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PubMed1984

Biologic functions of the OKT1 T cell surface antigen. I. The T1 molecule is involved in helper function.

The OKT1 (Leu-1) monoclonal antibody reacts with a 69 KD glycoprotein that is present on only a fraction of functionally mature thymocytes but is maintained on most peripheral T cells. In the study presented, we examined the role of this surface molecule in T cell function. We found that addition of the OKT1 antibody to B cells and autologous T4+ cells markedly enhances B cell differentiation. This enhancement was apparent when nonirradiated or irradiated T4+ cells but not T8+ cells were used. Moreover, the OKT1 antibody as well as the OKT1 F(ab')2 fragment enhanced B cell differentiation in a dose-dependent fashion. It is important to note that perturbation of the T1 molecule with OKT1 in the presence of autologous E- cells causes the rapid release of molecules that trigger B cells to proliferate and differentiate into Ig-secreting cells. These data when considered together suggest that OKT1 reacts with a T cell membrane determinant or a complex that is intimately involved in the execution of helper function on OKT4+ cells.

Antibodies, Monoclonal↗

PubMed1984

The structure-function relationship of I-A molecules: correlation of serologic and functional phenotypes of four I-Ak mutant cell lines.

We have isolated and characterized four mutant I-Ak-expressing cell lines derived from the B cell-B lymphoma hybrid antigen-presenting cell line TA3. The mutants were isolated by first selecting against expression of one Ak epitope by treatment with a monoclonal antibody in the presence of complement and then selecting for retention of a second Ak epitope by electronic cell-sorting of cells stained for fluorescence with a second monoclonal antibody. The serologic and functional phenotypes of the mutants were characterized by using panels of I-Ak-specific monoclonal antibodies and I-Ak-restricted T hybridomas. We obtained one Ak alpha mutant (J4) that no longer reacts with any Ak alpha-specific antibody and also is incapable of stimulating any I-Ak-restricted T hybridoma. We obtained three Ak beta mutants (LD3, K5, G1) that express a wide range of serologic and functional phenotypes. Correlation of the serologic and functional phenotypes reveals that the serologic epitope Ia.1 may overlap with a major site of T cell recognition, whereas the Ia.17 serologic epitope appears to be only a minor site for T cell recognition.

Animals↗

PubMed1983

[Mental function, functional hierarchy of the brain and glucoregulation].

Mental function in insulin-dependent diabetic (IDD) patients can be correlated with the endocrine and metabolic symptoms and signs of anxiety. In IDD patients, anxiety is usually accompanied by hyperactivity of the hyperglycemic hypothalamo-visceral axis. The hypothalamus is controlled by different superior nervous structures (limbic system and cortex) which, themselves, receive dopaminergic afferences. Two main patterns of reaction to anxiety associated with two distinct patterns of hypothalamo-visceral reactions, are suggested. In one, excessive hypothalamo-visceral reactions to stress can be associated with a deficient control of the hypothalamus. In the other, an appropriate control of the hypothalamus by limbic systems and prefrontal systems, via dopaminergic pathways, reduces the hyperglycemic reaction to stress. According to a psychosomatic approach, the principles of which are briefly recalled, some characterisation of mental function in IDD patients can be defined, as well as its psychiatric presentation. An improvement in mental function can be associated with a reduction in hypothalamic responses to the external or internal stimuli. An improvement in metabolic control can follow psychotherapy in such patients. Central dopaminergic pathways may play an important role in the control of anxiety and the subsequent endocrine and metabolic disorders caused by stress.

Blood Glucose↗

PubMed1983

[Effect of ethmozine on the automatic function of the sinus node and sinoatrial conduction in patients with normal and impaired function of the sinus node].

In this study involving 45 patients with the normal function of the sinus node and 10 patients showing signs of its damage (n-10), intravenous administration of ethmozine in a dose of 150 mg (1.5-2 mg/kg) exerted atropine like action. In four cases with dysfunction of the sinus node the drug significantly increased the time of the restoration of sinus node function. Ethmozine induced a Stage II sinoatrial block in 3 out of 10 patients with sinus node dysfunction. The above data suggest that ethmozine produces an atropine-like effect on the sinus node. In some patients with sinus node dysfunction, ethmozine may impair the function of the sinus node which calls for caution while employing the drug in such cases. The inhibitory effect of the agent on the sinoatrial conduction in the patients studied suggests that ethmozine may prove an effective antiarrhythmic drug for treating patients with paroxysmal sinoatrial tachycardia.

Adult↗

PubMed1981

Abnormalities of immunoregulation in progressive systemic sclerosis. Evidence for excess helper-cell function and altered B-cell function.

We investigated immunoregulatory function in patients with progressive systemic sclerosis (PSS) in terms of in vitro IgM synthesis. Suppressor-cell function seems normal in regard to the ability of concanavalin A-treated cells to inhibit IgM synthesis by normal cells. At 4 x 10(5) T cells to 3 x 10(5) allogeneic normal B cells per milliliter, T cells from patients with PSS induce significantly more IgM synthesis by normal B cells than do normal T cells. This increased helper T-cell function might be involved in the pathogenesis of the disease.

Adult↗

PubMed1983

Functional studies in 79-year-olds. II. Upper extremity function.

As part of the Gerontological and Geriatric Population Study of 79-year-old people in Göteborg, a representative subsample comprising 112 women and 93 men took part in a study of upper extremity function. Thirty-eight per cent of the women and 37% of the men had disorders in the upper extremities. The investigation included tests of co-ordination, static strength in the key-grip and the transversal volar grip, power capacity in opening jars and a bottle, basal movements in the upper extremities in personal hygiene and dressing activities, function in the kitchen e.g. reaching shelves, manual tasks including tests of pronation and supination of the forearm. In the key-grip as well as in the transversal volar grip men showed a generally larger decrease in strength with age than women compared to 70-year-olds in a previous population study. Significant correlations were found between strength in the key-grip and the performance time in the test of co-ordination. Women produced about 66% of the muscular force of the men when opening jars. Significant correlations were found between strength in the transversal volar grip and the maximal torque for opening the jars. Female and male subjects who were not capable of handling the electric plug in the manual ability test had significantly weaker strength in the key-grip. The importance of designing products and adapting the environment so as to correspond to the functional capacity of the elderly, is emphasized.

Activities of Daily Living↗

PubMed1982

[Evolutionistic significance of biological form-function relationship based on the example of the shoulder-blade in higher primates. II. Form and function, goal and random factor: literature].

The shoulder-blades of the monkeys are mainly constructed as a shock-absorbing platform, supporting the weight of the torso, which is hung up between the 2 forelegs in a muscle sling, composed by the M. serratus ventralis. The mobility of the arms are of less importance, although this mobility is more developed in monkeys than in other quadrupedal mammals. The shoulder-blades of the hominoids are freed from the supporting function and are mainly constructed for the mobility of the arms. Therefore all the areas are well developed, where the important arm-moving muscles originate. The constructions of the catarrhine shoulder-blades are in a very close accordance with the function. Under the modern viewpoint of scientific evolutionary theory the relation between form and function is causal and is developing in the time-space continuum. It can be shown that the thinking in categories of time, space and causality is inadequate for the understanding of the evolutionary process. The hazardness which plays an important role in the neo-darwinistic modell, where mutations occur, has to bee replaced by synchronistic phenomena. Therefore the facts of live refer empirically to the existence of the "One-beeing". According to this, evolution occurs as a psycho-physical process, which is experiencable by synchronistic phenomena in archetypical moments as a reference to a reality, which is feeling its way in a finalistic manner.

Adaptation, Physiological↗

PubMed1982

Functional heterogeneity of culture-grown bone marrow-derived macrophages. II. Lymphokine stimulation of antigen-presenting function.

The activation of immunostimulatory activity and Ia expression was studied in pure populations of murine macrophages (M phi) grown in vitro from bone marrow precursor cells in the presence of L cell-conditioned medium as the source of colony-stimulating factor. During exponential growth, the M phi developed maximal Ia-dependent antigen-presenting activity as detected by the induction of antigen-specific T cell proliferation, but the proportion of Ia+ M phi was low (less than 10%). Fractionation of the M phi according to size by velocity sedimentation resulted in concentration of the antigen-presenting cells in the smallest fraction, but the enrichment of Ia+ M phi in this fraction was less than twofold. All fractions also showed comparable degrees of antigen uptake regardless of their T cell-stimulating activity. Thus Ia and antigen, although obviously essential, are insufficient for full manifestation of antigen-presenting function. Activation of M phi with lymphokines from Mycobacterium-activated lymph node cells resulted in enhanced Ia expression in all fractions, but only small M phi showed an enhancement in antigen presentation. Large activation M phi were found to exert an immunosuppressive effect that probably neutralized any augmentation of stimulatory activity. thus heterogeneity can be demonstrated in i) the function of unstimulated M phi, ii) the responsiveness of subsets to stimulation, and iii) the manifestation of activated functions.

Animals↗

PubMed1995

[References for evaluation scales in quality assurance in rehabilitation--1. II. Measuring functional independence in rehabilitation with the Functional Independence Index].

Presented is an instrument assessing functional independence in rehabilitation. This instrument, the Functional Independence Measure (FIM), was developed in the USA and translated into German. Considerable experience and research has accumulated concerning its application, formal properties and function in interdisciplinary rehabilitation. Application and evaluation of the FIM is demonstrated in a case study. The FIM is shown to be a reliable and highly informative instrument measuring disability according to ICIDH criteria in clinical practice. It reflects reliably the amount of help and assistance required by the individual patient.

Activities of Daily Living↗

PubMed1994

The VLA-2 (alpha 2 beta 1) I domain functions as a ligand-specific recognition sequence for endothelial cell attachment and spreading: molecular and functional characterization.

The integrin VLA-2 (alpha 2 beta 1), generally considered to represent the specific collagen receptor on human endothelial cells, contains an alpha 2-subunit inserted I domain with structural similarity to the type A domains found within the recently described superfamily of receptor-ligand recognition proteins. This region of the cDNA has now been isolated and used for molecular and functional characterization of this heterodimeric receptor complex. Comparative sequence analysis with the porcine homologue revealed 93% amino acid sequence identity, suggestive of a developmentally conserved function. To complete structure/function studies, this region of the human cDNA was expressed as a chimeric protein in Escherichia coli, and a rabbit polyclonal antibody (anti-I domain) was used to study determinants of endothelial cell attachment and spreading in vitro. Quantifiable and visual disruption of endothelial cell attachment to gelatin, type I collagen, and laminin was evident using the specific anti-I domain antibody, with minimal inhibitory effects demonstrable using fibronectin or fibrinogen matrices. Therefore, these data would suggest that the alpha 2 beta 1 I domain confers ligand-binding specificity for both known alpha 2 beta 1 substrates (laminin and collagen), and that this region subserves a regulatory function in the molecular processes controlling endothelial cell attachment and spreading in vitro.

Amino Acid Sequence↗

PubMed1994

Concomitant administration of isradipine and spirapril prevents reduction of renal function induced by acute administration of spirapril in patients with reduced renal function.

Angiotensin-converting enzyme (ACE) inhibitors may cause a further decrease in renal function in patients who already have renal failure. The acute effects of the ACE inhibitor spirapril on renal function were investigated in 10 patients with mild-to-moderate renal failure (serum creatinine of 1.5-2.5 mg/dl). Acute oral administration of spirapril at 6 mg resulted in decreases in inulin clearance (from 53.7 +/- 12.8 to 44.6 +/- 8.8 ml/min; p < 0.02; n = 5) and in PAH clearances (from 215 +/- 141.9 to 184 +/- 37.8 ml/min; p < 0.006; n = 5). However, when the acute administration of 6 mg of spirapril was given concomitantly with isradipine at 5 mg, there were no changes in these renal function parameters.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1993

Function and "homing" of the lung macrophages. I. Evidence of functional heterogeneity of mobile cells of the murine lung parenchyma in the bronchoalveolar lavage (BAL).

The object of the present investigation was to extend fundamental understanding of the composition, function and origin of bronchoalveolar lavage (BAL) cells, and to reduce the considerable gaps in our existing knowledge. BAL cells from the B10.D2 mouse were identified by morphological, enzyme cytochemical and immunocytochemical methods and a further functional characterisation of macrophages was undertaken in vitro using latex phagocytosis. The possible bone marrow origin of BAL cells was investigated with a radiation chimera. The bone marrow from H2k-positive F1 mice (B10.BR x B10.D2) was transplanted into the irradiated H2k-negative parent animals. At various time intervals after transplantation, BAL cells were tested immunocytochemically for the presence of H2k-positive cells. The principal finding was that BAL cells are functionally heterogeneous. It was possible by morphological, enzyme cytochemical and immunocytochemical techniques to subdivide the total BAL cell count into 89% macrophages, 8.5% lymphocytes and 2.5% granulocytes. Only 14.3% of the macrophages expressed the corresponding epitope, and this small population could be further subdivided immunocytochemically into mature and immature (7:1) macrophages. The ability to phagocytose, which is typical of active macrophages, could be induced in vitro in only one-third of all BAL macrophages. Three-quarters of the macrophages carried the H2d antigen and 9.5% of the BAL cells were natural killer cells showing a macrophage phenotype. Subdivision of the lymphocytes showed a significant majority of T-cells (75%) to B-cells (20%), and 5% Asialo GM1-positive cells. The CD4/CD8 ratio amounted to 1.3:1 and 38% of the lymphocytes expressed on the surface the H2d antigen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

The effects of functional electrical stimulation on shoulder subluxation, arm function recovery, and shoulder pain in hemiplegic stroke patients.

The purpose of this study was to evaluate the effectiveness of a functional electrical stimulation (FES) treatment program designed to prevent glenohumeral joint stretching and subsequent subluxation and shoulder pain in stroke patients. Twenty-six recent hemiplegic stroke patients with shoulder muscle flaccidity were randomly assigned to either a control group (n = 13; 5 female, and 8 male) or experimental group (n = 13; 6 female, and 7 male). Both groups received conventional physical therapy. The experimental group received additional FES therapy where two flaccid/paralyzed shoulder muscles (supraspinatus and posterior deltoid) were induced to contract repetitively up to 6 hours a day for 6 weeks. Duration of both the FES session and muscle contraction/relaxation ratio were progressively increased as performance improved. The experimental group showed significant improvements in arm function, electromyographic activity of the posterior deltoid, range of motion, and reduction in subluxation (as indicated by x-ray) compared with the control group. We concluded that the FES program was effective in reducing the severity of shoulder subluxation and pain, and possibly facilitating recovery of arm function.

Aged↗

PubMed1993

Functional and phenotypic analysis of thymocytes in SCID mice. Evidence for functional response transitions before and after the SCID arrest point.

Thymocytes from severe combined immune deficient (SCID) mice undergo developmental arrest at an early stage, before most TCR gene rearrangement. They therefore represent a natural test case to assess those aspects of T cell development that are TCR independent. Multiparameter flow cytometry was used to analyze the array of immature phenotypes present in the SCID thymus at steady state, as defined by the markers CD4, CD5, Sca-1, NK1.1, CD44, heat-stable antigen (HSA), and IL-2R alpha. The results suggest a simple developmental block in SCID mice rather than a program of aberrant differentiation. SCID thymocytes displayed efficient, developmentally regulated functional responses. Approximately 20-25% of the cells, mostly within the IL-2R alpha +HSA+CD44low fraction, could be induced to express IL-2. This IL-2 inducibility was highly dependent on IL-1 costimulation, in agreement with the behavior of normal immature thymocytes. These results formally demonstrate that competence to express IL-2 is developed independently of TCR expression or gene rearrangement. Comparison of the response properties of various SCID thymocyte subsets indicated that IL-2 inducibility is first likely to be acquired at an early (Sca-1++CD44++HSAlow) stage. A later functional transition was revealed by comparing patterns of IL-2R alpha regulation in normal and SCID IL-2R alpha +HSA+CD44low thymocytes. The SCID thymocytes uniformly maintained IL-2R alpha expression on in vitro stimulation, whereas only a minority of the normal cells in the corresponding subset could do so unless IL-1 was also added. The SCID arrest point thus appears to separate the IL-2R alpha +HSA+CD44low stage into distinct early (TCR independent) and late phases. Normal cells that progress beyond the SCID arrest point appear to lose, rather than gain, competence to make various responses, even before they leave the IL-2R alpha +HSA+CD44low stage. A model is proposed in which discrete changes in functional competence define novel transitions in early thymocyte development, at least some of which may be linked to TCR-beta gene rearrangement before positive or negative selection.

Animals↗

PubMed1993

Structure-function analysis of the Bcl-2 oncoprotein. Addition of a heterologous transmembrane domain to portions of the Bcl-2 beta protein restores function as a regulator of cell survival.

The bcl-2 gene can potentially encode 26- and 22-kDa proteins that differ only in their carboxyl tails because of an alternative splicing mechanism. The larger of these proteins contains a hydrophobic transmembrane domain within its carboxyl terminus, resides (at least in part) in mitochondrial membranes and has been shown to prolong cell survival by blocking programmed cell death (also termed "apoptosis"). To explore the function of the shorter 22-kDa Bcl-2 protein that lacks a transmembrane domain, DNAs encoding p26-Bcl-2-alpha or p22-Bcl-2-beta were expressed in an interleukin-3 (IL-3)-dependent hematopoietic cell line 32D. In contrast to p26-Bcl-2 alpha that markedly prolonged cell survival, p22-Bcl-2-beta did not extend the survival of 32D cells when cultured in the absence of IL-3. Expression in 32D cells of a chimeric DNA that fused portions of the open reading frame common to Bcl-2-alpha and Bcl-2-beta (amino-acids 1-195) with sequences encoding the transmembrane and cytosolic domains of the IL-2 receptor-alpha protein resulted in production of a Bcl-2/IL-2R fusion protein that was capable of prolonging 32D cell survival in the setting of IL-3 withdrawal. Based on fractionation of cells to produce crude heavy membrane, light membrane, nuclei, and cytosolic preparations, much of the p22-Bcl-2-beta protein appeared to reside in the cytosol, whereas Bcl-2-alpha and the Bcl-2/IL-2R chimeric proteins were found exclusively in fractions that also contained the inner mitochondrial membrane protein F1-beta-ATPase. Taken together, these findings demonstrate the importance of membrane association for the function and intracellular targeting of the apoptosis-blocking Bcl-2 protein. Furthermore, despite the strong evolutionary conservation of the carboxyl regions of Bcl-2-alpha proteins observed previously for mammalian and avian species, these data suggest that a heterologous transmembrane domain can be substituted without loss of function.

Amino Acid Sequence↗

PubMed1996

[Functional MRI: imaging of motor cortex function].

OBJECTIVE: To image the motor cortex with functional MRI (fMRI), and locate the activated area with the proportional grid of Talairach. DESIGN: Descriptive. SETTING: St. Radboud Academic Hospital Nijmegen. METHODS: In ten volunteers functional images of the motor cortex were made during execution of a motor task (finger movements). From the functional images the positions of activated areas were calculated using the 3D Talairach grid system. RESULTS: fMRI of the motor cortex was possible using a 1.5 T MRI scanner. Task activation of the motor cortex gave a signal increase in Brodmann's area 4, the precentral gyrus. CONCLUSION: Imaging of the active motor cortex with fMRI is feasible. The use of the 3D Talairach proportional grid system for the calculation of the position of an activated area in the motor cortex is possible with adequate accuracy.

Adult↗

PubMed1996

[Anatomico-functional correlations between the pulmonary and portal circulations: the prerequisites for a modern functional imaging diagnosis].

This study was aimed at investigating the current knowledge on the similarities between pulmonary and portal circulation to try to improve the diagnostic capabilities of functional radiology in these two districts. These two organs are similar both from an anatomical and a functional viewpoints, sharing the same microarchitecture and a double vascular system with similar hemodynamic characteristics. In the past, the parameters to evaluate pulmonary flow and pressure consisted in the analysis of the distribution, diameter and number of vessels with conventional radiology, but today, HRCT permits the regional assessment of perfusion and air volume, using density values. Dynamic density changes (expiratory and prone scanning), together with the morphological features of peripheral bronchial and vascular structures, play a fundamental diagnostic role in differentiating small airway conditions from normal and hemodynamic changes. When HRCT shows a "mosaic" pattern--i.e., regions with different density values--reduced perfusion can be distinguished, because in this case hypodense areas are vascularized by fewer, and smaller, vessels. Expiratory scanning can exclude abnormal ventilation. Hyperperfusion is characterized by higher density areas vascularized by more, and bigger, vessels. Doppler US and MRA show, once again, their limitations in calculating the absolute values of flow velocity and flow volume in the splanchnic district; in clinical studies, only the semiquantitative data yielded by Doppler US are considered reliable. Therefore, also in this district, relative data must be preferred to absolute ones; for instance, it is interesting to analyze the hemodynamic changes occurring in patients under different physiologic or experimental conditions. We believe that, in the near future, technological progress and growing operators' skills will make functional radiology a major tool helping the clinician approach and treat these patients correctly.

Humans↗

PubMed1996

[Functional reliability and functional reserves of a flyer].

The paper shows the notions and approaches to evaluating an operator's functional reliability during his professional activity. By using an original approach to testing the functional reserves, i.e. defining the range of mental and physiological responses during activities, the authors propose a criterion apparatus, models and approaches to automating diagnosis and prediction of functional reliability.

Adult↗