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PubMed1994

[Clinical studies of kidney function in sheep. II. Effect of pregnancy, lactation and feed restriction and metabolic diseases on kidney function].

Investigations of renal function have been done in healthy ewes in different stages of reproduction, and after food restriction, as well as in ewes sick with ketosis, hypocalcemia, rumen acidosis and different nephropathies. The determination was based on the estimated weight dependent endogenous creatinine excretion (E). A reference population of 56 healthy non or early pregnant ewes (before day 120 of pregnancy) was used as control. Late pregnancy (121.-149. day, n = 14) and lactation (n = 14) lead to higher renal creatinine-clearance (approximately GFR). Food restriction in all stages of pregnancy was followed by lower plasma concentrations of potassium, calcium, magnesium and glucose, and a reduced fractional excretion of potassium, calcium and magnesium. Pregnancy and especially food restriction caused a marked rise of the 3-OH-hydroxybutyrate values in the plasma and a significant acetonuria. After withdrawal of feed in lactating sheep, in opposition to pregnant sheep, the plasma values of phosphate were higher. In ketotic sheep (n = 43) a failure of renal function could not be demonstrated, the pronounced acetonuria could be explained by acetonemia. In hypocalcemia (n = 23) disturbance of creatinine-clearance and tubular reabsorption of sodium, potassium, glucose and 3-OH-butyrate could be seen. Glucosuria and acetonuria were caused by increased plasma concentrations and reduced tubular reabsorption. In rumen acidosis (n = 10) disturbances of low degree of GFR and reabsorption could be seen, glucosuria was mainly due to hyperglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

[Physiologic validation of the method of functional hearing tests for evaluation of hearing function].

Physiological validation is presented for application of ototopicometry. This method is intended for measurements of minimal recognizable angles of a moving sound object localization in several space planes. Quantitative characteristics of ototopical function in healthy subjects upon localization of various sound stimuli are described. Ototopicometry is proposed as an additional audiological test for functional assessment of the acoustic human system.

Adolescent↗

PubMed1993

[The effect of disorders of thrombocyte functional activity on the microcirculatory status in the lungs and on external respiratory function in patients with aspirin-induced asthma].

Platelet aggregation, pulmonary microcirculation and external respiration were studied against clinical appearance of the disease in 20 patients with aspirin-sensitive asthma (ASA) and 10 asthmatics without aspirin intolerance. All ASA patients were found to exhibit higher intensity and rate of platelet aggregation induced by ATP and heparin. Capillary pulmonary circulation in them was decreased 2-fold compared to nonaspirin asthma patients. All ASA cases had obstructive impairment of pulmonary ventilation in peripheral bronchi. The more serious were defects in platelet function, the more significant were microcirculatory and external respiratory alterations in ASA. Thus, it is evident that changes in platelet function play an important role in the genesis of pulmonary microcirculation and external respiration affections in ASA patients.

Adult↗

PubMed1994

Erythropoietin structure-function relationships. Identification of functionally important domains.

In order to delineate functionally important domains in erythropoietin (Epo), we have prepared and tested a series of amino acid replacements at 51 conserved sites predicted to be on the surface of the molecule. Alanine replacements permitted preservation of alpha-helical structure. Wild type and mutant Epo cDNAs were transiently expressed at high levels in COS1 and COS7 cells. The biological activity of wild type and mutant Epos was assayed in three Epo-responsive cell types: primary murine erythroid spleen cells, the murine HCD57 erythroleukemia cell line, and the human UT7-EPO leukemia cell line. When Arg14 on predicted Helix A was replaced by Ala, biological activity was substantially reduced, whereas replacement with Glu resulted in total loss of specific bioactivity. In a similar manner, the mutein Arg103-->Ala in Helix C was completely lacking in biological activity, whereas both Ser104-->Ala and Leu108-->Ala had decreased bioactivity. In Helix D, the mutein Gly151-->Ala had markedly decreased bioactivity, whereas that of the adjacent Lys152-->Ala mutein was moderately impaired. In contrast, Ala replacements at three nearby sites on Helix D (147, 146, and 143) resulted in muteins with increased bioactivity. In conclusion, our mutagenesis experiments have identified functionally important domains on the surface of the Epo molecule, at sites comparable with those established for other cytokines.

Amino Acid Sequence↗

PubMed1976

The structure and function of immunoglobulin domains. IV. The distribution of some effector functions among the Cgamma2 and Cgamma3 homology regions of human immunoglobulin G1.

The fragments related to the Cgamma2 and Cgamma3 homology regions of human IgG, described in the preceding paper by Ellerson, et al. were assayed for their ability to interact with complement, engage in cytophilic activity toward macrophages, and to play a role in controlling the catabolism of the whole IgG. The Cgamma2-fragment retained about 3% of the activity of intact IgG in a whole complement-fixing assay in which the test proteins were absorbed as mono-layers onto polystyrene latex beads. However, in a fluid-phase C1-binding assay this fragment showed the same activity as IgG and Fc fragment, when compared on a molar basis. Since the Cgamma2-fragment represented only one intact domain, full expression of complement-fixing activity appeared to be independent of quaternary interactions. Thus IgG possesses two C1-binding sites. The Cgamma3-fragment was inactive in both of the complement assays. The ability of IgG to interact with the Fc-receptor on guinea-pig macrophages was shown to be entirely a function of the Cgamma3 region. This was demonstrated both in a direct assay in which tanned red cells coated with Cgamma3-fragment formed rosettes with macrophages and in an indirect assay in which this fragment was able to inhibit rosette formation between IgG-coated red cells and macrophages. The rate of clearance of radiolabeled Cgamma2-, Cgamma3-, Fab, Fc fragments, and IgG from the circulation was measured in rabbits. The Cgamma2 fragment was cleared with a half-time similar to that shown by intact IgG and Fc (about 70 hr) whereas Cgamma3- and Fab fragments were cleared more rapidly (half-time, about 15 hr). The rate of cleaance was not related to the presence of sialic acid or exposed galactosyl residues at the termini of the carbohydrate prosthetic groups. These data clearly show that at least three of the biologic functions of IgG are mediated fully and independently by one or other of the Fc domains.

Animals↗

PubMed1996

Functional inactivation in mice of the gene for the interleukin-3 (IL-3)-specific receptor beta-chain: implications for IL-3 function and the mechanism of receptor transmodulation in hematopoietic cells.

The receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 and -5 (IL-3, IL-5) share a common signaling subunit (beta c). However, in the mouse, IL-3 can also use an alternative IL-3-specific receptor beta-chain (beta IL-3). To assess the relative contributions of beta c and beta IL-3 to IL-3 receptor formation and function, mice were generated in which the beta IL-3 gene was functionally inactivated by replacement of exons 9-13 with a neomycin resistance cassette. Bone marrow cells from these mice displayed a lower affinity IL-3 receptor than normal and were hyporesponsive to IL-3, but the mice displayed no obvious hematopoietic abnormalities. The data suggested that beta c and beta IL-3 are normally coexpressed on IL-3-responsive cells and have identical qualitative signaling capacities. Receptor transmodulation studies on bone marrow cells from wild-type, beta c -/-, and beta IL-3 -/- mice showed that the previously described hierarchical pattern of transmodulation was dependent on the relative numbers of both beta IL-3 and beta c receptor chains and also provided evidence for an unexpected interaction between beta c chains and G-CSF and M-CSF receptors.

Animals↗

PubMed1996

[Hannover Functional Questionnaire in ambulatory diagnosis of functional disability caused by backache].

This paper describes conceptual and clinimetric aspects as well as fields of application of the Hannover Functional Ability Questionnaire for measuring back pain-related disability (FFbH-R). The FFbH-R belongs to a series of short self-administered questionnaires for the assessment of functional limitations in activities of daily living among patients with musculoskeletal disorders. In addition to the FFbH-R, a specific version is available for patients with polyarticular diseases (the FFbH-P), as well as a combined version of both questionnaires. A new questionnaire for patients with osteoarthritis is currently being developed. Data from various studies indicate that the FFbH-R meets the relevant psychometric criteria of acceptability, reliability, validity, and sensitivity to change. It has been successfully applied in (observational and controlled) clinical studies, in epidemiologic surveys, and in compensation disability evaluation.

Activities of Daily Living↗

PubMed1996

Structural and functional characterization of OmpF porin mutants selected for larger pore size. II. Functional characterization.

The effects on the channel characteristics of four single amino acid substitutions in OmpF porin and of a deletion mutant in the constriction loop L3 have been studied. These mutations are all located in the narrow section of the channel of the protein that forms pores across the outer membrane of Escherichia coli. The single channel conductance of the deletion mutant (Delta109-114) is decreased by one third, whereas the point mutations do not exhibit significant deviations from that of the wild-type protein. The mutants exhibit drastic changes in ion selectivities. In the wild-type protein, the critical threshold potential (Vc), above which channels close reversibly, exhibits a strong pH dependence, with a titration point of approximately pH 7.7, which is abolished in all mutants studied here. Diffusion of six monosaccharides is little affected in the point mutants, while four disaccharides are taken up at highly increased rates by the deletion mutant. The functional results, presented here, are correlated to the x-ray structures of the mutants (Lou, K.-L., Saint, N., Prilipov, A., Rummel, G., Benson, S.A., Rosenbusch, J.P., and Schirmer, T. (1996) J. Biol. Chem. 271, 20669-20675). In most, but not all, cases, the structural changes explain the functional alterations observed.

Bacterial Outer Membrane Proteins↗

PubMed1995

Presence of functional P2T and P2U purinoceptors on the human megakaryoblastic cell line, Meg-01 characterization by functional and binding studies.

The platelet receptor for ADP has been classified as a P2 purinoceptor of the P2T type where ADP is the natural agonist and ATP a competitive antagonist. Since the P2T receptor seems to be specific to platelets, we investigated the possibility that the human megakaryoblastic cell line Meg-01 might express the platelet ADP receptor, using functional studies and the ADP analogue [33P]2MeSADP as a specific P2T radioligand. ADP and 2MeSADP were able to induce shape change and pseudopod formation in Meg-01 cells. [33P]2MeSADP binding to membrane preparations was saturable and specific, binding sites being of high affinity (Kd = 13 +/- 3 nM) and present at a concentration of 13 +/- 7 fmoles/mu g protein. In contrast to UTP and GTP, ADP and ATP were able to displace the specific [33P]2MeSADP binding. ADP, 2MeSADP, UTP and ATP induced a dose dependent increase in intracellular calcium concentration. Desensitization experiments demonstrated that UTP, and ADP share a common P2U purinoceptor and that Meg-01 cells also express a P2T purinoceptor for which ADP and 2MeSADP are agonists and ATP a competitive antagonist. It was concluded that the human megakaryoblastic cell line Meg-01 expresses two distinct types of functional P2 receptor; a P2U and a P2T purinoceptor. This cell line could therefore provide the necessary material to clone the as yet unidentified platelet P2T purinoceptor.

Binding, Competitive↗

PubMedDate not supplied

[Social functioning of schizophrenic patients after 15 years from the first hospitalization (Part I -- evaluation of social functioning)].

Catamnestic data concerning 109 patients, inhabitants of Warsaw-Praga, hospitalized for the first time in the years 1978-79 with schizophrenia (92 persons) or paranoid psychosis-ICD IX number 297.9 (17 persons), were collected in 1993-94. Smaller number and shorter duration of hospitalisations has been observed during 15 years, in comparison with other Polish data. Twenty persons died during the period of observation. In the group of 85 investigated persons-69% were not working at all-15% were fully and 18% partially unable to meet their basic needs on their own-29% were temporarily or permanently unable to function adequately in their marital and/or parental roles, 31% were single and childless. Taking into account the mortality among 109 observed persons (18.7% during 15 years); good prognosis according to social functioning has been found in 48.6% of the group observed at first hospitalisation.

Adolescent↗

PubMed1998

The contribution of anti-prothrombin-antibodies to lupus anticoagulant activity--discrimination between functional and non-functional anti-prothrombin-antibodies.

The presence of lupus anticoagulant (LAC) is strongly correlated with a history of thrombosis in patients with SLE. LAC activity can be caused by anti-prothrombin (FII)- and/or anti-beta2glycoprotein I (beta2GPI)-antibodies. In the present study, the contribution of anti-FII-antibodies to LAC activity was measured in 28 LAC positive plasmas. Plasmas were incubated with prothrombin or BSA, immobilized on CNBr-activated Sepharose, to absorb all anti-FII-antibodies. In 4 out of the 28 plasmas LAC activity was completely dependent on anti-FII-antibodies. In 7 out of the 28 plasmas, anti-FII-antibodies did not contribute to LAC activity. These anti-FII-antibodies can be regarded as non-functional antibodies. In the majority (17/28) of the samples, LAC activity within a single plasma was caused by a combination of antibodies with different specificities. Both dRVVT and KCT showed comparable sensitivity for the detection of functional anti-FII-antibodies. In conclusion, in most samples LAC activity is not caused by anti-FII-antibodies alone but by a combination of different types of antibodies. The presence of LAC activity and anti-FII-antibodies in one plasma does not automatically implicate that these antibodies are responsible for the LAC activity.

Antibody Specificity↗

PubMed1998

Changes in visually guided behavior of Royal College of Surgeons rats as a function of age: a histologic, morphometric, and functional study.

PURPOSE: To compare the changes in visually guided performance as a function of age between Royal College of Surgeons (RCS) dystrophic and congenic rats and to correlate photoreceptor cell number with visually guided performance in age-matched populations of RCS dystrophic rats. METHODS: The visually guided performances of RCS dystrophic (n=6) and congenic (n=7) rats were studied from 0.75 to 12 months of age using a water escape paradigm that tested their ability to find a submersed, randomly placed platform that used a light source as a clue. The time to find the platform (latency) was recorded. In age-matched dystrophic RCS rats, histopathologic changes were described and the number of photoreceptor cell nuclear profiles per midsagittal retinal section was counted. Changes with age in visually guided behavior and photoreceptor cell populations of RCS dystrophic rats then were compared. RESULTS: The latency of RCS dystrophic rats increased significantly beyond that of congenic rats after 6 months of age. Photoreceptor cell number in dystrophic rats precipitously decreased through 6 months of age, stabilized at 9 months, and decreased further at 12 months. Two unexpected results were seen in the dystrophic animals: At 6 months of age, as few as 22+/-3 photoreceptor cell nuclei per midsagittal section provided similar latencies as at 2 months when there were as many as 400. Although the number of photoreceptor cells remained stable from 6 to 9 months of age, functional vision significantly deteriorated. CONCLUSIONS: Two important phenomena were observed. First, the RCS rats performed very well in the water escape test even while their photoreceptor cell population was being decimated. Second, once a low threshold was reached, a dramatic deterioration of visually guided behavior occurred without a further reduction in photoreceptor cell numbers.

Aging↗

PubMed1993

Cardiac function and functional capacity: implications for the failing heart.

The exercise capacity of patients with congestive heart failure is determined by factors including the interaction of the right and left ventricles and their respective circulations, lung mechanics, skeletal muscle metabolism, and blood flow. Therapeutic efforts should be directed at all of the units in this complex process rather than the response of an individual system. Multiple therapeutic regimens such as nitrates and angiotensin converting enzyme inhibitors in combination with physical training and other therapies that improve pulmonary function produce optimal results. Using this holistic approach to therapy, the physician may have a beneficial impact on the exercise capacity of patients with congestive heart failure.

Blood Circulation↗

PubMed1995

Diastolic function in patients with coronary artery disease: effect of angina and heart failure functional class.

The diastolic function of left and right parts of the heart using left and right mechanocardiogram method was investigated in 69 male patients with coronary artery disease and preceding myocardial infarction and in 18 normal patients. Nine patients were in angina class I, 28 were in class II, 32 were in class III. Forty-seven patients were in heart failure class II and 22 were in class III. The duration of isometric relaxation and atrium wave in left and right mechanocardiograms was more, and rapid filling wave was less in patients after myocardial infarction than in the control group. The duration of isometric relaxation and of atrium wave in left mechanocardiogram was more, and the duration of rapid filling wave was less in patients with heart failure class III than in patients in class II. The duration of isometric relaxation was more and the duration of rapid filling wave was less in right mechanocardiogram in patients with heart failure class III than in patients in class II. The diastolic abnormalities correlate more with the severity of heart failure than the angina severity. The diastolic abnormalities in right mechanocardiogram were found in patients without clinical manifestations of right ventricle failure.

Adult↗

PubMed2026

Effects of permissive hypercapnia on intraoperative cerebral oxygenation and early postoperative cognitive function in older patients with fragile brain function during the non-acute phase undergoing laparoscopic colorectal surgery: A randomized controlled trial.

BACKGROUND AND PURPOSE: Older adults with non-acute fragile brain function (NFBF) may be particularly susceptible to perioperative disturbances in cerebral oxygenation and postoperative neurocognitive decline. Permissive hypercapnia (PHC) may enhance cerebral oxygenation, but its effects in this population remain unclear. We examined whether PHC-based ventilation improves intraoperative regional cerebral oxygen saturation (rSO2) and early postoperative cognitive outcomes in older patients with NFBF undergoing elective laparoscopic colorectal surgery. METHODS: In this single-center, single-blind randomized trial, 76 patients were assigned in a 1:1 ratio to PHC-based or conventional ventilation. The primary outcome was the absolute change in rSO2 from baseline (T0) to the end of surgery (T4). Analyses followed the intention-to-treat principle, with prespecified per-protocol sensitivity analysis. Secondary outcomes included intraoperative rSO2 trajectories, cerebral oxygen extraction-related indices, early postoperative cognitive screening, serum neuron-specific enolase and interleukin-6, and safety outcomes. RESULTS: PHC significantly increased rSO2 relative to conventional ventilation (left: adjusted mean difference [aMD] 10.64, 95% CI 8.96-12.33; right: aMD 10.16, 95% CI 8.22-12.11; both P < 0.001), with consistent sensitivity results. Repeated-measures analyses showed persistently higher intraoperative rSO2 in the PHC group. Cerebral oxygen extraction-related indices were generally lower with PHC. However, early postoperative cognitive outcomes and serum biomarkers did not differ between groups. Emergence time was modestly longer with PHC, whereas adverse events were comparable. CONCLUSIONS: PHC-based ventilation favorably modified intraoperative cerebral oxygenation and oxygen-extraction profiles but did not translate into detectable early postoperative cognitive or biomarker benefits in older adults with NFBF.

Humans↗

PubMed1998

Ventricular late potentials, interstitial fibrosis, and right ventricular function in patients with ventricular tachycardia and normal left ventricular function.

We examined 40 patients with ventricular tachycardia (VT) and no evidence of heart disease, and found a 50% prevalence of ventricular late potentials (VLPs) on the signal-averaged electrocardiogram. This finding was associated with a significantly higher content of fibrous tissue on endomyocardial biopsy and a lower right ventricular ejection fraction. Thus, VLPs are frequently found in idiopathic VT, are a marker for subclinical anatomic and functional abnormalities of the right ventricle, and may be associated with a worse outcome.

Adult↗

PubMed1987

The role of monocyte lymphocyte function-associated antigen 1 (LFA-1) in accessory cell function.

Monoclonal antibodies directed against the common beta subunit shared by lymphocyte function-associated antigen-1 (LFA-1), CR3 and p150,95 or the alpha subunit of LFA-1, inhibited the T lymphocyte proliferative response to tetanus toxoid, pokeweed mitogen-1 and OKT3 but had little or no effect on the response to the leukoagglutinating lectins pokeweed mitogen-2 and phytohemagglutinin. The LFA-1 molecule was shown to participate in the adhesive interaction between monocytes and T lymphocytes that was required for the initiation of an immune response. Both monocyte and T lymphocyte LFA-1 were found to contribute to this interaction. These results further define the part played by the LFA-1 molecule in the activation of T lymphocytes.

Adult↗

PubMed1994

Intercellular adhesion molecules (ICAM)-1 ICAM-2 and ICAM-3 function as counter-receptors for lymphocyte function-associated molecule 1 in human immunodeficiency virus-mediated syncytia formation.

It has been previously demonstrated that lymphocyte function-associated molecule 1 (LFA-1) plays a major role in human immunodeficiency virus (HIV)-mediated syncytia formation. In the present study we investigated the involvement of intercellular adhesion molecule-1 (ICAM-1), ICAM-2 and ICAM-3 in the process. The ability of monoclonal antibodies (mAb) directed against ICAM-1, ICAM-2 and ICAM-3 to block syncytia was analyzed either in phytohemagglutinin (PHA)-activated lymphocytes infected in vitro with primary or laboratory strains of HIV or by coculturing a T cell line stably expressing HIV envelope with PHA-activated lymphocytes. Complete inhibition of syncytia formation was observed only by the simultaneous addition to the cell cultures of all (i.e. anti-ICAM-1, anti-ICAM-2 and anti-ICAM-3) mAb. These results indicate that the interaction between LFA-1 and ICAM is a critical step in HIV-mediated syncytia formation, and that ICAM-1, ICAM-2 and ICAM-3 are the receptor molecules for the LFA-1-dependent syncytia formation.

Antibodies, Monoclonal↗