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Biomedical subjects

T H The

Publications and source records attributed to T H The.

At least 163 records · Page 9Linked to original sources
PubMed1986

Kinetic analysis of the blood clearance and organ uptake curves of IgG-coated red cells in HLA-typed controls and patients with Wegener's granulomatosis.

Reticuloendothelial function and HLA type were studied in 22 controls and 15 patients with Wegener's granulomatosis (WG). IgG-coated red cells were injected intravenously and half-life times of blood disappearance and liver spleen uptake curves were related to the degree of antibody coating. Erythrocytes with 13,990 molecules of IgG per cell gave biexponential blood disappearance curves and were suitable for measuring splenic reticuloendothelial function. Half-life times thus obtained were not significantly different for individuals with the HLA-DR2 or DR3 phenotype. In WG patients with major disease activity, blood clearance of the injected cells was considerably decreased. Kinetic analysis of blood disappearance and spleen uptake curves revealed that this was partly due to a decrease in reversible trapping of the cells in the spleen. This suggests that a blocking effect of circulating immune complexes on splenic Fc receptors is not likely to be the sole cause of the observed hyposplenism.

Adult↗
PubMed1986

Characterization of the soluble immune complexes that are detected by three different techniques.

Three different tests which are based on different principles were used for the detection of soluble immune complexes (IC): (i) a PEG precipitation test, which is based on the solubility characteristics of IC; (ii) a solid-phase C1q binding assay, which is based on the complement binding property of IC, and uses peroxidase-linked anti-human IgG to detect the bound IC (C1q-ELISA); and (iii) the indirect granulocyte phagocytosis test (IGPT) which is based on the Fc R- and possibly the C3 R-binding of IC. Using heat-aggregated IgG (A-IgG) as a model for soluble IC all three tests showed a linear relation with the amount of A-IgG. The C1q-ELISA and the IGPT had a detection limit of less than 1 microgram/ml while the PEG test only detected quantities of more than 10 micrograms/ml. However, when using artificially produced soluble IC, which were prepared from human antibodies (ab) of different specificities and their respective antigens (ag) i.e., (i) tetanus toxoid, (ii) Helix pomatia hemocyanin (HPH), and (iii) dsDNA, and which consisted of the two components in a wide range of ag/ab ratios, distinct results were obtained with the three tests. Thus demonstrating that results obtained with A-IgG as a model for soluble IC can not simply be extrapolated to the behavior of real complexes in IC detection assays. No matter which ag was used, the composition of the IC, i.e., the ratio in which ag and ab were present, appeared to be the crucial factor for detectability in the different tests. The C1q-ELISA can detect IC over a wide range of ag/ab ratios, while it is particularly sensitive for IC formed in slight ag excess. The IGPT in contrast primarily detects, and is highly sensitive for, IC formed in ab excess. The PEG test appears to detect IC with freshly bound complement only. Another interesting finding has to be mentioned here: when increasing amounts of dsDNA were added to a SLE serum containing anti-DNA ab, the IC that had been detectable in the native serum with the IGPT completely disappeared, thus demonstrating that these complexes did consist of DNA and anti-DNA.

Antigen-Antibody Complex↗
PubMed1986

Sensitivity to hydrocortisone is a relevant factor in the immunoendocrine relationship. I. The cell-mediated immune response in relation to blood levels and in vitro immunosuppressive effects of hydrocortisone in patients with asthma and healthy control subjects.

The role of endogenous hydrocortisone in the regulation of lymphocyte activity was assayed in patients with asthma (patients with chronic nonspecific lung disease, characterized by attacks of dyspnea, alternating with symptom-free periods) and healthy control subjects. After priming, delayed-type hypersensitivity skin reactions were induced with Helix pomatia hemocyanin (HPH). Hydrocortisone blood levels were measured. The effect of hydrocortisone on HPH-induced lymphocyte proliferation was determined in vitro. The results demonstrate that hydrocortisone in low concentrations (100 ng/ml) inhibited in vitro lymphocyte proliferation equally in patients and control subjects. However, both groups demonstrated a large interindividual variation in hydrocortisone sensitivity. Therefore, in order to determine the immunologic effect of hydrocortisone blood levels in vivo, a hydrocortisone suppression index (HSI) was calculated by use of the information on hydrocortisone concentrations in vivo and the biologic effect of hydrocortisone in vitro. This HSI appeared to be inversely related with the in vivo cell-mediated immune response to HPH. This was reflected in an inverse correlation between HSI and delayed-type hypersensitivity skin reactions to HPH, both in patients (R = -0.64), in control subjects (R = -0.69), and in the total group (R = -0.68; p less than 0.001). No differences were observed between patients and control subjects. It is concluded that endogenous hydrocortisone is likely to play an important role in the regulation of lymphocyte activity in patients with asthma and healthy control subjects. This may have important consequences for the clinical expression of asthmatic symptoms, since the role of lymphocyte activity in the pathogenesis of asthma is increasingly recognized.

Adult↗
PubMed1986

Killing of human cytomegalovirus-infected fibroblasts by antiviral antibody and complement.

Complement-dependent cytolytic antibodies (CyAb) to cytomegalovirus (CMV)-infected fibroblasts were detectable in acute- and convalescent-phase sera from renal allograft recipients (n = 44) and nonimmunocompromised patients (n = 14) with symptomatic CMV infection but not in sera from control donors (n = 75; P less than .001 by Wilcoxon rank sum test). Renal allograft recipients with secondary CMV infection had the highest levels of CyAb activity. Activity closely correlated with the serum antibody titer to CMV membrane antigens (r = .9106 by linear regression analysis) and was present in both the IgM and IgG fractions of human sera. IgG F(ab)2 fragments were inactive, thus implicating the classical pathway of complement activation. Maximal CMV-specific lysis was obtained with target cells expressing CMV late membrane antigens (greater than or equal to 72 hr after inoculation) irrespective of the CMV strain used. Adsorption and cold target inhibition studies indicated that the target antigens for the CyAb response are specific for the plasma membrane of CMV-infected cells and may only partly be shared by the virion envelope.

Antibodies, Viral↗
PubMed1986

Primary cell-mediated immune response in bronchial asthma. Relationship between primary in vitro and in vivo cell-mediated and antibody responses in patients with asthma and healthy controls.

Eleven patients with asthma and ten sex and age matched healthy controls were immunized with the primary immunogen Helix pomatia Haemocyanin (HPH). The amplitude and the kinetics of in vitro cell-mediated immune response were measured by HPH-induced lymphocyte proliferation. Lymphocytes were also challenged in vitro with mitogens and recall antigens. In vivo cell-mediated immunity was determined by inducing delayed type hypersensitivity reactions with HPH. Anti-HPH antibody responses in the IgE, IgG and IgM classes were measured to gain an insight into the relation between cell-mediated and humoral immune responses in patients with asthma and healthy controls. The in vitro and in vivo cell-mediated response and the IgM antibody response did not differ between patients with asthma and controls. The IgE and IgG antibody responses, however, were increased in the patients. IgM antibody response correlated with both the in vitro and in vivo cell-mediated response (R = 0.45, P less than 0.05). IgE and IgG antibody responses however were not correlated with cell-mediated responses. These data suggest that the primary abnormality in immune regulation in patients with asthma concerns the control of the IgE and IgG class antibody responses.

Adult↗
PubMed1986

Immunofluorescence for detection of antibodies against human cytomegalovirus-induced membrane antigens.

This paper describes an improved method for the in vitro detection of antibodies specifically directed against human cytomegalovirus (CMV)-induced membrane antigens present on the surface of CMV-infected fibroblasts (CMV-MA). Viable cells were found to be essential for specific visualization of CMV-MA staining. The addition of divalent cations (2.6 mM Ca2+ and 2.2 mM Mg2+) and glucose (180 mM) to the incubation and washing buffers improved the viability and morphology of the cells and increased the cell yield at the end of the assay. Clustering of antigen-antibody complexes on the surface of viable CMV-infected cells was prevented by low-temperature incubation (0 to 4 degrees C) rather than by the addition of agents which act on the metabolism of the cell. No interaction with the CMV-induced Fc receptor was observed at 0 degrees C with either human sera or murine monoclonal antibodies. The specificity of the CMV-MA reaction was confirmed by using monoclonal antibodies to CMV nuclear, cytoplasmic, and membrane-associated antigens. Furthermore, a microplate modification of the membrane fluorescence test is described which is suitable for multisample screening purposes. This method can be applied to the determination of anti-CMV-MA antibody titers in human sera and to the screening of hybridoma supernatants for the presence of antibodies with specificity for CMV-MA.

Antibodies, Monoclonal↗
PubMed1986

Fluctuations in anti-nRNP levels in patients with mixed connective tissue disease are related to disease activity as part of a polyclonal B cell response.

In a follow up study of 11 patients with mixed connective tissue disease the levels of antibodies to nuclear ribonucleoprotein (nRNP) as measured by an enzyme linked immunosorbent assay (ELISA) were related to clinical activity of disease. To assess the relation between anti-nRNP levels and disease activity the levels of total immunoglobulin G, IgM rheumatoid factor (IgM RF), and antibodies to an unrelated antigen (tetanus toxoid) were determined simultaneously. No significant changes in anti-nRNP levels were noted in four patients with minor activity of disease. Major flares of disease were observed in seven patients. Clinical symptoms were preceded by a rise in anti-nRNP level in these patients unless they received immunosuppressive agents before the exacerbation. Conversely, when a rise in anti-nRNP level occurred a major flare of disease was followed in all but one case. Anti-nRNP levels fell during clinical improvement whether or not immunosuppressive treatment was given. All patients showed parallel fluctuations in anti-nRNP, IgM RF, and total immunoglobulin G levels. Furthermore, parallel fluctuations were seen in the levels of anti-nRNP and antibodies to tetanus toxoid except in one patient. We conclude that measurement of anti-nRNP by ELISA may be a guide for disease activity in connective tissue disease. Fluctuations of anti-nRNP are not restricted to this antibody, however, but are part of a more polyclonal activity of the B lymphocyte system.

Antibodies, Antinuclear↗
PubMed1986

Epidermodysplasia verruciformis. Skin carcinoma containing human papillomavirus type 5 DNA sequences and primary hepatocellular carcinoma associated with chronic hepatitis B virus infection in a patient.

In a case of epidermodysplasia verruciformis with impaired cell-mediated immunity and multiple skin cancers human papillomavirus type 5 (HPV5) DNA sequences were demonstrated in a cutaneous squamous cell carcinoma. HPV5 and HPV8 were detected in the benign disseminated skin lesions together with three newly characterized HPVs: HPV17, HPV19 and HPV24. A chronic infection with hepatitis B virus resulting in macronodular cirrhosis associated with a primary hepatocellular carcinoma was also acquired by this patient. This case provides an example of the circumstantial evidence which suggests that certain types of HPV are potentially oncogenic and stresses the importance of immune surveillance in the protection against virus-associated tumors.

Adult↗
PubMed1986

Cytomegalovirus immunity and T lymphocytes in bone marrow donors and acute graft-versus-host disease.

T lymphocyte subset numbers in bone marrow grafts were correlated with the cytomegalovirus (CMV) antibody status of the donors and with the occurrence of acute graft-versus-host disease (GVHD) in their recipients. We studied whether or not the (previously reported) association between donor CMV antibodies and GVHD could be explained by CMV-related changes in T cell subsets in the marrow grafts. There were no significant correlations between any of the T cell subsets in the marrow grafts and the occurrence of grades II-IV GVHD. A particular subset of CD8+ T cells carrying the HNK1 marker was significantly increased in the marrow grafts of CMV-seropositive donors. Although recipients of marrow from CMV-seropositive donors received an average of five times more CD8+ HNK1+ T cells than those with CMV-seronegative donors, that situation was not associated significantly with the development of GVHD.

Acute Disease↗
PubMed1985

HLA-DRw6 as a risk factor for active cytomegalovirus but not for herpes simplex virus infection after renal allograft transplantation.

To study genetically determined susceptibility to cytomegalovirus and herpes simplex virus infections in patients given renal transplants a prospective study was performed of 68 consecutive patients receiving their first cadaveric kidney allograft. The recipients positive for HLA-DRw6 showed a significantly increased incidence of active cytomegalovirus infection as early as the 10th week after transplantation (p less than 0.05). No relation with other human leucocyte antigens was found, nor did a correlation exist between HLA typing and the incidence of herpes simplex virus infections. Furthermore, recipients positive for HLA-DRw6 with secondary cytomegalovirus infections excreted infectious virus more often (p less than 0.01) and showed more clinical symptoms (p less than 0.01) than a comparable group of recipients negative for HLA-DRw6. These observations may have practical implications for the treatment of patients who have had renal transplant operations.

Adolescent↗
PubMed1985

Autoantibodies against neutrophils and monocytes: tool for diagnosis and marker of disease activity in Wegener's granulomatosis.

Immunoglobulin G (IgG) autoantibodies against extranuclear components of polymorphonuclear granulocytes were detected in 25 of 27 serum samples from patients with active Wegener's granulomatosis and in only 4 of 32 samples from patients without signs of disease activity. In a prospective study of 19 patients these antibodies proved to be better markers of disease activity than several other laboratory measurements used previously. The autoantibodies were disease specific and the titres were related to the results of an in-vitro granulocyte phagocytosis test, in which 7S IgG antibodies were internalised after specific binding to the cell, resulting in gradual formation of ring-like cytoplasmic structures. This autoantibody may have a pathogenetic role in Wegener's granulomatosis. The detection of this antibody is valuable for diagnosis and estimation of disease activity.

Adult↗
PubMed1985

Anti-acetylcholine receptor antibodies in myasthenia gravis. Part 3. The effect of thymectomy.

The clinical condition and the serum levels of antibodies to acetylcholine receptor protein were followed in 30 patients with myasthenia gravis before and in a period varying from 2 to 4 (mean 3) yr after thymectomy. Twenty-five patients improved in the 2 yr following thymectomy. A highly significant correlation was found between the change in clinical condition and the change in antibody levels. Only 3 patients improved without a fall of antibody level. Prethymectomy antibody levels were positively correlated with the severity of the clinical condition and with the degree of thymus hypertrophy.

Adolescent↗
PubMed1985

HLA-B8/DR3 phenotype and the primary immune response.

Increased frequency of HLA-B8/DR3 has been reported in many organ-specific and systemic autoimmune diseases. Immune responsiveness in 11 normal subjects with and 22 without the B8/DR3 phenotype was studied. The IgA class immune response after immunization with the primary test immunogen alpha-Helix pomatia hemocyanin (HPH) was increased in B8/DR3-positive subjects compared to the non-B8/DR3 group. Also, IgG class antibody levels tended to be higher in the former group. The in vitro lymphocyte proliferative response to optimal concentrations of HPH did not differ between the groups nor did the response to allogeneic cells. Lymphocyte proliferation on stimulation with pokeweed mitogen and suboptimal concentration of phytohemagglutinin was increased in B8/DR3 individuals. It is concluded that the phenotype B8/DR3 is associated with a high humoral immune response.

Adult↗
PubMed1985

The primary immune response in bronchial asthma. I. A kinetic study of Helix pomatia hemocyanin-specific IgE, IgG, IgA, and IgM antibody responses in patients with asthma and in matched controls.

Eleven asthmatic patients with allergy and 10 age- and sex-matched controls were immunized subcutaneously with 1 mg of the primary test immunogen Helix pomatia hemocyanin (HPH). The HPH-specific IgE, IgG, IgA, and IgM antibody response was measured by ELISA. After immunization, not only the IgE but also the IgG antibody response of the patients exceeded that of the controls (p less than 0.01). IgA antibody response also tended to be higher in the asthmatic group (NS). Except for an earlier rise after immunization in the asthmatic group (p less than 0.05), IgM peak responses did not differ significantly between the two groups. There was a high correlation (r = 0.9) between the magnitude of the IgE and the IgG antibody responses. IgM antibody response did not correlate with the response in any of the other antibody classes measured. The total serum immunoglobulin concentration was determined before immunization. Only the IgE level was significantly higher in the asthmatic group (p less than 0.01). No correlation was found between serum immunoglobulin concentrations and the magnitude of the HPH-specific antibody response in the same class. We conclude that the increased humoral responsiveness of asthmatic patients with allergy is not restricted to the IgE class nor to a limited number of commonly encountered antigens (allergens).

Adult↗
PubMed1985

Complement activation associated with active cytomegalovirus infection in renal transplant patients, and its absence in transplant rejection episodes.

In 20 patients with a cadaveric renal allograft, serial measurements were made of the serum complement factors C3, C4, factor B (FB), and C3d, the stable conversion product of C3. Measurements were started immediately before transplantation and continued thereafter once a week to investigate whether these assays help to differentiate between acute allograft rejection (R) and an active cytomegalovirus (CMV) infection. Fifteen patients had one or more R episodes, and 9 patients suffered from an active CMV infection. Six patients had an R episode and subsequently a CMV infection 13-64 days after R. No significant changes were found in the levels of C3, C4, and FB during R or CMV infection. C3d levels remained unchanged or decreased slightly during R. However, there was a 43-500% increase in the C3d level during CMV infection. This difference in the behavior of levels of C3d during R and CMV infection is significant (P less than 0.01), and suggests that serial measurements of C3d may be useful in differentiating CMV infection from R after renal transplantation.

Adult↗
PubMed1985

Cytomegalovirus immunity in allogeneic marrow grafting.

IgM and IgG class antibodies to cytomegalovirus (CMV) late antigen were studied in 58 bone marrow transplant (BMT) recipients and their donors using a sensitive enzyme-linked immunosorbent assay (ELISA) and with standard virological and histomorphological techniques. Patients who were CMV-seropositive before BMT had a significantly higher risk for active CMV infection after BMT than seronegative ones (23 of 29 vs. 3 of 26 patients; P less than 1 X 10(-6)). Transplantation of marrow from CMV-seropositive donors was associated with a higher incidence of active CMV infection after BMT than transplantation of marrow from seronegative donors (17 of 28 vs. 9 of 27 patients). Such transplantations also had a significantly higher incidence of grades II-IV acute graft-versus-host disease (23 of 29 vs. 11 of 27 patients; P = 0.007). Following BMT, the evolution of the IgG class CMV antibody response was influenced by the serological status of the marrow donor. First, a fall in IgG class CMV antibody titers during the first month after BMT was seen less often after transplantation of marrow from seropositive donors than after transplantation of marrow from seronegative donors. Second, recipients of marrow from CMV-seropositive donors who developed active CMV infection had an earlier IgG antibody response than those with seronegative marrow donors. These results suggest that the transfer of memory B and T cells occurs with the graft. Failure to mount a sustained IgM or IgG antibody response upon active CMV infection was associated with a fatal outcome.

Antibodies, Bacterial↗