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PubMed1991

Lichen planus.

During the past year, few articles have been published regarding the various aspects of oral lichen planus. The work reported dealt with a variety of aspects including patient profile, immunopathogenesis, and treatment. The papers served to confirm previous concepts of an immunologic etiology, the demographic consensus on patient profiles, and the use of topical or systemic corticosteroids as the most effective treatment approach. This review also summarizes some highlights of previous studies of oral lichen planus prior to 1990 and summarizes a current unpublished prospective study reflecting the findings in a large number of patients with oral lichen planus who have been followed for a long period of time.

Adrenal Cortex Hormones↗
PubMed2005

Diagnostic procedures in tularaemia with special focus on molecular and immunological techniques.

Tularaemia is a severe bacterial zoonosis caused by the highly infectious agent Francisella tularensis. It is endemic in countries of the northern hemisphere ranging from North America to Europe, Asia and Japan. Very recently, Francisella-like strains causing disease in humans were described from tropical northern Australia. In the last decade, efforts have been made to develop sensitive and specific immunological and molecular techniques for the laboratory diagnosis of tularaemia and also for the definite identification of members of the species F. tularensis and its four subspecies. Screening for the keyword 'Francisella' a Medline search over the last decade was performed and articles describing diagnostic methods for tularaemia and its causative agent were selected. Besides classical microbiological techniques (cultivation, biochemical profiling, susceptibility testing) several new immunological and molecular approaches to identify F. tularensis have been introduced employing highly specific antibodies and various polymerase chain reaction (PCR)-based methods. Whereas direct antigen detection by enzyme-linked immunosorbent assay (ELISA) or immunofluorescence might allow early presumptive diagnosis of tularaemia, these methods--like all PCR techniques--still await further evaluation. Therefore, diagnosis of tularaemia still relies mainly on the demonstration of specific antibodies in the host. ELISA and immunoblot methods started to replace the standard tube or micro-agglutination assays. However, the diagnostic value of antibody detection in the very early clinical phase of tularaemia is limited. Francisella tularensis is regarded as a 'highest priority' biological agent (category 'A' according to the CDC, Atlanta, GA, USA), thus rapid and reliable diagnosis of tularaemia is required not only for a timely onset of therapy, the handling of outbreak investigations but also for the surveillance of endemic foci. Only very recently, evaluated test kits for serological diagnosis of human tularaemia became available, while the introduction of standardized molecular techniques for detection and typing is still missing.

Animals↗
PubMed2006

Gene expression profiling in allergy and asthma.

DNA array technique was applied for the simultaneous analysis of multiple genes for the characterization of diseases and for cellular analysis. This technology implicated genes in the pathogenesis of allergic disease, which were previously not discussed in this context. This article summarizes results of gene expression profiling of allergic disease and immunologically relevant cells, using DNA array technology. The results of these studies are searchable in public databases and represent exciting tools to study gene expression of diseases on a global base.

Animals↗
PubMed2006

Uncoupling of T-cell effector functions by inhibitory killer immunoglobulin-like receptors.

Killer immunoglobulin-like receptors (KIRs) are a family of regulatory cell-surface molecules expressed on natural killer (NK) cells and memory T-cell subsets. Their ability to prevent the formation of an activation platform and to inhibit NK cell activation is the basis of the missing self model of NK cell function. The benefits of KIR expression for T-cell biology are unclear. We studied how KIR2DL2 regulates T-cell function. Engagement of KIR2DL2 by the ligand human leukocyte antigen (HLA)-Cw3 did not affect conjugate formation between CD4(+)KIR2DL2(+) T cells and superantigen-pulsed target cells or the development of mature immune synapses with lipid rafts. KIR2DL2 and the corresponding HLA-C ligand were initially recruited to the peripheral supramolecular activation cluster (pSMAC). Consequently, KIR2DL2 engagement did not inhibit the phosphorylation of early signaling proteins and T-cell-receptor (TCR)-mediated cytotoxicity or granule exocytosis. After 15-30 minutes, KIR2DL2 moved to the central supramolecular activation cluster (cSMAC), colocalizing with CD3. TCR synapses dissociated, and phosphorylated phospholipase C (PLC)-gamma1, Vav1, and extracellular signal-regulated kinase 1/2 (ERK1/2) were reduced 90 minutes after stimulation. Gene array studies documented that the inhibition of late signaling events by KIR2DL2 affected transcriptional gene activation. We propose that KIRs on memory T cells operate to uncouple effector functions by modifying the transcriptional profile while leaving granule exocytosis unabated.

CD4-Positive T-Lymphocytes↗
PubMed2005

The predominant Th1 cytokine profile in maternal plasma of preeclamptic women is not reflected in the choriodecidual and fetal compartments.

OBJECTIVE: Human pregnancy disorders such as preeclampsia are thought to involve variations in cytokine levels. It has been proposed that, in preeclamptic women, a balance favoring the Th1-type over the Th2-type cytokine profile determines local or systemic immunologic responses to pregnancy and that this may cause defective placental implantation and placental ischemia, which activate systemic endothelial cells. The purpose of this study was to determine whether cytokine expression differs in the maternal, choriodecidual, and fetal compartments, and between women with or without preeclampsia. METHODS: Plasma concentrations of interferon gamma (IFNgamma), interleukin (IL)-2, IL-4, and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA) in samples obtained from maternal peripheral blood (MPB), choriodecidual (CD), and fetal cord (FC) blood compartments of 17 women with preeclampsia and in 15 normotensive women. Intracellular concentrations of IFNgamma and IL-2 in T lymphocytes were assessed by flow cytometry. RESULTS: Plasma IFNgamma concentrations in both MPB and CD compartments were significantly higher in preeclamptic than in normotensive women. Maternal plasma IL-4 concentration was significantly lower in preeclamptic than in normotensive women. Intracellular IFNgamma and IL-2 concentrations did not differ significantly between preeclamptic and normotensive women. CONCLUSIONS: The dominant Th1-type over Th2-type cytokine profile is evident in MPB, but not in the CD and FC blood compartments. This might reflect the complex cytokine networks in the fetal-placental interface and might involve trophoblasts or decidual and endothelial cells, which could account for the increased plasma IFNgamma concentration and T-helper cell number.

Adult↗
PubMed2000

A randomized, controlled 24-week study of intermittent subcutaneous interleukin-2 in HIV-1 infected patients in Thailand.

OBJECTIVES: To assess the immunological and virological effects, safety profile and feasibility of subcutaneous interleukin-2 (scIL-2) therapy in an HIV-infected Thai population. DESIGN: Seventy-two patients with baseline CD4 cell count of > or = 350 x 10(6)/l and no history of opportunistic infection were randomized to receive antiretroviral therapy plus scIL-2 (scIL-2 group) or antiretroviral therapy alone (control group). scIL-2 was administered at one of three doses for at least 24 weeks. The main measure of treatment efficacy was change in CD4 cell count. RESULTS: The time-weighted mean change in CD4 cell count from baseline to week 24 was + 252 x 10(6)/l for the scIL-2 group compared with + 42 x 10(6)/l for the control group (P< 0.0001). Changes in plasma HIV RNA were not significantly different between the groups over the same time period: there was a 0.83 log10 copies/ml decrease for the scIL-2 group and a 0.70 log copies/ml decrease for the control group (P= 0.362). CONCLUSIONS: This study provides the most extensive experience of scIL-2 therapy in HIV-1 infected women and Asians, and demonstrates the immunological efficacy, tolerability and feasability of scIL-2 therapy in this population. Data from this study were instrumental in guiding the selection of the scIL-2 dosing regimen for ongoing phase III trials.

Adult↗
PubMed2005

Human embryonic stem cell derivation and directed differentiation.

Human embryonic stem cells (hESCs) are produced from normal, chromosomally aneuploid and mutant human embryos, which are available from in vitro fertilisation (IVF) for infertility or preimplantation diagnosis. These hESC lines are an important resource for functional genomics, drug screening and eventually cell and gene therapy. The methods for deriving hESCs are well established and repeatable, and are relatively successful, with a ratio of 1:10 to 1:2 hESC lines established to embryos used. hESCs can be formed from morula and blastocyst-stage embryos and from isolated inner cell mass cell (ICM) clusters. The hESCs can be formed and maintained on mouse or human somatic cells in serum-free conditions, and for several passages in cell-free cultures. The hESCs can be transfected with DNA constructs. Their gene expression profiles are being described and immunological characteristics determined. They may be grown indefinitely in culture while maintaining their original karyotype but this must be confirmed from time to time. hESCs spontaneously differentiate in the absence of the appropriate cell feeder layer, when overgrown in culture and when isolated from the ESC colony. All three major embryonic lineages are produced in differentiating attachment cultures and in unattached embryoid bodies. Cell progenitors of interest can be identified by markers, expression of reporter genes and characteristic morphology, and the culture thereafter enriched for further culture to more mature cell types. The most advanced directed differentiation pathways have been developed for neural cells and cardiac muscle cells, but many other cell types including haematopoietic progenitors, endothelial cells, lung alveoli, keratinocytes, pigmented retinal epithelium, neural crest cells and motor neurones, hepatic progenitors and cells that have some markers of gut tissue and pancreatic cells have been produced. The prospects for regenerative medicine are significant and there is much optimism for their contribution to human medicine.

Cell Differentiation↗
PubMed1993

Phenotypic and functional profile of peripheral blood mononuclear cells isolated from melanoma patients undergoing combined immunotherapy and chemotherapy.

In the present study we tested the phenotypic profile as well as several immunological responses of peripheral blood mononuclear cells (PBMC) isolated from melanoma patients. These patients underwent chemotherapy with dacarbazine and carboplatin from day 1 to day 22, followed by immunotherapy of low-dose recombinant interleukin-2 and recombinant interferon alpha administered subcutaneously from day 36 to day 75. The PBMC from 14 patients were isolated on day 0 before chemotherapy, on day 36 after chemotherapy and on day 76 after immunotherapy. After chemotherapy, a decrease in CD16+ cells and increase in CD3+ and CD4+ cells correlated with a significant decrease in the generation of lymphokine-activated killer (LAK) activity. After immunotherapy, an increase in CD16+ cells correlated with an increase in the induction of LAK activity. A comparison between responding and non-responding patients revealed statistically significant differences in LAK activity of PBMC and response to concanavalin A following chemotherapy, and in the percentage of CD8+ cells following immunotherapy. Our results point toward the value of continuing such a study on a larger population of cancer patients in order to select the appropriate bioassays for monitoring and predicting the clinical responsiveness to combined therapies.

Adult↗
PubMed1988

Biological, chromatographical, and radioimmunological evidence for a melanotropin-like peptide in the central nervous system of Locusta migratoria.

Our recent immunocytochemical study has demonstrated the existence of alpha-melanocyte stimulating hormone (alpha-MSH)-like material in the locust central nervous system. The aim of the present study was to further characterize alpha-MSH in the locust brain by its biological effect on frog skin and by high-pressure liquid chromatography in combination with radioimmunological and biological detection methods. Parallel radioimmunoassay (RIA) curves of crude nervous tissue extracts coupled with bioactivity in a very specific bioassay suggest similarity between the locust alpha-MSH-like substance and synthetic alpha-MSH. The highest concentration of alpha-MSH immunoreactive material in the central nervous system was found in the optic lobes, where alpha-MSH immunoreactive cell bodies are localized, as was previously shown by immunocytochemistry. High concentrations of alpha-MSH immunoreactive material were also detected in the thoracic ganglia of the locust ventral nervous system. The application of locust brain extracts to gel permeation HPLC resulted in a similar elution profile of the bioactive and immunologically active substances, both coeluting with synthetic alpha-MSH. As is the case for vertebrate brain material, reverse-phase HPLC revealed four alpha-MSH immunoreactive peaks. One of the peaks coelutes with monoacetyl-alpha-MSH and other RIA-positive material elutes at times close (but not identical) to the methionine sulfoxide forms of alpha-MSH. Peak three, however, elutes in a very different position from desacetyl-alpha-MSH. Peaks are absent in the position of desacetyl-alpha-MSH. Similarity between the locust alpha-MSH-related substance and authentic alpha-MSH is discussed.

Animals↗
PubMedDate not supplied

MHC expression in nonlymphoid tissues of the developing embryo: strongest class I or class II expression in separate populations of potential antigen-presenting cells in the skin, lung, gut, and inter-organ connective tissue.

We define expression of major histocompatibility complex (MHC) antigens in the nonlymphoid tissues of the developing rat. Antibodies to class I heavy and light chains (b2-m), and to class II MHC proteins were used. Strongest MHC expression was by individual cells in the skin, lung, gut, and inter-organ connective tissue. The class I+ and class II+ cells were distinct populations, differing in morphology, distribution, and expression of macrophage-associated antigens. A nonimmunologic role for MHC proteins in development has been proposed. Yet the distributions and antigenic profiles lead us to emphasize immunologic functions that may be served by the early presence of MHC+ cells outside the forming lymphoid organs. Potential contributions to establishment of extrathymic or maternal/fetal tolerance are discussed. Localization of strongest MHC expression to individual connective tissue cells of the developing organs, rather than parenchymal cells, is of clinical relevance to transplantation of fetal tissue.

Animals↗
PubMed2005

Intracellular cytokines may model immunoregulation of abacavir hypersensitivity in HIV-infected subjects.

BACKGROUND: The clinical treatment of patients with HIV and adverse drug events may be enhanced by an understanding of the underlying mechanisms. About 4% of patients with HIV receiving the potent antiretroviral drug abacavir develop a hypersensitivity reaction. This idiosyncratic reaction appears to have an immunologic component that has yet to be defined. Given that the T-cell type 2 cytokine IL-4 may be overproduced by patients with allergy or other immunologic dysregulation, an index cytokine profile could help elucidate the character of a drug-specific hypersensitivity reaction. OBJECTIVE: Quantitation of the production of the type 2 IL-4 and the counterregulatory type 1 cytokine IFN-gamma in patients with abacavir-related hypersensitivity. METHODS: Intracellular cytokines were enumerated in blood T cells by flow cytometry. Subjects were grouped for evaluation as patients with a hypersensitive response after abacavir treatment, patients initiating abacavir who also were evaluated again after 1 month on abacavir, patients on abacavir for 6 months without hypersensitivity, and HIV-naive control individuals. RESULTS: There was a significant association between increased IL-4 production by CD4 and CD8 T lymphocytes and hypersensitivity reactions to abacavir. Lymphocytes from hypersensitive subjects expressed CD28 and the anti-HIV chemokine macrophage inflammatory protein 1beta with a frequency comparable with HIV-naive control cells, suggesting the possibility that the activated T cells from patients with hypersensitivity are functional. CONCLUSION: The expansion of type 0 and type 2 T cells phenotyped by IL-4 production may correlate with abacavir-associated hypersensitivity. The data suggest a cytokine bias that may facilitate B-cell differentiation and downregulate T-cell cytotoxic responses.

Anti-HIV Agents↗
PubMed1998

DNA vaccination with HIV-1 expressing constructs elicits immune responses in humans.

Humoral and cellular immune responses have been produced by intramuscular vaccination with DNA plasmids expressing HIV-1 genes, suggesting possible immunotherapeutic and prophylactic value for these constructs. Vaccination with these constructs has decreased HIV-1 viral load in HIV-1-infected chimpanzees. In addition, naive (i.e. non-HIV-1-infected) chimpanzees were protected against a heterologous challenge with HIV-1. Ongoing phase I clinical trials show that therapeutic vaccinations indeed boost anti-HIV-1 immune responses in humans. A therapeutic phase I trial on humans with these constructs induced a good safety profile and also demonstrated an immunological potentiation. These findings indicate that further studies with these constructs in humans are warranted.

AIDS Vaccines↗
PubMed2000

New antibiotics for community-acquired lower respiratory tract infections: improved activity at a cost?

Opinions are changing as to the continued validity of traditional beta-lactam and macrolide therapy of community acquired LRTI, partly because of resistance and partly because of early evidence that suggests that some new agents may be more effective. Guidelines are altering to reflect this view, although there is conflicting evidence on their effects on outcome. Fluoroquinolones are becoming accepted in the treatment of community acquired pneumonia and are established choices for acute exacerbations of chronic bronchitis. The 8-methoxy fluoroquinolones, moxifloxacin and gatifloxacin, have excellent anti-pneumococcal activity and may become drugs of choice for penicillin/macrolide resistant infections. They appear free of the serious idiosyncratic reaction profiles, possibly related to the immunologically reactive 1-difluorophenyl substituent, which characterised the recently withdrawn temafloxacin, trovafloxacin and tosufloxacin. All quinolones so far tested appear to prolong the QTc interval, but only sparfloxacin and grepafloxacin caused clinical effects. Nevertheless, caution is required until this effect is fully investigated.

Administration, Oral↗
PubMed1989

Health and living conditions of centenarians in Hungary.

Demographic data of 218 centenarians in Hungary were collected, and 123 were examined by a medical team. This data showed that the centenarians are from families with a history of longevity. A larger proportion of the centenarians live in the capital, Budapest, than in the rural areas. The centenarians are mostly manual workers (rural) and nonmanual workers. Most of them live with their families. The centenarians are healthier than the general population, drug consumption is low, and they have good adaptative abilities. We compared the clinical laboratory findings of the centenarians with that of 60-80 year olds. Though age-related changes were present in the centenarians, these age-related biological changes did not hinder them from reaching very old age. Finally, we found a few differences in the immunological, clinical laboratory, and morphological profiles of this population. We anticipate more extensive elaboration on this data in future publications.

Aged↗
PubMed2001

Evolution of immunosuppression and continued importance of acute rejection in renal transplantation.

As steady improvement in short-term kidney graft survival and long-term outcomes prolongs the lives of transplant patients, responsibility for their care is shifting away from transplant specialists and into the hands of community nephrologists. Therefore, community nephrologists need to have a deeper understanding of immunosuppressive therapies than ever before. Pharmacologic immunosuppression has been continuously evolving over the past two decades. Azathioprine was introduced in the early 1960s. Introduction of cyclosporine (CsA) in 1983 revolutionized short-term outcomes after renal transplantation. The first monoclonal antibody immunosuppressant, OKT3, was introduced in 1986. The 1990s saw the introduction of a number of important new agents, including mycophenolate mofetil (MMF), tacrolimus, and a microemulsion CsA, as well as two new monoclonal antibodies. Combinations of these new agents, along with improving clinical care, have produced 1-year patient survival approaching 100% and graft survival exceeding 90%. The newest class of agents, the first of which is sirolimus, is called target of rapamycin (TOR) inhibitors and is used with CsA for maintenance therapy. Immunosuppressive drug therapy after kidney transplantation continues to evolve. There is a variety of pharmacologic combinations from which to choose, based on immunologic risk and side effect profiles. As new regimens are developed, ongoing communications between the transplant center and community nephrologists will be required to implement therapeutic changes and optimize patient care successfully.

Graft Rejection↗
PubMed2000

The evolving role of dendritic cell therapy in urologic oncology.

The recognition that dendritic cells, the most potent antigen-presenting cells, play a pivotal role in the induction of antitumor immunity has reshaped the development of tumor vaccines in clinical medicine. Early clinical trials of administration of dendritic cell-based vaccines to patients with genitourinary malignancies showed low toxicity profiles, and provided evidence for immunologic and clinical responses in some patients. Although the development of dendritic cell-based vaccines is still in its infancy, the prospects of ultimately generating clinically effective cancer vaccines have become more realistic.

Cancer Vaccines↗
PubMed1985

Oxidative transformations of arachidonic acid in human dispersed lung cells: disparity between the utilization of endogenous and exogenous substrate.

Eicosanoid release from human dispersed lung cells (HDLC) containing ca 5% mast cells was studied before and after cell activation with ionophore A23187 or anti-IgE. Basal release of eicosanoids synthesized from endogenous arachidonate was measured by radioimmunoassay. In descending order of abundance the products were: 5-hydroxyeicosatetraenoic acid (5-HETE) greater than thromboxane B2 (TXB2) greater than prostaglandin F2 alpha (PGF2 alpha) approximately immunoreactive (i)-PGE2 greater than PGD2 greater than 6-keto-PGF1 alpha approximately i-LTC4. Stimulation of HDLC with ionophore A23187 or, after passive sensitization, with anti-IgE resulted in 2-10 fold increases in the generation of individual eicosanoids. In terms of net generation the most abundant products were PGD2 and TXB2 with either stimulus. Activation with A23187 caused net release of i-LTC4 and 5-HETE, but these products were not measured after immunological activation. A more complete profile of lipoxygenase products released from HDLC dispersed from one lung was obtained after separation by high performance liquid chromatography combined with ultra violet spectroscopy and bioassay. The major products released from the cells from this lung with ionophore stimulation were 13-hydroxylinoleic acid greater than LTB4 greater than 5-HETE greater than 12-HETE greater than LTC4 greater than 15-HETE greater than 11-HETE approximately 9-HETE. When the utilization of exogenous [14C]-arachidonic acid for prostanoid biosynthesis was compared to that of endogenous unlabelled arachidonate the formation of TXB2 was consistently underestimated. These results imply compartmentalization of arachidonic acid utilization in Ca2+-activated HDLC. In unstimulated cells the proportional formation of PGD2 was overestimated when exogenous arachidonic acid was substrate. After activation with A23187 the proportions of PGD2 were similar with both substrate sources. The large proportions of PGD2 and TXB2 generated by HDLC further supports the view that these eicosanoids may be important inflammatory mediators in lung tissue.

Arachidonic Acid↗
PubMed2006

Epidemiological and clinical features, response to HAART, and survival in HIV-infected patients diagnosed at the age of 50 or more.

BACKGROUND: Over the last years, the mean age of subjects with HIV infection and AIDS is increasing. Moreover, some epidemiological and clinical differences between younger and older HIV-infected individuals have been observed. However, since introduction of HAART therapy, there are controversial results regarding their response to HAART. The aim of the present study is to evaluate epidemiological and clinical features, response to HAART, and survival in elderly HIV-infected patients with regard to younger HIV-infected patients. METHODS: A prospective cohort study (1998-2003) was performed on patients from Sabadell Hospital, in Northeast of Spain. The cohort includes newly attended HIV-infected patients since January 1, 1998. For the purpose of this analysis, data was censured at December 31, 2003. Taking into account age at time of diagnosis, it was considered 36 HIV-positive people aged 50 years or more (Group 1, G1) and 419 HIV-positive people aged 13-40 years (Group 2, G2). Epidemiological, clinical, biological and therapy data are recorded. Statistical analysis was performed using Chi-squared test and Fisher exact test, Mann-Whitney U test, Kaplan-Meier, Log Rank test, and Two-Way ANOVA from random factors. RESULTS: G1 showed higher proportion of men than G2. The most common risk factors in G1 were heterosexual transmission (P = 0.01) and having sex with men or women (P < 0.001). G1 and G2 show parallel profiles through the time regarding immunological response (P = 0.989) and virological response (P = 0.074). However, older people showed lower CD4 cell counts at first clinic visit (P < 0.001) and, eventually, they did not achieve the same counts as G2. G1 presented faster progression to AIDS (P < 0.001) and shorter survival (P < 0.001). CONCLUSION: Older patients have different epidemiological features. Their immunological and virological responses are good. However, older patients do not achieve the same CD4 cell counts likely due to they have lower counts at first clinic visit. Thus, it is essential physicians know older HIV-infected patients features to consider the possibility of HIV infection in these patients with the aim of treatment would not be delayed.

Adolescent↗