PubMed Health⌕ Search

Biomedical subjects

H M Surcel

Publications and source records attributed to H M Surcel.

At least 37 records · Page 2Linked to original sources
PubMed1997

Chlamydia pneumoniae infection in patients with chronic obstructive pulmonary disease.

The prevalence of chronic Chlamydia pneumoniae infection was assessed in 54 patients with established chronic obstructive pulmonary disease (COPD), 41 of these with severe COPD (group I), 13 with mild to moderate COPD (group II), and in 23 patients with community-acquired pneumonia (controls, group III). Specific IgG and IgA antibody levels and circulating immune complexes (ICs) were measured in paired sera, and specific secretory IgA (sIgA) levels in sputum specimens. A polymerase chain reaction (PCR) test was used for the detection of C. pneumoniae in sputum. According to our definite diagnosis criterion, 65% of the COPD patients showed evidence of suspected chronic C. pneumoniae infection and the prevalence was still higher (71%) in patients with severe disease. The occurrence of specific markers of infection was invariably highest in patients with severe COPD, next-highest in patients with mild to moderate COPD and lowest in pneumonia patients. The association between COPD and C. pneumoniae infection persisted after controlling for the potential confounding factors.

Adult↗
PubMed1997

Characterization of Chlamydia pneumoniae antigens using human T cell clones.

Chlamydia pneumoniae infection is followed by the development of antigen-specific cell-mediated immunity (CMI), which is detectable as a positive lymphocyte proliferation (LP) response to C. pneumoniae elementary body (EB) antigen, but the proteins inducing the T cell activation are not known. In the present work the authors used human T lymphocyte clones (TLC) raised against C. pneumoniae EB antigen to characterize C. pneumoniae proteins as T cell-stimulating antigens. A total of 55% of the TLC established recognized antigenic determinants only on C. pneumoniae species, while the rest of the TLC proliferated to both C. pneumoniae and C. trachomatis EB. The antigen specificity of the TLC was further analysed by stimulating with SDS-PAGE fractionated C. pneumoniae EB proteins. Chlamydia pneumoniae species-specific antigens were found in the molecular weight ranges 92-98, 51-55, 43-46 and 31.5-33 kDa and genus-specific antigens in the ranges 12, 26 and 65-70 kDa. The 46.5-49.5 and 55-61 kDa regions contained both species-specific and genus-specific antigens. Human leucocyte antigen (HLA) restriction analysis for the TLC isolated from an HLA DR4, 15(2) heterozygous person showed the majority (81.3%) to be restricted to the HLA DR4 molecule, the rest being DR15(2)-restricted. An interesting preliminary finding was that the expression of interferon-gamma (IFN-gamma) mRNA by the TLC was predominantly associated with antigen recognition in the context of the HLA DR4 molecule, while interleukin-4 (IL-4) production was linked to antigen recognition in the context of the HLA DR15(2) molecule.

Antigens, Bacterial↗
PubMed1997

Lymphocyte responses to Chlamydia antigens in patients with coronary heart disease.

AIMS: To clarify the relationship of Chlamydia pneumoniae infection and coronary atherosclerosis we studied cell-mediated and humoral immune responses to Chlamydia in 93 patients with angiographically confirmed coronary heart disease and in 115 controls without angiographically demonstrable lesions. METHODS AND RESULTS: Cell-mediated responses were analysed by measuring lymphocyte proliferative reactivity to whole elementary body antigens of C. pneumoniae. Control antigens included C. trachomatis and purified protein derivative of tuberculin. Chlamydia-specific antibodies were measured using microimmunofluorescence assay. Marked C. pneumoniae-specific immune reactivity, demonstrated by the high incidence of elevated IgG and IgA antibodies and strong lymphocyte proliferative response, was associated with coronary heart disease in male but not in female patients or controls. In male patients, the cell-mediated responses were strong to C. pneumoniae (median stimulation index 9,6) and to C. trachomatis (stimulation index 6,9). The females with coronary heart disease showed significantly stronger cell-mediated responses to C. pneumoniae (stimulation index 6,5) than to C. trachomatis (3,8; P < 0.001) and were comparable to the controls. CONCLUSION: Marked cell-mediated and humoral immunity to C. pneumoniae in males with coronary heart disease suggest that the immune mechanisms triggered by Chlamydia are a possible contributing factor in the disease pathogenesis of coronary atherosclerosis in males. The Chlamydia-specific cell-mediated responses seem to be predominantly induced by antigenic structures that are similar among different Chlamydia-species.

Antibodies, Bacterial↗
PubMed1997

Elevated circulating levels of inflammatory cytokines in patients with abdominal aortic aneurysm.

The basic feature in the pathogenesis of abdominal aortic aneurysm (AAA) is the degradation of extracellular matrix components. This process is induced partly by cytokines secreted from inflammatory and mesenchymal cells. Circulating levels of inflammatory cytokines were studied in AAA patients and compared with subjects suffering from atherosclerotic disease only. Furthermore, the predictive value of cytokine concentrations was evaluated for aneurysm expansion rate. Circulating levels of interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) were measured in 50 AAA patients (40 men, 10 women), 42 patients with coronary heart disease (CHD) (23 men, 19 women), and 38 controls whose angiogram was normal (17 men, 21 women). No differences in cytokine concentrations were found between the CHD patients and the controls. AAA disease was found to be associated with significantly higher IL-1 beta and IL-6 concentrations in both male patients (median concentrations of 19.40 pmol/L and 6.45 pmol/L, respectively) and female patients (19.26 pmol/L and 7.99 pmol/L) than in either the CHD patients or the controls (P < .005). TNF-alpha levels were slightly higher in the AAA patients (1.64 pmol/L in the males and 1.59 pmol/L in the females) than in the other groups (P < .05). IFN-gamma levels were elevated significantly in the female AAA patients (3.75 pmol/L) compared with levels found in the other female (P < .05) or male (P < .01) patient groups. The measured cytokine concentrations were not related to the size of the aneurysm or the maximal thickness of the thrombus within the aneurysm. IFN-gamma concentration showed a significant positive correlation to the aneurysm expansion (R = .37, P < .02) and negative correlation to the concentration of aminoterminal propeptide of type III procollagen during 6-month follow up (R = -.42, P < .005). The results show that circulating levels of inflammatory cytokines are elevated in patients with AAA disease, suggesting that the production of these cytokines is increased in these patients compared with CHD patients and controls. Elevated INF-gamma concentrations seem to predict an increased rate of expansion in AAA.

Aortic Aneurysm, Abdominal↗
PubMed1997

Cell mediated immunity to Chlamydia pneumoniae.

The association of Chlamydia pneumoniae to several chronic diseases such as atherosclerosis has been suggested serologically and by direct demonstration of organisms in disease lesions. Cell mediated immunity is crucial in host defense against intracellular pathogens such as C. pneumoniae. C. pneumoniae is a relatively recently recognized pathogen and the cellular mechanisms in C. pneumoniae immunity have so far remained unstudied. The present review includes the data available on C. pneumoniae proteins and their role as T cell activating antigens and Th1/Th2 balance in C. pneumoniae immunity.

Antigens, Bacterial↗
PubMed1996

HLA types in women with cervical human papillomavirus (HPV) lesions prospectively followed up for 10 years.

Certain genotypes of HPV have been recently implicated in the etiology of carcinoma of the uterine cervix. In order to determine whether HLA antigen-controlled immunoregulatory functions have a role in the pathogenesis of HPV infections, class I and II HLA antigen typing was carried out on a series of 96 randomly selected women who were part of a cohort of 530 women prospectively followed up for cervical HPV infections in our clinic since 1981. The frequency of the DQ3 antigen, which has previously been reported to be increased among cervical cancer patients, was decreased in our HPV patients compared with the control group of Finnish women, but it was slightly increased in HPV16-infected women (P = 0.0812). However, we were able to demonstrate that HLA-DR5 antigen is significantly increased (i) in patients with high grade cervical intraepithelial neoplasia (CIN) (P < 0.02), and (ii) in women harbouring the high risk HPV type 16 (P = 0.0003), thus confirming earlier reports of an association of this HLA antigen and cervical cancer. Such a close association between the high risk HPV type 16 with an HLA antigen might have important implications in the possible immunogenetic basis of the increased risk for squamous cell carcinoma of the uterine cervix.

Cytotoxicity Tests, Immunologic↗
PubMed1995

Measurement of sputum antibodies in the diagnosis of acute and chronic respiratory infections associated with Chlamydia pneumoniae.

The aim of this study was to develop methods for the measurement of sputum antibodies in the laboratory diagnosis of acute and chronic lower respiratory tract infections caused by Chlamydia pneumoniae. Paired serum specimens, sputum specimens, and pharyngeal or nasopharyngeal swabs were obtained from 97 patients; 51 of them had community-acquired pneumonia, and 46 had chronic obstructive pulmonary disease (COPD). C. pneumoniae-specific serum immunoglobulin G (IgG), IgA, and IgM antibodies were measured by the microimmunofluorescence (micro-IF) test. For sputa, specific IgA and IgG antibodies were measured by the micro-IF test and secretory IgA (sIgA) was measured by enzyme immune assay (EIA) with C. pneumoniae elementary bodies as the antigen. Sputum IgA and sIgA antibodies to C. pneumoniae were found, respectively, in 52 and 51% of the COPD patients. Elevated levels of stable serum IgG and IgA antibodies (IgG titer of > or = 128 and IgA titer of > or = 40), suggesting chronic infection, were found in 54% of the COPD patients. The sensitivity for the sputum IgA micro-IF test compared with elevated serum antibody levels was 87.5%, and that for the sputum sIgA EIA was 88%; the respective specificities were 90 and 95%. Acute C. pneumoniae infection was diagnosed in seven pneumonia patients, and two (29%) of these patients were positive by sputum EIA antibody measurements. Two pneumonia patients without acute infection had stable elevated IgG and IgA levels in their sera, and both of them were sputum antibody positive. We conclude that the measurement of IgA antibodies to C. pneumonia in sputum is a useful additional diagnostic tool for chronic C. pneumoniae infections.

Acute Disease↗
PubMed1994

Th1/Th2 profiles in tuberculosis, based on the proliferation and cytokine response of blood lymphocytes to mycobacterial antigens.

Proliferation and cytokine production profiles by blood mononuclear cells in response to in vitro stimulation with mycobacterial antigens were compared in patients with active tuberculosis and in sensitized healthy controls. Interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) were detected at single-cell level using the ELISPOT assay. Patients showed significantly (P < 0.01) increased numbers of IL-4-secreting cells and decreased thymidine incorporation, but no significant difference in IFN-gamma-producing cells in response to the 38,000 MW or 19,000 MW antigens and their immunodominant peptide epitopes. Pronounced individual variations were found in both patient and control groups, when comparing the responsiveness to the mycobacterial extract, two protein antigens and five synthetic peptides. None of the antigens or peptides tested showed preferential stimulation of either IL-4- or IFN-gamma-secreting T cells, and proliferation was not correlated with either IL-4 or IFN-gamma production. In particular, cytokine responsiveness was of similar frequency in subjects who did or did not show positive proliferation, indicating that the latter test was not fully representative of the active T-cell repertoire. It is concluded that the demonstrated Th2 type of profile in response to two prominent mycobacterial antigens may play a role in the mechanisms of defective host resistance in tuberculosis.

Adolescent↗
PubMed1993

Genetically permissive recognition of adjacent epitopes from the 19-kDa antigen of Mycobacterium tuberculosis by human and murine T cells.

The specificity of the T cell-immune repertoire at the level of individual antigenic determinants could play a fundamental role in the immunopathogenesis of tuberculous infections. Therefore, we analyzed the immunogenicity, genetic restriction, and epitope core structure of two adjacent, yet distinct, immunodominant T cell determinants from the 19-kDa Ag of Mycobacterium tuberculosis. After immunization with two peptides comprising residues 45 to 64 and 61 to 80, vigorous in vitro proliferative responses to the homologous peptide were elicited in five different strains of C57BL/10 mice (H-2b,k,d,s,f), indicating that both epitopes were recognized in a genetically permissive manner. When immunized with intact 19-kDa protein, lymph node cells from the same mouse strains responded to both peptides, with the exception of H-2b mice, which did not respond to p45-64. Delayed-type hypersensitivity responses in C57BL/10 (H-2b) mice were elicited by p61-80 only, whereas in H-2d mice both peptides were delayed-type hypersensitivity negative, despite eliciting pronounced proliferative responses. Analysis of the proliferative responses of human PBMC in purified protein derivative-positive healthy subjects and tuberculosis patients revealed significant differences in the antigenicity to the two peptides. All purified protein derivative-positive healthy and diseased individuals manifested strong responses to p45-64, indicating HLA permissive recognition. In contrast, pronounced responses to p61-80 were detected only in patients with lymphatic tuberculosis. Epitope core structures, composed of 6 or 7 residues within each peptide, have been mapped with peptides of overlapping sequence. Significantly, for both epitopes, the core sequences recognized by both human and murine T cells were almost identical. We conclude that despite many similarities between murine and human T cell epitope recognition, distinct differences in the responsiveness of the infected host could play a role in pathogenesis. Furthermore, the genetically permissive nature of the identified epitopes is a potentially important attribute for the development of peptide-based diagnostic reagents and vaccines.

Adult↗
PubMed1993

Cell-mediated immunity to Chlamydia pneumoniae measured as lymphocyte blast transformation in vitro.

The purpose of the present study was to analyze Chlamydia pneumoniae-induced, antigen-specific, cell-mediated immunity. Peripheral blood mononuclear cells of four persons infected with C. pneumoniae Kajaani 6 and 17 healthy volunteers were stimulated with antigen composed of whole elementary bodies of C. pneumoniae Kajaani 6 (CP-Ag). Definitive antigen-specific lymphoproliferation (LP) responses were developed after recent infection. The LP responses of healthy people to CP-Ag varied considerably. There was no clear correlation between LP responses to CP-Ag and those to an antigen prepared from Chlamydia trachomatis serotype L2 (r > or = 0.50, P < 0.1). A larger study is required to demonstrate whether the LP responses to CP-Ag can be used for the diagnosis of C. pneumoniae infection.

Adult↗
PubMed1992

T cell repertoire in tuberculosis: selective anergy to an immunodominant epitope of the 38-kDa antigen in patients with active disease.

It is generally accepted that both host protection and pathogenic reactions in tuberculosis are mediated by T lymphocytes. However, little is known about the structures and discreet functions of epitopes stimulating the immune response. In this study, proliferative responses of blood T lymphocytes to synthetic peptides derived from the sequence of the 38-kDa antigen from Mycobacterium tuberculosis have been investigated in 41 healthy individuals and in 36 patients with active tuberculosis. Of the healthy purified protein derivative (PPD)-positive donors, 90% responded to a permissively recognized peptide, 38.G (residues 350-359), located at the carboxy terminus of the molecule. Four other permissively recognized epitopes of this molecule (38.A, 38.I, 38.E, 38.K) were stimulatory for more than 50% of healthy PPD-positive individuals. Patients with lymphatic tuberculosis responded to these peptides in a similar manner. In contrast, we observed a selective anergy to stimulation with peptide 38.G in the majority of patients with pulmonary (11% responders) and nonlymphatic extrapulmonary tuberculosis (25% responders). The lack of responsiveness to 38.G was epitope specific since the degree of responsiveness to the other four permissively recognized peptide epitopes was similar for patients and PPD-positive controls. Using the PEPSCAN technology and truncated peptides, the core epitope of 38.G was localized to a peptide 10 amino acids long (HFQPLPPAVV). This minimal structure was capable of inducing a proliferative response in all healthy 38.G responders tested. The mechanisms influencing this epitope-specific anergy in patients could give new insights into the immunopathogenesis of tuberculosis.

Amino Acid Sequence↗
PubMed1991

Cytotoxic CD4+ T cells specific for Francisella tularensis.

The specific cell-mediated cytotoxicity of tularaemia-immune human T lymphocytes were studied in vitro. Peripheral blood mononuclear cells (PBMC) of six tularaemia-vaccinated healthy subjects were stimulated with F. tularensis LVS whole cell antigen for 6 days and used as effector cells in a conventional 4-h 51Cr release cytotoxicity assay. The target cells were phagocyting autologous monocytes, which were pulsed with F. tularensis or PPD antigen. The specific lysis of the F. tularensis-pulsed cells (42.6% +/- 11.7) was significantly higher (P less than 0.05) than that of the PPD-pulsed ones (22.2% +/- 8.3) or unpulsed control cells (15.9% +/- 5.2). The cytotoxicity was associated with CD4+ F. tularensis-specific T cell clones (TLC), which killed 36.3% +/- 12.3 of the F. tularensis-pulsed targets but only 6.9% +/- 6.5 of the unpulsed control targets. Their lysing was inhibited by monoclonal anti-HLA-DR and anti-HLA-DQ antibodies, but not by CD15 (monocyte/macrophage) antibody. The functional role of CD4+ lymphocytes in tularaemia immunity is discussed.

Antibodies, Monoclonal↗
PubMed1991

Low CD4/CD8 T lymphocyte ratio in acute myocardial infarction.

T lymphocyte subsets were analysed using monoclonal antibodies and flow cytometry to determine whether myocardial infarction and cardiopulmonary resuscitation induce changes in these. Groups of 11 infarct patients and 10 patients with past cardiopulmonary resuscitation were compared with 11 age- and sex-matched controls and 12 sepsis patients. The differences in the CD4/CD8 ratios between the four groups were significant (F = 7.71, P = 0.001). The infarct patients had lower CD4/CD8 ratios (mean +/- s.d. 0.83 +/- 0.43) than the control (2.12 +/- 1.13; P = 0.001) or sepsis cases (1.76 +/- 1.05; P = 0.004), but their ratios did not differ from those of the resuscitation group (0.93 +/- 0.79, P = 0.84). The latter group also had lower ratios than the control (P = 0.003) and sepsis groups (P = 0.013). Most infarct patients had an on admission inverted CD4/CD8 ratio which usually returned to normal in the next 2 days. A permanently low CD4/CD8 ratio may be a poor sign prognostically after both myocardial infarction and resuscitation.

Aged↗
PubMed1991

Abnormalities within CD4 and CD8 T lymphocytes subsets in type 1 (insulin-dependent) diabetes.

Abnormalities in the proportions of various T lymphocyte subpopulations have been found in a number of autoimmune diseases. Monoclonal antibodies labelled with various fluorochromes were used here to define the percentages of subsets, and especially to divide CD4+ (helper/inducer) and CD8+ (suppressor/cytotoxic) cells into phenotypic subgroups. Blood samples were analysed from 25 patients (age 10.1 +/- 3.7 years) with recently diagnosed insulin-dependent diabetes mellitus (IDDM) and 25 age- and sex-matched control subjects. The percentages of CD4+ cells and CD4+CD45RA+ cells described as naive T helper cells or suppressor/inducers were increased in the IDDM patients (P less than 0.05 and P less than 0.05. Student's t-test, respectively), whereas the percentage of CD4+CD45RA- cells (memory T-helper cells, helper/inducers) was similar in the patients and controls. The percentage of CD8+CD11b+ cells containing suppressor/effector lymphocytes was decreased in the IDDM patients as compared with the controls (P less than 0.01) but no significant difference was seen in total CD8+ cells. The percentages of CD3+ cells and the proportions of these simultaneously positive for HLA-DR antigen (activated T cells) were also increased in the recent IDDM patients (P less than 0.001 and P less than 0.05, respectively), while the proportion of CD20+ B cells was decreased (P less than 0.05). The findings support the view that disturbed immune regulation occurs in IDDM and indicate that further division of T cell subpopulations may clarify our understanding of the disease process.

Adolescent↗
PubMed1991

Decreased expression of class II major histocompatibility complex (MHC) molecules on monocytes is found in open-heart surgery related immunosuppression.

The expression of class II major histocompatibility complex (MHC) molecules on monocytes and the relative proportion of immunoregulatory lymphocyte subpopulations were studied from the blood of eight patients undergoing a cardiac operation. The aim of the study was to reveal mechanisms responsible for depression of cellular immunity and B-lymphocyte activation associated with open-heart surgery. A decreased staining of HLA-DR and even more of HLA-DQ class II MHC molecules was found on the monocyte surface in samples taken 2 and 7 days after operation when compared to preoperative values. The relative proportion of monocytes in mononuclear cells increased after surgery, but within lymphocyte subpopulations only a decrease in total T cells and an increased number of activated (HLA-DR positive) T cells were found, whereas the rations between various T cells subsets remained relatively stable.

Adult↗
PubMed1991

Development of Francisella tularensis antigen responses measured as T-lymphocyte proliferation and cytokine production (tumor necrosis factor alpha, gamma interferon, and interleukin-2 and -4) during human tularemia.

The lymphocyte immune reactivity of 12 tularemia patients to Francisella tularensis antigens prepared from the bacterial cell envelope was examined during a 14-week follow-up study. Lymphocyte blast transformation responses of peripheral blood mononuclear cells (PBMC) to different protein antigens appeared simultaneously 2 weeks after the first symptoms of tularemia, indicating that none of these antigens had any special role at the early phase of immunization. While the lymphocyte blast transformation responses of total lymphocytes to all bacterial antigens were negative in the week 1 samples, continuously growing F. tularensis-specific T-lymphocyte lines were obtained from PBMC at the same time, indicating that an immune response had already occurred. Later, the T-lymphocyte lines and lymphocyte blast transformation responses were similar. Lymphocyte activation among the PBMC was reflected in an increased number of HLA-DR antigen-expressing, CD4-positive T lymphocytes (CD4+ DR+). The mean secretion of soluble CD8 from F. tularemia antigen-stimulated PBMC increased 2 weeks after tularemia onset, but the mean number of CD8+ DR+ T lymphocytes did not vary during the study period and no correlation could be found between the soluble CD8 and number of CD8+ DR+ T lymphocytes. F. tularemia antigen-induced cytokine production was measured from the PBMC supernatants. High levels of tumor necrosis factor alpha were detected from the first week onwards. The highest levels of interleukin-2 and gamma interferon were recorded during the second and third weeks, respectively, after tularemia onset. Interleukin-4 could not be demonstrated in the lymphocyte supernatants.

Adult↗
PubMed1991

Francisella tularensis-induced in vitro gamma interferon, tumor necrosis factor alpha, and interleukin 2 responses appear within 2 weeks of tularemia vaccination in human beings.

Cell-mediated immunity is essential for protection against the intracellular bacterium Francisella tularensis, which causes tularemia. Positive in vitro T-cell responses in the form of lymphocyte proliferation and lymphokine interleukin 2 (IL-2) and gamma interferon (IFN-gamma) secretion are found in memory immunity. Studies on the secretion of lymphokines with regard to the developing immunity to F. tularensis have not been published. Therefore, 14 subjects with no clinical history of tularemia were vaccinated with a live F. tularensis vaccine strain. The in vitro responses of five subjects (antigen-induced mononuclear cell and whole blood culture DNA synthesis and cytokine secretion) were measured twice a week throughout the period from 0 to 35 days after vaccination, and the peripheral blood lymphocyte subpopulations of nine subjects were determined between days 0 and 14. Positive reactions, i.e., responses exceeding those on day 0, were reached on day 10 with regard to the whole blood culture DNA synthesis response and IL-2 and IFN-gamma secretion and on day 14 with regard to the mononuclear cell DNA synthesis response and tumor necrosis factor alpha (TNF-alpha) secretion. No measurable IL-4 was found in either the immune or nonimmune supernatants. Since the secretion of TNF-alpha was related to immunization, this points to the specificity of the phenomenon, even though the type of secreting cell is not yet known. If it is shown later that specific T cells produce it, the TNF-alpha response and the negative IL-4 finding may speak for the importance of the Th1-like pattern in immunity to F. tularensis.

Adult↗