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PubMed1993

Blood testosterone levels are correlated with beta-N-acetylhexosaminidase activity in human caput epididymis.

beta-N-acetylhexosaminidase exhibits a relatively high activity in human epididymis. Its isoenzymatic profile and immunological properties led us to conclude that the increased activity was not due to the expression of an isoform unrelated to the HEX A and B present in other human tissues. Measurement of enzyme levels in the three distinct epididymal regions revealed that in any given sample, activity was higher in the caput than in the corpus or cauda. Moreover, we found a striking correlation between beta-HEX activity in the caput region and concentrations of blood testosterone, suggesting a possible involvement of the hormone in modulating enzyme expression. Since the caput epididymis plays a role in the maturation of sperm cells, our data may be an indication that beta-HEX activity in the caput has a physiological relevance in human epididymis functions.

Chromatography, Ion Exchange↗
PubMed1998

[Systemic therapy of low malignancy non-Hodgkin lymphomas].

Substantial progress has been achieved in eludicating the molecular mechanisms of malignant transformation, in establishing therapeutic standards and in evaluating innovative treatment strategies in patients with low grade Non-Hodgkin's Lymphoma. Correlation of genetic aberrations and immunologic marker profiles to histopathological entities and the clinical course has lead to a new transatlantic lymphoma classification. Today, application of 6-8 courses of moderately intensive induction polychemotherapy induces partial or complete remissions in 80% of patients in stage III or IV. Longterm maintenance therapy with interferon alpha significantly prolongs progression free survival. Current multicenter trials evaluate the curative potential of high-dose chemotherapy with autologous stem cell transplantation. Recently, several new approaches including new cytostatic drugs, immunotherapy with monoclonal antibodies and gene therapy with antisense oligonucleotides have been developed and have achieved remissions in pretreated patients. In the future, intensification of chemotherapy and the new treatment options may offer the potential for cure in patients with low malignant Non-Hodgkins Lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1976

Immunological features in multiple sclerosis.

A clinical and laboratory profile of the immunological system of patients with multiple sclerosis (MS) strongly suggested that many specific immune deficiencies exist in MS. The immunological history showed that patients with MS had had more tonsillectomies, appendicectomies, and childhood infections than matched controls, which suggested that there had been problems in controlling various types of childhood infections. The cell-mediated immune response and the circulating antibody titres were specifically impaired against a variety of antigens. Patients with MS had significantly lower serum antibody titres than controls against many naturally occurring antigens-namely, diptheria and tetanus toxoids, adenovirus, and mumps viruses. Raised serum antibody titres were found against measles and varicella zoster viruses while no difference was found towards other antigens. The delayed hypersensitivity reaction and the immunological memory of patients with MS were also greatly reduced against the mumps skin test antigens. There were normal amounts of circulating T and B lymphocytes, and the phytohaemagglutinin, concanavallin A, pokeweed mitogen, and encephalitogens lymphocyte transformation was not different from that in controls. These results indicated that patients with MS have more infectious problems than normal people and that both their T and B cell systems cannot mount a fully normal immunological response to some viral and bacterial antigens, while they give an increased response to others.

Adult↗
PubMed1999

The relationship of host immune cells, cytokine and nitric oxide production to tumor cells in ovarian carcinoma.

AIMS: This brief review focuses on the current understanding of the complex relationship of tumor-associated mononuclear cells (TAMs) with neoplastic cells, summarizing their immunological efficiency, cytokine profile and production of nitric oxide (NO) in the tumor microenvironment, with current insights on how this might affect tumor growth. DATA SOURCE: Data was obtained through Medline from articles indexed during the last 10 years. The main key words used in the research were: cancer, ovarian cancer, cytokine, nitric oxide (NO), mononuclear cell, lymphocyte, macrophage. SELECTION OF STUDIES AND DATA COLLECTION: 30 studies were reviewed, which contained data regarding the production of cytokines and NO by TAMs or malignant cells, and tried to establish a correlation between these mediators and tumor growth, especially in ovarian carcinoma. DATA SUMMARY: TAMs consist mainly of macrophages and T lymphocytes which present lower proliferative indices and cytotoxicity compared to autologous blood monocytes, although they are able to release various cytokines. The profile of cytokine expression could help to explain both the immunological impairment observed in patients with advanced carcinoma diseases and the potential of TAMs to exert antitumor activity, which makes these cells an attractive target for therapeutic intervention. NO is also produced in the tumor microenvironment. Several reports in animals suggest a tumoricidal role for NO, but in human tumors its role has not been well-established and may change during tumor progression.

Cytokines↗
PubMed1990

Further characterization of surface membrane structures expressed on human basophils and mast cells.

Recently, we were able to establish the immunologic surface marker profile of human basophils and mast cells. In the present study, the characterization of these cell types was extended by the use of monoclonal antibodies (mAbs) to hemopoietic differentiation antigens. Basophils and mast cells were enriched by mAbs and complement from chronic myeloid leukemia blood (n = 5) and dispersed lung tissue (n = 4), respectively. A panel of 80 mAbs was tested for being reactive with purified cell populations using flow cytometry and/or a combined toluidine blue-immunofluorescence staining procedure. In addition to previous findings, basophils were found to react with mAbs directed against the 126-kilodalton dipeptidylpeptidase IV (CD26), platelet glycoprotein IIa (CD31), CD40 antigen known to share sequence homology with nerve growth factor receptor, leukosialin (CD43), CD44 antigen, the ICAM-1 antigen (CD54) and VIM2-reactive gangliosides involving the sialofucooligosaccharide sequence (CDw65L). Bsp-1 was found to be a specific marker for human basophils, whereas mast cells were not stained by this reagent. Basophils apparently lack CD22 antigen, gangliosides detected by CDw65 mAbs (except CDw65L) and CD71 antigen (transferrin receptor). Mast cells were found to express CD43 and CD44 antigen. In contrast, mast cells lack CD22, CD26, CD31, CD40 and CDw65 antigen. These results provide further evidence that both blood basophils and mast cells express a unique immunologic surface marker profile including binding sites for a variety of immunomodulating ligands and adhesion molecules.

Antibodies, Monoclonal↗
PubMed2004

Gene expression profile in corneal neovascularization identified by immunology related macroarray.

PURPOSE: To identify differentially expressed genes in corneal neovascularization using cDNA macroarray. METHODS: Mechanical denudation of corneal and limbal epithelium was performed to induce corneal vascularization in mice. Corneas were harvested 4 days after operation. Total RNA was isolated from both normal and vascularized corneas and used for the synthesis of cDNA probes. 32P labeled exponential cDNA probes were hybridized to mouse cDNA immunology arrays. To validate the gene expression patterns revealed by the cDNA expression array analysis, semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and statistical analysis were performed to compare the normal and vascularized corneal samples. RESULTS: Of 545 immunology related genes on the arrays, 6 genes were upregulated and 1 gene was downregulated in the vascularized corneas compared with the normal corneas. Semi-quantitative RT-PCR was performed on the 6 genes selected in the arrays study, and showed that calreticulin (calregulin), apolipoprotein E, HSP84 (HSP90beta), and pleiotrophin were upregulated while interferon regulatory factor-1 was downregulated in the vascularized corneas compared with the normal corneas. These genes possess a number of biological functions including molecular chaperon, growth factor, and transcriptional factors. CONCLUSIONS: The differentially expressed genes newly identified in the context of corneal neovascularization represent novel candidate factors for further functional studies of the mechanisms of corneal neovascularization. Our data may provide new insight into the biological process of inflammation induced corneal neovascularization.

Animals↗
PubMed2003

Polymorphism in clinical immunology - From HLA typing to immunogenetic profiling.

The pathology of humans, in contrast to that of inbred laboratory animals faces the challenge of diversity addressed in genetic terms as polymorphism. Thus, unsurprisingly, treatment modalities that successfully can be applied to carefully-selected pre-clinical models only sporadically succeed in the clinical arena. Indeed, pre-fabricated experimental models purposefully avoid the basic essence of human pathology: the uncontrollable complexity of disease heterogeneity and the intrinsic diversity of human beings. Far from pontificating on this obvious point, this review presents emerging evidence that the study of complex system such as the cytokine network is further complicated by inter-individual differences dictated by increasingly recognized polymorphisms. Polymorphism appears widespread among genes of the immune system possibly resulting from an evolutionary adaptation of the organism facing an ever evolving environment. We will refer to this high variability of immune-related genes as immune polymorphism. In this review we will briefly highlight the possible clinical relevance of immune polymorphism and suggest a change in the approach to the study of human pathology, from the targeted study of individual systems to a broader view of the organism as a whole through immunogenetic profiling.

Journal Article↗
PubMed2001

Identification of two subgroups of mantle cell leukemia with distinct clinical and biological features.

INTRODUCTION: Mantle cell leukemia (MCLeu) has been considered as a leukemic form of mantle cell lymphoma (MCL). However, the presence of certain features rarely observed in MCL, such as transformation to prolymphocytic leukemia (PLL) or indolent clinical course, suggests that MCLeu may represent a distinct disorder. METHODS: Seven cases of MCLeu with t(11;14)(q13;q32) and BCL1-IGH gene rearrangement were ascertained among 140 newly diagnosed chronic B-cell lymphoproliferative disorders with leukemic expression. Comparative genomic hybridization, FISH for specific gene loci, and immunological studies were preformed in them. RESULTS: In comparison with CLL, MCLeu cases had low immunological scores < or =2 with respect to B-CLL (P<0.0001). Expression of CD38 was absent in 43% of MCLeu and in 44% of B-CLL. Comparative genomic hybridization analysis identified genomic imbalances in 86% of MCLeu with a similar pattern than in MCL: gains of 3q, 8q involving MYC gene and 15q, and losses of 6q, 9p, 13q and 17p affecting P53 gene. Differently from MCL and CLL, genomic loss of 8p was frequently detected in MCLeu (83%). Although clinical presentation of MCLeu was indistinguishable from CLL, all patients but one had disease progression within three years. According to the immunologic and genomic profiles, two distinct subgroups of MCLeu were defined: one related to PLL, showing CD38-, deletion of P53, and MYC amplification and another which corresponds to a leukemic form of classical MCL, presenting with CD38+ and normal P53 and MYC status. CONCLUSION: MCLeu and MCL are closely related disorders, as they show similar genomic and molecular patterns. However, the deletion of the short arm of chromosome 8 may represent a specific marker for MCLeu. Two distinct subgroups of MCLeu may also be distinguished according to the immunologic and genomic cell profiles.

ADP-ribosyl Cyclase↗
PubMed1997

[The potentials of immunological laboratory diagnosis].

Clinicians of different profiles often direct their patients to immunological tests because of a high incidence of various immunopathological syndromes, such as immunodeficiencies and allergic and autoimmune diseases. The efficacy of an immunological study depends on the task of the laboratory verification of the tentative clinical diagnosis, on the disease stage, and planned treatment. Biological material for investigation is collected depending on the task of the study and localization of the pathological process. It is not only the traditional material-blood, but other biological fluids of the organism as well. The choice of an adequate and informative complex of methods is also determined by the tasks of investigation. Special attention is paid now to methods for assessing the cytokine status of the organism. Interpretation of the results is the most intricate step of immunological tests because the notion of "immunological norm" is ambiguous and it is necessary to take account of the individual shifts of immunological parameters in the course of disease.

Humans↗
PubMed2002

Recent developments in inflammatory bowel disease.

The evolving medical armamentarium holds promise for more precise and effective therapies for IBD. The experience with anti-TNF therapy, particularly infliximab, illustrates the potential efficacy of therapies targeted at specific mediators or pathways involved in the pathogenesis. Advances in molecular technology have enabled the development of novel and potentially effective targeted therapies. Equally important is the increasing scientific understanding of the pathogenesis of IBD, which will likely improve the ability to stratify disease and to select therapies based on genotypic, immunologic, and phenotypic profiles in the future.

Adjuvants, Immunologic↗
PubMedDate not supplied

Immune cells in bronchoalveolar lavage in peripheral lung cancer--analysis of 140 cases.

BACKGROUND: Changes in the bronchoalveolar lavage fluid (BALF) cell profile may reflect immunologic reactions of the lung in pulmonary malignancies. OBJECTIVE: Our aim was to analyse the BALF cell profile in peripheral lung cancer. METHODS: This study was a retrospective analysis of BALF samples containing tumor cells from patients with confirmed peripheral lung cancer (140 cases). Routine analysis and lymphocyte phenotyping by an immunoperoxidase technique with the monoclonal antibodies CD3, CD20, CD4, CD8, CD57, CD1, CD25, CD71 and HLA-DR were performed. The data were compared with those from healthy persons. RESULTS: We found a significantly lower proportion of macrophages (60%), and significantly elevated proportions of lymphocytes (24%) and neutrophils (13%) in cases with cancer when compared with controls. The proportion of eosinophils was higher in the cancer patients (2.4%), though not significantly. Regarding the lymphocyte phenotypes, we found a significantly elevated proportion of T cells (86%), a relatively low CD4/CD8 ratio (1.7 +/- 1.3), and a relatively higher percentage of HLA-DR+ lymphocytes (6.6%) in patients with cancer. There were no significant differences between smokers and nonsmokers in the cancer patients. In more than half of the cases, a positive staining for epithelial membrane antigen was found. CONCLUSION: Our observations confirm the possible participation of lymphocytes (activated and suppressor subtypes) and eosinophils in the response against tumor in peripheral airways.

Adenocarcinoma↗
PubMedDate not supplied

An immunoepidemiological approach to asthma: identification of in-vitro T-cell response patterns associated with different wheezing phenotypes in children.

BACKGROUND: Increasing evidence suggests that patterns of T-cell immunity to inhalant allergens in genetically diverse human populations are more heterogeneous than previously assumed, and that covert differences in expression patterns might underlie variations in airway disease phenotypes. We tested this proposition in a community sample of children. METHODS: We analysed data from 172 individuals who had been recruited antenatally to a longitudinal birth cohort study. Of the 194 birth cohort participants, data from the 147 probands (age range 8.6-13.5 years) who consented to blood collection were included along with data from 25 consenting siblings (mean age 11 years [range 7.4-17.4]). We ascertained clinical phenotypes related to asthma and allergy. We measured T-cell responses to allergens and mitogens, together with blood eosinophils and IgE/IgG antibodies, and assessed associations between these indices and clinical phenotypes. FINDINGS: Atopy was associated with allergen-specific T-helper (Th)2 responses dominated by interleukin 4, interleukin 5, interleukin 9, interleukin 13, whereas interleukin 10, tumour necrosis factor alpha, and interferon gamma responses were common to both atopics and non-atopics. The wheal size from skin prick with allergen was positively associated with in-vitro interleukin 5 and interferon gamma responses, and negatively associated with interleukin 10. Asthma, especially in atopics, was strongly associated with eosinophilia/interleukin 5, and bronchial hyper-responsiveness (BHR) was associated with eosinophilia plus polyclonal interferon gamma production. BHR in non-atopics was associated with elevated allergen-specific and polyclonal interleukin 10 production. INTERPRETATION: Parallel immunological and clinical profiling of children identified distinctive immune response patterns related to asthma and wheeze compared with BHR, in atopics non-atopics. Immunological hyper-responsiveness, including within the Th1 cytokine compartment, is identified as a hallmark of BHR. RELEVANCE TO PRACTICE: These findings highlight the heterogeneity of immune response patterns in asthmatic children, including those with seemingly homogeneous Th2-driven atopic asthma. Further elucidation of the covert relationships between wheezing phenotypes and underlying immunophenotypes in this age group will potentially lead to more effective treatments for what is an unexpectedly heterogeneous collection of disease subtypes.

Adolescent↗
PubMed2005

Multiplexed analysis of serum cytokines as biomarkers in squamous cell carcinoma of the head and neck patients.

OBJECTIVE: Our objective was to characterize cytokine profiles in the systemic circulation of patients with active squamous cell carcinoma of the head and neck (SCCHN) compared with long-term tobacco smokers as controls. Furthermore, we hypothesized that persistent immune dysregulation in patients cured of their disease may be reflected in altered cytokine profiles in the systemic circulation. STUDY DESIGN: Retrospective, case-control study. METHODS: Using three well-defined clinical cohorts of SCCHN patients and smoker controls, we analyzed 100 microL of serum for a panel of 10 cytokines to determine whether serum cytokine profiles could distinguish clinically defined groups of SCCHN patients. Statistical analysis of multiplexed cytokine profiles was applied to classify three clinically defined groups: active SCCHN patients, treated SCCHN patients with no evidence of disease for over 3 years, and matched disease-free controls. Discrimination of outcome status was accomplished using classification trees, and 10-fold cross-validation was implemented to assess classification accuracy using independent data. RESULTS: We show that multiplexed cytokine and chemokine profiling may be performed to reflect the immune status of SCCHN patients. Selected cytokine profiles indicate that immunologic responses to carcinogenesis may not normalize even in the absence of tumor for over 3 years. CONCLUSION: Multiplexed serum cytokine profiles may be applicable to early detection, for screening those at high risk for SCCHN, and as clinically predictive biomarkers of disease status in successfully treated patients.

Biomarkers↗
PubMed1995

Azure B-eosin APAAP staining: a method for simultaneous hematological and immunological cell analysis.

Azure B-eosin APAAP staining allows simultaneous analysis of peripheral blood and bone marrow cells for hematological characteristics and immunological cell marker profiles. A defined sequence of staining procedures maintains characteristic components of the Romanowsky-Giemsa stain whereas cell antigens can be detected immunologically using the alkaline phosphatase-anti-alkaline phosphatase (APAAP) detection system. Antigens are visualized by the staining product of the substrate-naphthol AS GR phosphate and variamine blue salt. The usefulness of the azure B-eosin APAAP method was demonstrated on blood and bone marrow smears of patients with various hematological disorders.

Alkaline Phosphatase↗
PubMed2026

Oxidative Stress Associated LncRNAs as Potential Biomarkers for Prognosis and Immune Responses in Lung Squamous Cell Carcinoma Patients.

Long-chain non-coding RNA (lncRNA) significantly influences lung squamous cell carcinoma's (LUSC) prognostic value and immune infiltration. This study aimed to demonstrate how oxidative stress-related lncRNAs impact lung squamous cell carcinoma (SCC). The Cancer Genome Atlas (TCGA) dataset gathered transcriptome information and related clinical data for LUSC. To build a prognostic model, 10 prognostic-related genes were identified using a series of bioinformatics analyses that compared the OS gene's aberrant expression in tumor and healthy tissues, as well as its association with malignancy. Subjects were stratified into high- and low-risk groups based on the median risk score derived from the 10-gene signature. While the mathematical risk model demonstrated limited independent predictive performance in the validation cohort (AUC ~ 0.5), functional and immunological evaluations revealed significant differences in the tumor microenvironment (TME) across risk strata. Specifically, high-risk patients exhibited distinct immune infiltration profiles and altered immunological scores relative to their low-risk counterparts. Therefore, rather than serving as a direct clinical prediction tool, this oxidative stress-related lncRNA signature provides valuable biological insights into the immune landscape of LUSC and highlights potential therapeutic targets for further mechanistic investigation.

Humans↗
PubMed1996

Lymphocyte subsets, apoptosis, and cytokines in patients with chronic fatigue syndrome.

Whether immunologic abnormalities correlate with fatigue severity and functional impairment in chronic fatigue syndrome (CFS) was investigated. Blood mononuclear cells were immunophenotyped and circulating ex vivo-produced cytokines were measured in 76 CFS patients and 69 healthy matched controls. Expression of CD11b on CD8 cells was significantly decreased in CFS patients. However, the previously reported increased expression of CD38 and HLA-DR was not confirmed. There was no obvious difference in apoptosis in leukocyte cultures, circulating cytokines, and ex vivo production of interleukin (IL)-1 alpha and IL-1 receptor antagonist. Endotoxin-stimulated ex vivo production of tumor necrosis factor-alpha and IL-beta was significantly lower in CFS. The immunologic test results did not correlate with fatigue severity or psychologic well-being was measured by Checklist Individual Strength, Beck Depression Inventory, and Sickness Impact Profile. Thus, these immunologic tests cannot be used as diagnostic tools in individual CFS patients.

ADP-ribosyl Cyclase↗
PubMed2003

Haptoglobin-alpha subunit as potential serum biomarker in ovarian cancer: identification and characterization using proteomic profiling and mass spectrometry.

PURPOSE: The objective of this study was to identify and characterize new serum biomarkers in ovarian cancer patients using mass spectrometric protein profiling and specific immunological assays. EXPERIMENTAL DESIGN: Serum samples from 80 cancer patients and 91 healthy women were analyzed by surface enhanced laser desorption and ionization-mass spectrometry (MS) profiling. A candidate biomarker was purified by affinity chromatography, and its sequence was determined by liquid chromatography-tandem MS. An antibody was generated from the synthesized peptide for quantitative validation in the cases and controls. CA125 was determined and compared with the same set of specimens. RESULTS: Using surface enhanced laser desorption and ionization, we found a serum biomarker at approximately 11700 Da, which had peak intensity significantly higher in cases (1.366) compared with controls (0.208, P = 0.002), and subsequently identified this as the alpha chain of haptoglobin. ELISA indicated that Hp-alpha was </=2-fold higher in cancer serum compared with normal, benign tumor, and other gynecological cancers (P < 0.05) and had 64% sensitivity at 90% specificity alone and 91% sensitivity and 95% specificity if combined with CA125. CONCLUSIONS: Haptoglobin-derived alpha subunit is a potential marker for ovarian cancer that is complementary to CA125. MS-based protein profiling is a valuable tool for screening protein markers and useful to detect post-translational modification of tumor-associated proteins or abnormal metabolic products. However, confirmation of protein identity with specific antibodies is crucial for clinical application and functional studies.

Amino Acid Sequence↗
PubMed2003

Thalidomide-based treatment for HIV-associated multiple myeloma: a case report.

The spectrum of hematologic and immunologic abnormalities induced by HIV infection is broad. Although the incidence of HIV-associated B-cell neoplasms has increased, relatively few cases of multiple myeloma have been reported, and even fewer cases have detailed treatment outcome. The case of an HIV-infected man in whom multiple myeloma was diagnosed following progressive anemia and fatigue is described. The patient began treatment consisting of thalidomide, dexamethasone, and clarithromycin, which led to a rapid and dramatic antitumor response. He experienced modest regimen-related toxicities while retaining a normal CD4+ T-lymphocyte count and a nondetectable HIV viral load. The immunologic and antitumor effects of thalidomide in the context of multiple myeloma and HIV infection are also briefly reviewed. Given thalidomide's relatively favorable side-effect profile and purported immunologic benefit, further studies of this drug in the treatment of HIV-associated multiple myeloma should be pursued.

Anti-Bacterial Agents↗