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Systemic Penicillium marneffei infection in a child with common variable immunodeficiency.

Penicillium marneffei is rarely pathogenic in humans. Most previously reported cases of P. marneffei infection were from Southeast Asia where patients were usually in an immunocompromised state due to human immunodeficiency virus (HIV) infection. The majority of the patients reported in Western countries were immunocompromised by malignancy, especially Hodgkin's lymphoma. In Taiwan, the first case of P. marneffei infection was reported in 1994 and involved an adult with HIV infection. We report a case of systemic P. marneffei infection in a child with common variable immunodeficiency (CVID). The patient, a 4-year, 5-month-old boy, had a 1-year history of oligoarthritis resembling juvenile rheumatoid arthritis (JRA). He developed a low grade fever (38 degrees C) and hepatosplenomegaly 1 month before admission to the hospital. Although cultures of synovial fluid obtained at the time of onset of oligoarthritis did not grow any organisms, cultures of blood, bone marrow, synovial fluid, and lymph node biopsy samples taken during this admission were positive for P. marneffei. Further immunologic studies revealed a profile characteristic of CVID. The fungal infection was finally eradicated by combined therapy with amphotericin B, fluconazole, itraconazole, and regular immunoglobulin replacement. This case reminds us that JRA or JRA-like arthritis should be differentiated from septic arthritis caused by rare pathogens in immunocompromised patients.

Arthritis, Infectious↗

MR imaging of the salivary glands in sicca syndrome: comparison of lipid profiles and imaging in patients with hyperlipidemia and patients with Sjögren's syndrome.

OBJECTIVE: We correlated abnormalities on MR imaging with the plasma lipid profiles of patients with hyperlipidemia and symptoms of sicca syndrome. SUBJECTS AND METHODS: MR imaging features of the salivary glands, salivary function, immunologic abnormalities, and plasma lipid profiles were analyzed in 24 patients with hyperlipidemia and symptoms of sicca syndrome and compared with those of 50 patients with Sjögren's syndrome. RESULTS: Swelling of the parotid gland, impaired salivary flow, or both were observed in 20 (83%) of 24 patients with hyperlipidemia and symptoms of sicca syndrome. MR imaging findings included an enlarged parotid gland replaced with extensive lipid infiltration, whereas sialography of the parotid gland revealed normal findings. Immunologic studies and analyses of the labial glands of the mouth revealed distinctive features in patients with Sjögren's syndrome. Importantly, elevated levels of plasma triglyceride correlated with parotid gland swelling, and increased cholesterol levels significantly affected salivary flow. CONCLUSION: Our findings suggest a distinct entity of sicca syndrome in patients with hyperlipidemia compared with patients with Sjögren's syndrome. Characteristic MR imaging findings of salivary glands in patients with hyperlipidemia included extensive lipid infiltration and gland enlargement.

Adolescent↗

[Suberosis and bird fancier's disease: comparative study of radiological, functional and bronchoalveolar characteristics profile].

Extrinsic Allergic Alveolitis (EAA) is an immunologically mediated interstitial lung disease that may result from repeated inhalation of many different environmental agents. Heterogeneity of the clinical presentation and bronchoalveolar lavage profiles has been described, possibly related to different occupational exposures. The aim of our study was to compare bronchoalveolar lavage fluid (BALF), clinical, functional and radiological characteristics of the two most frequent forms of EAA seen in our practice: Suberosis and Bird Fancier's Disease (BFD). We included 81 patients with Suberosis, with a mean age of 38.8+/-11.3 years and a mean exposure of 20.0 +/- 10.5 years and 32 patients with BFD, with a mean age of 46.3+/-11.8 years and mean exposure of 10.5 +/- 1.0 years. Patients with BFD had more acute forms, while subacute and chronic presentations predominated in Suberosis. Restrictive defect was the most frequent pattern of lung function impairment, and more severe in BFD. Ground glass opacities were the most frequent pattern in high-resolution computed tomography. A normal chest x-ray was more frequently seen in Suberosis. Both types of EAA had lymphocytic alveolitis in BALF: Suberosis - 6.6 +/- 5.7 x 105 ml-1 cells, 58.8 +/- 18.9% lymphocytes; bird fancier's disease - 9.0 +/- 6.5 x 105 ml-1 cells, 61.7 +/- 22.2% lymphocytes. Although BALF CD8+ lymphocytes predominated in both diseases, the proportion of CD4+ and CD4/CD8 ratios were significantly higher in Bird Fancier's Disease (Suberosis: 0.47 +/- 0.33 versus BFD: 1.1 +/- 1.5; p <0.005). Moreover, BALF cellularity and mast cell counts were also significantly higher in BFD. In conclusion, Suberosis and bird fancier's disease are EAA with different clinical and laboratory profiles, suggesting that despite their pathophysiological similarities, different antigenic exposures may cause different immune and inflammatory response dynamics in the lung.

Adult↗

Depletion of CD8+ cells abolishes the pregnancy protective effect of progesterone substitution with dydrogesterone in mice by altering the Th1/Th2 cytokine profile.

One of the most remarkable immunological regulations is the maternal immune tolerance toward the fetal semiallograft during pregnancy, which has been referred to as immunity's pregnant pause. Rejection of the semiallogeneic trophoblast cells must be selectively inhibited and pathways presumably include Th2 cytokines unopposed by Th1 cytokines. Steroid hormones, including progesterone, have similar effects. Low levels of progesterone and Th2 cytokines and high levels of Th1 cytokines are attributable for increased abortions in mammalians, which may be triggered by psychoemotional stress. Thus, the aim of the present study was to provide experimental evidence for the mechanism involved in the mediation of immune responses by endocrine signals during pregnancy and stress-triggered pregnancy failure. DBA/2J-mated CBA/J female mice were randomized in three groups: 1) control females, 2) mice exposed to stress on gestation day 5.5, and 3) mice exposed to stress and substituted with dydrogesterone, a progestogen with a binding profile highly selective for the progesterone receptor on gestation day 5.5. On gestation days 7.5, 9.5, and 10.5, mice of each group were sacrificed, and the frequency of CD8(+) cells and cytokine expression (IL-4, IL-12, TNF-alpha, IFN-gamma) in blood and uterus cells was evaluated by flow cytometry. Additionally, some mice were depleted of CD8 cells by injection of mAb. We observed that progesterone substitution abrogated the abortogenic effects of stress exposure by decreasing the frequency of abortogenic cytokines. This pathway was exceedingly CD8-dependent, because depletion of CD8 led to a termination of the pregnancy protective effect of progesterone substitution.

Abortion, Spontaneous↗

Selection of vaccine strains of foot and mouth disease virus for use in southern Africa.

In the countries of Southern Africa, types SAT 1, SAT 2 and SAT 3 (SAT: Southern African Territories) of foot and mouth disease (FMD) virus are the most widely represented, especially the SAT 2 virus. Since 1982, examinations have been conducted on 139 isolates of these virus types. Other viruses, types O and A, have been detected in the north of this area. The typing and sub-typing of viruses with the complement fixation (CF) test can be improved by using panels of monoclonal antibodies (MAbs), which provide an accurate antigenic profile of a new strain. A total of 33 SAT 2 strains have been investigated using MAbs, and the results enable the classification of viruses into groups presenting the same profile. The author presents comparisons of isolates and vaccine viruses using conventional methods of serotyping--CF and virus neutralisation (VN) tests--as well as profiling the isolates using MAbs. Both manners of analysis provide information on the relationships between the viruses. The CF and VN tests give details on how animals responded against a particular isolate and how this antibody response would recognise another isolate; from this, the serological relationships can be proposed with respect to how different isolates might induce a humoral immune response. With MAb profiling, details of antigenic relationships between the isolates are obtained, enabling the identification of individual epitopic variations. These analyses can provide the potential to place different isolates into 'antigenic' groups. When compared with vaccine viruses, one can attempt to identify the vaccine virus with the closest profile to the isolate group. Immunological analysis (e.g. using the CF tests employed in this paper) can provide further information on the relationship between a particular vaccine and an antigenic group identified by MAb profiling. Of course, this MAb profiling can provide essential information in a very short time, which is of particular benefit in an emergency situation. Confirmation of the conclusions from the profiling would then be forthcoming through the serological analyses. Such combined analyses offer a more extensive identification of antigenic and immunogenic relationships between FMD virus isolates, as well as between isolates and vaccine viruses.

Africa, Southern↗

Heterogeneity of corticotropin-immunoreactive compounds in human body fluids.

Using reversed-phase "high-performance" liquid chromatography and hydrophilic ion-pairing reagents, we studied the chromatographic profiles of corticotropin immunoreactivities in human plasma, cerebrospinal fluid, and urine. The chromatographic system we applied provides excellent separation of peptide molecules, with reproducibility (CV) of retention times better than 0.5%, and makes feasible the subsequent immunological quantitation of eluted fractions. Profiles of corticotropin immunoreactivities exhibited several chemically different compounds in each of the three body fluids studied. A considerable portion of these immunoreactive compounds is more hydrophilic and probably of lower molecular mass than the human corticotropin 1-39 molecule itself. These hydrophilic molecules are more predominant in urine and plasma than in cerebrospinal fluid.

Adrenocorticotropic Hormone↗

A longitudinal study of immunological parameters in multiple sclerosis: cell-mediated immunity and complement profiles.

In a 1 year longitudinal study of twenty-two patients with multiple sclerosis (MS) and twenty-one normal control subjects, peripheral blood leucocytes were stimulated with lipoplysaccharide (LPS), a B cell mitogen, and phytohaemagglutinin (PHA) a T cell mitogen. EA- and EAC-rosette formation was also performed to assay null and B cells respectively, and the serum concentration of the C3 component of complement was determined. For ten multiple sclerosis (MS) patients with stationary phases of the disease, percentages of lymphocytes significantly lower than normal were found with normal leucocyte counts in the peripheral blood. Lymphocyte stimulation by PHA was significantly lower than normal in stable MS, while neither LPS stimulation nor EA- and EAC-rosette formation differed significantly from the controls. The C3 serum concentration was found to be significantly higher than normal. For nine out of twelve MS patients with a fluctuating clinical course, the C3 concentration was elevated during remission, but dropped to normal levels during relapse. None of the other parameters studied could be correlated with the clinical course.

Adult↗

Immunologic aspects of leprosy with reference to extravascular immunoglobulins: their excretion profile in urine.

An aliquot of 24-hour urine collected from leprosy patients was concentrated and examined for the presence of albumin, transferrin, IgG, IgA, IgM, IgD, D3, kappa and lambda light chains by the gel diffusion technic using respective monospecific antisera. Urinary protein excretion profile in lepromatous leprosy patients showed that while excretion of transferrin in the urine was negligible; that of IgG molecules, a substance of higher molecular weight, was significant. It is suggested that the immunoglobulins excreted in the urine may not be plasma-derived, but extravascular in origin. They are probably synthesized in the urinary tract. In the present study, out of 25 leprosy patients, 2 female patients having severe lepra reactions developed urinary tract infections. E. coli and Klebsiella were isolated from their urine. The urinary IgG levels in those two cases were found to be the highest in the series.

Albuminuria↗

Immunological evaluation of four arc welders exposed to fumes from ignited polyurethane (isocyanate) foam: antibodies and immune profiles.

Four arc welders having a flu-like illness with multiple health complaints following an exposure to high concentrations of isocyanate fumes from ignited polyurethane foam underwent immunological tests as follows: ELISA antibody assays, activated lymphocyte profiles, and lymphocyte blastogenesis. ELISA procedures revealed the presence of antibodies to hexamethylene diisocyanate (HDI) and formaldehyde (F) conjugated to human serum albumin (HDI-SA and F-SA). The results from the activated lymphocyte profiles showed deviations from the norm as follows: three welders had elevated helper/suppressor (H/S) ratios; all four had elevated percentages of Tal positive cells; two had decreases in B cells; and one had low total white cell and lymphocyte counts. In contrast, the percentage and absolute numbers of ILS receptor cells were normal in the four subjects. T cell blastogenesis to PHA, Con A and PWM resulted in the following: T-cells from one subject responded normally; in another, a high response (212% of controls) to PHA occurred with normal mitogenesis to Con A and PWM. In the remaining two welders, the T cells responded abnormally low (50 to 75% of controls) to the three mitogens. In conclusion, the existence of IgG antibodies to HDI-SA and F-SA, the altered activated immune profiles, the elevated Tal cells, and the abnormal blastogenesis are interpreted as being linked with the episode of HDI and F exposure and the subsequent flu-like illness of the four welders.

Adult↗

Theoretical accounts of Gulf War Syndrome: from environmental toxins to psychoneuroimmunology and neurodegeneration.

Non-specific illness includes a wide variety of symptoms: behavioural (e.g., reduced food and water intake), cognitive (e.g., memory and concentration problems) and physiological (e.g., fever). This paper reviews evidence suggesting that such symptoms can be explained more parsimoniously as a single symptom cluster than as a set of separate illnesses such as Gulf War Syndrome (GWS) and chronic fatigue syndrome (CFS). This superordinate syndrome could have its biological basis in the activity of pro-inflammatory cytokines (in particular interleukin-1: IL-1), that give rise to what has become known as the 'sickness response'. It is further argued that the persistence of non-specific illness in chronic conditions like GWS may be (in part) attributable to a bio-associative mechanism (Ferguson and Cassaday, 1999). In the case of GWS, physiological challenges could have produced a non-specific sickness response that became associated with smells (e.g., petrol), coincidentally experienced in the Persian Gulf. On returning to the home environment, these same smells would act as associative triggers for the maintenance of (conditioned) sickness responses. Such associative mechanisms could be mediated through the hypothalamus and limbic system via vagal nerve innervation and would provide an explanation for the persistence of a set of symptoms (e.g., fever) that should normally be short lived and self-limiting. We also present evidence that the pattern of symptoms produced by the pro-inflammatory cytokines reflects a shift in immune system functioning towards a (T-helper-1) Th1 profile. This position contrasts with other immunological accounts of GWS that suggest that the immune system demonstrates a shift to a Th2 (allergy) profile. Evidence pertaining to these two contrasting positions is reviewed.

Association↗

[Application of DNA microarray technology in immunological research and its inspiration to researches on traditional Chinese medicine].

DNA microarray technology is a high throughout method that can analyze the expression of thousands of genes at the same time to form a complete cellular gene expression profile. It has been applied in immunological researches such as the development, maturation, activation and differentiation of immune cells, the regulation of immune responses, the molecular mechanism of allergy, the relation between phenotype and gene expression, and immunological pharmacology, etc. It has deepened our perception of the immune system. It will as well be helpful in the research of the regulative mechanism of traditional Chinese medicine (TCM) toward immune cells and immune responses, the therapeutic mechanisms of TCM toward allergy, the standardization of differentiation of syndrome and herbal pharmacology, etc. The data analysis of the results of DNA microarray experiments is aimed to compare the difference of gene expression levels of different samples and obtain diagnostic gene expression profiles. But there are controversies about the number of samples and choices of statistical methods. Researchers are striving in setting standards of DNA microarray experiments.

Allergy and Immunology↗

Phase I study of a vaccine using recombinant vaccinia virus expressing PSA (rV-PSA) in patients with metastatic androgen-independent prostate cancer.

BACKGROUND: A Phase I trial of recombinant vaccinia prostate specific antigen (rV-PSA) in patients with advanced metastatic prostate cancer was conducted. This report describes 42 patients who were treated with up to three monthly vaccinations. METHODS: All patients were entered on a dose-escalation phase I study of recombinant vaccinia containing the gene for PSA (rV-PSA). The primary objective of this study was to determine the safety of this vaccine in metastatic androgen-independent prostate cancer patients. A secondary objective was to assess evidence of anti-tumor activity by PSA measurements, radiologic findings, and immunologic methods. RESULTS: There was no significant treatment-related toxicity apart from erythema, tenderness, and vesicle formation that lasted several days at the site of injection in some patients. There were immunologic responses, in selected patients, as evidenced by an increase in the proportion of PSA-specific T cells after vaccination. Furthermore, we show that these patients' T cells can lyse PSA-expressing tumor cells in vitro. CONCLUSION: Given the low toxicity profile and the evidence of immunologic activity, we believe future study is warranted with PSA-based vaccines in prostate cancer. New PSA-based vaccines and vaccine strategies are currently being evaluated.

Adenocarcinoma↗

The integration of conventional and unconventional T cells that characterizes cell-mediated responses.

This review builds on evidence that cell-mediated immune responses to bacteria, viruses, parasites, and tumors are an integration of conventional and unconventional T-cell activities. Whereas conventional T cells provide clonal antigen-specific responses, unconventional T cells profoundly regulate conventional T cells, often suppressing their activities such that immunopathology is limited. By extrapolation, immunopathologies and inflammatory diseases may reflect defects in regulation by unconventional T cells. To explore the function of unconventional T cells, several extensive gene expression analyses have been undertaken. These studies are reviewed in some detail, with emphasis on the mechanisms by which unconventional T cells may exert their regulatory functions. Highlighting the fundamental nature of T-cell integration, we also review emerging data that the development of conventional and unconventional T cells is also highly integrated.

Animals↗

Long-term exposure of the HT-29 human intestinal epithelial cell line to TNF causes sustained up-regulation of the polymeric Ig receptor and proinflammatory genes through transcriptional and posttranscriptional mechanisms.

Transport of IgA Abs across intestinal epithelial cells into gut secretions is mediated by the polymeric Ig receptor (pIgR). The cytokine TNF plays a central role in initiating and amplifying inflammatory reactions, and is implicated in the pathogenesis of inflammatory bowel diseases. Acute exposure of intestinal epithelial cell lines to TNF has been shown to up-regulate transcription of genes encoding pIgR and a number of proinflammatory factors, but the effects of chronic exposure to TNF have not been studied. We found that exposure of HT-29 human colon carcinoma cells to TNF for up to 20 days reduced the rate of cell proliferation, but did not cause gross morphological changes. Expression of mRNA encoding pIgR and several proinflammatory genes increased acutely, and then diminished but remained elevated above control levels throughout the experiment. Changes in gene expression were paralleled by increased expression of the transcription factors IFN regulatory factor-1 and the RelB subunit of NF-kappaB. HT-29 cells activated the endogenous TNF gene in response to TNF treatment, but the level of TNF production was insufficient to maintain pIgR and proinflammatory gene expression after withdrawal of exogenous TNF. Chronic exposure to TNF caused a marked increase in pIgR mRNA stability and a small but significant decrease in TNF mRNA stability, but no change in the half-lives of IL-8, c-Myc, and GAPDH. In summary, we observed different effects of acute vs chronic exposure to TNF on gene expression, and found evidence for transcriptional and posttranscriptional regulation of expression of the pIgR.

Cell Proliferation↗

Methods and approaches in the analysis of gene expression data.

The application of high-density DNA array technology to monitor gene transcription has been responsible for a real paradigm shift in biology. The majority of research groups now have the ability to measure the expression of a significant proportion of the human genome in a single experiment, resulting in an unprecedented volume of data being made available to the scientific community. As a consequence of this, the storage, analysis and interpretation of this information present a major challenge. In the field of immunology the analysis of gene expression profiles has opened new areas of investigation. The study of cellular responses has revealed that cells respond to an activation signal with waves of co-ordinated gene expression profiles and that the components of these responses are the key to understanding the specific mechanisms which lead to phenotypic differentiation. The discovery of 'cell type specific' gene expression signatures have also helped the interpretation of the mechanisms leading to disease progression. Here we review the principles behind the most commonly used data analysis methods and discuss the approaches that have been employed in immunological research.

Classification↗

Characterization of six highly mosquitocidal Bacillus thuringiensis strains that do not belong to H-14 serotype.

Four strains belonging to Bacillus thuringiensis serovars thompsoni, malaysiensis, canadensis, jegathesan and two auto-agglutinating B.t. strains were identified as being highly toxic to the mosquito larvae of the species Aedes aegypti, Anopheles stephensi, and Culex pipiens. Their larvicidal and hemolytic activities were determined and compared with those of strains known to be highly mosquitocidal and/or cytolytic from serovars of B.t. israelensis, morrisoni, darmstadiensis, medellin, kyushuensis, and fukuokaensis. The electrophoretic protein profiles of purified crystals and immunological relationships with B.t.i. polypeptides were studied. Five out of the six new strains showed the same larvicidal and hemolytic activities and the same crystal proteins and toxin genes as B.t.i. One strain, B.t. jegathesan 367, presented a novel pattern of larvicidal activity and a protein profile different from those of other strains.

Animals↗

Biologically active luteinizing hormone (LH) in plasma. V. A re-analysis of the differences in the ratio of biological to immunological LH activities during the menstrual cycle.

The relationship between the biological and immunological activities of human luteinizing hormone (hLH) in plasma collected from female subjects was examined. The biological activity was measured by an in vitro bioassay and the immunological activity by an hLH radioimmunoassay (RIA), using improved reagents, such as the 1st IRP for human pituitary LH for immunoassay (code No. 68/40) as standard, a subunit-free biologically active iodinated hLH preparation as tracer and an anti-hLH serum of relatively high specificity. Similar profiles of biological (B) and immunological (I) activity were obtained in the plasma samples collected daily throughout 40 menstrual cycles (5 cycles from each of 8 subjects). However, the B/I ratios were significantly lower during the period of LH surge (P less than 0.001) than throughout the remainder of the cycle. The within- and between-assay variation in B/I ratios was investigated by the simultaneous assay of biological and immunological activities in plasma pools obtained by combining equal aliquots of plasma from each daily sample of the menstrual cycle from each of 5 cycles of each of 4 subjects. The analysis of these 20 pools revealed highly significant individual differences in B/I ratios, ranging from 0.81 to 1.33. The coefficient of variation was 20% between-subjects and 5% within-subjects. There was no seasonal variation in B/I ratios. That the individual differences in plasma B/I ratios were not attributable to the procedure of pooling was ascertained by the simultaneous assay of both activities in parellel in daily plasma samples and in the pools formed from these samples from three complete cycles. Thus the analysis of the differences in B/I ratios obtained throughout the menstrua- cycle revealed three major sources of variation. The first occurs in the form of generally elevated (higher than unity) B/I ratios, the second consists of a significant drop in B/I ratios during the midcycle LH surge, and the third source is represented by the significant between-subject differences. It is concluded that the first source is attributable to the relatively higher levels of "impurity" (i.e. biologically inactive, immunologically active material) in the standard preparation compared to those present in plasma of biologically inactive, immunologically active material of unknown composition and origin. If so, the latter source limits the quantitative significance of the RIA procedures employed. It is suggested that these three sources of variation account for most of the differences in B/I ratios for plasma lLH reported in the literature.

Adult↗

Profiling of CD4+, CD8+, and CD4+CD25+CD45RO+FoxP3+ T cells in patients with malignant glioma reveals differential expression of the immunologic transcriptome compared with T cells from healthy volunteers.

PURPOSE: Analyses of T-cell mRNA expression profiles in glioblastoma multiforme has not been previously reported but may help to define and characterize the immunosuppressed phenotype in patients with this type of cancer. EXPERIMENTAL DESIGN: We did microarray studies that have shown significant and fundamental differences in the expression profiles of CD4(+) and CD8(+) T cells and immunosuppressive CD4(+)CD25(+)CD45RO(+)FoxP3(+) regulatory T cells (T(reg)) from normal healthy volunteers compared with patients with newly diagnosed glioblastoma multiforme. For these investigations, we isolated total RNA from enriched CD4(+) and CD8(+) T cell or T(reg) cell populations from age-matched individuals and did microarray analyses. RESULTS: ANOVA and principal components analysis show that the various T cell compartments exhibit consistently similar mRNA expression profiles among individuals within either healthy or brain tumor groups but reflect significant differences between these groups. Compared with healthy volunteers, CD4(+) and CD8(+) T cells from patients with glioblastoma multiforme display coordinate down-regulation of genes involved in T cell receptor ligation, activation, and intracellular signaling. In contrast, T(regs) from patients with glioblastoma multiforme exhibit increased levels of transcripts involved in inhibiting host immunity. CONCLUSION: Our findings support the notion that key differences between expression profiles in T-cell populations from patients with glioblastoma multiforme results from differential expression of the immunologic transcriptome, such that a limited number of genes are principally important in producing the dysregulated T-cell phenotype.

Adult↗