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Expression of HLA-B27 antigens on mononuclear leucocytes in ankylosing spondylitis.

Differences in expression of HLA-B27 antigens on immune competent cells might play a role in the susceptibility to environmental factors which may be responsible for the initiation of ankylosing spondylitis (AS). Using a quantitative complement-mediated lymphocytotoxity assay we determined the expression of HLA-B27 antigens on the membranes of mononuclear cells obtained from 20 patients with AS, four patients with other seronegative arthropathies and eight healthy controls. The variation in expression of B27 between individuals was quite extensive, but there was no significant difference in the mean titration curves obtained for each of the three groups. These findings suggest that the expression of HLA-B27 antigens on the membrane of mononuclear leucocytes does not play a role in the pathogenesis of AS.

Antigens, Surface↗

Quantitative relationships of the fourth complement component in human cerebrospinal fluid.

A technique for the measurement of cerebrospinal fluid C4 concentration in unconcentrated specimens has been developed with the methods of electroimmunodiffusion and immunofixation. The method has proved to be reproducible and requires only microliter volumes of undiluted cerebrospinal fluid (CSF). The mean value for CSF C4 concentrations in 16 neurologically normal individuals was 325 +/- 32 mug/100 ml. A positive correlation between CSF C4 concentration and the concentration of CSF albumin and total protein was observed. The positive correlation between the concentrations of CSF C4 and albumin was, however, more clearly defined than the relationship of CSF C4 to total CSF protein.

Albumins↗

The acetylcholine system in the brain of cyclostomes with special references to the telencephalon.

The distribution of cholinergic neurons is studied in the brains of cyclostomes (Lampetra fluviatilis and Myxine glutinosa) representing an early stage of vertebrate evolution. Histochemical localization of acetylcholinesterase (AChE) is complemented by quantitative determinations of acetylcholine (ACh), cholinacetyltransferase (ChAT) and AChE. The determinations are carried out in homogenates of whole brains, the brain regions telencephalon, diencephalon, mesencephalon and medulla oblongata. The telencephalon is further subdivided and studied in more detail.The transmitter distribution found in cyclostomes is compared to data from other vertebrates. Observations on the ACh-distribution in the telencephalon are discussed with the problems of identifying telencephalic homologies.

Acetylcholine↗

[Focus groups: preliminary experiences in educational health programs in Brazil].

Since 1989, the public health education section of the University of São Paulo (USP), Brazil, has been using the focus group technique to identify educational problems and evaluate programs being developed. The focus group is a research technique that allows qualitative data to be collected through group sessions involving 6 to 15 persons with some shared trait (for example, sex, age, occupation, role in the community). The group discusses various aspects of a specified subject. This paper describes five research projects in which this technique was used. The projects were carried out by professors in the School of Public Health/USP in the state of São Paulo between 1989 and 1992 with population groups and in health institutions. These experiences showed that the technique is efficient, permitting rapid identification and in-depth analysis of problems from the point of view of the population. Among the drawbacks to the technique is that it uses a small and nonrandom sample, which means that in certain cases focus groups should be considered a complement to quantitative studies. The data described here provide knowledge of perceptions, ideas, opinions, expectations, and social images-in short, the cultural and verbal universe of the population. With this information, educators and administrators can plan and evaluate education programs on the basis of the needs and views of the people they serve, putting into practice the plan to make education more democratic and responsive to the needs of its public.

Adult↗

Quantitative histologic factors for grouping childhood supratentorial neuroglial tumors.

The histologic heterogeneity of childhood supratentorial neuroglial tumors, when quantified, identifies relatively homogeneous subgroups for prognostic purposes and for assignment in clinical trials. Our sample consisted of supratentorial tumors in the Childhood Brain Tumor Consortium. The data consist of reliably identified histologic features and demographic, clinical, operative, and survival information. Factor analysis was used to identify uncorrelated "factors," each represented by a different combination of histologic features in 703 tumors. The defining histologic features were used to label each factor. The heterogeneity of each tumor was summarized using the factor scores for each factor. We compared the survival estimates of subgroups of tumors within common diagnostic classes. We identified five uncorrelated quantitative factors that accounted for much of the histologic variation. Our factor labels were Jumbo, Fibrillary, Proliferative, Spongy, an Oligodendroglial. Two thirds of tumors had high scores on two or more factors, indicating a high degree of heterogeneity among these tumors. Eighty-four percent of supratentorial tumors were accounted for by 19 nonoverlapping relatively homogeneous histologic groups. The five quantitative factors complement standard qualitative taxonomies by summarizing more completely the histologic feature aspects of a tumor than by diagnosis alone and quantify the histologic heterogeneity of individual tumors. Histologically homogeneous groups of tumors are essential for clinical trials, biologic research, and prognostic models.

Adolescent↗

Quantitative histologic factors for grouping childhood infratentorial neuroglial tumors.

We employed factors analysis to quantify the degree of histologic heterogeneity of childhood infratentorial neuroglial tumors. Our data were 26 reliably ascertained histologic features in 1068 children in the Childhood Brain Tumor Consortium database. The factor analysis identified five uncorrelated quantitative "factors," each derived from a different linear combination of the 26 histologic features, that accounted for much of the histologic variation. Histologic features differed in their importance in each factor. The most important features in each factor were used for naming using simple, histologic, familiar descriptive terms: Spongy, Proliferative, Ring, Fibrillary, and Nuclear. Each tumor has a score on each factor. Two-thirds of tumors had high scores for at least two factors, indicating frequent histologic heterogeneity among these tumors. Ninety-five percent of tumors were allocated to 1 of 11 nonoverlapping histologically homogeneous groups. The five quantitative factors complement standard qualitative taxonomies by making explicit the histologic heterogeneity or homogeneity of individual tumors and provide the pathologist with a method that takes advantage of more of the histology of each tumor than conventional nomenclatures. Histologically homogeneous groups of tumors are likely to be of value in clinical trials and biologic research. Prognostic models based on these factors have been published.

Adolescent↗

Production of ultrastructural membrane lesions by the fifth component of complement.

A direct quantitative relationship has been demonstrated between the number of cell bound C4,2 complexes or C5 molecules and the number of ultrastructural lesions visualized on the cell membrane subsequent to immune hemolysis. When bound C4,2 complexes exceeded bound C5 molecules, the number of ultrastructural lesions seen corresponded to the number of C5 molecules. However, in the reverse situation, with bound C5 molecules in excess of bound C4,2 complexes, the latter determined the number of lesions. During the complement-reaction sequence, the lesions first became visible in the nonlytic intermediate complex EAC1,4,2,3,5 and their number was unaffected when lysis was induced by C6-C9. Since the lesions were also demonstrable on the intermediate complex EC5,6,7, it is concluded that the protein C5 is responsible for their production. Once formed, the physical presence of the C5 molecule is no longer required for the manifestation of the lesions as indicated by persistence of lesions after removal of C5 protein by trypsin. The C5-dependent ultra-structural phenomenon has therefore been interpreted to represent a true structural change of the membrane which, however, is not accompanied by a permeability defect.

Animals↗

Successful plasma therapy for atypical hemolytic uremic syndrome caused by factor H deficiency owing to a novel mutation in the complement cofactor protein domain 15.

Quantitative or functional deficiency of complement factor H results in uncontrolled complement activation. This leads to thrombotic microangiopathy and finally causes renal failure (atypical hemolytic uremic syndrome [aHUS]). By regular analysis of factor H in patients with aHUS, the authors found a complete factor H deficiency in an infant in whom aHUS developed at 8 months of age. Factor H was quantified by enzyme-linked immunosorbent assay and further analyzed by Western blot using a factor H-specific antibody. Complement activation was determined by measuring total hemolytic activity of the classical (CH50) and alternative (APH50) pathways, C3 and C3d. The sequence of factor H gene was determined. Serial factor H measurements after fresh frozen plasma infusion allowed calculation of a factor H half-life. Factor H was absent in plasma (<1 mug/mL), and the complement system was highly activated (CH50, APH50, C3 decreased; C3d increased). Genetic analysis identified a novel homozygous factor H mutation (T2770A; Y899Stop) in CCP domain 15, most likely causing defective protein secretion. Time course measurements of factor H after plasma infusion established a factor H half-life of about 6 days. By repetitive plasma infusions (20 mL/kg over about 2 to 3 hours) the authors were able to interrupt the vicious circle of thrombotic microangiopathy in a factor H-deficient patient with aHUS. Based on the measured factor H half-life of about 6 days, regular plasma infusions in 2-week intervals were given, which prevented further aHUS episodes and stopped the decline of kidney function.

Complement Factor H↗

Complement-dependent cell lysis assay for quantitation of rubella antibodies.

A comparison of the capacity to detect antibody titers to rubella virus was made between the complement-dependent cell lysis (CDCL) assay and the hemagglutination inhibition (HAI) test. Titers detected by CDCL assay correlated with the HAI test. Although the CDCL assay was less convenient to conduct, it proved to be more sensitive than the HAI test.

Antibodies, Viral↗

[Current overview of diagnostic possibilities of complement analysis].

The complement system is composed of at least 21 serum proteins and 8 cell surface receptors sensitive to complement components or their fragments. Qualitative and quantitative analysis of complement components in clinical samples has become standard procedure in many laboratories thanks to the availability of easy-to-perform test kits. However, interpretation of results is still a task that requires great skill and the situation are rare, in which analysis of the complement system goes beyond diagnosis into therapeutic consequences. The present paper is an update of previous similar reviews now available in the international literature; in addition, the author attempts at bringing the often complicated world of complement and clinical practice together and thus contributes to answering the question: what should the clinician know about complement?

Antigen-Antibody Complex↗