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Inflammatory and immunological cell profiles in a rat model of conjunctival immediate hypersensitivity.

A modified model of conjunctival immediate hypersensitivity in the rat is described. The advantages of this model over previously reported rat models are that it does not require invasive challenges, pre-treatment with mucolytic agents to enhance antigen penetration, or the use of haptens, and is therefore more representative of the mode of allergen challenge seen in human hay fever conjunctivitis. This model has been shown to have both early and late-phase cellular responses but only early phase clinical signs. During the early phase of the response the tarsal region accommodates a massive neutrophil infiltration and the fornix-bulbar region participates to a greater extent during the late-phase reaction, with a significant eosinophil infiltration. The development of this model has allowed us to gain a clearer insight into the mechanisms involved during conjunctival immediate hypersensitivity in the rat; and the simplicity of this model makes it attractive to use in the evaluation of new drug therapies prior to their introduction into human clinical trials.

Animals↗

The effect of intravenous infusion of Corynebacterium parvum on an immune profile of women with breast cancer.

An immunological profile has been measured in 21 patients with advanced breast cancer who were treated with C. parvum (Wellcome strain CN6134). Thirteen patients received a single i.v. dose of 15 mg of C. parvum and 8 received 4 mg i.v. on 5 successive days. The "profile" was recorded before and 7-10 days after treatment and included measurement of total white count, absolute lymphocyte and monocyte counts, PHA response, B and T cell percentages. DNCB and Mantoux skin tests, immunoglobulin classes G, A, M and E and spleen size. Most patients showed a rise in white count, due largely to a polymorph leucocytosis, but there was no consistent change in any of the immunological variables recorded. IgG levels increased significantly following the single injection but not after the 5-day course; suggesting the possibility of acquired immunological tolerance. These results fail to demonstrate a consistent effect of C. parvum on either T-lymphocyte dependent function or on the spleen size, properties well documented in the experimental animal.

Breast Neoplasms↗

The CD8+ T-lymphocyte profile as a modifier of iron overload in HFE hemochromatosis: an update of clinical and immunological data from 70 C282Y homozygous subjects.

Hereditary hemochromatosis (HH) is a clinically heterogeneous disease. Among other factors, the individual immunological profile of CD8+ T-lymphocytes has been described to influence the severity of iron overload, with low numbers being negatively correlated with the total amount of body iron stored. With the objective of testing the modifier effect of the individual CD8+ T-lymphocyte profile on the levels of iron stores with age in HH, we reviewed the clinical and immunological data from a group of well-characterized C282Y homozygous HH subjects, regularly followed-up for a period of 20 years. A total of 70 subjects were analyzed. Sixty-four were adults (> or = 18 years): 42 males (mean age 47 +/- 14; range 22-75 years) and 22 females (mean age 46 +/- 14; range 19-65 years). Six were younger than 18 years, 5 males (mean age 9 +/- 4; range 5-14 years) and 1 female (15 years). The characterization of subjects included measurements, at diagnosis, of the iron parameters, transferrin saturation (TfSat) and serum ferritin, quantification of total body iron stores (TBIS) removed by phlebotomies, presence of associated clinical manifestations, and the T-cell immunophenotype (CD4+ and CD8+ T-lymphocytes) determined by flow cytometry. In general, statistically significant lower values of TfSat (67 +/- 17% vs. 89 +/- 14%, P = 0.0006) and ferritin levels (58 +/- 9 vs. 949 +/- 233 ng/ml, P = 0.02) were found in the young subjects in comparison to adults. After the age of 18, however, no further effect of age was significantly found on the biochemical iron parameters either in males or females. A modifier effect of the individual CD8+ T-lymphocyte profile on the association between iron stores and age was demonstrated by multiple regression analysis, where a significant correlation between TBIS and age was found only in males with low (< or = 0.41 x 10(6)/ml) CD8+ T-cell numbers (R2 = 0.43, P < 0.0001). In conclusion, in the present population of C282Y homozygous subjects, the CD8+ T-lymphocyte profile could be considered a modifier of the iron overload with increasing age in males, with low numbers predicting a severe outcome.

Adult↗

A 'profile' of immune responsiveness in multiple sclerosis.

An 'immunological profile' of various indices of B-cell function and T-cell function was developed for the 'early' case of multiple sclerosis (MS). This was compared against two groups of controls comprising age and sex-matched healthy subjects, and patients with other disabling neurological diseases (CNS controls) who were matched for age, sex, and type and duration of disability. Some indices of humoral immune responsiveness, such as the induced primary response to monomeric flagellin and the 'resting' levels of antibody to measles and rubella viruses, showed significant augmentation. Cellular immune deficits were attributed to an illness effect per se because (a) cell-mediated immunity was depressed, but only when compared with that of healthy subjects and not when compared with that of the CNS controls, and (b) transformation responses of lymphocytes to viral antigens were inversely related to disability status. The abnormalities in humoral immune responses demonstrable in this study do not provide an explanation for this disease; if there is a relevant 'immunological fault', the nature of this needs to be sought from within the neuraxis rather than from the systemic circulation.

Adult↗

Immune dysfunction--a potential target for treatment in endometriosis.

The treatment approach towards endometriosis has been traditionally either surgical or hormonal in nature. Since endometriosis is, to a large extent, a microscopic disease, a surgical approach cannot be expected to eradicate the disease. Treatment is, therefore, generally attempted by hormonal manipulation, an approach based on the known oestrogen sensitivity of endometriosis. Hormonal manipulation can only temporarily affect endometriosis, and quite clearly does not address the underlying aetiology and/or pathophysiology of the disease. Since neither is, at present, well understood, one can only speculate as to the treatment approach that would, in fact, affect the pathophysiology of the condition. Endometriosis has, in recent years, been characterized by a large number of immunological abnormalities in the host. It is, therefore, very tempting to speculate that an immunological defect represents the basic abnormality which later leads to the occurrence of the disease. This assumption is supported by the observation that those immunological defects are already present in the mildest forms of the disease. In fact, if one believes that many cases of unexplained infertility represent undiagnosed microscopic endometriosis, then evidence suggests that this precursor stage of the disease is basically characterized by an identical immunological profile to that of endometriosis. An immunological aetiology and/or pathophysiology of endometriosis should lead to an immunological treatment approach toward the disease. Specifically, a number of non-specific immunomodulators, presently utilized in a variety of medical conditions with immunological aetiologies, would seem to represent promising new therapeutic strategies to conquer endometriosis at its roots. A new treatment approach to endometriosis appears urgently needed since, at least with regard to the effects of endometriosis on fertility and pregnancy loss, present approaches have proven ineffective.

Autoantibodies↗

Dendritic cells engineered to express CD40L continuously produce IL12 and resist negative signals from Tr1/Th3 dominated tumors.

TNFalpha-matured dendritic cells (DCs) pulsed with tumor antigens are being evaluated as cancer vaccines. It has been shown that DCs produce IL12 during a limited time span and subsequently enter a stage of IL12 exhaustion. If DCs are generated ex vivo, the patient could receive IL12-exhausted DCs which may be detrimental for stimulating anti-tumor Th1 responses. Furthermore, many cancer patients exhibit a cytokine profile skewed toward IL10 and TGFbeta. This immunological profile, called the Tr1/Th3 response, is associated with the presence of regulatory T-cells. Tr1/Th3 responses potently inhibit DC maturation, thereby regulating Th1 responses. In the present study, we produced genetically engineered DCs that continuously express Th1-related cytokines such as IL12, and resist negative signals from Tr1/Th3-dominated bladder carcinoma cells. Human immature DCs were genetically engineered by adenoviral vectors to express CD40L, or were treated with TNFalpha as a positive control for maturation. The expression of different Th1/Th3 and inflammatory cytokines was monitored. IL12 and IFNgamma were expressed by CD40L-engineered DCs, while TNFalpha-matured DCs lacked IFNgamma and exhibited low IL12 expression. The addition of recombinant IL10 to genetically engineered DCs did not abolish their Th1 profile. Likewise, coculture with tumor cell lines expressing TGFbeta with or without recombinant IL10 did not revert to the engineered DCs. We further demonstrate that the resistance of CD40L-expressing DCs to TGFbeta and IL10 may be due to decreased levels of TGFbeta and IL10 receptors. Thus, CD40L-engineered DCs are robust Th1-promoting ones that are resistant to Tr1/Th3-signaling via IL10 and TGFbeta.

CD40 Ligand↗

Immunologic abnormalities in homosexual men. Relationship to Kaposi's sarcoma.

Studies were performed to define the immunologic status of various groups of homosexual men including homosexual men with Kaposi's sarcoma, healthy homosexual men who were of similar ages to the homosexual patients with Kaposi's sarcoma and homosexual men with hyperplastic lymphadenopathy. Heterosexual men with Kaposi's sarcoma were also studied. Immunologic parameters which were examined included serum immunoglobulin levels, enumeration of B cells, T cells, and T-cell subsets, and quantitation of lymphocyte responsive to phytohemagglutinin (PHA) and pokeweed mitogen (PWM). Significant immunologic abnormalities were observed in all three groups of homosexuals studied. These were most severe in the homosexuals with Kaposi's sarcoma, somewhat less severe in homosexual men with lymphadenopathy, and least marked but still significant in healthy homosexual men. Heterosexual men with Kaposi's sarcoma displayed essentially normal immunologic profiles. The possible etiologic factors underlying the immunologic abnormalities in the male homosexual population studied and the role of an altered immune system in the development of and the fulminant course of Kaposi's sarcoma in these patients are discussed.

Homosexuality↗

Immunologically distinct p53 molecules generated by alternative splicing.

Transfection of a functional cloned p53 gene into an L12 p53 nonproducer cell line efficiently reconstituted p53 expression. The p53 protein synthesized in these clones was indistinguishable from that occurring naturally in tumor cells. When a p53 cDNA clone was used instead, we observed that the L12-derived clones exhibited a distinct immunological profile. In the present experiments we compared the immunological epitopes of p53 proteins encoded by several full-length cDNA clones. Immunoprecipitation of p53 proteins generated by in vitro transcription and translation of the various cDNA clones indicated variations in the content of immunological epitopes. Basically, two p53 protein species were detected. Both species contained the same antigenic determinants except the PAb421-PAb122 site, which was present in proteins encoded by p53-M11 and pcD-p53, but not in the p53 protein encoded by the p53-M8 cDNA clone. Sequence analysis of the various cDNA clones indicated the existence of a 96-base-pair (bp) insert in clone p53-M8 as compared with clone p53-M11 or pCD-p53. The 96-bp insert contained a termination signal which caused the premature termination of the protein, leading to the generation of a p53 product 9 amino acids shorter than usual. The existence of this insert also accounted for the lack of the PAb421-PAb122 epitope which was mapped to the 3' end of the cDNA clone, following the 96-bp insert. This insert shared complete homology with the p53 intron 10 sequences mapping 96 bp upstream of the 5' acceptor splicing site of p53 exon 11. It was therefore concluded that the different cDNA clones represented p53 mRNA species which were generated by an alternative splicing mechanism. Differential hybridization of the mRNA population of transformed fibroblastic or lymphoid cells with either the 96-bp synthetic oligonucleotide or the p53-M11 cDNA indicated that the various mRNA species are expressed in vivo.

Abelson murine leukemia virus↗

[Hepatitis B: role of chronic asymptomatic HBsAg carrier health personnel in the spread of the infection].

Using radioimmunoassay (RIA) we discovered 8 chronic healthy carriers of HBsAg among 1,370 sanitary workers in our hospital (0.58%) and we studied, also with RIA, their immunological profile. We have also made an epidemiological and immunological study of their family contacts. Comparing the results of both studies, we emphasize the significance of some immunological markers of these carriers, especially the HBe/anti-HBe system, in the evaluation of potential infective danger to their contacts. On the other hand, the results of our study reveal that the infection risk from the carriers of HBsAg is very slight by extra-hematic way. We correlate this smaller infectivity with HBe antigen absence and anti-HBe antibody presence in their serum. Finally, based on the results of the study, some prophylactic measures are proposed and certain social and working considerations are discussed concerning the health-care workers as chronic asymptomatic carriers of HBsAg.

Adult↗

Immune responses induced by repeated treatment do not result in protective immunity to Schistosoma haematobium: interleukin (IL)-5 and IL-10 responses.

The hypothesis that repeated treatments enhance acquired immunity against schistosomes by stimulating strong T helper 2 responses was tested. Schistosoma haematobium-infected schoolchildren were monitored for 3 years. During the first 2 years, children who did not receive chemotherapy were compared with those treated once or repeatedly. After specific immune responses were measured at 24 months, praziquantel was given to all children to clear any schistosome infections. Twelve months later, the infection status of the children was determined and compared with cytokine profiles at month 24, to gain insight into which immunologic profiles can predict resistance or susceptibility to schistosome infections. Repeated treatment led to high specific levels of interleukin (IL)-5 and low interferon-gamma production but did not protect against reinfection. After adjusting for variables, such as sex, age, and infection status at study onset, high levels of parasite-specific IL-10 were a risk factor for reinfection, and high levels of IL-5 were associated with hematuria development.

Adolescent↗

[Levels of certain immunologic parameters in patients with carcinoma of the epipharynx].

According to several histological and immunological features undifferentiated carcinoma of the nasopharynx (UCNT) is different from other ORL carcinomas (abundant lymphocytic infiltrate and frequent positive serology to EBV). Thus, immunological and virusological investigations were frequently performed in order to determine their diagnostic and prognostic significance. This study mainly concerned EBV serology and related immunological parameters. There are less data about immunological profile in those patients. In the present study, several standard immunological parameters were tested (number of different rosette-forming cells in peripheral blood, immunoglobulins serum levels and blastic transformation in the presence of PHA) in 17 patients with UCNT, 16 males and 1 female, aged 20 to 79 years. The aim of this study was to find out whether these patients were different from healthy controls, and if any of these parameters could be of prognostic value. Results point to the following disturbances in our group of patients: absolute lymphopenia caused by T-lymphopenia and significant decrease in ability of blastic transformation. Contrary to the registered suppression of cellular immunity there was a certain degree of stimulation of humoral response detected by hypergamaglobulinaemia and appearance of monoclonal immunoglobulin components in sera of few patients. All these immunological disturbances have no prognostic value in predicting the treatment response to chemotherapy.

Adult↗

Heterogeneity of host immunological risk factors in patients with aggressive periodontitis.

BACKGROUND: The pathogenesis of early-onset periodontitis (EOP) can be explained by various host risk factors. Previous studies have focused on a single (among many possible) immunological risk factor and the association among the factors has not been assessed. We comprehensively investigated the associations among multiple host immunological risk factors in EOP patients to further elucidate their role in the pathogenesis of EOP. METHODS: Sixty-eight EOP patients (50 generalized EOP, 18 localized EOP), 51 EOP-suspected patients (S-EOP), 43 adult periodontitis (AP) patients, and 36 periodontally healthy subjects (HS) participated in this cross-sectional study. We examined peripheral neutrophil functions, phenotypic and functional characterization of peripheral lymphocytes (lymphocyte subsets, T-cell proliferative activity), cytokine productivity (interleukin [IL]-1, IL-2, tumor necrosis factor [TNF]-alpha, interferon [IFN]-gamma, IL-4 and IL-6), serum immunoglobulin G (IgG) antibody titers against 12 periodontal bacteria, and HLA class II genotypes. RESULTS: G-EOP, S-EOP, and AP patient groups showed significantly lower percentages of pan T cells and CD8-positive cells (P < 0.02) compared with the HS group. L-EOP patients showed depressed IL-4 and TNF-alpha productivity compared with the HS group (P < 0.02). The EOP group showed significantly elevated antibody levels against Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola, and Fusobacterium nucleatum compared with the HS group (P < 0.05). The frequency with DQB1*0503 was significantly higher in the EOP patient group than the HS group (P = 0.045) due to the higher frequency in L-EOP patients than the HS group (P = 0.035). There were wide interindividual variations in each of the tests among patient and HS groups; however, EOP patients showed wider intradiagnostic group variations in certain host defensive cell functions than the other groups. There were some EOP patients who showed extremely low or high values in some tests; the EOP patients could be further divided into subgroups according to their host defensive and immunological profiles. However, there was heterogeneity in some of the other host immunological tests even in the subgroups. CONCLUSIONS: The association of host immunological risk factors in EOP patients is widely varied and more complex than previously thought. These results indicate the difficulty of explaining the pathogenesis of EOP based on a single host risk factor and also emphasize the importance of critical assessment of not only EOP patient groups, but also individual patients.

Adult↗

Phylogeny and polyphasic taxonomy of Caulobacter species. Proposal of Maricaulis gen. nov. with Maricaulis maris (Poindexter) comb. nov. as the type species, and emended description of the genera Brevundimonas and Caulobacter.

The genus Caulobacter is composed of prosthecate bacteria often specialized for oligotrophic environments. The taxonomy of Caulobacter has relied primarily upon morphological criteria: a strain that visually appeared to be a member of the Caulobacter has generally been called one without challenge. A polyphasic approach, comprising 16S rDNA sequencing, profiling restriction fragments of 16S-23S rDNA interspacer regions, lipid analysis, immunological profiling and salt tolerance characterizations, was used to clarify the taxonomy of 76 strains of the genera Caulobacter. Brevundimonas, Hyphomonas and Mycoplana. The described species of the genus Caulobacter formed a paraphyletic group with Caulobacter henricii, Caulobacter fusiformis, Caulobacter vibrioides and Mycoplana segnis (Caulobacter segnis comb. nov.) belonging to Caulobacter sensu stricto. Caulobacter bacteroides (Brevundimonas bacteroides comb. nov.), C. henricii subsp. aurantiacus (Brevundimonas aurantiaca comb. nov.), Caulobacter intermedius (Brevundimonas intermedia comb. nov.), Caulobacter subvibrioides (Brevundimonas subvibrioides comb. nov.), C. subvibrioides subsp. albus (Brevundimonas alba comb. nov.), Caulobacter variabilis (Brevundimonas variabilis comb. nov.) and Mycoplana bullata belong to the genus Brevundimonas. The halophilic species Caulobacter maris and Caulobacter halobacteroides are different from these two genera and form the genus Maricaulis gen. nov. with Maricaulis maris as the type species. Caulobacter leidyia was observed to cluster with species of the genus Sphingomonas. Caulobacter crescentus is synonymous with C. vibrioides and C. halobacteroides is synonymous with Maricaulis maris as determined by these analyses and DNA-DNA hybridization. Biomarkers discerning these different genera were determined. The necessary recombinations have been proposed and a description of Maricaulis is presented.

Antigens, Bacterial↗

Isoenzyme studies in human leukemia -- II. Carboxylic esterase (E.C. 3.1.1.1.).

Isoelectric focusing analysis of esterase activity (E.C. 3.1.1.1.) has been carried out on polyacrylamide gel slabs of a variety of immunologically defined acute leukemia subtypes. Distinct isoenzyme bands and isoenzyme groups have been identified and characterized biochemically with regard to their features for substrate specificity, pH optimum and inhibition experiments. The esterase isoenzyme patterns permitted the distinction between acute myeloid and non-myeloid leukemias. Acute lymphocytic leukemias localized by their immunological profile along the T-cell axis exhibited a readily recognizable isoenzyme group (T group). Reproducible differences in isoenzyme patterns were observed in childhood common ALL which indicate that the immunologically determined entity cALL displays a clear heterogeneity with respect to biochemical profiles of enzyme markers. These results suggest that further combined biochemical and immunological characterization may significantly contribute to a better understanding of lymphopoietic and leukemic cell differentiation.

Carboxylic Ester Hydrolases↗

Lymphocyte subpopulations in intrauterine growth retardation in women with or without previous pregnancies.

OBJECTIVE: To evaluate lymphocyte subpopulations in pregnant women with intrauterine growth retardation (IUGR). STUDY DESIGN: Forty-two normotensive and healthy women with singleton pregnancies and intrauterine growth retardation were studied in the third trimester of pregnancy and compared with 42 normal pregnant women. Peripheral blood lymphocytes were studied using murine monoclonal antibodies and flow cytometry. RESULTS: B-lymphocytes in both total number (312.54 vs. 163.19 cells/mm3; P = 0.000003) and percentage (11.04% vs. 7.07%; P = 0.000002) were significantly increased in patients with IUGR in comparison to normal pregnant women. Significant correlations were found between birthweight and both total number and percentage of lymphocytes B. In primigravid women, we found that women with IUGR had a higher total lymphocyte count (2749.09 vs. 2130 cells/mm3; P = 0.006), higher T-lymphocyte count (2053.77 vs. 1676.40 cells/mm3; P = 0.02), higher B-lymphocyte count and percentage (309.13 vs. 145.36 cells/mm3; P = 0.000001) (11.45 vs. 6.81%); P = 0.00001), higher CD4 lymphocyte count and percentage (1342.68 vs. 972.22 cells/mm3, P = 0.001) (49.18 vs. 44.04%; P = 0.04), lower CD8-lymphocytes percentage (28.27 vs. 32.9%; P = 0.04), and higher CD4/CD ratio (1.83 vs. 1.46; P = 0.02) than the normal control group. CONCLUSIONS: B-lymphocytes are increased in women with IUGR in comparison to women with normal pregnancies and there was a significant negative correlation between maternal B-lymphocytes and birthweight. With respect to T-lymphocytes, the immunological profile is different according to the presence or absence of a previous pregnancy. Fetal immunological rejection could be involved in the pathogenesis of IUGR in primigravid women, but in multigravid women there were no differences between women with IUGR and those with normal fetal growth.

Adult↗

Interstitial lung disease in polymyositis and dermatomyositis.

Interstitial lung disease (ILD) is common in patients with polymyositis (PM) and dermatomyositis (DM), and is a major cause of morbidity. Although its cause is unknown, it is known to be closely associated with autoimmune disorders. Its manifestation has been found to be quite heterogeneous, as demonstrated by the differences among PM/DM patients in their immunologic profiles and histopathologic findings, which suggest variations in immunopathogenetic mechanisms. We review the clinicopathologic and immunologic findings in ILD associated with PM/DM, and discuss recent advances in classification, autoantibodies, and treatment. The most critical issues are to clarify the immunopathogenesis of severe forms of ILD, such as rapidly progressive ILD associated with amyopathic DM, and to establish the most appropriate therapy.

Dermatomyositis↗

[Filarial eosinophilic lung diseases, value of immunology (apropos of 9 cases)].

The study of nine cases of "eosinophilic lung" using specific immunological techniques indicates that the latter completes the geographical, clinical, radiological and hematological criteria of this syndrome. The search of circulating antibodies confirms the filarial etiology and individualises a remarkable immunological profile thus, suggesting a diagnosis in the case of occult filariases. The intensity of the immunological reactions brings a supplementary argument in favor of the hypothesis of a poor host-parasite relationship in the pathogeny of secondary manifestations to an infestation by W. bancrofti, B. malayi and other animal filariae such as B. pahangi.

Brugia↗