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Biomedical subjects

T H The

Publications and source records attributed to T H The.

At least 199 records · Page 11Linked to original sources
PubMed1984

Cytomegalovirus hepatitis in normal and immune compromised hosts.

Liver biopsies of six previously normal hosts (Group I, NH), with recent or acute CMV infection, and autopsy liver samples of four immunocompromised hosts (Group II, ICH) with overwhelming CMV infection have been studied in an occasional survey. In both groups, portal tract involvement, bile duct inflammation, liver cell degeneration and parenchymal granulomas were present. In Group I, a randomly distributed hepatitis with predominant involvement of the periportal areas was present, including sinusoidal arrays of lymphocytes and lymphohistiocytic aggregates. In contrast, in Group II liver cell damage was more extensive and the inflammatory infiltration only scarce. Intracellular viral inclusion bodies were found only in Group II, both in liver cells and in bile duct epithelium. Morphologically, the presence of viral inclusion bodies correlated well with the immunohistologic demonstration of CMV specific "late" (CMV-LA) or structural antigens. In addition, CMV-specific "early" (CMV-EA) or non-structural antigens were present in liver cell nuclei of 2/6 NH and 2/4 ICH. The possible relations between the inflammation and the lack of structural antigenic viral expression are discussed. It is concluded that ICH with CMV infection have a prominent cytopathogenic effect and widespread lytic viral infection in the liver in the absence of adequate immunologic reactivity, whereas the opposite is found in NH.

Adult↗
PubMed1984

Detection of immunoglobulin M and G antibodies against cytomegalovirus early and late antigens by enzyme-linked immunosorbent assay.

A sensitive and reproducible enzyme-linked immunosorbent assay (ELISA) is described for the detection of immunoglobulin M and antibodies with specifity for human cytomegalovirus (CMV) early (CMV-EA) and late (CMV-LA) antigens. The emphasis is on the production of high-quality CMV antigens, CMV-EA and CMV-LA separately, and conditions for their application in the ELISA. The induction of CMV-EA and -LA in infected cell extracts was studied in detail by using human sera with defined antibody specificity for CMV-EA and CMV-LA. This resulted in the development of a simple whole cell extraction procedure that provided a high yield of CMV antigens with reproducible antigen quality. The antigens were specific for the detection of anti-CMV antibodies. The influence of autoantibodies on the determination of CMV-specific antibodies was investigated. Parallel analysis of 322 human sera by indirect immunofluorescence and ELISA showed a high correlation between both assays (r = 0.9674 for CMV-EA and 0.9362 for CMV-LA). Antibody titers determined by ELISA were equal to (for CMV-EA) or slightly higher (for CMV-LA) that those determined by immunofluorescence but significantly higher (20- to 5,120-fold) than those determined by complement fixation. From 191 sera positive by ELISA (titer greater than or equal to 40) 4 (2.1%) were negative by immunofluorescence (titer less than 40), and from 61 ELISA-positive sera 12 (19.6%) were negative (titer less than 8) when tested by complement fixation. Consequently, ELISA for CMV may prove to be more reliable for the selection of CMV-seronegative blood donors than these other methods. The use of high-quality antigens allows more economic handling of large-scale serum determinations. Possibilities for further automation are discussed.

Antibodies, Viral↗
PubMed1984

Steroid-responsive interstitial pulmonary disease in systemic sclerosis. Monitoring by bronchoalveolar lavage.

We describe a 38-year-old woman with systemic sclerosis of recent onset and progressive dyspnea. Studies of pulmonary function revealed a restrictive ventilatory disorder with decreased diffusing capacity. Interstitial fibrosis and infiltration with lymphocytes and plasma cells with formation of follicles were observed in the lung biopsy. Analysis of fluid from bronchoalveolar lavage showed an increase in the total number of cells, with a relative increase in neutrophils. Also, the relative amount of the immunoglobulins, IgG and IgM, was increased. During corticosteroid treatment, rapid improvement of pulmonary volumes occurred, together with disappearance of neutrophils and an increase in the percentage of lymphocytes in the lavage fluid. Later on, the total number of cells in the fluid from bronchoalveolar lavage and the percentage of lymphocytes reached normal values. Bronchoalveolar lavage may be of value in assessing and monitoring pulmonary disease in patients with systemic sclerosis.

Adult↗
PubMed1984

Antibody responses in vivo in chromosome instability syndromes with immunodeficiency.

The primary IgG, IgM and IgA antibody responses to Helix pommatia haemocyanin (HPH) were defective in patients with ataxia telangiectasia (AT) and Nijmegen breakage syndrome (NBS). The results in patients with Bloom's syndrome (BS) were heterogeneous, but all showed abnormal kinetics of the IgG response. The secondary response to diphtheria, tetanus and polio vaccine was normal in patients with AT and BS, but disturbed in the patients with NBS. The abnormalities of antibody response of AT and NBS are similar, although more profound in NBS; BS is different.

Adolescent↗
PubMed1984

Reticuloendothelial Fc receptor function in SLE patients. I. Primary HLA linked defect or acquired dysfunction secondary to disease activity?

Reticuloendothelial system (RES) Fc receptor-mediated immune clearance was measured in 18 patients with systemic lupus erythematosus (SLE). Only two patients, with major disease activity, had a prolonged T 1/2 of the blood disappearance curve of injected IgG coated red cells in comparison to 22 healthy controls. Circulating immune complexes (CIC) were studied with three methods: PEG precipitation, C1q-ELISA and the indirect granulocyte phagocytosis test (IGFT). The T 1/2 of the blood disappearance curve related significantly to the IGFT (r = 0.55, P less than 0.05) and not to the PEG and C1q-ELISA test. Although HLA-DR3 phenotype frequency was significantly increased in our SLE population (P less than 0.05), it was not related to Fc receptor function. Similarly, HLA-DR2 phenotype was not related to RES Fc receptor function. These data do not support the concept that a genetic HLA linked defect in reticuloendothelial Fc receptor function is a primary cause of SLE, predisposing the inflicted individual to immune complex deposition. However, Fc receptor-mediated immune clearance seems to be related to disease activity itself and to levels of CIC.

Adolescent↗
PubMed1984

Reticuloendothelial Fc receptor function in SLE patients. II. Associations with humoral immune response parameters in vivo and in vitro.

We studied the relationship between reticuloendothelial Fc receptor function and some parameters of the humoral immune response in vivo and in vitro in 18 SLE patients. Fc receptor-mediated immune clearance correlated remarkably well with (a) a decrease of antigen specific IgG after immunization with a primary test antigen (alpha-Helix pomatia haemocyanin) (P less than 0.01) and (b) the spontaneous IgG release in vitro of B cells obtained from peripheral blood (P less than 0.01). These two parameters were significantly interrelated. Reticuloendothelial Fc receptor function was not related to serum IgG levels. The study provides evidence for an association between polyclonal B cell activation and Fc receptor-mediated immune clearance in SLE patients. The possible nature of this association is discussed.

Adult↗
PubMed1984

Local immune complexes and inflammatory response in patients with chronic interstitial pulmonary disorders associated with collagen vascular diseases.

Evidence is accumulating that the lung injury in collagen vascular diseases (CVD) is triggered by immune complexes (IC). These reactions are neutrophil- and complement-dependent. The direct, in vivo phagocytosis of IC by bronchoalveolar lavage polymorphonuclear leucocytes (BAL-PMN), was studied in 15 patients with CVD and chronic interstitial pulmonary disorders. A control group (NC) consisted of nine healthy, non-smoking volunteers. Concentrations of soluble IC were measured using a solid phase Clq ELISA assay, and an indirect, in vitro phagocytosis assay performed using healthy donor PMN. Local Ig and C3 concentrations were determined using laser nephelometry and Mancini techniques, respectively. In the patient group the total cell counts/ml recovered lavage fluid and the proportions of BAL-PMN were significantly increased (P less than 0.05 and P less than 0.001, respectively). The influxed PMN showed high scores of direct IC phagocytosis. Soluble IC concentrations were significantly increased compared with controls (all comparisons P less than 0.01), and in the BAL relatively higher than in the serum of the same patients. Concomitantly high local IgG concentrations were observed. Corticosteroid treatment gave rise to significantly decreased total cell counts (P less than 0.05), and proportions of BAL-PMN (P less than 0.001), a decrease in the in vivo IC phagocytosis (P less than 0.05), in the indirect, in vitro IC phagocytosis, in the Clq ELISA and in the local IgG concentrations (all comparisons P less than 0.001). We concluded that locally formed IC may induce an inflammatory response in the lungs of patients with CVD.

Adult↗
PubMed1983

Cryopreservation of newly formed hybridomas.

A new freezing technique is described which permits time-consuming protocols as a first screening of newly formed hybridomas. In this procedure complete 96 well clustertrays with growing hybridomas are cryopreserved after programmed freezing. This procedure has been successfully applied to a number of fusion protocols for which the objective was to obtain monoclonal antibodies against tissue specific antigens. To this end hybridoma supernatants were screened by an immunoperoxidase technique on frozen sections. Freezing of the hybridoma containing clustertrays permitted extensive screening and partial characterization of the previously collected supernatants. After subsequent thawing of appropriate wells, the hybridoma clones proved to be viable and usually no loss of antibody production was observed.

Animals↗
PubMed1983

Abnormal reticuloendothelial function in patients with active vasculitis and idiopathic membranous glomerulopathy. A study with 99mTc-labeled heat-damaged autologous red blood cells.

Reticuloendothelial function was assessed in 11 patients with systemic lupus erythematosus, 8 patients with Wegener's granulomatosus, and 20 patients with idiopathic membranous glomerulopathy by using autologous 99mTc-labeled heat-damaged red blood cells. With this method organ uptake could be measured by quantitative scintigraphy. There was no relation between the T1/2 of the blood disappearance curve and the T1/2 of the splenic uptake curve. The T1/2 of the blood disappearance curve was normal in all three patient groups. However, there was a significant shift from spleen to liver uptake in patients with active systemic lupus erythematosus, active Wegener's granulomatosus, and membranous glomerulopathy in comparison with a control group. There was no relation with age, level of circulating immune complexes, complement level, kidney function, or immunosuppressive treatment. We conclude that an increase of the liver component of reticulo-endothelial function may compensate abnormalities in splenic function. This stresses the importance of quantitative scanning to detect such abnormalities. The study provides evidence for disease related hyposplenism in patients with active systemic lupus erythematosus, active Wegener's granulomatosus, and membranous glomerulopathy.

Adult↗
PubMed1983

Identification of three indolic compounds in a pigmented-melanoma cell-culture supernatant by gas chromatography-mass spectrometry.

In the supernatant of melanoma cell culture SK mel 25 three indolic compounds - 5-hydroxy-6-methoxyindole, 5-hydroxy-6-methoxyindolyl-2-carboxylic, and 6-hydroxy-5-methoxyindolyl-2-carboxylic acids - have been identified. The supernatants were extracted with ethyl acetate, derivatized, and analyzed by gas chromatography-mass spectrometry. The significance of this finding is discussed.

Cells, Cultured↗
PubMed1983

Lymphocyte characteristics and function in paroxysmal nocturnal haemoglobinuria.

In six patients with paroxysmal nocturnal haemoglobinuria (PNH) lymphocyte studies were performed to investigate whether the observed immunological dysfunction could be ascribed to a defect in lymphocytes as result of the PNH characteristics, or to an imbalance between T-cell subsets. The PNH characteristics were studied by means of the effect of serum and acidified serum on Indium111-oxine labelled lymphocytes. No increase in release of Indium111-oxine was found when lymphocytes were exposed to acidified sera. Thus a complement mediated lymphocyte lysis in PNH could not be demonstrated. T-cells were defined by monoclonal antibodies, directed at total T-cells (OKT3), helper T cells (OKT4) and suppressor/cytotoxic T-cells (OKT8). In two of the six patients a decreased proportion of OKT3 cells was found, while a significantly depressed ratio of OKT4/OKT8 cells was present in the whole group. No obvious correlation was found between a functional assay - the concanavalin-A suppressor cell activity - and the ratio of OKT4/OKT8 positive cells. It is concluded that the PNH characteristics could not be demonstrated in the lymphocytes; and that the immunological dysregulation in PNH may be ascribed to an imbalance of T-cell subsets, while a decreased number of monocytes, defined by the monoclonal antibody OKM1, may contribute to this defect.

Antibodies, Monoclonal↗
PubMed1983

Anti-acetylcholine receptor antibodies in myasthenia gravis. Part 1. Relation to clinical parameters in 250 patients.

We examined the significance of the presence or absence of anti-acetylcholine receptor (anti-AChR) antibodies in 250 myasthenia gravis (MG) patients and the relation between clinical features and anti-AChR levels. We found high anti-AChR levels in 2 out of 11 thymoma patients without MG, while 37 out of 250 MG patients had no detectable anti-AChR. The absence of these antibodies was related to purely ocular disease and to steroid therapy and/or thymectomy. Differences in anti-AChR levels did not correspond significantly to differences in disease activity when single measurements in patients were analysed. However, the results were influenced by both the presence or absence of a thymoma, the age at onset of disease and by steroid therapy. The thymic pathology and age at onset seemed to act independently. Early onset of disease was associated with high anti-AChR levels and absence of antibodies to striated muscle (anti-SM), whereas late onset was associated with low anti-AChR and the presence of anti-SM. Thymomas both have high anti-AChR and high anti-SM. The effect of steroid therapy on antibody levels was seen in all patient groups but was strongest in thymoma patients with early onset of disease.

Adolescent↗
PubMed1983

Anti-acetylcholine receptor antibodies in myasthenia gravis. Part 2. Clinical and serological follow-up of individual patients.

Circulating antibodies to acetylcholine receptor protein (anti-AChR) were measured in the sera collected from 75 patients (53 women, 22 men, ages 9-83 year, 20 with a thymoma) with myasthenia gravis (MG) during 5-44 (mean 25) months. The clinical state of each patient was graded on a 6-point scale. Anti-AChR concentrations were measured by a radioimmunoassay with human antigen. We analysed the relation between the change in clinical state and the change in anti-AChR concentration in 155 periods (1-7, mean 2.1 per patient). The change in clinical state is given as the difference in score at the onset and at the end of this period. The change in anti-AChR concentration is expressed as the percentage of the original concentration at the onset of the period. The results were analysed in relation to the therapy and to the severity of the MG at the onset of each period. A strong correlation between a change in anti-AChR concentration and a change in clinical condition existed during treatment with prednisone or immunosuppression and in the period after thymectomy, while a weaker correlation was present in periods without immunosuppression. In only 3 patients did the changes in anti-AChR concentration precede the clinical change. No changes in anti-AChR concentrations were found if improvement was due to the effect of anticholinesterases or if deterioration was caused by infection or emotion. The serial measurement of anti-AChR may be a valuable method of following the basic trend of the MG in severely affected patients.

Adolescent↗
PubMed1983

A stimulatory role for cytomegalovirus (CMV) antibodies in CMV-specific lymphocyte proliferation in vitro.

Cytomegalovirus(CMV)-specific lymphocyte proliferation in vitro was tested in the presence or absence of CMV-specific antibodies. CMV antibodies clearly enhanced CMV-specific lymphocyte proliferation but not lymphocyte proliferation induced by other antigens. Enhancement was most consistently found with cell-bound CMV antigens and often with cell-free CMV as stimulating antigen. CMV antibodies only stimulated when they were added at an early stage of the lymphocyte culture, and the stimulating effect was most pronounced at optimal and suboptimal antigen concentrations. Our data suggest that CMV antibodies stimulate CMV-specific lymphocyte proliferation at the level of antigen presentation.

Antibodies, Viral↗
PubMed1983

Human fibroblasts, a convenient nuclear substrate for detection of anti-nuclear antibodies including anti-centromere antibodies.

Human fibroblast monolayers were applied as a nuclear substrate in indirect immunofluorescence for the detection of anti-nuclear antibodies (ANA). Comparison of the results obtained with this substrate and with conventional rat liver sections led to the conclusion that the application of human fibroblast monolayers as a substrate has the following advantages: 1) better recognition of the distinct nuclear staining patterns; 2) more convenient serum titrations, since a cryostat is not needed and twelve tests can be performed on one slide; 3) detection of significantly higher ANA titres in sera from patients with SLE and MCTD; 4) recognition of a type of ANA that was not detected on rat liver sections. These latter antibodies produced a discrete speckled pattern of fluorescence, which was completely lost after acid elution of the fibroblasts. Using HEp-2 cells in metaphase, it was shown that the antibodies were directed against the centromere regions of the chromosomes. These anti-centromere antibodies were detected in sera from patients with severe Raynaud's phenomenon. Underlying disorders were scleroderma (8 patients, 5 of them with CREST syndrome), Sjögren's syndrome (2 patients), and Raynaud's phenomenon in combination with a few symptoms of connective tissue diseases without fulfilling the criteria for a specific disease (5 patients).

Adolescent↗
PubMed1983

B cell activity in systemic lupus erythematosus: depressed in vivo humoral immune response to a primary antigen (haemocyanin) and increased in vitro spontaneous immunoglobulin synthesis.

B lymphocyte studies, in vivo and in vitro, were performed in 28 patients with systemic lupus erythematosus (SLE). After immunization with the primary test antigen haemocyanin, a decreased antigen specific humoral immune response was observed for all three Ig classes, irrespective of disease activity or the use of corticosteroids. Levels of antibodies against (recall) viral and nuclear antigens were increased during active disease. The in vitro spontaneous production of IgM and IgG, determined in the supernatant of 8 days cultures by ELISA, was highly increased in patients with active disease (reversely correlated with levels of complement C3, r = 0.74). Pokeweed mitogen-induced synthesis was decreased in all patients. The distribution of T cell subsets (OKT3, Leu 3a and OKT8 positive cells) was not different from controls, irrespective of disease activity. It is concluded that the primary humoral immune response is decreased in SLE, whereas a polyclonally activated B cell appears to be present. The normal T cell subset distribution does not support the primary role of the cell in the state of hyperactivity of the B cell.

Adolescent↗