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PubMed1986

In vivo treatment with anti-I-A antibodies: differential effects on Ia antigens and antigen-presenting cell function of spleen cells and epidermal Langerhans cells.

The in vivo activation of T cells by a variety of antigens can be inhibited by the administration of anti-I-A antibodies (Ab) at the time of antigen priming. This inhibition can partially be explained by the temporary loss of Ia molecules from Ia-bearing antigen-presenting cells (APC) in the spleen. In this study, the effects of i.p. injected monoclonal Ab specific for I-A glycoproteins of different H-2 haplotypes on Ia antigen expression and APC function of spleen cells and epidermal Langerhans cells were compared. It was found that anti-I-A Ab quickly bound to both spleen cell and Langerhans cell Ia antigens. Although spleen cell Ia antigens were modulated and thus temporarily disappeared, Ia antigen expression by epidermal Langerhans cells was not modulated. In functional studies, the capacity of spleen cells and epidermal cells from anti-I-A Ab treated vs control animals to function as APC for antigen-specific, I-A- or I-E-restricted T cell clones was tested. A single injection of anti-I-A Ab completely abolished the APC function of spleen cells as shown in several inbred mouse strains, F1 animals, and with the use of several different Ab and T cell clones. In contrast, Langerhans cell-dependent APC function of epidermal cells remained completely unaltered. Even multiple injections of high doses of Ab never caused any inhibition of Langerhans cell function. Experiments with anti-I-Ak or anti-I-Ad Ab in an (H-2k X H-2d)F1 animal showed abrogation of APC function of spleen cells, but again not of Langerhans cells. Thus in vivo anti-I-A Ab administration appears to differentially affect Ia antigen expression and APC function from spleen and epidermis: Ia antigens are modulated from spleen cells but not from epidermis, and APC function disappears in the spleen but not in the epidermis. The abrogation of splenic but not of Langerhans cell APC function with anti-I-A Ab will facilitate the dissection of the relative contributions of Langerhans cells as compared with other APC in the generation of cutaneous immune responses.

Animals↗

PubMed1995

Psychosocial functioning and subjective experience in schizophrenia: a reanalysis.

Data collected by Brekke et al. (1993) on the symptomatology, psychosocial functioning, and subjective experience of schizophrenia outpatients were reanalyzed using LISREL to elucidate a causal model that would depict the functional relationships between the variables. The model that best fit the data parallels another model tested previously on cardiac patients and shows that subjective experience is much more influenced by symptomatology than by social functioning. This confirms Brekke et al.'s main finding. The implications of these results for intervention and for future research are considered.

Activities of Daily Living↗

PubMedDate not supplied

Interleukin-2-induced proliferation of CD4-CD8- human thymocytes. In vitro expression of CD3 and CD8 antigens and cytolytic activity.

Human thymocytes lacking both CD4 and CD8 differentiation antigens were prepared by treating total thymocyte suspensions with a mixture of anti-CD4 and anti-CD8 monoclonal antibodies and complement. The resulting populations contained less than 2% CD4+, CD8+ or WT31+ cells and variable percentages (less than 20%) of CD3+ cells. These cell populations were cultured in recombinant IL-2 in the presence of peripheral blood mononuclear cells as feeder cells. Cells underwent extensive proliferation accompanied by a progressive increase of CD3+ and CD8+ cells. On the other hand, appearance of neither WT31+, alpha/beta-positive T cell receptor (TCR), nor CD4+ cells could be observed in several independent experiments. Functional analyses revealed the appearance and the progressive increase of cytolytic activity against the natural killer (NK)-sensitive K562 cells as well as the NK-resistant fresh melanoma cells. Experiments of T cell cloning indicated that both the expression of CD8 and CD3 antigens and the appearance of cytolytic activity were consequent to cell maturation occurring at the level of CD4-CD8- non-cytolytic cell precursors. In these experiments, more than 30% of cells underwent clonal expansion and all the clonal progenies obtained displayed cytolytic activity and expressed the CD3+WT31- surface phenotype. The expression of CD8 was variable, whereas no CD4+ clones could be obtained. Cells expressing such surface phenotype are known to belong to the TCR gamma-positive T lymphocyte subset lacking the typical alpha/beta TCR and thus appear to be the only T cell type capable of in vitro proliferation and maturation under easily reproducible culture conditions.

Antigens, Differentiation, T-Lymphocyte↗

PubMed1994

CD27: marker and mediator of T-cell activation?

CD27 is a lymphocyte-specific member of the tumour necrosis factor receptor (TNF-R) family, expression of which is tightly regulated during T-cell ontogeny. Recently, the ligand for CD27 was identified and was shown to be identical to CD70, a novel member of the TNF family. Functional experiments show that the interaction between CD27 and its ligand generates a co-stimulatory signal for T-cell activation. Here, Rogier Hintzen and colleagues integrate the phenotypic and functional data available on CD27 and its ligand, and propose a role for CD27 in the amplification of T-cell responses.

Animals↗

PubMed1990

Functional impairment in Mexican Americans and non-Hispanic whites with diabetes.

There are virtually no data available describing the functional status of diabetic individuals. We therefore measured functional status using the Sickness Impact Profile (SIP) in 393 diabetic subjects and 486 nondiabetic control subjects identified from the San Antonio Heart Study, a population-based study of diabetes among Mexican Americans and non-Hispanic whites. The SIP is a validated instrument that assesses the presence of health-related behavior changes and activity restrictions in 12 different categories. Functional impairment, defined as a SIP score of 2.0% or greater, was present among 36.6% of diabetic subjects. Following adjustments for age, Mexican Americans were 1.63 times more likely to experience functional impairment that non-Hispanic whites, although this difference was not statistically significant (95% confidence interval: 0.92-2.89). The categories in which subjects experienced impairment varied widely, but the category with the highest prevalence of impairment was "eating" (greater than 40%). The prevalence of functional impairment was 45.9% among diabetic subjects with vascular complications, 31.8% among diabetic subjects without complications, and 16.7% among nondiabetic control subjects. Among all diabetic subjects impairment increased with age, duration of diabetes, fasting glucose, and BMI, and with insulin use and the presence of hypertension. In a multiple logistic regression model these factors (with the exception of insulin use) remained associated with the presence of functional impairment even after adjustment for the presence of vascular complications. If the factors responsible for this excess of functional impairment can be identified, an intervention might be designed which can lead to improvement in the quality of life for diabetic individuals.

Adult↗

PubMed1995

Pharmacological implications of inward rectifier K+ channels regulation by cytoplasmic polyamines.

The powerful combination of molecular biology and electrophysiology has allowed extraordinary progress in the field of ion channel structure-function. In fact, only 10 years have passed since the first amino acid sequence of a voltage-dependent ion channel, the Na+ channel, was deduced [1], and already the structural domains involved in ion channel permeation, block and gating have been identified in many channel types. Despite this progress, in most cases the correlation between specific domains and ion channel function is still speculative at present, due to the absence of direct structural information [2]. In this review we will describe recent progress in the field of structure-function of one class of K+ channels, the inward rectifiers (IRKs). In particular, we will review the sequences of structure-function experiments which have led to the discovery of a novel regulation of IRKs by cytoplasmic organic polycationic substances like polyamines (PAs). This discovery represents a paradigm for how structure-function information has preceded and made possible the identification of physiological mechanisms of ion channel regulation. Owing to the important role played by IRKs in the regulation of resting membrane potential, a major determinant of cellular transport and volume [3], and to the established link between PAs and cell growth and division, the direct regulation of IRKs by PAs assumes a critical importance for the pharmacological control of cell growth and neoplastic transformation.

Animals↗

PubMed1996

Simultaneous activation of granulocytes and extrathymic T cells in number and function by excessive administration of nonsteroidal anti-inflammatory drugs.

Nonsteroidal anti-inflammatory drugs (NSAIDs) sometimes show serious side effects such as damage to the gastroduodenal mucosa and dysfunction of the liver. Although many investigators have focused on some types of leukocytes, a comprehensive study concerning all types of leukocytes, especially recently identified extrathymic T cells, remains to be done. When mice were treated with an intraperitoneal injection of indomethacin (50 or 300 microg/mouse), the number of thymocytes decreased while the number of MNC in various peripheral organs increased. This increase in MNC was due mainly to the increase in the numbers of granulocytes and extrathymic T cells. Reflecting thymic atrophy, the proportion of thymus-derived T cells distributed in the periphery decreased. The use of other NSAIDs revealed that granulocytosis seen in the periphery arose from a selective activation of myelomonocytic cells in the bone marrow. Some functional experiments using the Ca2+ influx, iNOS mRNA expression, and autoreactive cytotoxicity as indicators suggested that granulocytes and extrathymic T cells were in activated states not only in number but also in function. Since both granulocytes and extrathymic T cells become cytotoxic effectors against self-tissues or self-cells when overactivated, these activated leukocytes may be intimately related to the etiology of the tissue damage inducible by NSAIDs (i.e., adverse drug reaction).

Animals↗

PubMedDate not supplied

[The effect of the removal of the pancreas and its resection on prostatic function].

Endogenic and/or exogenic pancreatic dysfunction as a result of chronic diseases or surgery have been detected in 87 patients with prostatic lesions. To specify the effect of hypo- and apancreatic conditions on prostatic structure and function experiments have been performed on 71 dogs. The animals were subjected to radical or partial pancreatectomy. The postoperative histological and histometric examination of the prostate provided evidence for the dependence of prostatic morphology and function on pancreatic performance. Both endo- and exogenic disorders of the pancreas can give rise to prostatopathy, carbohydrate dystrophy, formation of cysts, prostatic sclerosis. The above facts should be taken into consideration by clinicians.

Animals↗

PubMed1983

The spatial resolution of a rotating gamma camera tomographic facility.

An important feature determining the spatial resolution in transverse sections reconstructed by convolution and back-projection is the frequency filter corresponding to the convolution kernel. Equations have been derived giving the theoretical spatial resolution, for a perfect detector and noise-free data, using four filter functions. Experiments have shown that physical constraints will always limit the resolution that can be achieved with a given system. The experiments indicate that the region of the frequency spectrum between KN/2 and KN where KN is the Nyquist frequency does not contribute significantly to resolution. In order to investigate the physical effect of these filter functions, the spatial resolution of reconstructed images obtained with a GE 400T rotating gamma camera has been measured. The results obtained serve as an aid to choosing appropriate reconstruction filters for use with a rotating gamma camera system.

Air↗

PubMed1991

The cultural context of polio biographies.

Cultural contexts influence the ways individuals interpret and experience functional losses associated with post-polio sequelae. Using in-depth multiple interview case studies from two National Institute on Aging projects, the concept of "biographies" is presented to place the individuals' polio-related experiences within the context of their lives. Two major cultural contexts shape the construction of polio biographies: normative life course expectations and developmental tasks; and traditions associated with polio recovery and rehabilitation. The authors identify key dimensions of personal concern among polio survivors that can be used as entrance points for effective clinical intervention and to promote treatment compliance.

Activities of Daily Living↗

PubMed1984

Activation of cytotoxic activity of human blood lymphocytes by tumor-promoting compounds.

Three categories of tumor promoters and chemically related but inactive substances were tested for their effect on the cytotoxic activity of human blood lymphocytes against K562 and Daudi targets. Lymphocytes incubated overnight in the presence of phorbol esters 12-O-tetradecanoylphorbol-13-acetate and phorbol-12,13-dibutyrate [P(Bu)2] had enhanced function. Incubation with 4-alpha-phorbol-12,13-didecanoate was without effect. Enhancing activity was also exerted by the indole alkaloids, teleocidin and lyngbyatoxin A, and the polyacetates, aplysiatoxin and debromoaplysiatoxin, but not by dihydroteleocidin. Only the tumor-promoting compounds activated the cytotoxic potential. The substances acted in a dose-dependent manner with optimal activity at characteristic concentrations. Overnight incubation of lymphocytes at 4 degrees did not change their spontaneous cytotoxicity but abolished the enhancing effect of P(Bu)2. Thus, P(Bu)2-induced activation occurred only on metabolically active cells. The activation did not require DNA synthesis. Similar to controls, the P(Bu)2-treated cells required divalent cations and an intact cytoskeleton in order to perform their lytic function. Experiments with the various metabolic inhibitors indicate that phorbol ester treatment does not induce an alternative cytotoxic mechanism since, as with untreated lymphocytes, P(Bu)2-activated cells require contact with the target and intact secretory functions. The enhanced cytolytic potential was not due to induction of alpha-interferon (IFN-alpha) production, as shown by the fact that the effect was not abolished by addition of anti-IFN antibodies during the P(Bu)2 treatment of lymphocytes or during the cytotoxic assay. However, the presence of antiserum against IFN reduced the cytotoxic potential of control cells, suggesting that endogenous IFN production contributes to the maintenance of lytic function in cultured cells. If this mechanism is counteracted by addition of anti-IFN serum, the phorbol esters can provide an alternative activation signal. When P(Bu)2-activated lymphocytes were subsequently treated with IFN-alpha or IFN-gamma, their lytic capacity was further increased. These results indicate that P(Bu)2 and IFN activate cytotoxic potential through different pathways.

Burkitt Lymphoma↗

PubMed1994

Social and emotional functions in facial expression and communication: the readout hypothesis.

Fridlund (Fridlund, A.J. (1991). Biological Psychology, 32, 3-100) has argued that facial displays are specific to intent and context, rather than being readouts of underlying motivational-emotional states. This paper responds that these views are not incompatible, and that subjective emotional experience functions in part to enhance the learned control of emotional expression and communication. It summarizes the readout position, answers Fridlund's criticisms identifying it with the different notion of "spillover," and contends that the expressive readout functions in spontaneous communication. Fridlund's assertions that the readout is a reflex-like process, and that the readout view has ignored the receiver's coevolutionary role in communication, are addressed. Evidence supporting the readout view is presented, including studies suggesting that there are hierarchically organized neurochemical systems underlying subjective, expressive, and peripheral physiological responses. Such primary motivational-emotional systems (primes) are basic to the readout theory.

Animals↗

PubMed1983

Psychosocial and cognitive function after commissurotomy for intractable seizures.

Cerebral commissurotomy appears to be an effective treatment for persons with severe epilepsy that has not responded to pharmacological treatment. Psychosocial and neuropsychological evaluation of eight patients who have received this surgical treatment suggests that patients who have an uncomplicated operative and postoperative course do not experience functionally significant intellectual, emotional, or social impairment. Limiting the operation to extraventricular division of the corpus callosum may significantly reduce postoperative morbidity. The authors suggest ethical guidelines which they believe should be carefully followed when epileptic patients are being considered for this type of surgery.

Cognition↗

PubMed1995

Role of syntaxin in mouse pancreatic beta cells.

The role of syntaxin 1, a protein involved in the docking of synaptic vesicles at presynaptic active zones, has been investigated in pancreatic islet cells. Using two different monoclonal antibodies we have shown that syntaxin 1 is present in the pancreatic islet cell microsomal fraction. Furthermore, functional experiments demonstrate that anti-syntaxin antibodies inhibit CA(2+)-dependent insulin secretion in permeabilized islet cells. These data indicate that syntaxin 1 is present in the pancreatic beta cell and it is likely to play a functional role in the exocytosis of secretory granules.

Animals↗

PubMed1988

Steroid-induced enhancement of functional recovery of postischemic, reperfused myocardium in conscious dogs.

The effects of methylprednisolone sodium succinate (20 mg/kg, intravenously administered) on the time course of functional recovery of myocardium following a 15-minute coronary artery occlusion period and subsequent 5 hour reperfusion period were studied in chronically instrumented, conscious dogs. In comparison to a control group, animals receiving methylprednisolone 90 minutes prior to coronary occlusion demonstrated less depression of regional segment shortening following 15 minutes of reperfusion (52 +/- 13% vs control levels of 23 +/- 7% of preocclusion values) and improved recovery at 5 hours postreperfusion (106 +/- 6% vs control levels of 54 +/- 4% of preocclusion values). In animals receiving methylprednisolone immediately prior to reperfusion, there was also similar recovery of segment shortening at 5 hours (97 +/- 3%). In contrast, dogs receiving methylprednisolone 15 minutes after the onset of reperfusion or sodium succinate (5.5 mg/kg, intravenously administered) 90 minutes prior to occlusion demonstrated no improvement in recovery of function. Experiments in dogs not subjected to coronary occlusion documented that methylprednisolone sodium succinate lacked inotropic and vasodilator properties. The results suggest that methylprednisolone administered prior to or during coronary artery occlusion but not after reperfusion enhances the functional recovery of hypokinetic, postischemic, reperfused myocardium. These effects are unrelated to any direct hemodynamic action of steroids or to the sodium succinate salt.

Animals↗

PubMed1993

Characterization of muscarinic receptors in guinea-pig uterus.

To characterize the muscarinic receptor present in guinea-pig uterus smooth muscle the affinities of a series of 27 muscarinic receptor antagonists for M1 (rat cortex), M2 (rat heart), M3 (rat submandibular gland), m4 (transfected in CHO cells) and muscarinic binding sites in guinea-pig uterus smooth muscle were determined in radioligand binding studies. In addition, functional experiments were performed to assess pKB values of the antagonist for muscarinic receptors in guinea-pig atrium and uterus. The results obtained are consistent with the presence of M2 receptors in the uterus through which the functional contractile response is mediated. Correlation coefficients of 0.98, 0.91 and 0.91 were calculated for the following linear regressions: pKi uterus vs. pKi M2, pKB uterus vs. pKi M2 and pKB uterus vs. pKB atrium. This study also revealed that the compounds dicyclomine, DAU 5884, DAU 6202 as well as AQ-RA 721 could distinguish m4 from M2 sites and are therefore important tools to characterize muscarinic receptor subtypes. In addition, DAU 5884 and DAU 6202 have been identified as highly potent M1 selective antagonists.

Animals↗

PubMed1981

Functional effectiveness of a myo-electric prosthesis compared with a functional split-hook prosthesis: a single subject experiment.

The functional effectiveness of a myo-electric prosthesis with sensory feedback compared with that of a split-hook is described. Thirty independent observations were made on a single subject with a right below-elbow amputation wearing the myo-electric prosthesis and the split-hook prosthesis. Using a first order autoregressive model for making inferences about the two sets of data, the split-hook was found to be functionally better (p less than 0.001) than the myo-electric prosthesis. Functional effectiveness was defined operationally as scores on the Minnesota Rate of Manipulation Placing Test and the Smith Test of Hand Function. No predictions are made regarding the use of either prosthesis for other amputees. However clinical evidence suggested suitability of the myo-electric prosthesis with sensory feedback for some other functional tasks.

Adult↗

PubMed2026

MYBL2 promotes malignant phenotypes and M2-like macrophage polarization through CCL2 in non-small cell lung cancer.

Hub genes associated with non-small cell lung cancer (NSCLC) were identified through bioinformatics screening. In vitro experiments analyzed the potential mechanisms by which these genes regulate tumor malignant phenotypes and macrophage polarization. Differentially expressed genes were identified from The Cancer Genome Atlas (TCGA)-NSCLC and GSE32175 datasets, followed by protein-protein interaction (PPI) network analysis to screen hub genes. The effects of MYB Proto-Oncogene Like 2 (MYBL2) on NSCLC progression and macrophage polarization were evaluated using in vitro models. The regulatory relationship between MYBL2 and C-C motif chemokine ligand 2 (CCL2) was investigated by Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays, and rescue experiments were performed to validate the role of the MYBL2-CCL2 axis. Bioinformatics screening identified BUB1B, CDCA2 and MYBL2 as key hub genes with high expression in NSCLC, among which MYBL2 was significantly upregulated in NSCLC cells. Functional experiments confirmed that MYBL2 silencing markedly inhibited the malignant proliferation, migration and invasion of NSCLC cells. Tumor cell MYBL2 knockdown effectively reversed M2-like polarization and promoted M1-like polarization in the co-culture system. Mechanistically, MYBL2 directly bound to the CCL2 promoter region to enhance CCL2 transcriptional activity and upregulate CCL2 expression in NSCLC cells. Exogenous CCL2 supplementation significantly rescued the inhibitory effect of MYBL2 knockdown on macrophage M2-like polarization, verifying the mediating role of CCL2 in this regulatory axis. MYBL2 is strongly expressed in NSCLC cells and is associated with enhanced malignant phenotypes. It may affect macrophage M2-like polarization by upregulating CCL2, thus participating in NSCLC immune microenvironment remodeling.

CCL2↗