Biomedical subjects

H M Surcel

Publications and source records attributed to H M Surcel.

53 records · Page 3Linked to original sources

PubMed1990

T-lymphocyte subsets defined by double immunofluorescence in multiple sclerosis.

T-lymphocyte subpopulations were studied in the blood of 25 multiple sclerosis patients and 25 healthy age and sex-matched controls. Monoclonal antibodies labelled with different fluorochromes were used to define the percentages of CD4 (helper/inducer) and CD8 (suppressor/cytotoxic) positive cells and to dissect them into phenotypic subgroups. The results confirm the decrease in CD8 positive cells in the blood associated with multiple sclerosis. The subset showing the most marked decrease was the CD11 marker negative population, which has been reported to be associated with cytotoxicity rather than suppression. There was no significant decrease in the percentage of cells positive for both CD4 and CD45R markers reported to contain suppressor-inducer or naive T-helper cells in the MS patients. The results suggest that further dissection of T-cell subpopulations may clarify our understanding of this disease process.

Adult↗

PubMed1990

Diversity of Francisella tularensis antigens recognized by human T lymphocytes.

The Francisella tularensis T-lymphocyte antigens, which may have a role in protection against tularemia, were investigated with vaccine-immunized subjects. Preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was used to fractionate the bacterial envelope preparation. The 23 fractions obtained represented membrane proteins of different apparent molecular masses ranging from 10 to 150 kilodaltons. Different fractions contained one to four separate protein bands stained with Coomassie blue. The lymphocyte blast transformation responses of five tularemia vaccine-immunized and three nonimmunized subjects were tested against bacterial material eluted out of SDS-PAGE fractions. Every fraction stimulated lymphocytes from at least one of the subjects. No clearly immunodominant or inhibitory antigens were detected among the envelope fractions. Expression of the HLA-DR antigen at the surface of CD4- and CD8-positive lymphocytes was also studied as a measure of cell activation. The numbers of CD4+ DR+ cells varied directly with the lymphocyte proliferation profiles, and very few CD8+ cells were found in the preparations stimulated with the different fractions. The diversity of the antigens recognized by immune T lymphocytes was confirmed by using F. tularensis-specific T-lymphocyte clones obtained from vaccinated subjects. Most of the 36 T-lymphocyte clones tested were stimulated by one SDS-PAGE fraction only.

Antigens, Bacterial↗

PubMed1990

Analysis of impaired in vitro immunoglobulin synthesis in rheumatoid arthritis.

Decreased immunoglobulin production in pokeweed mitogen driven lymphocyte cultures has been reported in rheumatoid arthritis (RA). Here various activators and experimental designs have been used to determine the contribution of B cells, T cells, or monocytes to this low response. Sixty patients with RA and paired controls were studied at the onset of disease and again six months later. Concentrations of IgA, IgG, and IgM in cultures of RA peripheral blood mononuclear cells stimulated with thymus dependent activators were already decreased at the onset of the disease. Six months later RA mononuclear cells produced even lower concentrations of immunoglobulin. In contrast, stimulation with a T cell independent activator showed that RA B lymphocytes had retained normal potential to synthesise immunoglobulin. Poor helper function was indicated by costimulation experiments and cultures of mixed mononuclear cells from patients and controls. This notion was supported also by the fact that phytohaemagglutinin induced interleukin-2 production by RA mononuclear cells was less than half of the control values. Nonspecific suppressor activity was similar in RA and controls. Monocyte functions were normal when tested by addition of indomethacin or 2-mercaptoethanol to the mitogen activated cultures. The defect in mitogen stimulated immunoglobulin production in vitro of RA mononuclear cells thus was more pronounced with time and probably reflects impaired mediator associated help in the differentiation of B lymphocytes into immunoglobulin secreting cells.

Adolescent↗

PubMed1989

A comparison of childhood and adult type I diabetes mellitus.

The incidence rate of insulin-dependent (Type I) diabetes mellitus is bimodal: one peak occurs close to puberty, and the other in the fifth decade. To evaluate possible differences in these forms of the disease, we examined the clinical, biochemical, autoimmune, and genetic features of 82 children and adolescents (1.3 to 18.2 years old) and 44 adults (20.0 to 55.8 years old) when they presented with Type I diabetes. The mean (+/- SEM) duration of symptoms before diagnosis was longer in the adults (7.5 +/- 1.0 vs. 3.9 +/- 0.4 weeks; P less than 0.001), and their serum C-peptide concentrations at diagnosis were higher (0.29 +/- 0.03 vs. 0.17 +/- 0.01 nmol per liter; P less than 0.001), suggesting that they had more residual beta-cell function. There were no significant differences between the two groups in sex ratio, blood glucose levels, hemoglobin A1 values, degree of metabolic decompensation, or frequency of Type I diabetes in first-degree relatives. Thirty-four of 80 children tested (42.5 percent) were positive for insulin autoantibodies, as compared with only 1 of 26 adults (3.8 percent; P less than 0.001). However, the frequencies of islet-cell autoantibodies were similar in the adults and children (conventional autoantibodies, both 81 percent; complement-fixing autoantibodies, 46.2 percent and 60 percent). More children than adults were heterozygous for both HLA-Dw3/4 antigens (26.6 percent vs. 9.8 percent; P less than 0.05) and HLA-DR3/4 antigens (36.6 percent vs. 12.5 percent; P less than 0.05). We conclude that Type I diabetes that begins in adulthood is characterized by a longer symptomatic period before diagnosis, better preservation of residual beta-cell function, and lower frequencies of insulin autoantibodies and HLA-D3/D4 heterozygosity than Type I diabetes that begins in childhood or adolescence.

Adolescent↗

PubMed1989

Membrane proteins of Francisella tularensis LVS differ in ability to induce proliferation of lymphocytes from tularemia-vaccinated individuals.

T lymphocyte-mediated immunity is important for resistance to Francisella tularensis. To characterize the specificity of this immunity, we used membrane proteins and two lipopolysaccharide (LPS) preparations. Both membrane proteins were heat-modifiable, as indicated by their migration in sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). One had an apparent molecular mass (Mm) of 120 kilodaltons (kDa) when solubilized in the SDS buffer at room temperature, but 17 kDa after heating. The respective values for the other protein were 35 kDa before and 40 kDa after heating. Both proteins were purified by a preparative SDS-PAGE. The LPS-containing preparations were isolated by aqueous phenol (WP) or PCP (phenol-chloroform-petroleum ether) extraction (LPS-R), and rendered protein-free by treatment with proteinase K. Lymphocytes from nine subjects immunized with a live tularemia vaccine from one to three years earlier responded specifically to both an F. tularensis whole cell antigen and the 17 kDa protein in the lymphocyte blast transformation test. By contrast, the 40 kDa protein and the two LPS preparations did not stimulate any detectable lymphocyte proliferation.

Adult↗

PubMed1989

Francisella tularensis-specific T-cell clones are human leukocyte antigen class II restricted, secrete interleukin-2 and gamma interferon, and induce immunoglobulin production.

T-cell clones (TLC) were established from a Francisella tularensis-vaccinated subject in order to study the cells responsive for cell-mediated immunity against F. tularensis. All the clones were human leukocyte antigen (HLA) class II restricted to one of the HLA-DR specificities of the original donor. The TLC cells were CD4+ and produced interleukin-2 and gamma interferon after stimulation with specific antigen. Seven of the eight clones tested assisted in the production of immunoglobulin G (IgG), IgA, and IgM antibodies.

Clone Cells↗

PubMed1988

Extended HLA haplotypes in families with insulin-dependent diabetes mellitus in northern Finland.

Haplotypes including HLA, Bf and C4 loci were analyzed in a material comprising 55 families with diabetic children. One hundred and ten haplotypes found in IDDM patients were compared with 101 haplotypes present only in healthy family members. Two complotypes, BfSC4A3B3 and SC4A0B1, were significantly more common (P less than 0.05) in the diabetic haplotypes, and these were in most cases found in haplotypic combinations with HLA-B15,Dw4,DR4 and HLA-B8,Dw3,DR3 genes, respectively. The B8/DR3 haplotype was better conserved, as 72% included the BfSC4A0B1 complotype as compared with only 35% of the B15/DR4 haplotypes with "high risk" C4A3B3 complement alleles (p less than 0.05). DR3 was found in 26% of the diabetic haplotypes and DR4 in 43%. DR4 associated with the Dw4 in 69% of cases and with Dw14 in 26% of the diabetic haplotypes. Our results confirm that the two phenotypes found earlier to be associated with IDDM in Northern Finland, e.g. "B15,BfS,C4A3B3,Dw4,DR4" and "B8,Bfs,C4A0B1,Dw3,DR3" are inherited as haplotypes.

Diabetes Mellitus, Type 1↗

PubMed1988

Infection by multiple viruses and lymphocyte abnormalities at the diagnosis of diabetes.

Evidence for an ongoing adenovirus infection and preceding EB and Coxsackie B virus infections was found in a 2-year-old boy at the diagnosis of insulin-dependent diabetes. An inverted T-helper/T-suppressor lymphocyte ratio and activation of T cells with a suppressor-cytotoxic phenotype were detected. A combination of multiple viral infections may be responsible for the rapid destruction of pancreatic beta cells in this case.

Adenoviridae Infections↗

PubMed1988

Mumps infections in the etiology of type 1 (insulin-dependent) diabetes.

The epidemiology of Type 1 (insulin-dependent) diabetes was studied during a period starting after an unusually sharp epidemic of mumps. The number of diabetic cases increased significantly 2-4 years after the epidemic. Incidence rates were highest in geographical areas with the highest incidence of mumps and lowest in areas with the smallest numbers of reported mumps cases. Serological studies employing EIA-assays indicated recent mumps infections more often among newly diagnosed diabetic children than among matched controls although the incidence was low (13% of patients and 4% of controls had serological markers of recent mumps). Those patients, who had had serologically verified recent mumps had more often HLA-DR4 associated risk antigens (Dw4 and Dw14) than other patients. Also clinical history of mumps was obtained more often from diabetic children than from controls as 27% of the patients and 14% of the controls had had clinical mumps during the five years preceding the diagnosis of diabetes. These results confirm several earlier reports suggesting a connection between mumps and Type 1 diabetes and that the onset of diabetes may be delayed by several years.

Child↗

PubMed1987

Interleukin 2 and gamma interferon production, interleukin 2 receptor expression, and DNA synthesis induced by tularemia antigen in vitro after natural infection or vaccination.

The T-cell response induced by Francisella tularensis antigen in sensitized subjects was characterized in vitro by measuring DNA synthesis in whole-blood and mononuclear cell cultures, interleukin 2 (IL-2) and gamma interferon (IFN-gamma) production, and IL-2 receptor expression. Correlations between these variables were estimated. The strengths of the responses were compared in 21 subjects naturally infected 2 years ago, 6 subjects vaccinated 5 to 6 years ago, and 13 control subjects with no history of infection or vaccination. Subjects with a history of natural infection synthesized more DNA in both whole-blood and mononuclear cell cultures, secreted more IL-2 and IFN-gamma, and expressed more IL-2 receptors than control subjects did. All these responses differed highly significantly (P less than 0.001) from those of the control subjects. The vaccinees exhibited somewhat lower responses than the naturally immunized subjects did, but the vaccinees could be distinguished from the control subjects by their DNA synthesis, receptor expression, and IFN-gamma production (P less than 0.01 to 0.001). The vaccinees showed a lower response, in terms of DNA synthesis and IL-2 secretion (P less than 0.05), than the infected group did but responded in a manner similar to that of this group, with respect to receptor positivity and IFN-gamma secretion (P greater than 0.10). The correlations between all the T-cell functions were good, with highly significant correlations (P less than 0.001) between whole-blood DNA synthesis and IL-2 and IFN-gamma secretion and between the two lymphokines (P less than 0.001). The results not only increase our knowledge of the T-cell response to tularemia antigen but also give an alternative approach to DNA synthesis measurement for the quantitation of T-cell responses. The results for the low-responding sensitized subjects seem to indicate that the parameters were comparable in sensitivity.

Adult↗

PubMed1987

Characterization of in vivo activated lymphocytes found in the peripheral blood of patients undergoing cardiac operation.

We studied in vivo lymphocyte activation in patients who underwent cardiac operation. A large number of deoxyribonucleic acid-synthesizing cells characterized by 3H-thymidine uptake and morphologically atypical lymphocytes were found after operation in the peripheral blood samples of patients, the peak level occurring on the sixth or seventh postoperative day. Most of the deoxyribonucleic acid-synthesizing cells were in the B cell fraction. The number of antibody secreting cells in the patients' peripheral blood samples was found increased from the normal level after operation. Immunoglobulin A-secreting cells were the most elevated fraction. The percentage of helper (OKT4) and suppressor (OKT8) cells in the postoperative samples was not significantly different from that in the preoperative samples. Only a few were Ia antigen positive cells. Co-culture of patients' B cells with their own T cells and with the T cells taken from two healthy controls revealed no signs of any helper or suppressor effect on these antibody-secreting cells. The results show that after cardiac operation the peripheral blood of patients contains an increased number of immunoglobulin secreting cells. The regulatory T-lymphocytes seem not to have any effect in vitro on these in vivo activated cells.

Adult↗

PubMed1987

Lymphocyte responsiveness and interleukin 2 production in type 1 (insulin-dependent) diabetes mellitus.

Peripheral blood lymphocytes from 24 long-standing IDDM patients (mean age 11.4 +/- 3.2 yrs) and 24 matched controls (mean age 7.7 +/- 4.4 yrs) were stimulated with phytohaemagglutinin (PHA) mitogen and PPD, tetanus and diphtheria antigens. Interleukin-2 (IL-2) production was measured from the supernatants of lymphocytes stimulated with PHA in vitro. There was no difference in lymphocyte blast transformation responses between the patients and controls, and IL-2 production was equal in both. It was thus concluded that there is no general immune deficiency in IDDM such as described in the BB rat even though specific immune aberration to certain virus antigens may exist.

Child↗

PubMed1986

Cell-mediated and humoral immunity to mumps virus antigen.

In the present study, cell-mediated and humoral immunity to mumps virus was investigated. The study population consisted of 25 subjects of whom 17 were initially seropositive for mumps. Serum antibody levels and lymphocyte blast transformation activity were measured before and after vaccination with inactivated vaccine. In addition, the subjects were skin tested and HLA-typed. Significant antibody responses, measured by enzyme-linked immunosorbent assay (ELISA), were observed after vaccination in all immunoglobulin classes. However, the elevation in antibody levels was usually transient in both seronegative and seropositive subjects. The IgA response was significantly higher in the seropositive than in the seronegative group, but no such difference was found in IgM or IgG antibodies. Vaccination also caused a significant but transient rise in lymphocyte blast transformation activity. Transformation results parallelled skin-test results and seropositivity, but not antibody levels, in the seropositive group. Pronounced IgA reactivity was significantly associated with Dw3 and Dw4 (DR3 and DR4) antigens. No HLA association was observed in IgG or IgM levels or in transformation activity.

Antibodies↗

PubMed1984

Lymphocyte subpopulations at the onset of type 1 (insulin-dependent) diabetes.

Percentages of various T-lymphocyte subpopulations in the blood were studied at the onset of Type 1 (insulin-dependent) diabetes. The number of lymphocytes with OKT8 markers was higher in the diabetic patients than in control subjects (p less than 0.005) and the ratio between helper and suppressor/cytotoxic T-cells (OKT4/OKT8 ratio) was lower in the diabetic patients than in the control group (p less than 0.005). The values in the diabetic patients were, however, essentially within the normal range. When Ia-antigen-positive cells were analysed in T-cell enriched cell populations, Type 1 diabetic patients had higher percentages of these cells (p less than 0.01), suggesting T-cell activation. When patients with either of the two major HLA risk antigens (Dw3 or Dw4) were compared, there was a significant difference in the OKT4/OKT8 ratio (p less than 0.005), as Dw3-positive patients had higher and Dw4-positive patients lower ratios. This finding supports the concept of heterogeneity of the disease and can also explain the discrepant findings of earlier studies. When patients with complement-fixing islet cell antibodies were compared with patients without islet cell antibodies, there was no significant difference, although the OKT4/OKT8 ratio was slightly lower in the complement-fixing islet cell antibody-positive patients.

Antibodies↗

PubMed1984

A 'new' DR4 associated D specificity 'JA' in type 1 (insulin-dependent) diabetes: A9, Bw16, DJA, DR4 haplotype.

The HLA antigen combination A9, Bw16 has been found to be associated with Type 1 (insulin-dependent) diabetes characterized by some special features in Northern Finland. This antigen combination has now been associated with a 'new' DR4-associated D antigen, provisionally called 'JA' or 'SN'. This 'new' D specificity was also associated with HLA-B18. Although the combination, Dw3/DJA, was common in Type 1 diabetic patients, the frequency of the combination Dw4/DJA was decreased compared with the expected value. This supports the hypothesis of two different risk factors associated with DR3 and DR4.

Diabetes Mellitus, Type 1↗

PubMed1984

Cell-mediated immunodeficiency in Down's syndrome: normal IL-2 production but inverted ratio of T cell subsets.

To get more information on the mechanism of cell-mediated immunodeficiency associated with Down's syndrome, 18 patients were studied for PHA-induced lymphocyte transformation and interleukin-2 (IL-2) production. A normal amount of IL-2 was produced although half of the patients showed decreased blast transformation. T cell subpopulations were studied in some patients with decreased and with normal blast transformation. All studied patients with decreased blast transformation had inverted helper/suppressor T cell ratio.

Adolescent↗

PubMedDate not supplied

Heat shock protein 60 specific T-cell response in chlamydial infections.

Heat shock proteins (HSPs) of most pathogens, including Chlamydia, are major immune targets of both humoral- and cell-mediated immune mechanisms. During the last decade, many investigators have focused their research to elucidate the complex relationship of chlamydial HSPs, especially chlamydial HSP60, and the host immune response. A central issue is whether the pathologic mechanisms in chronic chlamydial diseases are associated with an enhanced immune response to chlamydial HSP60 which can mediate tissue destruction through cytotoxic reactions, or whether they are related to the Th2 type of response that eventually leads to partial or temporary suppression of an effective antichlamydial response. Our review highlights the available knowledge between immune responses to chlamydial HSP60 and chronic chlamydial infections in human.

Animals↗