PubMed Health⌕ Search

Biomedical subjects

I J Check

Publications and source records attributed to I J Check.

At least 37 records · Page 2Linked to original sources
PubMed1989

Human immunoglobulin G and immunoglobulin G subclasses: biochemical, genetic, and clinical aspects.

Human IgG consists of two identical heavy (H) chains and two identical light (L) chains joined by interchain disulfide bridges. Heterogeneity in the amino acid sequences of the H and L polypeptides results in at least three types of IgG variants at the structural and genetic levels. The four isotypic forms are IgG1, IgG2, IgG3, and IgG4, which share extensive homologies in the primary structure of their H chains. As a result, the subclasses cross-react antigenically, but they can be differentiated on the basis of subtle architectural dissimilarities. The biological and effector properties of the IgG isotypes have been associated, in part, with their structural differences. Genes determining the synthesis of human IgG heavy chains are located on chromosome 14. In several clinical situations the isotypes appear to be regulated or expressed in patterns reflecting the gene arrangement. The numeric designations of the subclasses correspond to the order of their proportional amounts in healthy adult serum: IgG1 greater than IgG2 greater than IgG3 greater than IgG4. Awareness of the importance of the roles of the four IgG isotypes in human health has steadily increased since they were first described in the 1960s. The recognition that deficits or increases in selected IgG subclasses may have clinical consequences has prompted considerable interest in quantifying the four isotypes in clinical specimens. In particular, deficiencies of IgG2, IgG3, and IgG4, singly or combined, are associated with chronic infections which may not be readily recognized in otherwise healthy people with normal serum total IgG concentrations. Different assay methods using polyclonal or monoclonal antisera with various calibrants have been applied; however, no standardized method exists at the present. IgG deficits are associated with gene defects and are acquired in secondary immunodeficiencies in conjunction with other disorders. IgG isotype selectivity has been recognized in autoimmune diseases and in response to carbohydrate and protein antigens derived from pathogenic microorganisms and common allergens.

Dysgammaglobulinemia↗
PubMed1987

Analysis of homogeneity of alveolitis in pulmonary sarcoidosis by bilateral bronchoalveolar lavage, gallium-67 lung uptake, and chest radiograph.

The use of unilateral lobar bronchoalveolar lavage (BAL) to assess disease activity in pulmonary sarcoidosis assumes that the alveolitis is homogeneous throughout the lung parenchyma. Three studies were used to evaluate this premise in 21 patients with sarcoidosis who had a broad range of abnormalities: bilateral BAL cell counts, quantitated regional gallium-67 lung uptake, and analysis of chest radiographs. Based on results of these studies, we conclude that the alveolitis in sarcoidosis is homogeneous in the majority of patients, although lavage of the lingula may give erroneous results due to the frequently increased proportion of neutrophils. The only moderate level of correlation between the BAL % lymphocytes and gallium-67 lung uptake, even when the same regions of the lung are studied, suggests that these tests may measure different aspects of disease activity.

Adult↗
PubMed1986

Densitometric quantitation of high resolution agarose gel protein electrophoresis.

The authors developed a cost-effective procedure for high-resolution protein electrophoresis in agarose gel which results in electrophoretic patterns that can be both visually interpreted and densitometrically quantitated. Unique features include the development of special molds for the preparation of several gels simultaneously and the combination of chemical with densitometric procedures to accurately quantitate the protein fractions in both normal and pathologic sera. Since the albumin concentrations obtained by densitometric scan of either cellulose acetate or agarose gel were erratic with respect to colorimetric (ACA) or immunochemical (ICS) measurements, the authors incorporated colorimetric measurements of albumin and total protein with densitometric quantitation of the electrophoretic bands into an algorithm for calculating protein concentrations. The densitometric quantitation of the gamma globulin fractions compared well with the sum of the immunochemically determined IgG and IgM concentrations (r = 0.98). Alpha and beta globulins were calculated using mathematically adjusted densitometric scan percentages and the total alpha and beta globulin protein concentration. The agarose gel procedure was more sensitive than cellulose acetate in the detection of paraprotein bands in a comparison of 93 sera containing paraproteins.

Blood Protein Electrophoresis↗
PubMed1986

Systemic and lung protein changes in sarcoidosis. Lymphocyte counts, gallium uptake values, and serum angiotensin-converting enzyme levels may reflect different aspects of disease activity.

BAL lymphocyte percentages, quantitated gallium-67 lung uptake, and SACE levels have all been proposed as measures of disease activity in sarcoidosis. We analyzed 32 paired sera and BAL fluids from sarcoidosis patients by high-resolution agarose electrophoresis to look for protein changes characteristic of systemic or local inflammation and compared the results with those from the above tests. Nine patients (group 1) had serum inflammatory protein changes and increased total protein, albumin, beta 1-globulin (transferrin), and gamma-globulin levels in fluid recovered by BAL. Thirteen patients (group 2) had normal protein levels in sera but abnormal protein levels in BAL specimens. Ten patients (group 3) had normal protein levels in sera and in BAL specimens. Patients in groups 1 and 2 had a disproportionate increase in beta 1-globulin (transferrin) and gamma-globulin levels in their BAL specimens. The BAL lymphocyte percentage changes paralleled the BAL protein level changes, suggesting relationships among the immunoregulatory role of these cells, increased local immunoglobulin synthesis, and the pathogenesis of altered alveolar permeability. Gallium-67 uptake was highest in patients with serum inflammatory protein changes. Thus, systemic inflammation may facilitate pulmonary gallium-67 uptake, possibly by changes in BAL fluid or serum transferrin saturation and/or kinetics. SACE levels showed no relationship to changes in the levels of serum or BAL proteins. These data suggest that the various proposed measures of disease activity reflect different aspects of inflammation in sarcoidosis.

Blood Protein Electrophoresis↗
PubMed1986

Comparison of clinical parameters, bronchoalveolar lavage, gallium-67 lung uptake, and serum angiotensin converting enzyme in assessing the activity of sarcoidosis.

A major problem in pulmonary sarcoidosis is the assessment of disease activity. We established a clinical score system composed of degree of dyspnea, chest radiographic stage, forced vital capacity, and clinical assessment of disease activity (normal = 0, maximum = 16). We evaluated this score in 50 patients with sarcoidosis along with other proposed measures of disease activity: bronchoalveolar lavage percent lymphocytes (% lymphs), Gallium-67 lung uptake measured as total lung to background ratio (TL/B ratio), and serum angiotensin converting enzyme (SACE) levels. The patients we studied had an average clinical score of 5.6 +/- 2.7 (+/- SD). Though bronchoalveolar lavage % lymphs (32 +/- 20%), TL/B ratio (192 +/- 73), and SACE (137 +/- 66) were all significantly elevated in these patients, Gallium-67 uptake was most frequently abnormal (80% of patients). However, the TL/B ratio was higher in smokers (231 +/- 91) than nonsmokers (178 +/- 64, p less than 0.05). There was no correlation between our clinical score, or any part of the clinical score, and other laboratory measures of alveolitis. Bronchoalveolar lavage % lymphs and TL/B ratio correlated weakly (n = 50, r = 0.36, p less than 0.02), while % lymphs and SACE correlated less well (n = 29, r = 0.36, p = 0.051). There was no correlation between TB/L ratio and SACE.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Bronchoalveolar lavage cell differential in the diagnosis of sarcoid interstitial lung disease. Likelihood ratios based on computerized data base.

With the use of a microcomputer, the authors prospectively stored the bronchoalveolar lavage (BAL) cell differential counts from 208 patients undergoing initial evaluation for chronic interstitial lung disease. Sarcoidosis subsequently was diagnosed in 46% of these patients; the remainder had several other etiologies of their lung disease. The BAL lymphocyte count did not allow for clear separation between these two groups. To facilitate the interpretation of the BAL percent lymphocyte data, the authors applied a modification of Bayes' theorem to calculate likelihood ratios for the differential diagnosis of sarcoidosis versus other interstitial lung disease. These values ranged from 0.15 for patients with less than 6% lymphocytes to 3.5 when more than 40% lymphocytes were found. Similar results were obtained with a subsequent, independently analyzed group of 46 patients. To provide a more meaningful interpretation of the BAL fluid lymphocyte count, the authors designed a reporting scheme that includes both a written description and a graphic representation of the likelihood ratio. Prospective collection of data using microcomputers should extend this useful form of reporting to additional laboratory studies.

Bayes Theorem↗
PubMed1985

Prediction of therapeutic response in steroid-treated pulmonary sarcoidosis. Evaluation of clinical parameters, bronchoalveolar lavage, gallium-67 lung scanning, and serum angiotensin-converting enzyme levels.

To find a pretreatment predictor of steroid responsiveness in pulmonary sarcoidosis we studied 21 patients before and after steroid treatment by clinical evaluation, pulmonary function tests, bronchoalveolar lavage (BAL), gallium-67 lung scan, and serum angiotensin-converting enzyme (SACE) level. Although clinical score, forced vital capacity (FVC), BAL percent lymphocytes (% lymphs), quantitated gallium-67 lung uptake, and SACE levels all improved with therapy, only the pretreatment BAL % lymphs correlated with the improvement in FVC (r = 0.47, p less than 0.05). Pretreatment BAL % lymphs of greater than or equal to 35% predicted improvement in FVC of 10/11 patients, whereas among 10 patients with BAL % lymphs less than 35%, 5 patients improved and 5 deteriorated. Clinical score, pulmonary function parameters, quantitated gallium-67 lung uptake, and SACE level used alone, in combination with BAL % lymphs or in combination with each other, did not improve this predictive value. We conclude that steroid therapy improves a number of clinical and laboratory parameters in sarcoidosis, but only the pretreatment BAL % lymphs are useful in predicting therapeutic responsiveness.

Adult↗
PubMed1985

Monoclonal antibody-based solid-phase immunoenzymometric assays for quantifying human immunoglobulin G and its subclasses in serum.

We developed quantitative immunoenzymometric assays for human IgG and its subclasses by using monoclonal antibodies, an avidin-biotin detection system and, as the calibrant, the U.S. National Reference Preparation for Specific Human Proteins. The assays are sensitive (detecting as little as 6 micrograms/L), precise (average inter-assay CV less than 11%), and vary linearly with concentrations over a five- to 10-fold range, depending on the monoclonal antibody. We evaluated 22 different monoclonal antibodies, many of which remained highly reactive when immobilized in wells of microtiter plates coated with bovine serum albumin-glutaraldehyde to "capture" total IgG or subclasses of IgG in the sample. We demonstrated the specificity of the most reactive antibodies by using a panel of 20 purified myeloma proteins. The sum of IgG subclass concentrations correlated well (r = 0.84, p less than 0.001) with the total IgG measured in sera from 63 apparently healthy adults (26 men, 37 women). We estimated 95 percentile reference intervals for the immunoglobulins in these subjects and determined the following mean percentage distributions of IgG subclasses: IgG1 49, IgG2 33, IgG3 9, and IgG4 7. The availability of these assays should facilitate studies of the clinical significance of the subclasses.

Adult↗
PubMed1985

Quantitation of apo-, mono-, and diferric transferrin by polyacrylamide gradient gel electrophoresis in patients with disorders of iron metabolism.

We have developed a polyacrylamide gradient gel electrophoretic method to quantitate apo-, mono-, and diferric transferrin based upon differences in their molecular size. Purified transferrin saturated to different extents (3% to 98%) with iron showed proportions of the three forms as predicted from an approximately random distribution of iron between the two metal-binding sites. The iron distributions in sera of 14 normal individuals similarly correlated with the predicted values. In contrast, 22 of 43 patients with diseases associated with abnormalities in iron or transferrin metabolism had a disproportionate increase in monoferric transferrin. This abnormality occurred in seven of nine patients who had received bone marrow transplants, seven of 14 with chronic liver disease, and eight of nine menstruating women with probable iron deficiency anemia. Interestingly, 11 patients with malabsorption or chronic renal disease had normal iron distributions. The finding of abnormal distributions of iron on transferrin suggests that gradient gel analysis may be a useful tool for studying the physiologic mechanisms controlling iron utilization.

Anemia, Hypochromic↗
PubMed1984

Decreased serum transferrin concentration in children with the nephrotic syndrome: effect on lymphocyte proliferation and correlation with serum immunoglobulin levels.

Recent evidence suggests that transferrin has immunoregulatory functions. In the nephrotic syndrome, excessive urinary losses can produce hypotransferrinemia. Whether low serum transferrin concentration in children with the nephrotic syndrome is related to their decreased immunoglobulin concentrations and to the decreased in vitro response of lymphocytes to a mitogen was studied. Twenty patients, 2 to 15 years of age, were studied. Fifteen patients had the nephrotic syndrome and 5 had other renal disorders. Of 13 patients with nephrotic syndrome in relapse, serum transferrin and gamma-globulin concentrations were decreased in 10 and 11 patients, respectively. Transferrin levels correlated with the concentrations of total protein (r = 0.87, P less than 0.001), albumin (r = 0.91, P less than 0.001), and gamma-globulin (r = 0.78, P less than 0.001). Urinary electrophoretic analyses suggested that hypogammaglobulinemia was not explained simply by urinary losses. In order to determine whether decreased serum transferrin concentrations might limit immunoglobulin synthesis, the effect of hypotransferrinemic sera on lymphocyte proliferation in vitro was tested. At low concentrations of serum, tritiated thymidine uptake was directly proportional to the serum transferrin concentration (r = 0.86, P less than 0.001 at 0.02% serum concentration). Addition of transferrin completely restored the ability of patients' sera to support lymphocyte proliferation. These results suggest that hypotransferrinemia might influence in vivo lymphocyte function and immunity in the nephrotic syndrome.

Adolescent↗
PubMed1984

T-cell imbalance in neutropenia of uncertain etiology.

The authors studied 16 consecutive patients with chronic neutropenia of uncertain etiology in whom bone marrow biopsies were performed. Using monoclonal antibodies, they measured the levels of the two major subclasses of T lymphocytes, cells with the T-suppressor/cytotoxic cell phenotype (Ts), and cells with the T helper/inducer cell phenotype (Th) in the blood of eight of these patients. Five patients had Ts lymphocytosis or increased proportions of Ts cells and Th lymphocytopenia. All five patients had greatly increased proportions of large lymphocytes with prominent cytoplasmic azurophilic granules. Since cells with similar morphology from normal individuals have been shown to express cytotoxic activities, the authors measured the cytotoxic function of cells from three of the patients with Ts lymphocytosis. All three possessed antibody-dependent cell-mediated cytotoxicity (ADCC) but not natural killer (NK) cell activity. Many patients had evidence of autoimmune disorders, conditions in which Ts cells usually are decreased. None had hypogammaglobulinemia, a disorder that has been associated with increased Ts activity. The high incidence of an imbalance in T lymphocyte subpopulations in patients with neutropenia suggests that disturbed immunoregulation involving T cells may play an important role in the pathogenesis of this disorder.

Adult↗
PubMed1984

Agarose electrophoresis and immunonephelometric quantitation of cerebrospinal fluid immunoglobulins: criteria for application in the diagnosis of neurologic disease.

The cerebrospinal fluid (CSF) IgG index, the CSF to serum albumin ratio, and electrophoresis on agarose gel of CSF and serum were evaluated retrospectively for their usefulness in the differential diagnosis of multiple sclerosis (MS). Standardized procedures were adopted for grading the intensity of oligoclonal banding and for the certainty of diagnosis of MS. One hundred and forty-nine patients were studied, including 23 with definite multiple sclerosis (MS), 12 with probable MS, 20 with possible MS, 20 with inflammatory neurologic disease, 65 with noninflammatory neurologic disease, and nine with no neurologic disease. The CSF IgG index and the CSF to serum albumin ratio were calculated from nephelometric measurements of serum and CSF IgG and albumin. The intensity of oligoclonal banding was graded relative to the density of the prealbumin band. Eighty-eight per cent of cases of definite MS had distinct oligoclonal bands, and an equal number had an elevated IgG index. These tests were not specific for MS, however, since 50% of cases of inflammatory neurologic disease and 5% of those with noninflammatory neurologic disease had an elevated IgG index. Similarly, 48% of cases with inflammatory disease and 25% with noninflammatory disease had oligoclonal bands. However, only patients with definite MS (21%) or possible MS (4%) had prominent oligoclonal bands whose density was greater than or equal to that of prealbumin, together with a CSF IgG index greater than 1.50. This combination of findings therefore may enhance the level of suspicion of MS. By contrast, an isolated increase in the CSF to serum albumin ratio may suggest a diagnosis other than MS.

Albumins↗
PubMed1984

Assessing the activity of sarcoidosis: quantitative 67Ga-citrate imaging.

Three different methods of quantitating 67Ga-citrate lung images--a visual index, a computer-assisted index, and the total-lung-to-background ratio--were compared in 71 studies of patients with biopsy-proven sarcoidosis. Fifty consecutive cases were analyzed independently by two different observers using all three methods. In 45 patients, both gallium lung scans and bronchoalveolar lavage were performed within 2 weeks. In these studies, each index was correlated with the cell differential in the bronchoalveolar lavage fluid. The total-lung-to-background ratio proved to be the simplest to perform; correlated best with the original visual index (r = 0.81, p less than 0.00001) and the percentage of lymphocytes obtained in bronchoalveolar lavage fluid (r = 0.39, p less than 0.004); and showed the lowest interobserver variation. Sensitivity for detecting active disease was 84% compared with 64% and 58% for the visual and computer-assisted indices, respectively, with no sacrifice in specificity.

Cell Count↗
PubMed1983

T helper-suppressor cell imbalance in pyoderma gangrenosum, with relapsing polychondritis and corneal keratolysis.

We found decreased T helper/inducer and increased T suppressor/cytotoxic cells in a 45-year-old woman with pyoderma gangrenosum. Serum immunoglobulin levels were normal, suggesting that these T suppressor cells did not function primarily to regulate antibody synthesis. The patient had diminished cutaneous delayed hypersensitivity responses, reacting to only one of six antigens tested, but responded in vitro to three of three antigens. Because of their various regulatory functions, excess T suppressor cells, or a lack of T helper cells, could be a common factor underlying many of the humoral and cell-mediated immune derangements, as well as the neutrophil abnormalities, that have been found in pyoderma gangrenosum. Our patient also had relapsing polychondritis and corneal keratolysis, consistent with the systemic nature of the disorder. The T-cell imbalance persisted even as the ulcer improved. Since monoclonal antibodies against T cell subpopulations are readily available, measuring these cell types as part of the immunological workup of patients with pyoderma gangrenosum might yield valuable clues concerning the pathogenesis of this disorder.

Corneal Ulcer↗
PubMed1983

Inflammatory meningeal masses of unexplained origin. An ultrastructural and immunological study.

Two patients with inflammatory meningeal masses were studied. Lesions in both patients showed varying proportions of meningothelial and inflammatory components. The non-neoplastic nature of the inflammation was confirmed in one case by lymphocyte surface marker study, which showed T and B cells in one to four ratio, and by immunohistochemistry, which revealed polyclonal plasma cells. The abundant histiocytes contained muramidase and often enclosed intact lymphocytes or plasma cells within their cytoplasm, i.e., emperipolesis. Their surfaces bore slender interdigitating pseudopodia, intercellular junctions, and subplasmalemmal linear densities. The derivation of these histiocytes is uncertain: mononuclear phagocytes, meningothelial cells, and multipotential meningeal cells are all possible progenitors. A comparison with eleven similar reported cases reveals a tendency for inflammatory meningeal masses to occur in the young, as well as a predilection for posterior fossa involvement. They resemble the extranodal lesions of sinus histiocytosis with massive lymphadenopathy, as well as plasma cell granulomas or inflammatory pseudotumors of lung and other tissues. However, it is possible that these lesions represent a variant of meningioma in which an unusual immunological response has been evoked.

Adult↗
PubMed1982

Prolymphocytic leukemia of helper cell phenotype: report of a case and review of the scientific literature.

A case of prolymphocytic leukemia was studied by using light and electron microscopy, cytochemistry and multiple immunological markers for T and B lymphocytes. Cytochemical and immunological studies showed that the cells were T-lymphocytes. By using monoclonal antibodies to human T-cell subsets, we found that these cells had the T-helper cell phenotype. The usefulness of multiparameter studies in subclassifying T-cell malignancies is discussed and the literature on T-prolymphocytic leukemia reviewed.

Female↗
PubMed1982

Immunologic abnormalities in two patients with pulmonary hyalinizing granuloma.

Pulmonary hyalinizing granuloma (PHG) is a disease of slowly enlarging pulmonary nodules made up of dense bundles of collagen accompanied by an infiltrate of chronic inflammatory cells. The etiology is unknown. Although it has been suggested that the lesions represent an exaggerated immune response to unidentified agents, results of a detailed immunologic work-up of these patients have not been published. This report presents the laboratory findings of two patients with biopsy-proven PHG who have been followed four and eighteen years. Autoantibodies were detected (antinuclear antibody, rheumatoid factor, and positive antiglobulin tests), although clinically there was no evidence of a specific collagen-vascular disorder. Both patients had elevated levels of circulating immune complexes. These data suggest that immune complex mechanisms may be important in the pathogenesis of PHG.

Adult↗