seroconversion, T helper activity on normal B cell differentiation significantly decreased, whereas anti-CD3-induced T cell proliferation and monocyte accessory function were not significantly affected. Our results demonstrate that in almost all HIV-infected individuals B cell functional defects are the first leukocyte abnormalities observed preceding defects in T helper activity.

Antibody Formation↗

PubMed1988

Nuclear factor NF-kappa B can interact functionally with its cognate binding site to provide lymphoid-specific promoter function.

Enhancers and promoters, cis-acting regulators of mammalian gene expression, are modular units containing multiple short binding sites for specific trans-acting transcription factors. To investigate if factors binding to enhancer sequences are functionally different from promoter-binding factors, we asked if a short DNA sequence element in the immunoglobulin kappa (kappa) light chain enhancer that binds to the nuclear factor NF-kappa B could also serve as a functional promoter element. A synthetic oligonucleotide containing this binding site was placed in either orientation upstream of the beta-globin TATA-element. In myeloma cells, the NF-kappa B binding site efficiently directed transcription. The promoter activity was directly correlated with the presence of the nuclear factor NF-kappa B: there was no transcription in fibroblasts or in unstimulated pre-B cells where the factor was absent. Transcription could be stimulated in pre-B cells by treatments known to activate NF-kappa B. Thus, the same nuclear factor can act as a positive activator of both enhancer and promoter function, suggesting that the two functions involve similar events in the transcription process.

Animals↗

PubMed1990

Modulation of endothelial function by hypoxia: perturbation of barrier and anticoagulant function, and induction of a novel factor X activator.

Exposure of the vessel wall to hypoxemia is a central feature of ischemic cardiovascular disease. This led us to examine the perturbation of endothelial cell properties under hypoxia. An atmosphere of pO2 of 12 mmHg is not lethal to the endothelial cells for up to five days, but barrier function was impaired. Increased passage of macromolecule tracers were observed in time- and dose-dependent manner and electron microscopy demonstrated small gaps (0.5-1.0 micron) between cells. Expression of the anticoagulant cofactor thrombomodulin was also perturbed: thrombomodulin activity and antigen decreased in parallel. Northern blots showed almost complete suppression of thrombomodulin in hypoxic culture. Furthermore, synthesis of other proteins, such as fibronectin, was slightly enhanced under hypoxia. In addition to the suppression of these anticoagulant cofactor, hypoxic endothelial cell displayed a noval procoagulant activity distinct from tissue factor. Further study revealed that hypoxic endothelial cultures directly activated Factor X, as assessed by functional assays and SDS-PAGE. In addition to this no activation of Factor IX or prothrombin was observed. The hypoxia-induced Factor X activator was membrane-associated, required calcium to form Factor Xa, was inhibited by HgCl2 but not by PMSF, and had Km approximately 25 micrograms/ml. Co-incubation of hypoxic cultures with cycloheximide prevented the expression of this activity, suggesting that protein synthesis is required for its expression. These functional perturbations of endothelial cells were reversible following reoxygenation. These data indicate that hypoxia imposes a selective perturbation on endothelial cell function, suggesting the possible contribution of hypoxemia to vascular dysfunction in ischemia.

Animals↗

PubMed1991

Acquisition of mature functional responsiveness in T cells: programming for function via signaling.

The results discussed here provide strong evidence that different T-cell effector gene programs are activated by different signals, and that in several cases their responses to the same exogenous stimuli shift during the development and antigen responses of the cells. T-cell responses are thus conditional and plastic at the individual cell level. In the formalism of the introductory section, the results support elements of Models 2 and 3, and suggest a fusion between them as differentiation is explained in terms of alteration in the relative strengths of different intracellular signaling pathways. Returning to an initial question, how are different functional capabilities assigned nonrandomly to cells with different antigen recognition specificities? This question has not been answered, but it can be reformulated. If all virgin T cells can transiently make IL-2, then we must ask what features of cell biology explain the preferential preservation of IL-2 inducibility in CD4+ cells as opposed to CD8+ cells. If the capacity to induce IL-4 expression is not acquired in the thymus, then we may ask whether the initial opening of this locus depends on a CD4-transmitted signal. Similarly, the CD8 molecule itself might participate in inducing the initial differentiation events that render CTL-p inducible for granzyme C and perforin. This would be in accord with a large literature showing that CD8 engagement is much more important in the initial induction of CTL activity than in the exercise of function by pre-primed CTL effectors. The subtext of each of these "questions", however, is that intrathymic events may not directly affect the genes used by terminal effectors for function at all. They may instead bias a cell's complement of triggering receptors, thus rendering it differentially sensitive to particular signals generated during antigen reception. This view is extreme, and will probably turn out to be an overstatement. But it does inspire a unique set of investigations into the basis of T-cell function. It lends urgency to the question of whether CD4+ and CD8+ cells differ in their G proteins, kinases, or inducible proto-oncogenes. If they do, we can then ask whether such differences themselves arise in the periphery, or whether they can be traced back to thymocytes fresh from positive selection--or before.

Animals↗

PubMedDate not supplied

The effect of magnesium added to secondary cardioplegia on postischemic myocardial metabolism and contractile function--a 31P NMR spectroscopy and functional study in the isolated pig heart.

This study investigated whether increasing the magnesium concentration during secondary cardioplegia improves postischemic myocardial recovery. Twenty-four isolated pig hearts were divided into four groups. All hearts were initially subjected to control perfusion with modified Krebs-Henseleit solution for 30 min, followed by a single infusion of St. Thomas' solution #2. The hearts were then maintained without perfusion at 12 degrees C for 4 h. Following this hypothermic preservation, the hearts in group I were reperfused with modified Krebs-Henseleit solution for 50 min, while hearts in group II and III were reperfused with a secondary cardioplegic solution containing 16 or 0 mmol/L magnesium, respectively, for 20 min followed by 30 min of perfusion with modified Krebs-Henseleit solution. In group IV, the hearts were initially reperfused with Krebs-Henseleit solution containing 16 mmol/L potassium for 20 min, followed by 30 min of reperfusion with modified Krebs-Henseleit solution. The changes in high-energy phosphates and intracellular pH were monitored throughout the experiments using 31P nuclear magnetic resonance (NMR) spectroscopy. Heart rate, left-ventricular systolic developed pressure, and rates of pressure increase and decrease were measured during control perfusion and reperfusion to calculate the percent contractile functional recovery. Needle biopsies for measurement of energy metabolites with high performance liquid chromatography were performed at the end of preservation and reperfusion to confirm the NMR measurements. All six hearts in group I showed significantly less recovery of contractile function during reperfusion when compared to the hearts in groups II, III, IV (p less than 0.05). There was no difference in either recovery of metabolism or mechanical function among the latter three groups of hearts. None of hearts in groups II, III, and IV showed ventricular fibrillation, which occurred in all six hearts of group I upon reperfusion. The results suggest that a short period of re-arrest perfusion following ischemia ("secondary cardioplegia") improves postischemic contractile functional recovery and prevents reperfusion-induced ventricular fibrillation. Increased magnesium concentration in the secondary cardioplegia did not provide additional benefit to the ischemic myocardium, possibly due to the low permeability of the sarcolemmal membrane to magnesium.

Animals↗

PubMed1991

Functional hepatic imaging with receptor-binding radiopharmaceutical: clinical potential as a measure of functioning hepatocyte mass.

Asialoglycoprotein receptor (ASGP-R) is a hepatic cell surface receptor specific for galactose-terminated glycoproteins. Technetium-99m diethylenetriaminepentaacetic acid-galactosyl human serum albumin (TcGSA) is a newly developed analog ligand to ASGP-R. Fourteen human subjects were studied: three normal volunteers, one with chronic hepatitis, 6 with liver cirrhosis, and 4 with hepatocellular carcinoma associated with liver cirrhosis. The receptor index parameter (LHL15), was obtained from the liver and heart time-activity data as the ratio of radioactivity of the liver over that of the liver plus heart at 15 min after intravenous injection of 1 mg of TcGSA. Means +/- standard deviations of LHL15 in normal volunteers (3 cases), patients with mild (4 cases), moderate (2 cases), and severe liver damage (5 cases) were 0.933 +/- 0.006, 0.789 +/- 0.045, 0.723 +/- 0.033, and 0.488 +/- 0.094, respectively. The difference between the mean values of each group was statistically significant (P less than 0.05). LHL15 correlated well with classical indicators for hepatic functional capacity such as serum albumin level, serum bilirubin level, prothrombin time, ICG R15 or Child-Turcotte criteria score. Our preliminary experiences of high correlations of TcGSA functional imaging data with clinical data suggest that the dynamic data using this receptor-binding radiopharmaceutical provides invaluable information with regard to liver function, and thus, the TcGSA study is potentially a noninvasive practical tool to measure functioning hepatocyte mass.

Asialoglycoprotein Receptor↗

PubMed1986

A comparative study on the effects of inhibitors of the lipoxygenase pathway on neutrophil function. Inhibitory effects on neutrophil function may not be attributed to inhibition of the lipoxygenase pathway.

The effects of five inhibitors of the lipoxygenase pathway were evaluated on oxygen radical production, degranulation, chemotaxis, leukotriene B4 (LTB4) production by neutrophils. The lipoxygenase inhibitors tested were nordihydroguaiaretic acid (NDGA), esculetin, eicosatetraynoic acid (ETYA), 2-(12-hydroxydodeca-5,10-diynyl)-3,5,6-trimethyl-1,4-benzoqu inone (AA-861), and 6,9-deepoxy-6, 9-(phenylimino)-delta 6.8-prostaglandin I1 (U-60,257). Neutrophils were activated by n-formyl-methionyl-leucyl-phenylalanine (fMLP), phorbol myristate acetate (PMA), A23187, or platelet activating factor (PAF). The effects of these inhibitors on NADPH oxidase activity and phospholipase A2 activity of isolated particulate fraction of neutrophils were also evaluated. ETYA inhibited neutrophil function induced by all the stimulators except PMA. AA-681 was unique in that it did not inhibit PAF-induced neutrophil activation. U-60,257 had virtually no effect on oxygen radical production and degranulation, but chemotaxis was moderately suppressed. NDGA effectively inhibited neutrophil function, except for chemotaxis. Esculetin inhibited only oxygen radical production, but this was due to inhibition on NADPH oxidase activity of neutrophil membrane. The inhibitory effect on neutrophil function and that of LTB4 production were not closely correlated. It is suggested that lipoxygenase inhibitors may modify neutrophil function by the mechanism not involving the lipoxygenase pathway. It is also suggested that LTB4 may not be a mediator in neutrophil oxygen radical production and degranulation induced by the stimulators used in the present study.

5,8,11,14-Eicosatetraynoic Acid↗

PubMed1990

Functional substitution of the basic domain of the HIV-1 trans-activator, Tat, with the basic domain of the functionally heterologous Rev.

The tat gene of HIV is a strong activator of the viral LTR. The Tat protein contains a highly basic domain that is important for its transport to the nuclear/nucleolar locations. The Tat basic domain when fused to Escherichia coli beta-galactosidase directed the chimeric protein to the nucleus and nucleolus. Tat mutants lacking the entire basic domain were severely defective in trans-activation. Substitution of the basic domain of Tat with that of the functionally unrelated HIV-1 Rev protein targeted the chimeric protein to the nucleolus and restored the function of Tat. In contrast, substitution with the nuclear targeting signal (NLS) of SV40 T antigen targeted the chimeric protein to the nucleus and accumulation in the nucleolar region was excluded. The Tat-NLS chimeric protein did not restore the trans-activation function of Tat efficiently. These results indicate that the arginine-rich basic domain of the trans-activator, Tat, and post-transcriptional trans-regulator, Rev, are functionally similar with regard to trans-activation of HIV-1 LTR.

Amino Acid Sequence↗

PubMed1991

Phenotypic and functional characteristics of activated CD8+ cells: a CD11b-CD28- subset mediates noncytolytic functional suppression.

Freshly isolated human CD8+ cells can be divided into mutually exclusive subsets bearing the phenotypes CD11b+(CD28-) or CD28+(CD11b-). We found that activation of CD8+ cells with anti-CD3 mAb and IL-2 preferentially expanded the CD11b-(CD28+) subset. This subset, when separated and activated independently, mediated both functional suppression and lectin-dependent cell cytotoxicity (LDCC). CD28- cells, prepared by elimination of the CD 28+ cells from expanded unfractionated CD8+ cell cultures, retained functional suppressor activity but demonstrated reduced LDCC compared to either the CD28+(CD11b-)-enriched fraction or the unfractionated CD8+ population. The majority of the CD28- cells were also CD11b-, reflecting the observation that initially CD11b+ cells lose CD11b expression following activation with anti-CD3 mAb and IL-2. Our results therefore indicate that CD8+ cells deriving from the CD11b+CD28- subset, but expressing neither CD11b nor CD28 after activation, represent the main noncytotoxic functional suppressor cell in the mitogen "activated" suppressor assay. The preferential expansion of CD8+CD28+ cells relative to CD8+CD28- cells, if occurring in vivo in the central nervous system (CNS) compartment, would be consistent with observed phenotypic analysis of cerebrospinal fluid-derived T cells and might contribute to the reduced functional suppressor activity previously found for CNS compared to peripheral blood-derived lymphocytes.

Antibodies, Monoclonal↗

PubMed2026

Divergent PXR function in seals: Endocrine adaptation or functional loss?

Seals accumulate xenobiotics through dietary biomagnification and exposure to polluted marine environments, with contaminants concentrating in their blubber. Biotransformation mitigates xenobiotic toxicity by converting lipophilic compounds into excretable hydrophilic metabolites, a process coordinated by nuclear receptors including the Pregnane X Receptor (PXR), whose plastic ligand-binding domain enables broad xenobiotic sensing. By examining PXR in pinnipeds, we investigated the evolutionary conservation and functional characterization of PXR using genomic sequence analysis, protein structural prediction, and transactivation assays, revealing broadly conserved structural features alongside species-specific functional divergence in receptor responsiveness to environmental stressors. Specifically, the obtained results highlight divergent gene and functional landscapes with ORF-disrupting mutations identified in Monachus monachus and Neomonachus schauinslandi that abolish receptor activation toward known PXR ligands. In contrast, Leptonychotes weddelli retained an intact PXR ORF but showed reduced receptor activity, revealing functional divergence in PXR among pinnipeds.

Biotransformation↗

PubMed1988

A transcription-translation activation feedback circuit as a function of protein degradation, with the quality of protein mass adaptation related to the average functional load.

The balance between protein synthesis and degradation, and between active skeletal muscle cell hypertrophy and atrophy can be described as a function of protein degradation rate by a transcription-translation activation control loop. Transcription activity is presumed to be determined by the concentration of protein-specific fragments (PSF) occurring as intermediate products of protein degradation. If PSF acts as an apoinducer at the gene or operon enhancer region, formation and dissociation of PSF-enhancer complex, as a function of PSF concentration, determines the gene or operon transcription activity. The assumed regulation can be converted to a mathematical model that allows simulation of steady-state protein balance and active adaptation, according to the level of functional activity. The relationship between steady-state transcription activity and PSF concentration can be described by Michaelis-Menten or weak sigmoidicity kinetics. Similar dependency is presumed in translation activity as a function of mRNA concentration. The relationship of protein to mRNA, PSF and ribosome content, and their formation and degradation, are determined by first-order differential equations. The assumed regulation scheme may also contribute to the theory of transcription activation, and can be used to explain the mechanism determining active adaptation in living systems.

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