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Exploring the emerging concept of precision rehabilitation: a qualitative study.

PURPOSE: This descriptive qualitative study explored knowledge users' perspectives on precision rehabilitation concepts, barriers, facilitators, and future directions as part of a convergent mixed methods scoping review. MATERIALS AND METHODS: Sixteen clinicians, administrators, and researchers from three North American tertiary care rehabilitation centers were recruited using convenience and snowball sampling to participate in individual semi-structured interviews. Conventional qualitative content analysis followed a deductive thematic approach based on predetermined categories. RESULTS: Analyses revealed three main themes: (1) Although precision rehabilitation shares foundational concepts with precision medicine, there are certain elements, such as personalization, that are uniquely expressed; (2) Rehabilitation-specific facilitators to precision approaches include the use of unobtrusive technology to collect large amounts of data in real-world contexts, while barriers include rehabilitation's typically small, heterogeneous sample sizes; and (3) The future of precision rehabilitation will require collaborative data-sharing to focus on determining care trajectories that enhance functional outcomes. CONCLUSION: Findings provide the first qualitative synthesis of knowledge users perspectives to complement quantitative evidence and inform the emerging field of precision rehabilitation.

Humans

Yersinia pestis: correlation of ultrastructures and immunological status.

Ultrastructural identification and localization of the fraction 1 "envelope" antigen in the plague bacillus Yersinia pestis were the primary objectives of this brief study. The antigenicity of extra-cellular material between the bacilli in undisturbed cultured colonies and that of the pathogen per se were measured and correlated by means of the semi quantitative complement fixation method after incubation for 72 h at 37 C. When the amount of extracellular substance in wild-type T1 (virulent) bacteria was compared by electron microscopy with that in avirulent strains of Y. pestis, with and without passage through guinea pigs, we found that the material of interest was greatly attenuated or even absent in colonies that had not been passed through animals, whereas passage markedly augmented production of the material. We also explored the requirement for larger quantities of Ca(2+) and Mg(2+) in the culture media and discovered that without these ions production of the extracellular material was limited. These observations support the hypothesis that this extracellular substance between cultured Y. pestis bacilli of various strains represents the source of the fraction 1 envelope antigen.

Antigens, Bacterial

Genetic analysis of bacteriophage phi 29 of Bacillus subtilis: integration and mapping of reference mutants of two collections.

Reference mutants of Bacillus subtilis phage phi 29 of the Madrid and Minneapolis collections were employed to construct a genetic map. Suppressor-sensitive and temperature-sensitive mutants were assigned to 17 cistrons by quantitative complementation. Three-factor crosses were used to assign an unambiguous order for the 17 cistrons. Recombination frequencies determined by two-factor crosses were used to construct a linear genetic map of 24.4 recombination units. The genes were numbered sequentially from left to right (1 to 17) according to their relative map position.

Bacillus subtilis

Antigenic determinants of bovine myelin encephalitogenic protein recognized by rabbit antibody to myelin encephalitogenic protein.

The antigenic determinants of bovine myelin encephalitogenic protein were investigated by quantitative complement fixation and hapten inhibition using rabbit anti-monkey protein and anti-bovine protein and purified and characterized fragments of bovine protein. The two regions of bovine encephalitogenic protein containing determinants were sequences 1 to 43 and 90 to 170. One rabbit antiserum recognized a determinant(s) probably in residues 15 to 40 while for another rabbit antiserum the determinant of 1 to 43 resided in 1 to 20. The determinant(s) of residues 90 to 170 involved the region around the tryptophan at position 116. Fragment 44-89, which contains the major encephalitogenic determinant for the rabbit, was virtually devoid of any reactivity with the rabbit anti-encephalitogenic protein. It appears that portions of the protein other than the encephalitogenic site are responsible for stimulation of bone marrow-derived cells and antibody production. In demonstrating selected regions of the protein as sites for antigenic determinants, the present immunochemical studies also suggest that the protein might have a more folded conformational alignment than previously suspected.

Amino Acids

Antigenic similarity of morphologic type CIII1 bacteriophages.

The aim of the study was to demonstrate antigenic differentiation among bacteriophages belonging to the same morphologic type--CIII1 according to Krzywy and Slopek or A2 according to Ackermann. Twenty-six bacteriophages which multiplied on various strains of bacteria of the genera Escherichia, Shigella and Klebsiella, were studied. Serologic tests were done by the quantitative complement fixation test. Immune sera against 5 phi E. coli. D8 Sh. flexneri, G35 Sh. sonnei and Kl7 Klebsiella bacteriophages were obtained from rabbits. It was shown that bacteriophages of CIII1 morphologic type, with morphologically identical virion had different antigenic specificity. On the basis of results obtained the phages could be divided into eight serologic groups. The bacteriophages for which antisera were obtained belonged to four different serologic groups. All bacteriophages had some common antigens with 5 phi E. coli phage. The similarity points to a phylogenetic relationship among phages of CIII1 morphologic type.

Antibodies, Viral

Quantitation of antibody-complement mediated lysis of tumor cells.

An assay for quantitating antibody-complement mediated killing based on the release of 125I from 125IUdR labelled target cell is described. The temporal delay between antibody--complement damage and the release of nuclear material was shortened by treatment of the cells with a combination of trypsin and DNase. This treatment increased the rate of release of the labelled nuclear material from damaged cells without causing labelled nuclear material to be released from undamaged cells. The low level of spontaneous release of 125I from the target cells allows this assay to be used for experiments carried out over long time periods or in experiments involving extensive manipulations of the cells.

Animals

Immunologic studies in hypersensitivity pneumonitis--quantitative precipitins and complement-fixing antibodies in symptomatic and asymptomatic pigeon breeders.

Quantitative precipitation and complement fixation tests were performed on sera from a group of patients with hypersensitivity pneumonitis (pigeon breeders' disease). Their antibody levels were compared to a selected group of similarly exposed but asymptomatic subjects. The quantity of precipitating antibodies was generally greater in serum from symptomatic breeders, although quantities in the serum from some of the asymptomatic subjects were greater than that seen in ill breeders. Complement-fixing antibodies were detected in the serum of both groups. Here again, complement-fixing activity was generally greater in the serum of ill breeders. However, one asymptomatic breeder showed complement-fixing activity greater than most of the symptomatic breeder group. These findings indicate that the presence of complement-fixing antibodies per se in serum to pigeon gamma-globulin is not sufficient to cause the symptoms of pigeon breeders' disease. We suggest that other factor(s) may be involved, such as lgE- or cell-mediated hypersensitivity.

Animals

Comparison of several in vitro assay methods for the quantitative determination of complement consumption ('binding') by gammaglobulin preparations.

Unspecifically induced activation of Complement (C) in solution can be caused either by denatured Ig molecules and by polymeric aggregates of same or more specifically by antigen-antibody complexes. As a quality criteria, e.g. for i.v.-IgG preparations, it is agreed by the majority of people concerned that the activation of C via the classical pathway might not be unspecifically initiated. Therefore, the generally used assay systems are based on quantitating the degree of consumption of C undergoing an antigen-independent, 'frustrated' activation via the classical pathway. There are principally two different types of test modifications which were investigated: a) C is being kept constant and protein is diluted or b) protein is being kept constant and C is titrated. When a group of differing IgG preparations or IgG fragments was assayed for its so-called 'anticomplementary' activity in various already described test methods, the particular test results from the individual test methods could not unequivocally be compared with each other because some of the methods had not been optimized with regard to the amount of reagents or test substance used; only a rough estimate of the data was obtained. The value of the not standardized assays remains, therefore, questionable reasonably good and reproducible results are obtained when the amount in particular of C added as well as its quality have been adequately optimized and standardized. This allows a refined differentiation of various IgG preparations by a reliable and unadjusted quantitation of C consumption. If for example, inappropriate and not optimized rations of C amboceptor (e.g. slight C excess) was used, a suppressed C consumption was found. It seems advisable to accept prophylactic testing of anticomplementary activity for quality control as one out of several other in vitro and in vivo parameters which potentially might predict safety for the patient, the physician, and also for the producer. However, it is agreed that, irrespective of in vitro tests, in vivo testing in animals and clinical proof of safety is undoubtedly needed.

Animals

Quantitation of serum complement components and plasma C3d in patients with malignant lymphoma: relation to the stage of the tumor and circulating immune complexes.

Total hemolytic complement activity (CH 50) and complement component levels were measured in 27 patients with Hodgkin's disease and 31 patients with non-Hodgkin malignant lymphoma. CH 50 values were higher than normal in almost all the patients. Increased levels of serum C4, C3 and factor B were observed in 62%, 31% and 19% of these patients, respectively. However, plasma concentration of C3d, a breakdown product of C3, was elevated in 29% of the cases. The hypercatabolism of C3 was not closely associated with the presence of circulating immune complexes, as assessed by the C1q binding assay, nor with the presence of general symptoms in the patients. On the contrary, it appeared to be in relation with the extent of the malignant disease.

Adolescent

Direct demonstration and quantitation of the first complement component in human serum.

The first component of complement, C1, can be demonstrated and quantitated in normal and pathological human serums by simple immunochemical techniques. All of the C1q, C1r, and C1s detected in normal serum was found to be in the C1 complex. A simple modification of these methods permitted the quantitation of free C1s in the presence of macromolecular C1, a technique which may prove useful in screening pathological serums.

Calcium

A complement fixation method for quantitative differentiation of reactions to 45/20 vaccine and Brucella infection.

Brucella complement fixing antibodies may be titrated independently in adult vaccinated (strain 45/20) and in naturally infected cattle by serological tests utilizing a specially prepared antigen. Serum samples are subjected to the standard complement fixation test for the diagnosis of brucellosis (MacKinnon 1963) and subsequently retested by the same method but with a saline extract antigen prepared from strain 45/20 Brucella abortus. The results obtained in the two tests are compared in five specific categories of brucella reactors. An evaluation and discussion of the test method, on the basis of the results obtained, indicates that informed diagnoses can be made in parallel with a continuous adult vaccination programme.

Animals

Complement components in normal serum and plasma quantitated by electroimmunoassay.

Sjöholm, A. G. Complement Components in Normal Serum and Plasma Quantitated by Electroimmunoassay. Scand. J. Immunol. 4, 25-30, 1975. The concentrations of C1q, C1s, C3, C4, C5, C3 proactivator, and C1 inactivator in serum and EDTA plasma from 100 normal adults were determined by electroimmunoassay. The normal range of each of the proteins is given. The C1q values varied more closely with the C1s values than with the levels of the other complement components. C3, C5, and C3 proactivator seemed to form a fairly interdependent group. The reproducibility of double determinations (interplate variation) was 4.9% to 7.9%. The variation of the complement component levels on repeated sampling from normal individuals was investigated. Also, repeated freezeing and thawing and storage at room temperature of serum and plasma were studied for their effect on the quantitation of the complement components. C3 and C4 values obtained by electroimmunoassay were in agreement with the values obtained by single radial immunodiffusion.

Adult

The quantitation of alternative pathway complement function by timed lysis assay.

A simple timed lysis assay is described for quantifying haemolytic complement activity in human serum. Classical pathway complement function was determined by measuring the time taken to lyse 50% of a standard suspension of antibody-coated sheep erythrocytes; the time required for 50% lysis of a standard rabbit erythrocyte suspension was similarly used to evaluate alternative pathway function. Because target erythrocytes prepared on different days gave slightly different 50% lysis times, it was necessary first to construct a series of calibration curves for converting 50% lysis times into CH50 U/ml. For this purpose, a range of dilutions of the standard human serum, of known haemolytic activity, was tested against erythrocytes prepared on 10 separate occasions. The standard serum was subsequently included with each batch of unknown sera and used to select the appropriate calibration curve for direct conversion of the 50% lysis time into CH50 U/ml. Eleven samples of normal human serum were tested by both the timed lysis assay and by the dilution methods of Mayer (1971) (classical) and Platts-Mills and Ishizaka (1974) (alternative pathway). Comparable results were obtained in all cases.

Animals

Gingival fluid and serum in periodontal diseases. I. Quantitative study of immunoglobulins, complement components, and other plasma proteins.

1. Gingival fluid from severely inflamed periodontal tissue represents a 15 to 30% dilution of serum with respect to the proteins studied, with the exception of C3 and in some subjects, C4. 2. A marked decrease in C3 levels is found in most, if not all, gingival fluids, and a marked decrease of C4 levels is found in some gingival fluids. This suggests that complement might be activated during periodontal inflammation. 3. The concentrations of proteins in the gingival fluid are not related to their molecular weight.

Blood Proteins

Factors affecting assay of myoglobin by complement fixation or immunodiffusion.

Quantitative micro-scale complement-fixation and semi-quantitative gel immunodiffusion assays for myoglobin have been evaluated experimentally and used to measure myoglobin in the sera of more than 1500 patients. We report certain problems, observations, and methodological improvements. Serum caused enhancement of precipitin lines in the immunodiffusion assay. In the complement-fixation assay, serum interfered both by enhancing or inhibiting complement fixation. Suggested modifications in the complement-fixation assay are: (a) routine threefold or greater dilution of serum with buffer and (b) use of serum-based rather than buffer-based calibration materials in preparing standard curves. Three cycles of freeze-thaw of serum or buffer decreased detectable myoglobin by 50-100%. We conclude that certain serum-related factors and freeze-thaw phenomena are important causes of error in immunological assays for myoglobin.

Complement Fixation Tests