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Sample records for patients exhibiting immunological

  1. [Immunologic parameters in patients with malignant melanoma].

    PubMed

    Koníková, E; Babusíková, O; Havránková, M

    1989-12-01

    In an attempt to better define the immunological reactivity of patients with malignant melanoma, the electrophoretic mobility of lymphocytes and their reactivity were studied in poly-L-lysine agglutination and in nucleolar test. Blood samples were examined before treatment and repeatedly after surgical removal of the tumor. A microagglutination test induced by poly-L-lysine was used for the detection of sensitized lymphocytes in peripheral blood of melanoma patients. The number of positive results was increasing with the progression of the disease. After incubation with poly-L-lysine the electrophoretic mobility of lymphocytes was changed in melanoma patients. The nucleolar test was used for the study of quantitative and morphological changes of the nucleoli in lymphocytes. Elevated values of the nucleolar coefficient and an increased number of active nucleoli provided evidence on the higher immunological reactivity of melanoma patients. The decline in the number of lymphocytes with ring-shaped nucleoli, signaling immunologic exhaustion, are of prognostic value. Lymphocytes were assayed also for the presence of receptors for sheep erythrocytes (E active and total rosettes) and C3d component of complement (EAC rosettes). The reported findings may be used to advantage in evaluating the immunological reactivity of melanoma patients. PMID:2627650

  2. Immunologic profile of patients with fibromyalgia.

    PubMed

    Smart, P A; Waylonis, G W; Hackshaw, K V

    1997-01-01

    Fibromyalgia is a musculoskeletal disorder characterized by generalized myalgias, arthralgias widespread tender points in discreet areas on examination. It is frequently accompanied by fatigue, stiffness, and a nonrestorative sleep pattern. These patients generally have a normal blood count and chemistry profile. There is a subset of people with fibromyalgia (FM) who test positive for the antinuclear antibody (ANA) and have constitutional symptoms that resemble those of patients with early lupus. We studied the immunologic profile of patients with FM who are ANA-positive (+). A retrospective review of patient records in a university-based rheumatology practice was conducted. In a group of 66 FM patients, 30% (20) were ANA+, with a 75% preponderance of the speckled pattern and 20% diffuse pattern. The remaining 5% were equally split between diffuse-speckled and speckled-nucleolar patterns. All had negative staining for extractable nuclear antibodies. The Smart Index (SI), a ratio of the sedimentation rate to one-half the patient's age, was developed to characterize each patient's inflammatory response. The FM patients who were ANA negative (-) had a mean SI of 0.55, whereas the FM patient's who were ANA+ had a SI of 1.07. These ANA+ patients represent a subgroup of patients who have FM with an inflammatory response profile larger than that of the ANA-patients. PMID:9207710

  3. Cellular and molecular immunologic mechanisms in patients with atopic dermatitis.

    PubMed

    Werfel, Thomas; Allam, Jean-Pierre; Biedermann, Tilo; Eyerich, Kilian; Gilles, Stefanie; Guttman-Yassky, Emma; Hoetzenecker, Wolfram; Knol, Edward; Simon, Hans-Uwe; Wollenberg, Andreas; Bieber, Thomas; Lauener, Roger; Schmid-Grendelmeier, Peter; Traidl-Hoffmann, Claudia; Akdis, Cezmi A

    2016-08-01

    Atopic dermatitis (AD) is a complex skin disease frequently associated with other diseases of the atopic diathesis. Recent evidence supports the concept that AD can also recognize other comorbidities, such as chronic inflammatory bowel or cardiovascular diseases. These comorbidities might result from chronic cutaneous inflammation or from a common, yet-to-be-defined immunologic background leading to immune deviations. The activation of immune cells and their migration to the skin play an essential role in the pathogenesis of AD. In patients with AD, an underlying immune deviation might result in higher susceptibility of the skin to environmental factors. There is a high unmet medical need to define immunologic endotypes of AD because it has significant implications on upcoming stratification of the phenotype of AD and the resulting targeted therapies in the development of precision medicine. This review article emphasizes studies on environmental factors affecting AD development and novel biological agents used in the treatment of AD. Best evidence of the clinical efficacy of novel immunologic approaches using biological agents in patients with AD is available for the anti-IL-4 receptor α-chain antibody dupilumab, but a number of studies are currently ongoing with other specific antagonists to immune system players. These targeted molecules can be expressed on or drive the cellular players infiltrating the skin (eg, T lymphocytes, dendritic cells, or eosinophils). Such approaches can have immunomodulatory and thereby beneficial clinical effects on the overall skin condition, as well as on the underlying immune deviation that might play a role in comorbidities. An effect of these immunologic treatments on pruritus and the disturbed microbiome in patients with AD has other potential consequences for treatment. PMID:27497276

  4. [Effect of Jinshuibao capsule on the immunological function of 36 patients with advanced cancer].

    PubMed

    Zhou, D H; Lin, L Z

    1995-08-01

    Jinshuibao Capsule (JSBC), produced by Jiangxi Jinshuibao pharmaceutical Company Limited, possesses the similar active principles and pharmacological activity with those of Cordyceps sinensis. The effect of JSBC on the immunological function of 36 patients with advanced cancer showed that it could restore cellular immunological function, improve quality of life, but had no significant effect on humoral immunological function. The results suggested that JSBC could be used as adjuvant drug in advanced cancer. PMID:8580695

  5. [Immunologic and genetic status of a patient with 4 primary neoplasms].

    PubMed

    Fuith, L C; Zwierzina, H; Schröcksnadel, H; Dapunt, O

    1988-01-01

    Case report of patient with four primary malignancies manifested independently (carcinoma in situ of uterine cervix, vulvar cancer, malignant lentigo on the face and rectal cancer). Immunologic and genetic changes could be demonstrated. PMID:3376614

  6. Clinical Immunology Review Series: An approach to the patient with recurrent superficial abscesses

    PubMed Central

    Johnston, S L

    2008-01-01

    ARTICLES PUBLISHED IN THIS CLINICAL IMMUNOLOGY REVIEW SERIES allergy in childhood, allergy diagnosis by use of the clinical immunology laboratory, anaphylaxis, angioedema, management of pulmonary disease in primary antibody deficiency, recurrent infections in childhood, recurrent infections in adulthood, recurrent oro-genital ulceration, recurrent superficial abscesses, urticaria, vasculitis/CTD Patients may be referred to the immunology clinic for investigation of recurrent superficial abscess formation. In the majority of adult patients this clinical presentation does not equate with an underlying primary immune deficiency. Nevertheless, recurrent mucocutaneous abscesses can be associated with significant morbidity and long-term complications, including scarring and fistula formation, and may be associated with underlying immune-mediated disease. This review sets out an approach to the patient with recurrent superficial abscesses, focusing on the differential diagnoses, investigation and management of both the common causes and those associated with specific immune deficiency. PMID:18422735

  7. Parasitological and immunological diagnosis of Strongyloides stercoralis in patients with gastrointestinal cancer.

    PubMed

    Machado, Eleuza R; Teixeira, Eliane M; Gonçalves-Pires, Maria Do Rosario F; Loureiro, Zaira M; Araújo, Rogério A; Costa-Cruz, Julia M

    2008-01-01

    This study examined the frequency of Strongyloides stercoralis infection in patients with gastrointestinal cancer through parasitological and immunological tests. A total of 77 patients were evaluated, 33 with gastrointestinal cancer and 44 controls with other types of cancers. All the patients were undergoing chemotherapy and 14 (18.2%) were receiving concomitant radiotherapy. For a parasitological diagnosis, we applied the Baermann and Lutz methods. The immunological diagnosis involved the indirect fluorescence antibody test (IFAT) and enzyme linked immunosorbent assay (ELISA) to detect IgG antibodies using Strongyloides ratti antigens. The frequency of positive S. stercoralis in gastrointestinal cancer diagnosed by parasitological methods was 3 cases (9.1%), by serology it was 8 cases (24.2%). In the control group 1 case (2.3%) of S. stercoralis was diagnosed by parasitological methods and 2 cases (4.5%) by immunological tests (p<0.05). Patients with gastrointestinal cancer had a 6.7-fold greater chance of testing positive for S. stercoralis infection. Our data highlight the importance of parasitological and immunological diagnosis for S. stercoralis in patients with gastrointestinal cancer living in endemic areas of strongyloidiasis, since they have a higher risk of becoming infected with S. stercoralis than patients with other types of cancer. PMID:17852953

  8. Prognostic and predictive value of immunological parameters for chemoradioimmunotherapy in patients with pancreatic adenocarcinoma

    PubMed Central

    Karakhanova, S; Ryschich, E; Mosl, B; Harig, S; Jäger, D; Schmidt, J; Hartwig, W; Werner, J; Bazhin, A V

    2015-01-01

    Background: Chemoradioimmunotherapy of patients with pancreatic adenocarcinoma from the CapRI trial did not show any benefit of interferon-α in addition to a 5-fluorouracil (5FU)-based treatment. The aim of this study was to identify immunological parameters in patients from this trial to be used for predictive and/or prognostic purposes. Methods: The following methods were used: tumour immunohistology, FACS analyses, cytokine measurement, as well as cytotoxicity and ELIspot. Immunological parameters were correlated with patients' survival using the Kaplan–Meier method. Results: Irrespective of therapy type, high lymphocyte accumulation in tumours and frequencies of NK cells and effector (eff) CD8+ T cells in peripheral blood of the patients were associated with patients' survival. Amount of CD3+ and effector-memory CD8+ blood lymphocytes, expression of CD152 and interleukin (IL)-2 serum level showed a predictive value for chemoradioimmunotherapy. Tumoural accumulation of CD3+ and CD8+ cells was predictive for outcome of chemotherapy alone. Besides, we identified the frequencies of CD3+ lymphocytes, effCD8+ T cells and NK cells in the peripheral blood of the patients, and IL-10 amount in serum, to be predictive values for 5FU-based chemotherapy. Conclusions: Immunological parameters, identified in this trial as possible markers, may be of interest in personalized medicine towards the improvement of the treatment and prognosis of pancreatic carcinoma patients. PMID:25742476

  9. Immunological studies of cerebrospinal fluid from patients with CNS symptoms after human papillomavirus vaccination.

    PubMed

    Takahashi, Yukitoshi; Matsudaira, Takashi; Nakano, Hitoshi; Nasu, Hirosato; Ikeda, Hitoshi; Nakaoka, Kentaro; Takayama, Rumiko; Oota, Masayasu

    2016-09-15

    In 32 patients with prolonged central nervous system symptoms after human papillomavirus (HPV) vaccination, we measured conventional and immunological markers in cerebrospinal fluid (CSF) and compared with the levels in disease controls. Our studies revealed significantly decreased chloride and neuron-specific enolase (NSE) levels in CSF of patients with CNS symptoms after HPV vaccination compared to disease controls. IL-4, IL-13, and CD4(+) T cells increased significantly in patients, and IL-17 increased significantly from 12 to 24months after symptom onset. Chemokines (IL-8 and MCP-1) were also elevated, but CD8(+) T cells, PDGF-bb and IL-12 were reduced. Antibodies to GluN2B-NT2, GluN2B-CT and GluN1-NT increased significantly. These results suggest biological, mainly immunological, changes in the CSF of patients after HPV vaccination. PMID:27609278

  10. Immunological findings in epileptic and febrile convulsion patients before and under treatment.

    PubMed

    Tartara, A; Verri, A P; Nespoli, L; Moglia, A; Botta, M G

    1981-01-01

    Serum immunoglobulin levels of 86 epileptic patients have been evaluated in order to investigate the relationship between epilepsy, antiepileptic drugs and humoral immunity. The results confirm a high incidence of immunological disorders in the epileptic and febrile convulsion patients. These abnormalities were not related to clinical type of epilepsy nor to the therapy; the common feature seems the early onset of seizures and antiepileptic treatment. PMID:6791931

  11. Kidney transplantation in immunologically high-risk patients.

    PubMed

    Keven, K; Sengul, S; Celebi, Z K; Tuzuner, A; Yalcin, F; Duman, T; Tutkak, H

    2013-04-01

    An increased number of sensitized patients await kidney transplantation (KTx). Sensitization has a major impact on patient mortality and morbidity due to prolonged waiting time and may preclude live donor transplantation. However, recent reports have shown that KTx can be performed successfully using novel immunosuppressive protocols. This study presents our experience with patients displaying donor-specific antibody (DSA) (+). We enrolled 5 lymphocyte cross-match (LCM) negative (complement-dependent cytotoxicity) and panel-reactive antibody (PRA) plus DSA-positive patients mean fluorescein intensity [MFI] > 1000) who underwent living kidney donor procedures. All subjects were females and their mean age was 36.7 years. In our protocol, we started mycophenolate mofetil (2 g/d), tacrolimus (0.01 mg/kg) and prednisolone (0.5 mg/kg) on day -6. We performed 2 sessions of total plasma exchange (TPE) with albumin replacement and administered 2 doses of IVIG (5 g/d). On day -1, we added rituximab (200 mg). On the operation day and on day +4, the patients received doses of basiliximab. Serum samples were taken on days -6, 0, and 30 as well as at 1 year after transplantation. All patients displayed immediate graft function. Mean basal DSA titer was 5624 MFI. After desensitization, the MFI titers decreased at the time of transplantation to 2753 MFI, and were 2564 MFI at the 1st month and 802 MFI at 1st year. Three patients experienced acute rejection episodes (60%). After treatment for rejection, the average follow-up was 17 months and last creatinine levels were 0.6-0.8 mg/dL (minimum-maximum). In conclusion, KTx can be succesfully performed in sensitized patients displaying DSA. However, there seems to be a greater acute rejection risk. There is no consensus regarding adequate doses of IVIG or plasmapheresis treatments; furthermore, more studies are needed to clarify the safe MFI titer of the DSA. PMID:23622587

  12. Immunological Markers for PML Prediction in MS Patients Treated with Natalizumab

    PubMed Central

    Antoniol, Caroline; Stankoff, Bruno

    2015-01-01

    Natalizumab (NTZ), a monoclonal antibody recognizing the alpha4 integrin chain, has been approved for the treatment of active multiple sclerosis, but expose to the onset of a rare side effect, progressive multifocal leukoencephalopathy (PML). Estimating the individual risk of PML in NTZ-treated patients is a major challenge, and therapeutic strategies are mainly guided by the overall PML risk assessed by identified risk factors: JC virus (JCV) seropositivity, treatment duration (with peak incidence after 24 months), and the previous use of immunosuppressive therapies. Given that this stratification does not yet allow a precise individual prediction of PML, other predictive markers are needed, and several immunological biomarkers have been described. Quantification of anti-JCV antibody levels may improve individual predictive value, with higher baseline titers indicating increased risk. Other immunological biomarkers such as leukocyte cell membrane markers (CD49d, CD11a, and CD62L), detection of circulating JCV-specific activated T effector memory cells (TEM) or genetic screening have been proposed. In this review, we discuss how recent progress in immunology has paved the way for «new combined monitoring», which will include immunological screening, in NTZ-treated patients. PMID:25601865

  13. Mucosal immunologic responses in cholera patients in Bangladesh.

    PubMed

    Uddin, Taher; Harris, Jason B; Bhuiyan, Taufiqur Rahman; Shirin, Tahmina; Uddin, Muhammad Ikhtear; Khan, Ashraful Islam; Chowdhury, Fahima; LaRocque, Regina C; Alam, Nur Haque; Ryan, Edward T; Calderwood, Stephen B; Qadri, Firdausi

    2011-03-01

    Vibrio cholerae O1 causes dehydrating diarrhea with a high mortality rate if untreated. The infection also elicits long-term protective immunity. Since V. cholerae is noninvasive, mucosal immunity is likely important for protection. In this study, we compared humoral immune responses in the duodenal mucosa and blood of cholera patients at different time points after the onset of disease and compared them with those of healthy controls (HCs). Immune responses to lipopolysaccharide (LPS) and the recombinant cholera toxin B subunit (rCTB) were assessed by enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunospot (ELISPOT) assay. Significant increases in V. cholerae LPS-specific IgA and IgG antibody levels were seen in duodenal extracts on day 30, but the levels decreased to baseline by day 180; plasma V. cholerae LPS-specific IgA levels remained elevated longer. Levels of mucosal CTB antibodies also peaked on day 30, but the increase reached statistical significance only for IgG. A significant correlation was found between the CTB antibody-secreting cell (ASC) response in the circulatory system on day 7 and subsequent CTB-specific IgA levels in duodenal extracts on day 30 and the numbers of CTB-specific IgA ASCs in duodenal tissues on day 180. The proportion (0.07%) of mucosal V. cholerae LPS IgA ASCs peaked on day 30 and remained elevated through day 180 compared to that of HCs (P = 0.03). These results suggest that protective immunity against V. cholerae is not likely mediated by the constitutive secretion of antibodies at the mucosal surface; our results are consistent with those of other studies that suggest instead that anamnestic immune responses of mucosal lymphocytes may play a major role in protection against cholera. PMID:21248157

  14. Association between circulating galectin-3 levels and the immunological, inflammatory and nutritional parameters in patients with colorectal cancer

    PubMed Central

    Shimura, Tatsuo; Shibata, Masahiko; Gonda, Kenji; Nakajima, Takahiro; Chida, Shun; Noda, Masaru; Suzuki, Satoshi; Nakamura, Izumi; Ohki, Shinji; Takenoshita, Seiichi

    2016-01-01

    Galectin-3, a β-galactoside-binding lectin, exhibits pleiotropic biological functions and has a role as one of the immunological modulators. However, the associations between circulating galectin-3 and immunological, inflammatory and nutritional parameters have not yet been fully elucidated. The serum concentration of galectin-3 was examined in association with interleukin-10 (IL-10), IL-12 and IL17 production, lymphocyte stimulation, neutrophil/lymphocyte ratio (NLR), white blood cell count (WBC), C-reactive protein (CRP) and rapid turnover proteins, including retinol-binding protein (RBP), prealbumin (PA) and transferrin (TF) in 50 patients with untreated colorectal cancers. Significant increases (P<0.05) were observed in the serum galectin-3 levels in patients with untreated colorectal cancer (9.6±4.5 ng/ml) compared with the normal controls (3.2±1.6 ng/ml). Higher serum galectin-3 concentrations were observed in patients with colon cancer (11.5±4.4 ng/ml) compared to in patients with rectal cancer (8.0±4.0 ng/ml) (P=0.005). The levels of circulating galectin-3 inversely correlated with the production of IL-10 (r=−0.59, P<0.001), and IL-12 (r=−0.69, P<0.001). Galectin-3 concentration also inversely correlated with the lymphocyte stimulation assay stimulation index (r=−0.42, P=0.021). However, the level of serum galectin-3 correlated with IL-17 production (r=0.67, P<0.001). Serum galectin-3 levels exhibited significant correlations with NLR (r=0.41, P=0.009), WBC (r=0.32, P=0.035), and CRP (r=0.63, P<0.001), and statistically significant inverse correlations with RBP (r=−0.45, P=0.002), PA (r=−0.46, P=0.001) and TF (r=−0.72, P<0.001). Galectin-3 may be one of the key factors in the regulation of immunological, inflammatory and nutritional conditions.

  15. IMMUNOLOGICAL EVALUATION OF PATIENTS WITH TYPE 2 DIABETES MELLITUS SUBMITTED TO METABOLIC SURGERY

    PubMed Central

    BORGES, Marisa de Carvalho; TERRA, Guilherme Azevedo; TAKEUTI, Tharsus Dias; RIBEIRO, Betânia Maria; SILVA, Alex Augusto; TERRA-JÚNIOR, Júverson Alves; RODRIGUES-JÚNIOR, Virmondes; CREMA, Eduardo

    2015-01-01

    Background : Immunological and inflammatory mechanisms play a key role in the development and progression of type 2 diabetes mellitus. Aim : To raise the hypothesis that alterations in immunological parameters occur after duodenojejunal bypass surgery combined with ileal interposition without gastrectomy, and influences the insulin metabolism of betacells. Methods : Seventeen patients with type 2 diabetes mellitus under clinical management were submitted to surgery and blood samples were collected before and six months after surgery for evaluation of the serum profile of proinflammatory (IFN-γ, TNF-α, IL-17A) and anti-inflammatory cytokines (IL-4, IL-10). In addition, anthropometric measures, glucose levels and insulin use were evaluated in each patient. Results : No changes in the expression pattern of proinflammatory cytokines were observed before and after surgery. In contrast, there was a significant decrease in IL-10 expression, which coincided with a reduction in the daily insulin dose, glycemic index, and BMI of the patients. Early presentation of food to the ileum may have induced the production of incretins such as GLP-1 and PYY which, together with glycemic control, contributed to weight loss, diabetes remission and the consequent good surgical prognosis of these patients. In addition, the control of metabolic syndrome was responsible for the reduction of IL-10 expression in these patients. Conclusion : These findings suggest the presence of low-grade inflammation in these patients during the postoperative period, certainly as a result of adequate glycemic control and absence of obesity, contributing to a good outcome of surgery. PMID:26734798

  16. Analysis of Lymphocyte Immunological Reactivity in Patients with Pleural Effusions of Different Aetiology

    PubMed Central

    Goseva, Zlatica; Kaeva, Biserka Jovkovska; Gjorcev, Angelko; Janeva, Elena Jovanovska; Arsovski, Zoran; Pejkovska, Sava; Tatabitovska, Aleksandra

    2016-01-01

    BACKGROUND: The proportion of T and B lymphocytes in pleural fluids and blood may point to the presence of local immunological phenomena in pleural disorders. AIM: Aim of study was to evaluate the lymphocyte phenotype and the ratio between helper (CD4+) and cytotoxic/suppressor (CD8+) lymphocytes in malignant and non-malignant effusions. MATERIAL AND METHODS: We studied 48 patients with pleural effusions. First group had 18 patients with tuberculosis pleural effusions; second group had 20 patients with malignant pleural fluids, third group had 10 patients with transudates and 30 healthy controls. We investigated the distribution of T and B lymphocytes, T cells with helper/inducer CD4 or suppresser/cytotoxic CD8 phenotypes and the CD16 subset. RESULTS: Results showed decreases levels of CD3, CD4, and CD16 T cells in blood of patients versus healthy controls. There were increases in the percentage of the CD3 and CD4 T cells in the pleural fluid compared with values in the blood with statistical significance in tuberculous pleurisy. The values of CD8 were similar in the pleural fluid and in blood. Levels of CD16 were non-significantly higher in pleural fluid in all groups. CONCLUSION: This study confirms the hypothesis that pleural cavity is compartment with immunological reactivity and results could be used in differential diagnosis together with other examinations. PMID:27275329

  17. NY-ESO-1-specific immunological pressure and escape in a patient with metastatic melanoma.

    PubMed

    von Boehmer, Lotta; Mattle, Muriel; Bode, Peter; Landshammer, Alexandro; Schäfer, Carolin; Nuber, Natko; Ritter, Gerd; Old, Lloyd; Moch, Holger; Schäfer, Niklaus; Jäger, Elke; Knuth, Alexander; van den Broek, Maries

    2013-01-01

    During cancer progression, malignant cells may evade immunosurveillance. However, evidence for immunological escape in humans is scarce. We report here the clinical course of a melanoma patient whose initial tumor was positive for the antigens NY-ESO-1, MAGE-C1, and Melan-A. Upon immunization with a recombinant vaccinia/fowlpox NY-ESO-1 construct, the patient experienced a mixed clinical response and spreading of the NY-ESO-1 epitopes in the CD4+ T cell compartment. After NY-ESO-1 protein + CpG immunization, the patient's anti-NY-ESO-1 IgG response increased. Over the following years, progressing lesions were resected and found to be NY-ESO-1-negative while being positive for MAGE-C1, Melan-A, and MHC-I. The fatal, inoperable brain metastasis was analyzed after his death and also proved to be NY-ESO-1-negative, while being positive for MAGE-C1 and Melan-A, as well as MHC-I. We propose that cancer control and cancer escape in this patient were governed by NY-ESO-1-specific immunological pressure. Our findings provide evidence for the existence of immunoediting and immunoescape in this cancer patient. PMID:23882157

  18. Immunological evaluation of peptide vaccination for cancer patients with the HLA-A26 allele.

    PubMed

    Sakamoto, Shinjiro; Matsueda, Satoko; Takamori, Shinzo; Toh, Uhi; Noguchi, Masanori; Yutani, Shigeru; Yamada, Akira; Shichijo, Shigeki; Yamada, Teppei; Suekane, Shigetaka; Kawano, Kouichiro; Sasada, Tetsuro; Hattori, Noboru; Kohno, Nobuoki; Itoh, Kyogo

    2015-10-01

    To develop a peptide vaccine for cancer patients with the HLA-A26 allele, which is a minor population worldwide, we investigated the immunological responses of HLA-A26(+) /A26(+) cancer patients to four different CTL epitope peptides under personalized peptide vaccine regimens. In personalized peptide vaccine regimens, two to four peptides showing positive peptide-specific IgG responses in pre-vaccination plasma were selected from the four peptide candidates applicable for HLA-A26(+) /A26(+) cancer patients and administered s.c. Peptide-specific CTL and IgG responses along with cytokine levels were measured before and after vaccination. Cell surface markers in PBMCs and plasma cytokine levels were also measured. In this study, 21 advanced cancer patients, including seven lung, three breast, two pancreas, and two colon cancer patients, were enrolled. Their HLA-A26 genotypes were HLA-A26:01 (n = 24), HLA-A26:03 (n = 10), and HLA-A26:02 (n = 8). One, 14, and 6 patients received two, three, and four peptides, respectively. Grade 1 or 2 skin reactions at the injection sites were observed in the majority of patients, but no severe adverse events related to the vaccination were observed. Peptide-specific CTL responses were augmented in 39% or 22% of patients after one or two cycles of vaccination, respectively. Notably, peptide-specific IgG were augmented in 63% or 100% of patients after one or two cycles of vaccination, respectively. Personalized peptide vaccines with these four CTL epitope peptides could be feasible for HLA-A26(+) advanced cancer patients because of their safety and higher rates of immunological responses. PMID:26212219

  19. Immunological evaluation of peptide vaccination for cancer patients with the HLA-A26 allele

    PubMed Central

    Sakamoto, Shinjiro; Matsueda, Satoko; Takamori, Shinzo; Toh, Uhi; Noguchi, Masanori; Yutani, Shigeru; Yamada, Akira; Shichijo, Shigeki; Yamada, Teppei; Suekane, Shigetaka; Kawano, Kouichiro; Sasada, Tetsuro; Hattori, Noboru; Kohno, Nobuoki; Itoh, Kyogo

    2015-01-01

    To develop a peptide vaccine for cancer patients with the HLA-A26 allele, which is a minor population worldwide, we investigated the immunological responses of HLA-A26+/A26+ cancer patients to four different CTL epitope peptides under personalized peptide vaccine regimens. In personalized peptide vaccine regimens, two to four peptides showing positive peptide-specific IgG responses in pre-vaccination plasma were selected from the four peptide candidates applicable for HLA-A26+/A26+ cancer patients and administered s.c. Peptide-specific CTL and IgG responses along with cytokine levels were measured before and after vaccination. Cell surface markers in PBMCs and plasma cytokine levels were also measured. In this study, 21 advanced cancer patients, including seven lung, three breast, two pancreas, and two colon cancer patients, were enrolled. Their HLA-A26 genotypes were HLA-A26:01 (n = 24), HLA-A26:03 (n = 10), and HLA-A26:02 (n = 8). One, 14, and 6 patients received two, three, and four peptides, respectively. Grade 1 or 2 skin reactions at the injection sites were observed in the majority of patients, but no severe adverse events related to the vaccination were observed. Peptide-specific CTL responses were augmented in 39% or 22% of patients after one or two cycles of vaccination, respectively. Notably, peptide-specific IgG were augmented in 63% or 100% of patients after one or two cycles of vaccination, respectively. Personalized peptide vaccines with these four CTL epitope peptides could be feasible for HLA-A26+ advanced cancer patients because of their safety and higher rates of immunological responses. PMID:26212219

  20. [The effect of dietotherapy on the clinico-immunological indices of rheumatoid arthritis patients].

    PubMed

    Sharafetdinov, Kh Kh; Denisov, L N; Samsonov, G R; Pokrovskaia, G R; Voĭtko, N E

    1990-01-01

    The main requirements for the dietotherapy of rheumatoid arthritis (RA) patients have been formulated, and for the first time a pathogenetically balanced diet has been developed that produces antiinflammatory and immunocorrective effects. The effectiveness of the dietotherapy included into the combined treatment was studied in 41 patients with classic and proved RA. The authors have studied the influence of the dietotherapy on the clinical signs characterizing the activity of inflammation in the joints, and laboratory immunological parameters (IgG, IgM, IgA, IgD, the complement components: C1-inhibitor, C3, C4, C5, C9; haptoglobin, orrhozomucoid, transferrin, ceruloplasmin, alpha 1-antitrypsin, alpha 2-macroglobulin, prealbumin). The results of the study have shown that the dietotherapy is not only conducive to the improvement of the clinical picture of the disease, that permits diminishing the amount of nonsteroid antiinflammatory drugs used, but also produces a favourable effect on the RA patients' immunological state. It has been concluded that inclusion of the dietotherapy into the combined treatment of RA patients is advisable. PMID:2346005

  1. Clinical, Immunologic and Genetic Profile of DOCK8-Deficient Patients in Kuwait

    PubMed Central

    Al-Herz, Waleed; Ragupathy, Raj; Massaad, Michel J.; Al-Attiyah, Raja’a; Nanda, Arti; Engelhardt, Karin R.; Grimbacher, Bodo; Notarangelo, Luigi; Chatila, Talal; Geha, Raif S.

    2013-01-01

    Deficiency of dedicator of cytokinesis 8 (DOCK8) is a newly described combined primary immunodeficiency disease. It was found to account for 15% of combined immune deficiency cases in the National Primary Immunodeficiency Disorders Registry in Kuwait, a country with high prevalence of consanguinity. We present the clinical, immunologic and molecular characteristics of 9 Kuwaiti patients with DOCK8 deficiency and discuss differences that distinguish DOCK8 deficiency from atopic dermatitis. Clinical immunologists in areas with high incidence of consanguinity should have a high index of suspicion of DOCK8 deficiency in children with recalcitrant eczema, recurrent non-cutaneous infections and lymphopenia. PMID:22534316

  2. Evaluation of immunological indices in HIV-infected patients with chronic hepatitis C in Kazakhstan

    PubMed Central

    Sarsekeyeva, Nazgul; Kosherova, Bakhyt

    2016-01-01

    Aim To evaluate immunological indices in HIV-infected patients with chronic hepatitis C (CHC) who are injecting drug users. Materials and methods The study examined 38 patients coinfected with HIV and CHC who were injecting drug users and 36 patients with HIV/CHC who were not injecting drug users. In the study of immune status, the relative and absolute numbers of CD3+, CD4+, CD8+, CD16+, and CD20+ cells were determined by means of flow cytofluorometry of “FACSCount” using monoclonal antibodies of the company Becton Dickinson. The level of circulating immune complexes in blood serum was determined by means of precipitation in polyethylene glycol solution. Results It was found that T-cell immunodeficiency was developing in patients coinfected with HIV and CHC. T-cell immunodeficiency was characterized by a decrease in the number of T-helpers, mainly for injecting drug users. At the same time, patients coinfected with HIV and CHC experienced markedly elevated levels of circulating immune complexes, mainly among injecting drug users. The evaluation of immunogram indices in injecting drug users coinfected with HIV and CHC, depending on the stage of HIV infection, revealed a greater degree of immune-suppression of T-helper cells in clinical stage III. Conclusion Our comprehensive immunological study of patients coinfected with HIV and CHC revealed a pronounced dysfunction of the immune system. The comparison of the immune system indices in patients with HIV/CHC showed a more pronounced T-cell suppression in injecting drug users than in patients with HIV/CHC but who were not injecting drug users. PMID:27284263

  3. Primary Sjögren syndrome in Han Chinese: clinical and immunological characteristics of 483 patients.

    PubMed

    Zhao, Yun; Li, Ya; Wang, Li; Li, Xiao-Feng; Huang, Ci-Bo; Wang, Guo-Chun; Zhang, Xue-Wu; Zhang, Zhuo-Li; Zhang, Xiao; Xiao, Wei-Guo; Dai, Lie; Wang, Yong-Fu; Hu, Shao-Xian; Li, Hong-Bin; Gong, Lu; Liu, Bin; Sun, Ling-Yun; Zhang, Miao-Jia; Zhang, Xuan; Li, Yong-Zhe; Du, De-Shun; Zhang, Shun-Hua; Sun, Yuan-Yuan; Zhang, Feng-Chun

    2015-04-01

    The epidemiological characteristics of Sjögren syndrome (SS) are significantly varied in different countries. We conducted the present study to survey the epidemiological characteristics of primary SS in China. We recruited 483 primary SS patients from 16 Chinese medical centers nationwide from January 2009 to November 2011 and assessed salivary and lacrimal gland dysfunction, organ involvement, and autoimmunity in these patients. The cohort included 456 women and 27 men (ratio, 17:1; mean age at onset, 42 ± 11 years; median age at diagnosis, 49 years; range, 41-56 years). Male patients showed a lower frequency of xerophthalmia (37.0% vs 60.7%) and a higher frequency of arthritis (40.7% vs 16.4%). Young-onset patients showed a higher frequency of low C3 levels (57.7% vs 36.3%) and pancytopenia (22.2% vs 8.8%). Patients with systemic involvement had a higher frequency of immunoglobulin A (IgA) (39.4% vs 22.5%) and immunoglobulin M (IgM) (12.4% vs 37.9%). Patients with pulmonary involvement had a higher parotid enlargement (21.4% vs 10.2%), purpura (12.1% vs 5.7%) and higher anti-La/SS-B (61.7% vs 41.8%), immunoglobulin G (IgG) (80.7% vs 64.6%) and IgA (48.9% vs 30.6%) levels. Patients with anti-Ro/SSA antibodies had more frequent exocrine gland symptoms and some extraglandular symptoms and immunological alterations. Compared with previous studies performed in other countries, SS patients in China showed particular clinical manifestation, systemic involvement, and immunological alterations. PMID:25906094

  4. Immunological fluctuations during intrathecal immunotherapy in three patients affected by CNS tumours disseminating via CSF.

    PubMed

    Salmaggi, A; Dufour, A; Silvani, A; Ciusani, E; Nespolo, A; Boiardi, A

    1994-07-01

    The immunological therapy of cancer has been proposed in a number of neoplasms (Borden, Sondel, 1989; Foon, 1989; Rosenberg, 1992) and has recently been adopted in the treatment of Central Nervous System (CNS) tumors in combination with conventional surgical and radiotherapeutical approach. In this context, loco-regional administration of immunomodulating agents (for instance in post-surgical cavity) allows to achieve much higher in situ concentrations than by systemic route. Since these treatments have potential adverse effects, careful assessment of clinical and immunological parameters in phase I trials is needed. CNS tumors disseminating via Cerebrospinal Fluid (CSF) pathways offer a stimulating opportunity for intrathecal immunotherapy. In this context, alpha-IFN and IL2 (alone or in combination with LAK cells) have been employed either loco-regionally or intrathecally (Merchant, Mc Vicar, Merchant & Young, 1992; Schiller, Hank, Storer, Borchert, Moore, Albertini, Bechhofer, Wesley, Brown, Bastin & Sondel, 1993). The rationale for the use of both these substances includes the known anti-tumor action of alpha-IFN (Mahaley, Urso, Whaley, Blue, Williams, Guaspari & Selker, 1985; Nagai, 1988) and the ability of r-IL2 to generate activated cells effective in lysing tumor cell targets (Hayes, Moore, Pierz, Chen, Da Rosso, Nirenberg & Allen, 1993). We treated 3 patients (2 affected by disseminating cerebellar medulloblastoma, 1 by disseminating thalamic glioblastoma) by intrathecal r-IL2 via recervoir. In the first 2 patients, this treatment was preceded by alpha-IFN (also intrathecally). Monitoring of immunological effects of the treatment schedule involved kinetics of CSF and serum TNF-alpha, IL2s and IL2R during the first day of r-IL2 treatment, as well as on day +2 and +4 of both r-IL2 cycles, and assessment of CSF cells, protein and CSF and PB NK cell activity and CD3-CD56+ cells during the course of all treatment cycles. We also assessed clinical and

  5. Clinical and Immunologic Characteristics of Patients With ANCA-Associated Glomerulonephritis Combined With Membranous Nephropathy

    PubMed Central

    Zou, Rong; Liu, Gang; Cui, Zhao; Chen, Min; Zhao, Ming-Hui

    2015-01-01

    Abstract The concurrent antineutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN) and membranous nephropathy (MN) have been increasingly documented, mainly in case studies and case series; however, the differences of clinical and pathologic characteristics as well as outcomes between ANCA-GN patients with and without MN remain unclear. The current study investigated the clinical and immunologic features of patients with combined ANCA-GN and MN in a large cohort. Twenty-seven of 223 patients had combined ANCA-GN and MN; they had significantly higher levels of initial serum creatinine, higher Birmingham Vasculitis Activity Score and poorer renal outcome than ANCA-GN patients without MN (P < 0.05). ANCA-GN patients with MN could recognize the light chain of myeloperoxidase more frequently than those without MN (P < 0.05). The prevalence of circulating anti-PLA2R antibodies and glomerular PLA2R deposits was significantly lower in patients with combined ANCA-GN and MN than that in patients with idiopathic MN (P < 0.05). Compared with the idiopathic MN patients, the patients with combined ANCA-GN and MN had significantly higher recognition frequency of immunoglobulin (Ig) G2 and IgG3, and significantly lower recognition frequency of IgG4 (P < 0.05). Patients with combined ANCA-GN and MN had distinct clinical features and a different pathogenesis of MN. PMID:26376387

  6. [A specific rosette formation method in assessing the immunological status of acute leukemia patients].

    PubMed

    Moroz, I A

    1985-01-01

    The paper deals with the evaluation of immunologic vigor in 88 patients suffering acute lymphoblastic leukemia. It involved a modified test of specific rosette formation of blood-circulating lymphocytes and those of the bone marrow with erythrocytes bearing leukemia cell extracts. The highest levels of rosette-forming lymphocytes were registered in the acute period prior to treatment and in recurrence. The said levels decreased gradually following chemoimmunotherapy, falling to nil in complete remission. Patients in whom the treatment had failed revealed no changes in lymphocyte response. The control group (healthy subjects and cases of nonmalignant hematologic pathology) showed levels of rosette-forming lymphocytes similar to those in acute lymphoblastic leukemia patients in remission. PMID:3861026

  7. [Clinical and experimental parallels between immunological observations of irradiated animals and patients injured during Chernobyl accident].

    PubMed

    Mal'tsev, V N

    2011-01-01

    Immunological parameters in different periods of acute radiation syndrome (ARS) of experimental animals and Chernobyl reactor accident-injured patients have been studied. 148 patients and experimental animals (123 dogs and 198 monkeys) were observed after radiation exposure of different levels (from a sub-lethal dose to the minimal absolute lethal dose). We have found the increase in the C-reactive protein, fluctuation of normal antibody titers and the complement in blood serum, as well as the growing number of skin microbes after exposures to lethal doses. Experimental results match clinical data in terms of ARS progress phases but differ from the latter in terms of the time of clinical manifestations. The highest rate of clinical manifestations is observed on the 7-14 days for experimental animals (rats, dogs and monkeys) and on the 20-30 days for patients after radiation exposure. Regenerative processes in animals run faster than those in humans. PMID:22279769

  8. Immunological recovery in 48 patients following syngeneic marrow transplantation for hematological malignancy. [/sup 60/Co

    SciTech Connect

    Whiterspoon R.P.; Kopecky, K.; Storb, R.F.

    1982-02-01

    Immunological function of 48 syngeneic transplant patients prepared with 120 mg of cyclophosphamide per kg and 9.2 to 12.0 Gy (920 to 1000 rad) total body irradiation was compared with that of 153 allogeneic recipients. Lymphocyte counts and T cell numbers in syngeneic recipients were low during the first post-transplant month but higher than those of allogeneic recipients. Serum immunoglobulin levels in syngeneic recipients were normal by completion of the first post-transplantation month and were higher than allogeneic recipients at that time. Total hemolytic complement (CH/sub 50/) and third (C3) and fourth (C4) components were normal throughout the post-transplantation course in both groups of patients. Antibody production to primary injection of bacteriophage THETAX174 (Phage) was low in both syngeneic and allogeneic recipients during the first post-transplantation month and rose gradually thereafter. Some syngeneic recipients failed to produce normal amounts of IgG in their secondary response to phage. Antibody production after primary and secondary injection of keyhole limpet hemocyanin or pneumococcal polysaccharide was lower than normal early after grafting and rose later, comparable to that seen in allogeneic recipients. We conclude that immunological recovery in syngeneic recipients is very similar to recovery in allogeneic recipients except in the first month postgrafting where twins are slightly better than allogeneic recipients for lymphocyte and immunoglobulin levels. Other mechanisms than those listed here must play an important role in protecting the syngeneic marrow graft recipient from opportunistic infection. (JMT)

  9. Immunological factors influencing clinical outcome in lung cancer patients after telomerase peptide vaccination.

    PubMed

    Hansen, Gaute Lund; Gaudernack, Gustav; Brunsvig, Paal Fredrik; Cvancarova, Milada; Kyte, Jon Amund

    2015-12-01

    We have previously reported two trials in non-small cell lung cancer (NSCLC) evaluating vaccine therapy with the telomerase peptide GV1001. The studies demonstrated considerable differences in survival among immune responders, highlighting that an immune response is not necessarily beneficial. In the present study, we conducted long-term clinical follow-up and investigated immunological factors hypothesized to influence clinical efficacy. Peripheral blood mononuclear cells from 33 NSCLC trial patients and 15 healthy donors were analyzed by flow cytometry for T regulatory cells (Tregs, CD4(+)CD25(+)CD127(low/-)FOXP3(+)) and two types of myeloid-derived suppressor cells (MDSCs, HLA-DR (low) CD14 (+) or Lin (-/lo) HLA-DR (-) CD33 (+) CD11b (+)). T cell cultures were analyzed for 17 cytokines. The results demonstrated that immune responders had increased overall survival (OS, p < 0.001) and progression-free survival (p = 0.003), compared to subjects without immunological response. The mean OS advantage was 54 versus 13 months. Six patients were still alive at the last clinical update, all belonging to the immune responders. No serious toxicity had developed (maximum observation 13 years). Most patients developed a polyfunctional cytokine profile, with high IFNγ/IL-4 and IFNγ/IL-10 ratios. Low Treg levels were associated with improved OS (p = 0.037) and a favorable cytokine profile, including higher IFNγ/IL-10 ratios. High CD33(+) MDSC levels were associated with poorer immune response rate (p = 0.005). The levels of CD14(+) MDSC were significantly higher in patients than in healthy controls (p = 0.012). We conclude that a randomized GV1001 trial in NSCLC is warranted. The findings suggest that Tregs and MDSCs are associated with a tolerogenic cytokine milieu and impaired clinical efficacy of vaccine responses. PMID:26498005

  10. Clinical and Immunological Changes of Immunotherapy in Patients with Atopic Dermatitis: Randomized Controlled Trial

    PubMed Central

    Sánchez Caraballo, Jorge Mario; Cardona Villa, Ricardo

    2012-01-01

    Background. Immunotherapy has proven to be an useful tool in the management of allergic respiratory diseases; however, little has been studied in atopic dermatitis. Objective. To evaluate the clinical and immunological impact of immunotherapy with mites allergen extracts in atopic dermatitis. Methods. Patients with atopic dermatitis were assigned with computer-generated randomization to either of the following groups: (a) controls received only topical treatment with steroids and/or tacrolimus and (b) actively treated patients received topical treatment plus immunotherapy. Levels of serum total IgE, mites-specific IgE and IgG4 were assessed at study start and after one year of immunotherapy. Results. 31 patients in the active group and 29 in the control group completed the study. Symptoms and medication scores were significantly reduced in the active group after six months. Three patients in the control group showed new sensitizations to mites, while 3 patients in the active group showed neosensitization to shrimp with negative oral food challenge. We observed significant increase of mites-specific IgG4 levels in active group. Conclusion. Specific allergen immunotherapy induced a tolerogenic IgG4 response to mite allergens associated with favorable clinical effects in atopic dermatitis patients. PMID:23724240

  11. Identification of patients with increased immunological risk among potential kidney recipients in the Polish population.

    PubMed

    Moszkowska, Grażyna; Zielińska, Hanna; Zieliński, Maciej; Dukat-Mazurek, Anna; Dębska-Ślizień, Alicja; Rutkowski, Bolesław; Lewandowska, Dorota; Danielewicz, Roman; Trzonkowski, Piotr

    2014-07-01

    Pretransplant identification of allosensitized patients is possible thanks to new technologies, which allow for accurate detection of clinically relevant alloantibodies. Implementation of these methods in the screening of patients awaiting transplantation increased their chance for successful donor-recipient matching. Here, 1460 patients reported to the Polish National Waiting List were screened with the Luminex Screen (LS) solid phase test for anti-HLA antibodies. The patients with detected anti-HLA antibodies were assayed with the Luminex Single Antigen (LSA) tests in order to establish defined antigen specificity of the alloantibodies. The results were compared with data on the immunization assessed with the routine complement-dependent-cytotoxicity panel-reactive-antibody assay (PRA CDC). The study showed significantly higher sensitivity of the LS method when compared with PRA CDC. It has been shown that LSA test is a useful technique identifying the specificities of alloantibodies. In particular, LSA allowed to assess donor specific antibodies (DSA) to previous mismatches (MM) and to determine acceptable HLA mismatches of the potential donors. The introduction of solid phase tests in routine pretransplant diagnostics allowed for faster and more accurate assessment of the immunological risk of the recipients and optimal donor-recipient matching. Hence, the presented algorithm of solid phase assays has become a new standard for the identification of allosensitized patients awaiting kidney transplantation in Poland. PMID:24768949

  12. Immunological profile of HTLV-1-infected patients associated with infectious or autoimmune dermatological disorders.

    PubMed

    Coelho-dos-Reis, Jordana Grazziela Alves; Passos, Livia; Duarte, Mariana Costa; Araújo, Marcelo Grossi; Campi-Azevedo, Ana Carolina; Teixeira-Carvalho, Andréa; Peruhype-Magalhães, Vanessa; Trindade, Bruno Caetano; Dos Santos Dias, Raquel; Martins, Marina Lobato; Carneiro-Proietti, Anna Barbara de Freitas; Guedes, Antônio Carlos; Gonçalves, Denise Utsch; Martins-Filho, Olindo Assis

    2013-01-01

    In the present study, the frequency, the activation and the cytokine and chemokine profile of HTLV-1 carriers with or without dermatological lesions were thoroughly described and compared. The results indicated that HTLV-1-infected patients with dermatological lesions have distinct frequency and activation status when compared to asymptomatic carriers. Alterations in the CD4(+)HLA-DR(+), CD8(+) T cell, macrophage-like and NKT subsets as well as in the serum chemokines CCL5, CXCL8, CXCL9 and CXCL10 were observed in the HTLV-1-infected group with skin lesions. Additionally, HTLV-1 carriers with dermatological skin lesions showed more frequently high proviral load as compared to asymptomatic carriers. The elevated proviral load in HTLV-1 patients with infectious skin lesions correlated significantly with TNF-α/IL-10 ratio, while the same significant correlation was found for the IL-12/IL-10 ratio and the high proviral load in HTLV-1-infected patients with autoimmune skin lesions. All in all, these results suggest a distinct and unique immunological profile in the peripheral blood of HTLV-1-infected patients with skin disorders, and the different nature of skin lesion observed in these patients may be an outcome of a distinct unbalance of the systemic inflammatory response upon HTLV-1 infection. PMID:23936564

  13. Immunological Profile of HTLV-1-Infected Patients Associated with Infectious or Autoimmune Dermatological Disorders

    PubMed Central

    Duarte, Mariana Costa; Araújo, Marcelo Grossi; Campi-Azevedo, Ana Carolina; Teixeira-Carvalho, Andréa; Peruhype-Magalhães, Vanessa; Trindade, Bruno Caetano; dos Santos Dias, Raquel; Martins, Marina Lobato; Carneiro-Proietti, Anna Barbara de Freitas; Guedes, Antônio Carlos; Gonçalves, Denise Utsch; Martins-Filho, Olindo Assis

    2013-01-01

    In the present study, the frequency, the activation and the cytokine and chemokine profile of HTLV-1 carriers with or without dermatological lesions were thoroughly described and compared. The results indicated that HTLV-1-infected patients with dermatological lesions have distinct frequency and activation status when compared to asymptomatic carriers. Alterations in the CD4+HLA-DR+, CD8+ T cell, macrophage-like and NKT subsets as well as in the serum chemokines CCL5, CXCL8, CXCL9 and CXCL10 were observed in the HTLV-1-infected group with skin lesions. Additionally, HTLV-1 carriers with dermatological skin lesions showed more frequently high proviral load as compared to asymptomatic carriers. The elevated proviral load in HTLV-1 patients with infectious skin lesions correlated significantly with TNF-α/IL-10 ratio, while the same significant correlation was found for the IL-12/IL-10 ratio and the high proviral load in HTLV-1-infected patients with autoimmune skin lesions. All in all, these results suggest a distinct and unique immunological profile in the peripheral blood of HTLV-1-infected patients with skin disorders, and the different nature of skin lesion observed in these patients may be an outcome of a distinct unbalance of the systemic inflammatory response upon HTLV-1 infection. PMID:23936564

  14. Spinal muscular atrophy patient-derived motor neurons exhibit hyperexcitability

    PubMed Central

    Liu, Huisheng; Lu, Jianfeng; Chen, Hong; Du, Zhongwei; Li, Xue-Jun; Zhang, Su-Chun

    2015-01-01

    Spinal muscular atrophy (SMA) presents severe muscle weakness with limited motor neuron (MN) loss at an early stage, suggesting potential functional alterations in MNs that contribute to SMA symptom presentation. Using SMA induced pluripotent stem cells (iPSCs), we found that SMA MNs displayed hyperexcitability with increased membrane input resistance, hyperpolarized threshold, and larger action potential amplitude, which was mimicked by knocking down full length survival motor neuron (SMN) in non-SMA MNs. We further discovered that SMA MNs exhibit enhanced sodium channel activities with increased current amplitude and facilitated recovery, which was corrected by restoration of SMN1 in SMA MNs. Together we propose that SMN reduction results in MN hyperexcitability and impaired neurotransmission, the latter of which exacerbate each other via a feedback loop, thus contributing to severe symptoms at an early stage of SMA. PMID:26190808

  15. Immunological findings in psychotic syndromes: a tertiary care hospital's CSF sample of 180 patients

    PubMed Central

    Endres, Dominique; Perlov, Evgeniy; Baumgartner, Annette; Hottenrott, Tilman; Dersch, Rick; Stich, Oliver; Tebartz van Elst, Ludger

    2015-01-01

    Immunological mechanisms and therapy approaches in psychotic syndromes were recently supported by the discovery of autoantibody-associated limbic and non-limbic encephalitis. However, how clinical diagnostic procedures in psychiatry should be adapted to these new insights is still unclear. In this study, we analyzed the cerebrospinal fluid (CSF) and neuroimmunological alterations and their association with cerebral MRI (cMRI) and electroencephalographic (EEG) findings. From 2006 to 2013, we acquired 180 CSF samples from psychotic patients. Between 2006 and 2009, CSF examinations were only performed in cases in which organic brain disease was suspected. Since then, this procedure has been integrated into our routine diagnostic workup. CSF basic diagnostics were supplemented by measuring antineuronal antibodies against intracellular synaptic antigens, antibodies against intracellular onconeural antigens, antibodies against neuronal cell surface antigens and thyroid antibodies. In addition, cMRIs and EEGs were conducted. We found white cell counts elevated in 3.4% of the cases, albumin quotient elevated in 21.8%, and protein concentration elevated in 42.2%. Evidence of intrathecal immunoglobulin synthesis was found in 7.2% of the cases. Antibodies measured against neuronal cell surface antigens were positive in 3.2%. Reactivity on antibodies against intracellular onconeural antigens were detected in 3.5%. Serum thyroid antibodies were elevated in 24.7%. Abnormalities were found in 39.5% of cMRIs and in 34.3% of EEGs. The main finding of our study was the high prevalence of CSF and autoantibody abnormalities in 54.4% of psychotic patients. In combination with cMRIs and EEGs, 75.6% showed abnormal findings. Our results are discussed with regard to the concept of immunological encephalopathy. Future studies should analyze the efficacy of immunomodulatory therapies. PMID:26441585

  16. [Clinical and immunological profile of HIV-infected patients at the initiation of antiretroviral therapy in Douala].

    PubMed

    Essomba, N E; Mbatchou Ngahane, B H; Nida, M; Temfack, E; Mapoure Njankouo, Y; Abeng, R L; Fokalbo, Z Kobe; Achu Joko, H; Mbenoun, M; Meledie, A P; Halle, M P; Malongue, A; Tchente, C; Nana Njamen, T; Halle Ekane, G; Ngwane, S; Barla, E; Abena, P; Ndobo, P; Moungo Kuidjeu, C; Adiogo, D; Mouelle Sone, A; Luma Namme, H; Coppieters, Y

    2015-10-01

    The aim of this study was to describe the clinical and immunological profile of patients infected with HIV after initiation of antiretroviral therapy. Sociodemographic characteristics, clinical and immunological patients were recorded. Chi square test and Mann-Whitney were used to compare variables. The multivariate regression model identified risk factors. So that, 936 (56.2%) patients were in stages III and IV of the WHO and 65.2% at an advanced stage of the disease. Factors associated with initiation at an advanced stage, were male sex (p = 0.007) and time to diagnosis (p = 0.005). In 2/3 cases, treatment is started at an advanced stage of disease. It is therefore important to intensify awareness campaigns for early detection and encourage patients to ensure regular medical follow-up screening. PMID:26296430

  17. IMMUNOLOGICAL METHODS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Environmental microbiology does not deal with all aspects of immunology or the immune responses per se, but instead adapts immunology-based research technologies or immunoassays for the study of microorganisms and chemical contaminants in association with the environment. The primary immunologic-bas...

  18. Unrelated cord blood transplantation can restore hematologic and immunologic functions in patients with Chediak-Higashi syndrome.

    PubMed

    Rihani, Rawad; Barbar, Maha; Faqih, Nesreen; Halalsheh, Hadeel; Hussein, Ayad Ahmad; Al-Zaben, Abdul Hadi; Rahman, Fawzi Abdel; Sarhan, Mahmoud

    2012-06-01

    CHS is a rare hereditary fatal disease, if not treated. APs occur in 85% of patients and are usually the main cause of mortality, and HSCT from HLA-matched related and unrelated donors is the only effective treatment for CHS and prevents recurrences of APs. We reviewed the records of three patients with CHS who underwent UCBT at KHCC. Records were examined for clinical features at the time of UCBT, conditioning regimens, morbidities, and outcomes. Conditioning comprised BU, cyclophosphamide, horse ATG, and etoposide. All patients tolerated the conditioning well. Two patients are alive, one with mixed and the other with full donor chimerism; hematologic and immunologic defects of CHS have been corrected in both patients. They show no evidence of recurrences of APs and have normal growth and development. In patients with CHS who lack HLA-matched related and unrelated donors, UCBT is a suitable alternative source of stem cells to restore immunologic and hematologic functions and prevent AP relapses, even in mixed chimeric states. Long follow-up and close monitoring are essential to evaluate the long-term benefits of using UCBT in patients with CHS. PMID:21450011

  19. Performance of automated platelet quantification using different analysers in comparison with an immunological reference method in thrombocytopenic patients

    PubMed Central

    Trabuio, Ernesto; Valverde, Sara; Antico, Francesco; Manoni, Fabio; Gessoni, Gianluca

    2009-01-01

    Background Rapidly available and accurate platelet counts play an important role in the evaluation of haemorrhagic status and in assessing the need for platelet transfusions. We, therefore, evaluated platelet counting performance of haematology analysers using optical, impedance and immunological methods in thrombocytopenic patients. Materials and Methods We considered 99 patients with a platelet (plt) count under 50x109 plt/L. We compared the platelet counts obtained using ADVIA 2120 (optical method), Cell-Dyn Sapphire (optical, impedance and immunological methods with CD61) and a reference, double staining (CD41+CD61) immunological method. Results The platelet counts of all the considered methods showed good correlation with those of the reference method, despite an overestimation in platelet quantification. The degree of inaccuracy was greater for platelet counts under 20 x109 plt/L. Conclusions Clinicians who use platelet thresholds below 20 x109 plt/L for making clinical decisions must be aware of the limitations in precision and accuracy of cell counters at this level of platelet count. Inaccurate counts of low platelet numbers could create problems if attempts are made to reduce the threshold below 20x109 plt/L. PMID:19290080

  20. Visceral leishmaniasis in a patient with cutaneous lesions, negative Leishman-Donovan bodies and immunological test: A case report

    PubMed Central

    Khorvash, Farzin; Naeini, Alireza Emami; Behjati, Mohaddeseh; Abdi, Fatemeh

    2011-01-01

    We report a case of visceral leishmaniasis (VL) in a patient from Shush in Iran with cutaneous lesions, negative for Leishman-Donovan bodies, enlarged spleen filled by leishmania protozoa and negative immunological test. The patient was a 26-year-old male, who attended hospital with fever and two deep purulent lesions on the distal part of his left leg. On physical examination, the patient had splenomegaly. Laboratory results were as follows: pancytopenia, positive C-reactive protein (CRP), elevated erythrocyte sedimentation rate (ESR) and lactate dehydrogenase (LDH) levels .The necessary treatment was administrated to the patient. Biopsy of lesion for Leishman-Donovan body was negative. In addition, indirect fluorescent antibody (IFA) screening for leishmaniasis was negative. Diagnostic splenectomy was performed which pathological exploration showed a bulk of leishmania protozoa in patient's spleen. Twenty days later, this patient expired. PMID:22973355

  1. Impact of the radiotherapy combined with cisplatin plus paclitaxel chemotherapy on the immunologic functions in the patients with esophageal cancer.

    PubMed

    Liu, Ru; Zhang, Jianlong; He, Chunyu; Jiang, Qiong; Liu, Jinsong; Fan, Ruitai

    2016-07-01

    To study the impact of radiotherapy combined with cisplatin plus paclitaxel chemotherapy on the immunologic functions in the patients with esophageal cancer, from July 2012 to September 2014, 82 patients of esophageal cancer which were receiving treatment in our hospital chose out for this research. Among them, 42 patients received radiotherapy only, as the control group; while the other 40 patients with concurrent cisplatin plus paclitaxel chemo radiotherapy was taken as the observation group. Then the immunologic functions, toxic and side effects were compared between the two groups as well as the survival rates after 3-year-followup-visit, Th level of the total T cells, Th cells and the ratio of Th cells to Ts cells after receiving treatment all increased significantly compared with prior treatment. And the difference was statistically significant (P<0.05). After the treatment, the level of T cells, Th cells and the ratio of Th cells to Ts cells of the observation group were all significantly lower than the control group, and the difference was statistically significant (P<0.05). While the difference of the ratio of Ts cells to natural killer cells (NK cells) between the two groups were not significant. The toxic and side effects were mainly myelosuppression, decrease leukocyte, esophagit, nausea and vomiting, and it was not statistically significant in the difference between the two groups (P >0.05), the survival rates from the first year to the third year in the observation group were respectively significantly higher than the control group, and the difference was statistically significant (P<0.05). Radiotherapy combined with cisplatin plus paclitaxel chemotherapy could properly increase the immunologic functions in patients with esophageal cancer, benefiting for the survival rate with a good security. Therefore, it was worth promoting. PMID:27592476

  2. Clinical and immunological analysis of measles patients admitted to a Beijing hospital in 2014 during an outbreak in China.

    PubMed

    Tu, B; Zhao, J-J; Hu, Y; Fu, J-L; Huang, H-H; Xie, Y-X; Zhang, X; Shi, L; Zhao, P; Zhang, X-W; Wu, D; Xu, Z; Zhou, Z-P; Qin, E-Q; Wang, F-S

    2016-09-01

    At the end of 2013, China reported a countrywide outbreak of measles. From January to May 2014, we investigated the clinical and immunological features of the cases of the outbreak admitted to our hospital. In this study, all 112 inpatients with clinically diagnosed measles were recruited from the 302 Military Hospital of China. The virus was isolated from throat swabs from these patients, and cytokine profiles were examined. By detecting the measles virus of 30 of the 112 patients, we found that this measles outbreak was of the H1 genotype, which is the major strain in China. The rates of complications, specifically pneumonia and liver injury, differed significantly in patients aged 18 years: pneumonia was more common in children, while liver injury was more common in adults. Pneumonia was a significant independent risk factor affecting measles duration. Compared to healthy subjects, measles patients had fewer CD4+IL-17+, CD4+IFN-γ +, and CD8+IFN-γ + cells in both the acute and recovery phases. In contrast, measles patients in the acute phase had more CD8+IL-22+ cells than those in recovery or healthy subjects. We recommend that future studies focus on the age-related distribution of pneumonia and liver injury as measles-related complications as well as the association between immunological markers and measles prognosis. PMID:27251754

  3. Long-term survival correlates with immunological responses in renal cell carcinoma patients treated with mRNA-based immunotherapy

    PubMed Central

    Rittig, Susanne M.; Haentschel, Maik; Weimer, Katrin J.; Heine, Annkristin; Müller, Martin R.; Brugger, Wolfram; Horger, Marius S.; Maksimovic, Olga; Stenzl, Arnulf; Hoerr, Ingmar; Rammensee, Hans-Georg; Holderried, Tobias A.; Kanz, Lothar; Pascolo, Steve; Brossart, Peter

    2016-01-01

    ABSTRACT Renal cell carcinoma (RCC) is an immunogenic tumor for which immunotherapeutic approaches could be associated with clinically relevant responses. It was recently shown, that induction of T-cell responses against multiple tumor-associated antigen (TAA) epitopes results in prolonged overall survival in RCC patients. In 2003–2005, we performed a phase I/II trial testing an mRNA-based vaccine formulation consisting of a mixture of in vitro transcribed RNA coding for six different TAAs (MUC1, CEA, Her2/neu, telomerase, survivin, MAGE-A1) in 30 metastatic RCC (mRCC) patients. In the first 14 patients, vaccinations were applied i.d. on days 0, 14, 28, and 42. In the consecutive 16 patients, an intensified protocol consisting of i.d. injections (daily on days 0–3, 7–10, 28, and 42) was used. After the respective induction periods, patients in both cohorts were vaccinated monthly until tumor progression. At survival update performed in July 2015, one of the 30 patients was still alive. One patient was lost to follow-up. Median survival of 24.5 mo (all patients) and 89 mo (favorable risk patients) exceeded predicted survival according to Memorial Sloan Kettering Cancer Center (MSKCC) risk score. Impressively, long-term survivors displayed immunological responses to the applied antigens while vice versa no patient without detectable immune response had survived more than 33 mo. The current survival update shows a clear correlation between survival and immunological responses to TAAs encoded by the naked mRNA vaccine. This is one of the first vaccination studies and the only RNA trial that reports on safety and efficacy after a follow-up of more than 10 y.

  4. Long-term survival correlates with immunological responses in renal cell carcinoma patients treated with mRNA-based immunotherapy.

    PubMed

    Rittig, Susanne M; Haentschel, Maik; Weimer, Katrin J; Heine, Annkristin; Müller, Martin R; Brugger, Wolfram; Horger, Marius S; Maksimovic, Olga; Stenzl, Arnulf; Hoerr, Ingmar; Rammensee, Hans-Georg; Holderried, Tobias A; Kanz, Lothar; Pascolo, Steve; Brossart, Peter

    2016-05-01

    Renal cell carcinoma (RCC) is an immunogenic tumor for which immunotherapeutic approaches could be associated with clinically relevant responses. It was recently shown, that induction of T-cell responses against multiple tumor-associated antigen (TAA) epitopes results in prolonged overall survival in RCC patients. In 2003-2005, we performed a phase I/II trial testing an mRNA-based vaccine formulation consisting of a mixture of in vitro transcribed RNA coding for six different TAAs (MUC1, CEA, Her2/neu, telomerase, survivin, MAGE-A1) in 30 metastatic RCC (mRCC) patients. In the first 14 patients, vaccinations were applied i.d. on days 0, 14, 28, and 42. In the consecutive 16 patients, an intensified protocol consisting of i.d. injections (daily on days 0-3, 7-10, 28, and 42) was used. After the respective induction periods, patients in both cohorts were vaccinated monthly until tumor progression. At survival update performed in July 2015, one of the 30 patients was still alive. One patient was lost to follow-up. Median survival of 24.5 mo (all patients) and 89 mo (favorable risk patients) exceeded predicted survival according to Memorial Sloan Kettering Cancer Center (MSKCC) risk score. Impressively, long-term survivors displayed immunological responses to the applied antigens while vice versa no patient without detectable immune response had survived more than 33 mo. The current survival update shows a clear correlation between survival and immunological responses to TAAs encoded by the naked mRNA vaccine. This is one of the first vaccination studies and the only RNA trial that reports on safety and efficacy after a follow-up of more than 10 y. PMID:27467913

  5. NY-ESO-1–specific immunological pressure and escape in a patient with metastatic melanoma

    PubMed Central

    von Boehmer, Lotta; Mattle, Muriel; Bode, Peter; Landshammer, Alexandro; Schäfer, Carolin; Nuber, Natko; Ritter, Gerd; Old, Lloyd; Moch, Holger; Schäfer, Niklaus; Jäger, Elke; Knuth, Alexander; van den Broek, Maries

    2013-01-01

    During cancer progression, malignant cells may evade immunosurveillance. However, evidence for immunological escape in humans is scarce. We report here the clinical course of a melanoma patient whose initial tumor was positive for the antigens NY-ESO-1, MAGE-C1, and Melan-A. Upon immunization with a recombinant vaccinia/fowlpox NY-ESO-1 construct, the patient experienced a mixed clinical response and spreading of the NY-ESO-1 epitopes in the CD4+ T cell compartment. After NY-ESO-1 protein + CpG immunization, the patient’s anti-NY-ESO-1 IgG response increased. Over the following years, progressing lesions were resected and found to be NY-ESO-1-negative while being positive for MAGE-C1, Melan-A, and MHC-I. The fatal, inoperable brain metastasis was analyzed after his death and also proved to be NY-ESO-1-negative, while being positive for MAGE-C1 and Melan-A, as well as MHC-I. We propose that cancer control and cancer escape in this patient were governed by NY-ESO-1-specific immunological pressure. Our findings provide evidence for the existence of immunoediting and immunoescape in this cancer patient. PMID:23882157

  6. An Immunological Analysis of Dystroglycan Subunits: Lessons Learned from a Small Cohort of Non-Congenital Dystrophic Patients

    PubMed Central

    Pavoni, Ernesto; Sciandra, Francesca; Tasca, Giorgio; Tittarelli, Roberta; Bozzi, Manuela; Giardina, Bruno; Ricci, Enzo; Brancaccio, Andrea

    2011-01-01

    The dystroglycan (DG) expression pattern can be altered in severe muscular dystrophies. In fact, some congenital muscular dystrophies (CMDs) and limb-girdle muscular dystrophies (LGMDs) are caused by point mutations identified in six glycosyltransferase genes which are likely to target different steps along the posttranslational “O-glycosylation route” leading to a fully decorated and functional α-DG subunit. Indeed, hypoglycosylation of α-DG is thought to represent a major pathological event, in that it could reduce the DG’s ability to bind the basement membrane components, thus leading to sarcolemmal instability and necrosis. In order to set up an efficient standard immunological protocol, taking advantage of a wide panel of antibodies, we have analyzed the two DG subunits in a small cohort of adult dystrophic patients, whom an extensive medical examination had already clinically classified as affected by LGMD (5), Miyoshi (1) or distal (1) myopathy. Immunofluorescence analysis of skeletal muscle tissue sections revealed a proper sarcolemmal localization of the DG subunits in all the patients analyzed. However, Western blot analysis of lectin enriched skeletal muscle samples revealed an abnormal glycosylation of α-DG in two patients. Our work reinforces the notion that a careful immunological and biochemical analysis of the two DG subunits should be always considered as a prerequisite for the identification of new putative cases of dystroglycanopathy. PMID:22046204

  7. Clinical Pharmacokinetics of Rifampin in Patients with Tuberculosis and Type 2 Diabetes Mellitus: Association with Biochemical and Immunological Parameters

    PubMed Central

    Medellín-Garibay, S. E.; Cortez-Espinosa, N.; Milán-Segovia, R. C.; Magaña-Aquino, M.; Vargas-Morales, J. M.; González-Amaro, R.; Portales-Pérez, D. P.

    2015-01-01

    Tuberculosis (TB) remains a major public health issue due to the increasing incidence of type 2 diabetes mellitus (T2DM), which exacerbates the clinical course of TB and increases the risk of poor long-term outcomes. The aim of this study was to characterize the pharmacokinetics of rifampin (RIF) and its relationship with biochemical and immunological parameters in patients with TB and T2DM. The biochemical and immunological parameters were assessed on the same day that the pharmacokinetic evaluation of RIF was performed. Factors related to the metabolic syndrome that is characteristic of T2DM patients were not detected in the TB-T2DM group (where predominant malnutrition was present) or in the TB group. Percentages of CD8+ T lymphocytes and NK cells were diminished in the TB and TB-T2DM patients, who had high tumor necrosis factor alpha (TNF-α) and low interleukin-17 (IL-17) levels compared to healthy volunteers. Delayed RIF absorption was observed in the TB and TB-T2DM patients; absorption was poor and slower in the latter group due to poor glycemic control. RIF clearance was also slower in the diabetic patients, thereby prolonging the mean residence time of RIF. There was a significant association between glycemic control, increased TNF-α serum concentrations, and RIF pharmacokinetics in the TB-T2DM patients. These altered metabolic and immune conditions may be factors to be considered in anti-TB therapy management when TB and T2DM are concurrently present. PMID:26438503

  8. Qualitative Immune Modulation by Interleukin-2 (IL-2) Adjuvant Therapy in Immunological Non Responder HIV-Infected Patients

    PubMed Central

    Sabbatini, Francesca; Bandera, Alessandra; Ferrario, Giulio; Trabattoni, Daria; Marchetti, Giulia; Franzetti, Fabio; Clerici, Mario; Gori, Andrea

    2010-01-01

    Background Treatment of HIV-infected patients with interleukin-2 (IL-2) produces significant increases in CD4 T cell counts; however an associated qualitative improvement in cells function has yet to be conclusively demonstrated. By measuring mycobacterial killing activity, we evaluated IL-2-mediated functional immune enhancement ex vivo in immunological non-responders (INRs). Methods and Findings PBMC from 12 immunological non-responders (INRs) (CD4+<200/µl, HIV-RNA<50 cp/ml) on combination antiretroviral treatment (cART) were collected at baseline, and after 3 IL-2 cycles. Eight INRs receiving only cART were studied as controls. After 21 days of PBMC incubation with a virulent M. avium suspension, counts of residual colony forming units (CFUs) and concentrations of TNF-α, IL-10 and IFN-γ were determined. In IL-2 treated patients, a significant reduction in mean residual CFUs of PBMC cultures was observed (p<0.01). Moreover, following IL-2 treatment, significant increases in PBMC's IFNγ production (p = 0.02) and substantial reductions in IL-10 levels were observed. Conclusions IL-2 therapy restores the ability of the lympho-monocyte system in eliciting an effective response against mycobacterial infections. Our data indicate the possibility of a clinical role held by IL-2 in enhancing the immune function of subjects unable to achieve immune competence through cART alone. PMID:21124762

  9. Myelodysplastic Syndrome Revealed by Systems Immunology in a Melanoma Patient Undergoing Anti-PD-1 Therapy.

    PubMed

    Greenplate, Allison R; Johnson, Douglas B; Roussel, Mikael; Savona, Michael R; Sosman, Jeffrey A; Puzanov, Igor; Ferrell, P Brent; Irish, Jonathan M

    2016-06-01

    Antibodies aimed at blocking the interaction between programmed cell death-1 (PD-1) and its ligands have shown impressive efficacy in a variety of malignancies and are generally well tolerated. Research has focused intensely on T cells and their interaction with cells within melanoma tumors, while relatively little is understood about the systems immunology of the cells in the blood during checkpoint inhibitor therapy. Longitudinal cytomic analysis using mass cytometry can characterize all the cells in a small sample of blood and has the potential to reveal key shifts in the cellular milieu occurring during treatment. We report a case of advanced melanoma in which mass cytometry detected abnormal myeloid cells resulting from myelodysplastic syndrome (MDS) in the blood following treatment with an anti-PD-1 agent. Myeloid blasts comprised <1% of peripheral blood mononuclear cells (PBMC) 1 month after the start of treatment. Six months after starting therapy, myeloid blasts comprised 5% of PBMCs, and a bone marrow biopsy confirmed refractory anemia with excess blasts-2 (RAEB-2). Longitudinal mass cytometry immunophenotyping comprehensively characterized blast phenotype evolution and revealed elevated PD-1 expression on the surface of nonblast myeloid cells. These findings highlight the clinical significance of cytomic monitoring, indicate that the myeloid compartment should be monitored during checkpoint inhibitor therapy, and emphasize the value of systems immunology in medicine. Cancer Immunol Res; 4(6); 474-80. ©2016 AACR. PMID:26966176

  10. Assessment of the magnitude and associated factors of immunological failure among adult and adolescent HIV-infected patients in St. Luke and Tulubolo Hospital, Oromia Region, Ethiopia

    PubMed Central

    Bayou, Bekelech; Sisay, Abay; Kumie, Abera

    2015-01-01

    Introduction The use of antiretroviral therapy (ART) has become a standard of care for the treatment of HIV infection. However, cost and resistance to ART are major obstacles for access to treatment especially in resource-limited settings. In this study, we aimed to assess the magnitude and associated factors of Immunological failure among adult and adolescent HIV infected Patients (with age ‘15yrs) on Highly Active Antiretroviral Therapy (HAART) in St. Luke and Tulu Bolo Hospitals, Oromia Region, Ethiopia. Methods A retrospective follow-up study was conducted among HIV-infected patients initiated 1st line ART at St. Luke and Tulu Bolo Hospitals, South West Shoa Zone, Oromia, Ethiopia. Results A total of 828 patient charts were reviewed. 477(57.6%) were female and the median age was 32 years. The median baseline CD4 count was 148cells/mm3. The most common prescribed ART was TDF based (36.7%). Out of 828 patients chart reviewed 6.8% (56) were developed immunological failure. Out of them only 20 (2.4%) were detected and put on second line regimen. The incidence of immunological failure was 1.8 cases per 100 person years of follow-up. Patients who had not disclosed their HIV status to any one had high risk of immunological failure compared with patients those who had disclosed their HIV status (AHR, 0.429; 95% CI 0.206 - 0.893; P-value=0.024). Conclusion Non disclosures of HIV status and with ambulatory of baseline functional status were found to be predictors of immunological failure. Most of the immunological failure cases were not detected early and not switched to second line ARV regimen. So patients with the above risk factors should be considered for a timely switch to second line HAART. PMID:26587140

  11. Relationship Between Clinical and Immunological Features with Magnetic Resonance Imaging Abnormalities in Female Patients with Neuropsychiatric Systemic Lupus Erythematosus

    PubMed Central

    Wang, Hai-Peng; Wang, Cui-Yan; Pan, Zheng-Lun; Zhao, Jun-Yu; Zhao, Bin

    2016-01-01

    Background: Conventional magnetic resonance imaging (MRI) is the preferred neuroimaging method in the evaluation of neuropsychiatric systemic lupus erythematosus (NPSLE). The purpose of this study was to investigate the association between clinical and immunological features with MRI abnormalities in female patients with NPSLE, to screen for the value of conventional MRI in NPSLE. Methods: A total of 59 female NPSLE patients with conventional MRI examinations were enrolled in this retrospective study. All patients were classified into different groups according to MRI abnormalities. Both clinical and immunological features were compared between MRI abnormal and normal groups. One-way analysis of variance was used to compare the systemic lupus erythematosus disease activity index (SLEDAI) score for MRI abnormalities. Multivariate logistic regression analysis investigated the correlation between immunological features, neuropsychiatric manifestations, and MRI abnormalities. Results: Thirty-six NPSLE patients (61%) showed a variety of MRI abnormalities. There were statistically significant differences in SLEDAI scores (P < 0.001), incidence of neurologic disorders (P = 0.001), levels of 24-h proteinuria (P = 0.001) and immunoglobulin M (P = 0.004), and incidence of acute confusional state (P = 0.002), cerebrovascular disease (P = 0.004), and seizure disorder (P = 0.028) between MRI abnormal and normal groups. In the MRI abnormal group, SLEDAI scores for cerebral atrophy (CA), cortex involvement, and restricted diffusion (RD) were much higher than in the MRI normal group (P < 0.001, P = 0.002, P = 0.038, respectively). Statistically significant positive correlations between seizure disorder and cortex involvement (odds ratio [OR] = 14.90; 95% confidence interval [CI], 1.50–151.70; P = 0.023) and cerebrovascular disease and infratentorial involvement (OR = 10.00; 95% CI, 1.70–60.00; P = 0.012) were found. Conclusions: MRI abnormalities in NPSLE, especially CA

  12. Cytokine mRNA expression in lung tissue from toxic oil syndrome patients: a TH2 immunological mechanism.

    PubMed

    del Pozo, V; de Andrés, B; Gallardo, S; Cárdaba, B; de Arruda-Chaves, E; Cortegano, M I; Jurado, A; Palomino, P; Oliva, H; Aguilera, B; Posada, M; Lahoz, C

    1997-03-14

    In 1981, an epidemic occurred in Spain, toxic oil syndrome (TOS), in people who consumed rapeseed oil denatured with 2% aniline, and it was one of the largest intoxication epidemics ever recorded. In 1989, a similar disease, eosinophilia-myalgia syndrome (EMS) was reported in the USA and was associated with the ingestion of L-tryptophan. The pathologic findings in TOS showed primary endothelial injury, with cell proliferation and perivascular inflammatory infiltrates. Immunologic mechanisms have presumably been operative in the pathogenesis and perpetuation of TOS. Our previous findings pointed to a T-cell activation during acute phase of the disease. In order to analyze which T-cell subset is involved on TOS, we have developed an mRNA extraction procedure from paraffin-embedded lung tissues in patients with pulmonary involvement. We analyzed mRNA expression from different cytokines (IL-1, IL-2, IL-4, IL-5, IFN-gamma, GM-CSF) and CD25 (interleukin 2 receptor) and CD23 (low affinity IgE receptor), using RT-PCR technique. In lung tissues from these patients a T-cell activation was observed. We found a significant increase in Th1 (P = 0.006) and Th2 (P = 0.003) cytokine profile in TOS patients with respect to controls. The increment in TH2 response with respect to TH1 is significant (P = 0.03) in TOS lung specimens. Non-significant differences were obtained in other cytokines and receptors studied as IL-1, CD25, CD23 and GM-CSF. Data presented in this paper are the first clear evidence that an immunological mechanism is directly implicated in this illness. PMID:9074654

  13. Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity

    PubMed Central

    Min, Chan-Ki; Cheon, Shinhye; Ha, Na-Young; Sohn, Kyung Mok; Kim, Yuri; Aigerim, Abdimadiyeva; Shin, Hyun Mu; Choi, Ji-Yeob; Inn, Kyung-Soo; Kim, Jin-Hwan; Moon, Jae Young; Choi, Myung-Sik; Cho, Nam-Hyuk; Kim, Yeon-Sook

    2016-01-01

    Despite the ongoing spread of MERS, there is limited knowledge of the factors affecting its severity and outcomes. We analyzed clinical data and specimens from fourteen MERS patients treated in a hospital who collectively represent a wide spectrum of disease severity, ranging from mild febrile illness to fatal pneumonia, and classified the patients into four groups based on severity and mortality. Comparative and kinetic analyses revealed that high viral loads, weak antibody responses, and lymphopenia accompanying thrombocytopenia were associated with disease mortality, whereas persistent and gradual increases in lymphocyte responses might be required for effective immunity against MERS-CoV infection. Leukocytosis, primarily due to increased neutrophils and monocytes, was generally observed in more severe and fatal cases. The blood levels of cytokines such as IL-10, IL-15, TGF-β, and EGF were either positively or negatively correlated with disease mortality. Robust induction of various chemokines with differential kinetics was more prominent in patients that recovered from pneumonia than in patients with mild febrile illness or deceased patients. The correlation of the virological and immunological responses with disease severity and mortality, as well as their responses to current antiviral therapy, may have prognostic significance during the early phase of MERS. PMID:27146253

  14. Immunological and histological evaluation of clinical samples from psoriasis patients treated with anti-CD6 itolizumab

    PubMed Central

    Aira, Lazaro E; López-Requena, Alejandro; Fuentes, Dasha; Sánchez, Liset; Pérez, Teresita; Urquiza, Aleida; Bautista, Heber; Falcón, Leopoldina; Hernández, Patricia; Mazorra, Zaima

    2014-01-01

    Psoriasis is a chronic inflammatory disease with a prevalence of approximately 2–3% in the general population. The majority of diagnosed patients have plaque psoriasis, and about 20% have moderate-to-severe disease. Itolizumab, a new monoclonal antibody specific for the CD6 molecule mainly expressed on T lymphocytes, has demonstrated to inhibit in vitro ligand-induced proliferation and pro-inflammatory cytokine production. We assessed the immunological and histopathological effect of the antibody using clinical samples taken from 26 patients with moderate-to-severe psoriasis included in a clinical trial. The precursor frequency of lymphocytes activated with anti-CD2/CD3/CD28 beads, as well as the number of interferon (IFN)-γ-secreting T cells after stimulation, were measured at different time points of the study. Serum cytokine levels and anti-idiotypic antibody response to itolizumab were also evaluated. Additionally, lymphocyte infiltration and epidermis hyperplasia were studied in five patients. A significant reduction in T cell proliferation capacity and number of IFN-γ-producing T cells was found in treated patients. Serum levels of interleukin-6, tumor necrosis factor and IFN-γ showed an overall trend toward reduction. No anti-idiotypic antibody response was detected. A significant reduction in the epidermis hyperplasia was observed in analyzed patients. These results support the relevance of the CD6 molecule as a therapeutic target for the treatment of this disease. PMID:24594862

  15. Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity.

    PubMed

    Min, Chan-Ki; Cheon, Shinhye; Ha, Na-Young; Sohn, Kyung Mok; Kim, Yuri; Aigerim, Abdimadiyeva; Shin, Hyun Mu; Choi, Ji-Yeob; Inn, Kyung-Soo; Kim, Jin-Hwan; Moon, Jae Young; Choi, Myung-Sik; Cho, Nam-Hyuk; Kim, Yeon-Sook

    2016-01-01

    Despite the ongoing spread of MERS, there is limited knowledge of the factors affecting its severity and outcomes. We analyzed clinical data and specimens from fourteen MERS patients treated in a hospital who collectively represent a wide spectrum of disease severity, ranging from mild febrile illness to fatal pneumonia, and classified the patients into four groups based on severity and mortality. Comparative and kinetic analyses revealed that high viral loads, weak antibody responses, and lymphopenia accompanying thrombocytopenia were associated with disease mortality, whereas persistent and gradual increases in lymphocyte responses might be required for effective immunity against MERS-CoV infection. Leukocytosis, primarily due to increased neutrophils and monocytes, was generally observed in more severe and fatal cases. The blood levels of cytokines such as IL-10, IL-15, TGF-β, and EGF were either positively or negatively correlated with disease mortality. Robust induction of various chemokines with differential kinetics was more prominent in patients that recovered from pneumonia than in patients with mild febrile illness or deceased patients. The correlation of the virological and immunological responses with disease severity and mortality, as well as their responses to current antiviral therapy, may have prognostic significance during the early phase of MERS. PMID:27146253

  16. Severe adverse immunologic reaction in a patient with glioblastoma receiving autologous dendritic cell vaccines combined with GM-CSF and dose-intensified temozolomide

    PubMed Central

    Mitchell, Duane A.; Sayour, Elias J.; Reap, Elizabeth; Schmittling, Robert; De Leon, Gabriel; Norberg, Pamela; Desjardins, Annick; Friedman, Allan H.; Friedman, Henry S.; Archer, Gary; Sampson, John H.

    2015-01-01

    Therapeutic vaccination of patients with cancer-targeting tumor-associated antigens is a promising strategy for the specific eradication of invasive malignancies with minimal toxicity to normal tissues. However, as increasingly potent modalities for stimulating immunologic responses are developed for clinical evaluation, the risk of inflammatory and autoimmune toxicities also may be exacerbated. In this report, we describe the induction of a severe (Grade 3) immunologic reaction in a patient with newly-diagnosed glioblastoma (GBM) receiving autologous RNA-pulsed dendritic cell (DC) vaccines admixed with GM-CSF and administered coordinately with cycles of dose-intensified temozolomide (diTMZ). Shortly after the eighth administration of the admixed intradermal vaccine, the patient experienced dizziness, flushing, conjunctivitis, headache, and the outbreak of a disseminated macular/papular rash and bilateral indurated injection sites. Immunologic work-up of patient reactivity revealed sensitization to the GM-CSF component of the vaccine and the production of high levels of anti-GM-CSF autoantibodies during vaccination. Removal of GM-CSF from the DC vaccine allowed continued vaccination without incident. Despite the known lymphodepletive and immunosuppressive effects of TMZ, these observations demonstrate the capacity for the generation of severe immunologic reactivity in patients with GBM receiving DC-based therapy during adjuvant diTMZ. PMID:25387895

  17. Characteristics of patients with severe heart failure exhibiting exercise oscillatory ventilation.

    PubMed

    Matsuki, Ryosuke; Kisaka, Tomohiko; Ozono, Ryoji; Kinoshita, Hiroki; Sada, Yoshiharu; Oda, Noboru; Hidaka, Takayuki; Tashiro, Naonori; Takahashi, Makoto; Sekikawa, Kiyokazu; Ito, Yoshihiro; Kimura, Hiroaki; Hamada, Hironobu; Kihara, Yasuki

    2013-01-01

    This study aims to elucidate the characteristics of patients with severe nonischemic heart failure exhibiting exercise oscillatory ventilation (EOV) and the association of these characteristics with the subjective dyspnea. Forty-six patients with nonischemic heart failure who were classified into the New York Heart Association (NYHA) functional class III underwent cardiopulmonary exercise testing (CPX) and were divided into two groups according to the presence or absence of EOV. We evaluated the patients by using the Specific Activity Scale (SAS), biochemical examination, echocardiographic evaluation, results of CPX and symptoms during CPX (Borg scale), and reasons for exercise termination. EOV was observed in 20 of 46 patients. The following characteristics were observed in patients with EOV as compared with those without EOV with statistically significant differences: more patients complaining dyspnea as the reason for exercise termination, lower SAS score, higher N-terminal pro-brain natriuretic peptide level, larger left atrial dimension and volume, left ventricular end-diastolic volume, higher Borg scale score at rest and at the anerobic threshold, higher respiratory rate at rest and at peak exercise, and higher slope of the minute ventilation-to-CO₂ output ratio, and lower end-tidal CO₂ pressure at peak exercise. Among the subjects with NYHA III nonischemic heart failure, more patients with EOV had a stronger feeling of dyspnea during exercise as compared with those without EOV, and the subjective dyspnea was an exercise-limiting factor in many cases. PMID:23537269

  18. Cutaneous manifestations in patients with mastocytosis: Consensus report of the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology.

    PubMed

    Hartmann, Karin; Escribano, Luis; Grattan, Clive; Brockow, Knut; Carter, Melody C; Alvarez-Twose, Ivan; Matito, Almudena; Broesby-Olsen, Sigurd; Siebenhaar, Frank; Lange, Magdalena; Niedoszytko, Marek; Castells, Mariana; Oude Elberink, Joanna N G; Bonadonna, Patrizia; Zanotti, Roberta; Hornick, Jason L; Torrelo, Antonio; Grabbe, Jürgen; Rabenhorst, Anja; Nedoszytko, Boguslaw; Butterfield, Joseph H; Gotlib, Jason; Reiter, Andreas; Radia, Deepti; Hermine, Olivier; Sotlar, Karl; George, Tracy I; Kristensen, Thomas K; Kluin-Nelemans, Hanneke C; Yavuz, Selim; Hägglund, Hans; Sperr, Wolfgang R; Schwartz, Lawrence B; Triggiani, Massimo; Maurer, Marcus; Nilsson, Gunnar; Horny, Hans-Peter; Arock, Michel; Orfao, Alberto; Metcalfe, Dean D; Akin, Cem; Valent, Peter

    2016-01-01

    Cutaneous lesions in patients with mastocytosis are highly heterogeneous and encompass localized and disseminated forms. Although a classification and criteria for cutaneous mastocytosis (CM) have been proposed, there remains a need to better define subforms of cutaneous manifestations in patients with mastocytosis. To address this unmet need, an international task force involving experts from different organizations (including the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology) met several times between 2010 and 2014 to discuss the classification and criteria for diagnosis of cutaneous manifestations in patients with mastocytosis. This article provides the major outcomes of these meetings and a proposal for a revised definition and criteria. In particular, we recommend that the typical maculopapular cutaneous lesions (urticaria pigmentosa) should be subdivided into 2 variants, namely a monomorphic variant with small maculopapular lesions, which is typically seen in adult patients, and a polymorphic variant with larger lesions of variable size and shape, which is typically seen in pediatric patients. Clinical observations suggest that the monomorphic variant, if it develops in children, often persists into adulthood, whereas the polymorphic variant may resolve around puberty. This delineation might have important prognostic implications, and its implementation in diagnostic algorithms and future mastocytosis classifications is recommended. Refinements are also suggested for the diagnostic criteria of CM, removal of telangiectasia macularis eruptiva perstans from the current classification of CM, and removal of the adjunct solitary from the term solitary mastocytoma. PMID:26476479

  19. Clinical, immunologic, and genetic characteristics of RAG mutations in 15 Chinese patients with SCID and Omenn syndrome.

    PubMed

    Bai, Xiaoming; Liu, Jing; Zhang, Zhiyong; Liu, Chaohong; Zhang, Yongjie; Tang, Wenjing; Dai, Rongxin; Wu, Junfeng; Tang, Xuemei; Zhang, Yu; Ding, Yuan; Jiang, Liping; Zhao, Xiaodong

    2016-04-01

    Mutations in Recombination Activating Genes (RAG1 and RAG2) are common genetic causes of severe combined immunodeficiency (SCID) and Omenn syndrome (OS). The clinical, immunologic, and genetic characteristics of RAG mutations in Chinese patients with SCID or OS have not been studied in detail. In this research, 22 RAG mutations were identified in 15 Chinese patients, including 10 novel mutations in RAG1 (R108X, M630T, E510X, S666P, E669K, C730Y, A857V, K847E, L922PfsX7, and L1025FfsX39) and 4 in RAG2 (R73C, I427GfsX12, P432L, and 311insL). L1025FfsX39 is a potential RAG1 hot-spot mutation in the Chinese population. The distribution of RAG1 mutations rather than mutation type seemed to differ between SCID and OS patients. The thymic output of T lymphocytes, TCR rearrangement, and T cell proliferation were severely impaired in RAG mutant patients. These findings will contribute to the early diagnosis and treatment of SCID and OS to a certain extent. PMID:26476733

  20. Variable alterations of the microbiota, without metabolic or immunological change, following faecal microbiota transplantation in patients with chronic pouchitis

    PubMed Central

    Landy, J.; Walker, A. W.; Li, J. V.; Al-Hassi, H. O.; Ronde, E.; English, N. R.; Mann, E. R.; Bernardo, D.; McLaughlin, S. D.; Parkhill, J.; Ciclitira, P. J.; Clark, S. K.; Knight, S. C.; Hart, A. L.

    2015-01-01

    Faecal microbiota transplantation (FMT) is effective in the treatment of Clostridium difficile infection, where efficacy correlates with changes in microbiota diversity and composition. The effects of FMT on recipient microbiota in inflammatory bowel diseases (IBD) remain unclear. We assessed the effects of FMT on microbiota composition and function, mucosal immune response, and clinical outcome in patients with chronic pouchitis. Eight patients with chronic pouchitis (current PDAI ≥7) were treated with FMT via nasogastric administration. Clinical activity was assessed before and four weeks following FMT. Faecal coliform antibiotic sensitivities were analysed, and changes in pouch faecal and mucosal microbiota assessed by 16S rRNA gene pyrosequencing and 1H NMR spectroscopy. Lamina propria dendritic cell phenotype and cytokine profiles were assessed by flow cytometric analysis and multiplex assay. Following FMT, there were variable shifts in faecal and mucosal microbiota composition and, in some patients, changes in proportional abundance of species suggestive of a “healthier” pouch microbiota. However, there were no significant FMT-induced metabolic or immunological changes, or beneficial clinical response. Given the lack of clinical response following FMT via a single nasogastric administration our results suggest that FMT/bacteriotherapy for pouchitis patients requires further optimisation. PMID:26264409

  1. Maraviroc Intensification of cART in Patients with Suboptimal Immunological Recovery: A 48-Week, Placebo-Controlled Randomized Trial

    PubMed Central

    van Lelyveld, Steven F. L.; Otto, Sigrid A.; Richter, Clemens; Soetekouw, Robin; Prins, Jan M.; Brinkman, Kees; Mulder, Jan Willem; Kroon, Frank; Middel, Ananja; Symons, Jori; Wensing, Annemarie M. J.; Nijhuis, Monique; Borghans, José A. M.; Tesselaar, Kiki; Hoepelman, Andy I. M.

    2015-01-01

    Objective The immunomodulatory effects of the CCR5-antagonist maraviroc might be beneficial in patients with a suboptimal immunological response, but results of different cART (combination antiretroviral therapy) intensification studies are conflicting. Therefore, we performed a 48-week placebo-controlled trial to determine the effect of maraviroc intensification on CD4+ T-cell counts and immune activation in these patients. Design Double-blind, placebo-controlled, randomized trial. Methods Major inclusion criteria were 1. CD4+ T-cell count <350 cells/μL while at least two years on cART or CD4+ T-cell count <200 cells/μL while at least one year on cART, and 2. viral suppression for at least the previous 6 months. HIV-infected patients were randomized to add maraviroc (41 patients) or placebo (44 patients) to their cART regimen for 48 weeks. Changes in CD4+ T-cell counts (primary endpoint) and other immunological parameters were modeled using linear mixed effects models. Results No significant differences for the modelled increase in CD4+ T-cell count (placebo 15.3 CD4+ T cells/μL (95% confidence interval (CI) [1.0, 29.5] versus maraviroc arm 22.9 CD4+ T cells/μL (95% CI [7.4, 38.5] p = 0.51) or alterations in the expression of markers for T-cell activation, proliferation and microbial translocation were found between the arms. However, maraviroc intensification did increase the percentage of CCR5 expressing CD4+ and CD8+ T-cells, and the plasma levels of the CCR5 ligand MIP-1β. In contrast, the percentage of ex-vivo apoptotic CD8+ and CD4+ T-cells decreased in the maraviroc arm. Conclusions Maraviroc intensification of cART did not increase CD4+ T-cell restoration or decrease immune activation as compared to placebo. However, ex-vivo T-cell apoptosis was decreased in the maraviroc arm. Trial Registration ClinicalTrials.gov NCT00875368 PMID:26208341

  2. Immunologic response in treatment-naïve HIV-2-infected patients: the IeDEA West Africa cohort

    PubMed Central

    Balestre, Eric; Ekouevi, Didier Koumavi; Tchounga, Boris; Eholie, Serge Paul; Messou, Eugène; Sawadogo, Adrien; Thiébaut, Rodolphe; May, Margaret T; Sterne, Jonathan Ac; Dabis, François

    2016-01-01

    Introduction Response to antiretroviral therapy (ART) among individuals infected with HIV-2 is poorly described. We compared the immunological response among patients treated with three nucleoside reverse-transcriptase inhibitors (NRTIs) to boosted protease inhibitor (PI) and unboosted PI-based regimens in West Africa. Methods This prospective cohort study enrolled treatment-naïve HIV-2-infected patients within the International Epidemiological Databases to Evaluate AIDS collaboration in West Africa. We used mixed models to compare the CD4 count response to treatment over 12 months between regimens. Results Of 422 HIV-2-infected patients, 285 (67.5%) were treated with a boosted PI-based regimen, 104 (24.6%) with an unboosted PI-based regimen and 33 (7.8%) with three NRTIs. Treatment groups were comparable with regard to gender (54.5% female) and median age at ART initiation (45.3 years; interquartile range 38.3 to 51.8). Treatment groups differed by clinical stage (21.2%, 16.8% and 17.3% at CDC Stage C or World Health Organization Stage IV for the triple NRTI, boosted PI and unboosted PI groups, respectively, p=0.02), median length of follow-up (12.9, 17.7 and 44.0 months for the triple NRTI, the boosted PI and the unboosted PI groups, respectively, p<0.001) and baseline median CD4 count (192, 173 and 129 cells/µl in the triple NRTI, the boosted PI and the unboosted PI-based regimen groups, respectively, p=0.003). CD4 count recovery at 12 months was higher for patients treated with boosted PI-based regimens than those treated with three NRTIs or with unboosted PI-based regimens (191 cells/µl, 95% CI 142 to 241; 110 cells/µl, 95% CI 29 to 192; 133 cells/µl, 95% CI 80 to 186, respectively, p=0.004). Conclusions In this observational study using African data, boosted PI-containing regimens had better immunological response compared to triple NRTI combinations and unboosted PI-based regimens at 12 months. A randomized clinical trial is still required to determine

  3. Patients suffering from nonspecific work-related upper extremity disorders exhibit insufficient movement strategies.

    PubMed

    Bloemsaat, Jules G; Ruijgrok, Joop M; Van Galen, Gerard P

    2004-01-01

    The purpose of this research was to investigate whether patients experiencing nonspecific complaints of the forearm caused by sustained use of the personal computer exhibit deviant movement strategies as compared to healthy participants. Patients (N=10) and controls (N=24) performed a graphical aiming task combined with an auditory memory task. Force production (pen pressure), kinematic- and performance variables were recorded. During a trial, the control group gradually increased pen pressure from the stationary phases to the dynamic phase. The patients increased their pen pressure much more abruptly and to such a degree that the final pressure during real-time movement far exceeded that of the controls. Memory load led to a greater increase of pen pressure from the stationary phase to the dynamic phase in the patient group. Patients further displayed longer reaction times. The results are discussed within the framework of our recent theory on the role of neuromotor noise in the regulation of task performance under conditions of stress. PMID:14734239

  4. Comparison of viro-immunological marker changes between HIV-1 and HIV-2-infected patients in France

    PubMed Central

    Drylewicz, Julia; Matheron, Sophie; Lazaro, Estibaliz; Damond, Florence; Bonnet, Fabrice; Simon, François; Dabis, François; Brun-Vezinet, Françoise; Chêne, Geneviève; Thiebaut, Rodolphe

    2008-01-01

    Background HIV-2 is known to be less pathogenic than HIV-1, although the underlying mechanisms are still debated. We compared the changes over time in viro-immunologic markers in HIV-1 and HIV-2 infected patients living in France during natural history and after initiation of the first Combination of AntiRetroviral Treatment (CART). Method Patients were included in the ANRS CO3 HIV-1 cohort (N=6707) or the ANRS CO5 HIV-2 cohort (N=572). HIV-1 infected patients were matched to HIV-2 patients according to sex, age, HIV transmission group and period of treatment initiation. Changes in markers have been estimated with linear mixed models. Results Analyses were performed for three groups of patients: (1) those with estimated date of contamination (98 HIV-1 and 49 HIV-2 seroincident patients), (2) untreated seroprevalent patients (320 HIV-1 and 160 HIV-2) and (3) those who initiated a first CART (59 HIV-1 and 63 HIV-2). In group 1, CD4 T-cell decreased less rapidly in HIV-2 than HIV-1 patients (−9 vs. −49 cells/mm3/year, p<10−4). Estimated slopes in untreated group 2 were similar to those estimated in group 1 (−11 vs. −49 cells/mm3/year, p=0.003). In group 3, baseline CD4 at CART initiation was not different according to the type of infection (269 vs.220 cells/mm3). During the first two months of treatment, CD4 count increased by +59 cells/mm3/month (95% Confidence Interval [CI]=34;84) for HIV-1 and +24 (CI=6;42) for HIV-2. The plasma viral load drop was 3-fold more important in HIV-1 patients: −1.56 log10/ml/month (CI=−1.83; − 1.30) vs. −0.62 (CI=−0.84; −0.40) among HIV-2 patients (p<10−4). Conclusion Differences between the two infections during natural history are similar to those previously described in Africa. Paradoxically, once treatment is started, response is poorer in HIV-2 patients than in HIV-1 patients. PMID:18301058

  5. Clinical and immunologic outcome of patients with cartilage hair hypoplasia after hematopoietic stem cell transplantation.

    PubMed

    Bordon, Victoria; Gennery, Andrew R; Slatter, Mary A; Vandecruys, Els; Laureys, Genevieve; Veys, Paul; Qasim, Waseem; Waseem, Qasim; Friedrich, Wilhelm; Wulfraat, Nico M; Scherer, Franziska; Cant, Andrew J; Fischer, Alain; Cavazzana-Calvo, Marina; Cavazanna-Calvo, Marina; Bredius, Robbert G M; Notarangelo, Luigi D; Mazzolari, Evelina; Neven, Benedicte; Güngör, Tayfun; Tayfun, Güngör

    2010-07-01

    Cartilage-hair hypoplasia (CHH) is a rare autosomal recessive disease caused by mutations in the RMRP gene. Beside dwarfism, CHH has a wide spectrum of clinical manifestations including variable grades of combined immunodeficiency, autoimmune complications, and malignancies. Previous reports in single CHH patients with significant immunodeficiencies have demonstrated that allogeneic hematopoietic stem cell transplantation (HSCT) is an effective treatment for the severe immunodeficiency, while growth failure remains unaffected. Because long-term experience in larger cohorts of CHH patients after HSCT is currently unreported, we performed a European collaborative survey reporting on 16 patients with CHH and immunodeficiency who underwent HSCT. Immune dysregulation, lymphoid malignancy, and autoimmunity were important features in this cohort. Thirteen patients were transplanted in early childhood ( approximately 2.5 years). The other 3 patients were transplanted at adolescent age. Of 16 patients, 10 (62.5%) were long-term survivors, with a median follow-up of 7 years. T-lymphocyte numbers and function have normalized, and autoimmunity has resolved in all survivors. HSCT should be considered in CHH patients with severe immunodeficiency/autoimmunity, before the development of severe infections, major organ damage, or malignancy might jeopardize the outcome of HSCT and the quality of life in these patients. PMID:20375313

  6. Combination Antiretroviral Therapy With Raltegravir Leads to Rapid Immunologic Reconstitution in Treatment-Naive Patients With Chronic HIV Infection

    PubMed Central

    Pallikkuth, Suresh; Fischl, Margaret A.; Pahwa, Savita

    2013-01-01

    Background. In treatment-naive, human immunodeficiency virus (HIV)–infected persons, combination antiretroviral therapy (cART) incorporating raltegravir (RAL) is highly effective for virologic suppression, but characteristics of immunologic recovery have not been described. Methods. We performed a 48-week substudy of 15 patients, median age 40 years, within a phase 2 randomized trial of RAL-cART in treatment-naive patients with chronic HIV infection. Results. Plasma viral load decreased from 5.2 ± 5.3 log10 HIV RNA copies/mL to 2.2 ± 2.4 log10 copies/mL at week 4, reaching <50 copies/mL at week 8 in 13 of 15 patients. Total CD4 T cells increased at week 4, as did central memory CD4 T cells in association with reduction of the immune activation markers HLA-DR and CD38 and immune exhaustion marker PD1 in CD4 and CD8 T cells. Naive CD4 T cells increased at week 24 with appearance of HIV gag–specific interleukin 2, interferon-γ, and CD107a responses in CD4 and CD8 T cells at week 48. Plasma lipopolysaccharide and soluble CD14 decreased, but at week 48 were elevated as compared to healthy volunteers. Altogether, the week 48 immune profile was more favorable in patients taking RAL-cART than in patients treated with non–RAL-cART. Conclusions. RAL in first-line treatment regimens results in rapid immune reconstitution with residual low-level microbial translocation. PMID:23922374

  7. Impact of Strength Training on Bone Mineral Density in Patients Infected With HIV Exhibiting Lipodystrophy.

    PubMed

    Santos, Wlaldemir R; Santos, Walmir R; Paes, Pedro P; Ferreira-Silva, Isac A; Santos, André P; Vercese, Natan; Machado, Dalmo R L; de Paula, Francisco José A; Donadi, Eduardo A; Navarro, Anderson M; Fernandes, Ana Paula M

    2015-12-01

    This study aimed to evaluate the impact of strength training on bone mineral density (BMD) in individuals harboring HIV exhibiting lipodystrophy. The study included 20 subjects (16 men) aged 50.60 ± 6.40 years with reduced BMD, presenting positive serology for HIV, using highly active antiretroviral therapy, and performing no regular practice of physical exercise before being enrolled in the study. Bone mineral density levels were evaluated by dual-energy x-ray absorptiometry in the lumbar spine, femoral neck, and 1/3 radius, before and after 36 sessions (12 weeks) of strength training. Compared with pre-exercise period, the results showed increased BMD in lumbar spine (3.28%; p = 0.012), femoral neck (8.45%; p = 0.044), and 1/3 radius (5.41%; p = 0.035). This is the first study evaluating the impact of strength training in patients living with HIV and exhibiting lipodystrophy, showing an increased BMD in all the regions measured (lumbar spine, femoral neck, and 1/3 radius). This study showed the beneficial impact of the strength training on BMD increase in patients living with HIV as an effective and available approach to improve bone health. PMID:25970490

  8. Assessment of clinico-immunological profile of newly diagnosed HIV patients presenting to a teaching hospital of eastern India

    PubMed Central

    Bishnu, Saptarshi; Bandyopadhyay, Dipanjan; Samui, Samiran; Das, Indrani; Mondal, Pradip; Ghosh, Pramit; Roy, Deeptarka; Manna, Sukanta

    2014-01-01

    Background & objectives: Newly diagnosed HIV patients may be asymptomatic or present with a wide range of symptoms related to opportunistic infections, acute seroconversion illness or other medical illnesses. This study was designed to evaluate the socio-demographic parameters, spectrum of the presenting clinical conditions and concurrent immunological status of newly diagnosed HIV patients and document the WHO clinical stages at the time of HIV diagnosis. Methods: This cross-sectional, observational study was undertaken over a 12 month period at a tertiary referral hospital in eastern India. Three hundred sixty consecutive newly diagnosed HIV patients were selected for the study from the HIV clinic and medicine wards of this hospital. Demographic and clinical data and relevant laboratory investigations of the patients were recorded and analyzed. Results: Mean age of patients was 36.38 ± 10.62 yr, while 63.89 per cent were males. The main mode of transmission of HIV for males and females were unprotected exposure to commercial sex (139, 60.44%) and intercourse with HIV seropositive spouses (89, 68.46%), respectively. Fever (104, 28.89%), weight loss (103, 28.61%) and generalized weakness (80, 22.22%) were the predominant symptoms. Overall mean CD4 count was 176.04 ± 163.49 cells/μl (males 142.19 ± 139.33 cells/μl; females 235.92 ± 185.11 cells/μl). Overall, 224 opportunistic infections were documented in 160 patients, opportunistic diarrhoea (44, 12.22%) and pulmonary tuberculosis (39, 10.83%) being the commonest. There were 83 and 133 patients in WHO clinical stages 3 and 4, respectively; 291 (80.83%) patients were eligible for initiation of first-line antiretrovirals at presentation. Interpretation & conclusions: Advanced immunodeficiency and burden of opportunistic infections characterize newly diagnosed HIV patients in eastern India. The physicians should keep in mind that these patients may have more than one clinical condition at presentation. PMID

  9. Hemodynamic effects of high intensity interval training in COPD patients exhibiting exercise-induced dynamic hyperinflation.

    PubMed

    Nasis, I; Kortianou, E; Vasilopoulou, Μ; Spetsioti, S; Louvaris, Z; Kaltsakas, G; Davos, C H; Zakynthinos, S; Koulouris, N G; Vogiatzis, I

    2015-10-01

    Dynamic hyperinflation (DH) has a significant adverse effect on cardiovascular function during exercise in COPD patients. COPD patients with (n = 25) and without (n = 11) exercise-induced DH undertook an incremental (IET) and a constant-load exercise test (CLET) sustained at 75% peak work (WRpeak) prior to and following an interval cycling exercise training regime (set at 100% WRpeak with 30-s work/30-s rest intervals) lasting for 12 weeks. Cardiac output (Q) was assessed by cardio-bio-impedance (PhysioFlow, enduro, PF-O7) to determine Q mean response time (QMRT) at onset (QMRT(ON)) and offset (QMRT(OFF)) of CLET. Post-rehabilitation only those patients exhibiting exercise-induced DH demonstrated significant reductions in QMRT(ON) (from 82.2 ± 4.3 to 61.7 ± 4.2 s) and QMRT(OFF) (from 80.5 ± 3.8 to 57.2 ± 4.9 s ). These post-rehabilitation adaptations were associated with improvements in inspiratory capacity, thereby suggesting that mitigation of the degree of exercise-induced DH improves central hemodynamic responses in COPD patients. PMID:26112284

  10. Immunological comparison of patients with rheumatoid arthritis with and without nephropathy.

    PubMed Central

    Korpela, M; Mustonen, J; Helin, H; Pasternack, A

    1990-01-01

    Serum immunoglobulins IgG, IgA, and IgM, serum complement components C3 and C4, circulating immune complexes, antinuclear antibodies, and rheumatoid factor were measured in 56 patients with rheumatoid arthritis (RA) and nephropathy (23 with mesangial glomerulopathy; 13 with membranous glomerulonephritis; and 20 with amyloidosis) and 35 patients with RA without nephropathy (controls). Renal immunofluorescence findings in patients with mesangial glomerulopathy were compared with the serologic data. There were no differences in the occurrence of rheumatoid factor, antinuclear antibodies, and circulating immune complexes and the concentrations of serum complement C3 and C4 between various RA nephropathy groups and controls. Serum IgA and IgM concentrations were significantly higher in patients with mesangial glomerulopathy and amyloidosis than in controls. In patients with mesangial glomerulopathy glomerular IgM, IgA, and C3 were the most prominent findings in immunofluorescence examination. The serum IgA concentration was significantly higher in those patients with mesangial glomerulopathy with mesangial IgA deposits than in those without (4.97 (SD 1.03) g/l v 2.07 (1.21) g/l). The highest serum IgA concentrations (5.08 (1.39) g/l) were seen in the four patients with IgA glomerulonephritis. The prevalence of IgA glomerulonephritis in the renal biopsy material of the patients with RA was 5%, which possibly differs little from that seen in the general population. The results suggest that circulating immune complexes may not have any major role in the pathogenesis of various nephropathy types in patients with RA, contrary to their role in most extra-articular manifestations of RA. PMID:2339901

  11. Depletion of autoreactive immunologic memory followed by autologous hematopoietic stem cell transplantation in patients with refractory SLE induces long-term remission through de novo generation of a juvenile and tolerant immune system.

    PubMed

    Alexander, Tobias; Thiel, Andreas; Rosen, Oliver; Massenkeil, Gero; Sattler, Arne; Kohler, Siegfried; Mei, Henrik; Radtke, Hartmut; Gromnica-Ihle, Erika; Burmester, Gerd-Rüdiger; Arnold, Renate; Radbruch, Andreas; Hiepe, Falk

    2009-01-01

    Clinical trials have indicated that immunoablation followed by autologous hematopoietic stem cell transplantation (ASCT) has the potential to induce clinical remission in patients with refractory systemic lupus erythematosus (SLE), but the mechanisms have remained unclear. We now report the results of a single-center prospective study of long-term immune reconstitution after ASCT in 7 patients with SLE. The clinical remissions observed in these patients are accompanied by the depletion of autoreactive immunologic memory, reflected by the disappearance of pathogenic anti-double-stranded DNA (dsDNA) antibodies and protective antibodies in serum and a fundamental resetting of the adaptive immune system. The latter comprises recurrence of CD31(+)CD45RA(+)CD4(+) T cells (recent thymic emigrants) with a doubling in absolute numbers compared with age-matched healthy controls at the 3-year follow-up (P = .016), the regeneration of thymic-derived FoxP3(+) regulatory T cells, and normalization of peripheral T-cell receptor (TCR) repertoire usage. Likewise, responders exhibited normalization of the previously disturbed B-cell homeostasis with numeric recovery of the naive B-cell compartment within 1 year after ASCT. These data are the first to demonstrate that both depletion of the autoreactive immunologic memory and a profound resetting of the adaptive immune system are required to reestablish self-tolerance in SLE. PMID:18824594

  12. New immunological investigations on Helicobacter pylori-induced gastric ulcer in patients.

    PubMed

    Rahimi, Hamid Reza; Rasouli, Manoochehr; Jamshidzadeh, Akram; Farshad, Shohreh; Firoozi, Mehdi Saberi; Taghavi, Ali Reza; Kiany, Simin

    2013-06-01

    Although Helicobacter pylori (Hp) plays an important role in the pathogenesis of chronic gastritis and gastric ulcer, little is known about the probable mechanisms of these types of gastrointestinal damage. To determine the precise mechanisms involved in ulcer formation, immune responses in patients with gastric ulcer (GUP) caused by Hp infection (Hp(+)) were compared with those of other gastritis patients (GP). The sensitivity and proliferation of peripheral blood mononuclear cells (PBMNCs) obtained from patients were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay against exposure with complex Hp crude antigen (HPCA) and mitogen (phytohemagglutinin, PHA). Production of inflammatory cytokines, including interleukin (IL)-1β and IL-8, in serum and supernatants of PBMNCs were then measured by ELISA. It was found that, after stimulation with PHA, both IL-8 and IL-1β concentrations in sera and supernatants as well as proliferation and sensitivity were statistically greater in GUP Hp(+) than GP Hp(-) . Furthermore, HPCA inhibited the proliferation of PBMNCs dose-dependently; however, it stimulated IL-8 and IL-1β production in supernatants of mononuclear cells. Therefore, the up-regulated concentrations of IL-8 and IL-1β may have been caused by increase in the size of mononuclear cell subpopulations or in their cytokine secretory activity, indicating the greatest cell responsiveness in GUP Hp(+) patients. These results suggest that tissue damage and ulcers occur in patients who produce more IL-8 and IL-1β than patients who do not develop ulcers; the former consequently have more activated immune cells at the site of infection. Therefore, both host responses and Hp virulence factors may be involved in the development of gastric ulcers. PMID:23773024

  13. Immunological changes in different patient populations with chronic hepatitis C virus infection

    PubMed Central

    Szereday, Laszlo; Meggyes, Matyas; Halasz, Melinda; Szekeres-Bartho, Julia; Par, Alajos; Par, Gabriella

    2016-01-01

    AIM: To investigate killer inhibitory and activating receptor expression by natural killer (NK), natural killer T-like (NKT-like) and CD8+ T lymphocytes in patients with chronic hepatitis C virus (HCV) infection with elevated and with persistently normal alanine aminotransferase (PNALT). METHODS: The percentage of peripheral blood Treg cells, KIR2DL3, ILT-2, KIR3DL1, CD160, NKG2D, NKG2C expressing NK, T and NKT-like cells, cytokine production and NK cytotoxicity were determined by flow cytometry. Twenty-one patients with chronic HCV infection with elevated alanine aminotransferase, 11 HCV carriers with persistently normal alanine aminotransferase and 15 healthy volunteers were enrolled. RESULTS: No significant differences were observed in the percentage of total T, NK or NKT-like cells between study groups. Comparing the activating and inhibitory receptor expression by NK cells obtained from HCV carriers with PNALT and chronic HCV hepatitis patients with elevated alanine aminotransferase, NKG2D activating receptor expression was the only receptor showing a significant difference. NKG2D expression of NK cells was significantly lower in patients with elevated alanine aminotransferase. The expression of CD160, NKG2D and NKG2C activating receptor by CD8+ T cells were significantly lower in patients with chronic HCV hepatitis than in healthy controls and in HCV carriers with PNALT. Plasma TGF-β1 levels inversely correlated with NKG2D expression by NK cells. In vitroTGF-β1 treatment inhibited NK cells cytotoxic activity and downregulated NKG2D expression. CD8+ T cells from HCV carriers with PNALT showed significantly elevated expression of CD160, NKG2D and NKG2C activating receptors compared to chronic HCV patients with elevated alanine aminotransferase. Enhanced expression of inhibitory KIR2DL3 receptor, and decreased ILT-2 expression on NK cells were also found in chronic hepatitis C patients compared to healthy controls. CONCLUSION: Our study demonstrated a complex

  14. Clinical and immunological data of nine patients with chronic mucocutaneous candidiasis disease

    PubMed Central

    Dotta, Laura; Scomodon, Omar; Padoan, Rita; Timpano, Silviana; Plebani, Alessandro; Soresina, Annarosa; Lougaris, Vassilios; Concolino, Daniela; Nicoletti, Angela; Giardino, Giuliana; Licari, Amelia; Marseglia, Gianluigi; Pignata, Claudio; Tamassia, Nicola; Facchetti, Fabio; Vairo, Donatella; Badolato, Raffaele

    2016-01-01

    This paper describes the heterogeneous clinical phenotype of a cohort of nine patients diagnosed with heterozygous mutations in STAT1. We report data of extended immunophenotyping over time and we show lung damage in four patients. The increased phosphorylation of STAT1 in response to IFNγ and IFNα stimulation proves the gain-of-function nature of the defects. The data are supplemental to our original article concurrently published “Clinical heterogeneity of dominant chronic mucocutaneous candidiasis disease: presenting as treatment-resistant candidiasis and chronic lung disease” [1], where additional results and interpretation of our research can be found. PMID:26981552

  15. Clinical and immunological data of nine patients with chronic mucocutaneous candidiasis disease.

    PubMed

    Dotta, Laura; Scomodon, Omar; Padoan, Rita; Timpano, Silviana; Plebani, Alessandro; Soresina, Annarosa; Lougaris, Vassilios; Concolino, Daniela; Nicoletti, Angela; Giardino, Giuliana; Licari, Amelia; Marseglia, Gianluigi; Pignata, Claudio; Tamassia, Nicola; Facchetti, Fabio; Vairo, Donatella; Badolato, Raffaele

    2016-06-01

    This paper describes the heterogeneous clinical phenotype of a cohort of nine patients diagnosed with heterozygous mutations in STAT1. We report data of extended immunophenotyping over time and we show lung damage in four patients. The increased phosphorylation of STAT1 in response to IFNγ and IFNα stimulation proves the gain-of-function nature of the defects. The data are supplemental to our original article concurrently published "Clinical heterogeneity of dominant chronic mucocutaneous candidiasis disease: presenting as treatment-resistant candidiasis and chronic lung disease" [1], where additional results and interpretation of our research can be found. PMID:26981552

  16. Some immunological properties of lymphoid cells from patients with acute lymphatic leukaemia (ALL)

    PubMed Central

    Melief, C. J. M.; Schweitzer, Marjan; Zeylemaker, W. P.; Verhagen, E. H.; Eijsvoogel, V. P.

    1973-01-01

    The in vitro responses of lymphoid cells from the blood of children with acute lymphatic leukaemia to stimulation with phytohaemagglutinin, pokeweed mitogen, allogeneic lymphocytes and a cocktail of five different antigens were studied. In addition the stimulatory capacity in mixed lymphocyte culture was investigated as well as the formation of rosettes with sheep erythrocytes which were either uncoated or coated with antibody and complement. Whereas lymphocytes from acute lymphatic leukaemia patients in remission responded well to all stimuli tested, lymphoid cells from all seven patients in leukaemic stages with at least 80% lymphatic cells in the differential leucocyte count uniformly displayed strongly reduced or even absent responses. The phytohaemagglutinin response of cells from leukaemic stages was not only reduced but also delayed and the stimulatory capacity in mixed lymphocyte culture was always stronger than the responding capacity. These data indicate that the responses of cells from leukaemic stages are due to the presence of a small proportion of residual normal lymphocytes whereas the leukaemic cells themselves are unable to respond. The stimulatory capacity in mixed lymphocyte culture was reduced in four cases. The cells from two patients, however, displayed increased stimulatory capacity. The cells from different patients varied strongly with respect to the presence of surface markers as tested by rosette formation with sheep erythrocytes either uncoated or coated with antibody and complement. PMID:4520119

  17. Immunologically confirmed disseminated, asymptomatic Encephalitozoon cuniculi infection of the gastrointestinal tract in a patient with AIDS.

    PubMed

    Franzen, C; Schwartz, D A; Visvesvara, G S; Müller, A; Schwenk, A; Salzberger, B; Fätkenheuer, G; Hartmann, P; Mahrle, G; Diehl, V

    1995-12-01

    Microsporidia are obligate intracellular protozoan parasites that infect a broad range of vertebrates and invertebrates. They are increasingly recognized as human pathogens, especially in patients infected with human immunodeficiency virus (HIV). Organisms of the genus Encephalitozoon have been implicated as a major cause of disseminated microsporidian infections in persons with AIDS. Until recently, E. hellem was the only Encephalitozoon species confirmed by antigenic or nucleic acid methods to have infected humans. We describe the clinical course and morphological features of a case of disseminated microsporidian infection with Encephalitozoon cuniculi in an HIV-infected patient with chronic sinusitis, rhinitis, and keratoconjunctivitis. Parasites were found in conjunctival swab, nasal discharge, sputum, urine, stool, and duodenal biopsy specimens, but no pulmonary, renal, or gastrointestinal symptoms were documented. The patient was treated with albendazole (400 mg po b.i.d.), resulting in complete remission of his ocular and nasal symptoms, and microsporidian spores disappeared from all sites. To our knowledge, this case is only the second of E. cuniculi infection in humans that has been confirmed by either antibody- or nucleic acid-based methods, and it is the first in which an Encephalitozoon species has been found in the intestinal tract of a human. Microsporidiosis is an important emerging opportunistic infection in HIV-infected patients and, as documented in this report, has an expanding clinicopathologic spectrum. PMID:8749639

  18. DOCK8 deficiency: clinical and immunological phenotype and treatment options - a review of 136 patients.

    PubMed

    Aydin, Susanne E; Kilic, Sara Sebnem; Aytekin, Caner; Kumar, Ashish; Porras, Oscar; Kainulainen, Leena; Kostyuchenko, Larysa; Genel, Ferah; Kütükcüler, Necil; Karaca, Neslihan; Gonzalez-Granado, Luis; Abbott, Jordan; Al-Zahrani, Daifulah; Rezaei, Nima; Baz, Zeina; Thiel, Jens; Ehl, Stephan; Marodi, László; Orange, Jordan S; Sawalle-Belohradsky, Julie; Keles, Sevgi; Holland, Steven M; Sanal, Özden; Ayvaz, Deniz C; Tezcan, Ilhan; Al-Mousa, Hamoud; Alsum, Zobaida; Hawwari, Abbas; Metin, Ayse; Matthes-Martin, Susanne; Hönig, Manfred; Schulz, Ansgar; Picard, Capucine; Barlogis, Vincent; Gennery, Andrew; Ifversen, Marianne; van Montfrans, Joris; Kuijpers, Taco; Bredius, Robbert; Dückers, Gregor; Al-Herz, Waleed; Pai, Sung-Yun; Geha, Raif; Notheis, Gundula; Schwarze, Carl-Philipp; Tavil, Betül; Azik, Fatih; Bienemann, Kirsten; Grimbacher, Bodo; Heinz, Valerie; Gaspar, H Bobby; Aydin, Roland; Hagl, Beate; Gathmann, Benjamin; Belohradsky, Bernd H; Ochs, Hans D; Chatila, Talal; Renner, Ellen D; Su, Helen; Freeman, Alexandra F; Engelhardt, Karin; Albert, Michael H

    2015-02-01

    Mutations in DOCK8 result in autosomal recessive Hyper-IgE syndrome with combined immunodeficiency (CID). However, the natural course of disease, long-term prognosis, and optimal therapeutic management have not yet been clearly defined. In an international retrospective survey of patients with DOCK8 mutations, focused on clinical presentation and therapeutic measures, a total of 136 patients with a median follow-up of 11.3 years (1.3-47.7) spanning 1693 patient years, were enrolled. Eczema, recurrent respiratory tract infections, allergies, abscesses, viral infections and mucocutaneous candidiasis were the most frequent clinical manifestations. Overall survival probability in this cohort [censored for hematopoietic stem cell transplantation (HSCT)] was 87 % at 10, 47 % at 20, and 33 % at 30 years of age, respectively. Event free survival was 44, 18 and 4 % at the same time points if events were defined as death, life-threatening infections, malignancy or cerebral complications such as CNS vasculitis or stroke. Malignancy was diagnosed in 23/136 (17 %) patients (11 hematological and 9 epithelial cancers, 5 other malignancies) at a median age of 12 years. Eight of these patients died from cancer. Severe, life-threatening infections were observed in 79/136 (58 %); severe non-infectious cerebral events occurred in 14/136 (10 %). Therapeutic measures included antiviral and antibacterial prophylaxis, immunoglobulin replacement and HSCT. This study provides a comprehensive evaluation of the clinical phenotype of DOCK8 deficiency in the largest cohort reported so far and demonstrates the severity of the disease with relatively poor prognosis. Early HSCT should be strongly considered as a potential curative measure. PMID:25627830

  19. ZPLD1 gene is disrupted in a patient with balanced translocation that exhibits cerebral cavernous malformations.

    PubMed

    Gianfrancesco, F; Esposito, T; Penco, S; Maglione, V; Liquori, C L; Patrosso, M C; Zuffardi, O; Ciccodicola, A; Marchuk, D A; Squitieri, F

    2008-08-13

    The past few years have seen rapid advances in our understanding of the genetics and molecular biology of cerebral cavernous malformations (CCM) with the identification of the CCM1, CCM2, and CCM3 genes. Recently, we have recruited a patient with an X/3 balanced translocation that exhibits CCM. By fluorescent in situ hybridization analysis, sequence analysis tools and database mining procedures, we refined the critical region to an interval of 200-kb and identified the interrupted ZPLD1 gene. We detected that the mRNA expression level of ZPLD1 gene is consistently decreased 2.5-fold versus control (P=0.0006) with allelic loss of gene expression suggesting that this protein may be part of the complex signaling pathway implicated in CCM formation. PMID:18632209

  20. Infectious dengue vesicles derived from CD61+ cells in acute patient plasma exhibited a diaphanous appearance

    PubMed Central

    Hsu, Alan Yi-Hui; Wu, Shang-Rung; Tsai, Jih-Jin; Chen, Po-Lin; Chen, Ya-Ping; Chen, Tsai-Yun; Lo, Yu-Chih; Ho, Tzu-Chuan; Lee, Meed; Chen, Min-Ting; Chiu, Yen-Chi; Perng, Guey Chuen

    2015-01-01

    The levels of neutralizing antibody to a pathogen are an effective indicator to predict efficacy of a vaccine in trial. And yet not all the trial vaccines are in line with the theory. Using dengue virus (DENV) to investigate the viral morphology affecting the predictive value, we evaluated the viral morphology in acute dengue plasma compared to that of Vero cells derived DENV. The virions in plasma were infectious and heterogeneous in shape with a “sunny-side up egg” appearance, viral RNA was enclosed with CD61+ cell-derived membrane interspersed by the viral envelope protein, defined as dengue vesicles. The unique viral features were also observed from ex vivo infected human bone marrow. Dengue vesicles were less efficiently neutralized by convalescent patient serum, compared to virions produced from Vero cells. Our results exhibit a reason why potencies of protective immunity fail in vivo and significantly impact dengue vaccine and drug development. PMID:26657027

  1. Immunology of infusion reactions in the treatment of patients with acute lymphoblastic leukemia.

    PubMed

    Asselin, Barbara

    2016-07-01

    Infusion reactions are potentially dose-limiting adverse events associated with intravenous administration of several common agents used to treat patients with acute lymphoblastic leukemia. True clinical hypersensitivity reactions are antibody-mediated and can occur only after repeated exposure to an antigen. Conversely, anaphylactoid infusion reactions are nonantibody-mediated and often occur on the initial exposure to a drug. Cytokine-release syndrome comprises a subset of nonantibody-mediated infusion reactions associated with the use of monoclonal antibodies and immune therapies. Clinical symptoms of hypersensitivity reactions and nonantibody-mediated infusion reactions heavily overlap and can be difficult to distinguish in practice. Regardless of the underlying mechanism, any infusion reaction can negatively affect treatment efficacy and patient safety. These events require prompt response, and potentially, modification of subsequent therapy. PMID:27086555

  2. The use of cultures and immunologic procedures to predict oropharyngeal candidiasis in patients on steroid aerosols.

    PubMed

    Spector, S L; Wangaard, C; Bardana, E J

    1982-05-01

    Sixty-seven asthmatic individuals treated with either beclomethasone diproprionate or flunisolide were sequentially evaluated for up to 32 months to determine the incidence of oropharyngeal candidiasis as well as laboratory parameters which might be predictive of this complication. Throat cultures and measurements of Candida antibody by immunodiffusion and radioimmunoassay were performed and compared over time and treatment groups. Unlike other studies, pre-treatment Candida precipitins did not predict increased risk for clinical thrush nor did quantitative determinations of Candida antibody. Those patients with positive cultures pre-trial, however, had a significantly higher incidence of clinical thrush than those with negative cultures (P less than 0.01). No significant changes occurred over time or between drugs for any of the parameters. Symptomatic thrush, however, was slightly more common in those patients treated with beclomethasone. PMID:7105391

  3. A phase I/II trial of a polysaccharide extract from Grifola frondosa (Maitake mushroom) in breast cancer patients: immunological effects

    PubMed Central

    Lin, Hong; Seidman, Andrew; Fornier, Monica; D’Andrea, Gabriella; Wesa, Kathleen; Yeung, Simon; Cunningham-Rundles, Susanna; Vickers, Andrew J.; Cassileth, Barrie

    2013-01-01

    Background Cancer patients commonly use dietary supplements to “boost immune function”. A polysaccharide extract from Grifola frondosa (Maitake extract) showed immunomodulatory effects in preclinical studies and therefore the potential for clinical use. Whether oral administration in human produces measurable immunologic effects, however, is unknown. Methods In a phase I/II dose escalation trial, 34 postmenopausal breast cancer patients, free of disease after initial treatment, were enrolled sequentially in five cohorts. Maitake liquid extract was taken orally at 0.1, 0.5, 1.5, 3, or 5 mg/kg twice daily for 3 weeks. Peripheral blood was collected at days −7, 0 (prior to the first dosing), 7, 14, and 21 for ex vivo analyses. The primary endpoints were safety and tolerability. Results No dose-limiting toxicity was encountered. Two patients withdrew prior to completion of the study due to grade I possibly related side effects: nausea and joint swelling in one patient; rash and pruritus in the second. There was a statistically significant association between Maitake and immunologic function (p < 0.0005). Increasing doses of Maitake increased some immunologic parameters and depressed others; the dose–response curves for many endpoints were non-monotonic with intermediate doses having either immune enhancing or immune suppressant effects compared with both high and low doses. Conclusions Oral administration of a polysaccharide extract from Maitake mushroom is associated with both immunologically stimulatory and inhibitory measurable effects in peripheral blood. Cancer patients should be made aware of the fact that botanical agents produce more complex effects than assumed, and may depress as well as enhance immune function. PMID:19253021

  4. Pediatric Patients with Vitiligo in Eastern China: Abnormalities in 145 Cases Based on Thyroid Function Tests and Immunological Findings

    PubMed Central

    Xianfeng, Cheng; Yuegen, Jiang; Zhiyu, Yin; Yan, Yang; Xuesi, Zeng; Fenglai, Wang; Ansheng, Li; Wei, Wang

    2015-01-01

    Background The aim of this study was to evaluate abnormalities in thyroid function according to tests and the humoral immune systems of patients from Eastern China with pediatric vitiligo. Material/Methods A total of 145 pediatric patients with vitiligo were investigated in this study, along with 59 children without autoimmune diseases as controls. Laboratory tests of thyroid function were conducted, and these tests examined free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), thyroglobulin antibody (TG-Ab), thyroid peroxidase antibody (TPO-Ab), antinuclear antibodies (ANAs), immunoglobulins (IgA, IgM, and IgG), and complements (C3 and C4). Results A total of 63 patients (43.4%), including 39 boys (44.3%) and 24 girls (42.1%), displayed abnormalities in thyroid function according to the tests. This finding indicated that patients with vitiligo differed significantly from those in the control group (P<0.001), particularly in terms of FT3 and TSH abnormalities (P<0.05). However, these groups did not deviate significantly with respect to FT4, Tg-Ab, and TPO-Ab abnormalities (P>0.05). Thirteen patients (8.9%) and 1 (1.7%) control were positive for ANA. All 12 specific antibodies were detected in 8 patients. Anti-SSA/Ro-60 and anti-SSA/Ro-52 were the most prevalent antibodies, followed by anti-dsDNA and then by anti-SmD1 and CENB-P. The serum levels of IgA and IgG decreased more significantly in the vitiligo group than in the control group (P<0.001). However, no significant difference was observed in terms of IgM levels (P>0.05). C4 serum levels also decreased more significantly in the vitiligo group than in the control group (P=0.035). Conclusions Results suggest that the incidence of abnormalities in the thyroid functions of children and adolescents is significantly higher in those with vitiligo than that in those in the control group. In addition, immunological dysfunction is common in the vitiligo group. PMID:26496247

  5. ITGAM coding variant (rs1143679) influences the risk of renal disease, discoid rash, and immunologic manifestations in lupus patients with European ancestry

    PubMed Central

    Kim-Howard, Xana; Maiti, Amit K.; Anaya, Juan-Manuel; Bruner, Gail R.; Brown, Elizabeth; Merrill, Joan T.; Edberg, Jeffrey C.; Petri, Michelle A.; Reveille, John D.; Ramsey-Goldman, Rosalind; Alarcon, Graciela S.; Vyse, Timothy J.; Gilkeson, Gary; Kimberly, Robert P.; James, Judith A.; Guthridge, Joel M.; Harley, John B.; Nath, Swapan K.

    2010-01-01

    Purpose We hypothesized that the coding variant (R77H), rs1143679, within ITGAM could predict specific clinical manifestations associated with lupus. Method To assess genetic association, 2366 lupus cases and 2931 unaffected controls with European ancestry were analyzed. Lupus patients were coded by the presence or absence of individual ACR criteria. Logistic regression and Pearson chi-square tests were used to assess statistical significance. Results First, for overall case-control analysis, we detected highly significant (p=2.22×10−21, OR=1.73) association. Second, using case-only analysis we detected significant association with renal criteria (p=0.0003), discoid rash (p=0.02), and immunologic criteria (p=0.04). Third, we compared them with healthy controls, the association became stronger for renal (p=4.69×10−22, OR=2.15), discoid (p=1.77×10−14, OR=2.03), and immunologic (p=3.49×10−22, OR = 1.86) criteria. Risk allele frequency increased from 10.6% (controls) to 17.0% (lupus), 20.4% (renal), 18.1% (immunologic), and 19.5% (discoid). Conclusion These results demonstrated a strong association between the risk allele (A) at rs1143679 and renal disease, discoid rash, and immunological manifestations of lupus. PMID:19939855

  6. Clinical, microbiological, and immunological effects of fructo‐oligosaccharide in patients with Crohn's disease

    PubMed Central

    Lindsay, J O; Whelan, K; Stagg, A J; Gobin, P; Al‐Hassi, H O; Rayment, N; Kamm, M A; Knight, S C; Forbes, A

    2006-01-01

    Background and aims The intestinal microbiota play a pivotal role in the inflammation associated with Crohn's disease through their interaction with the mucosal immune system. Some bifidobacteria species are immunoregulatory and induce increased dendritic cell interleukin 10 (IL‐10) release in vitro. Fructo‐oligosaccharides (FOS) increase faecal and mucosal bifidobacteria in healthy volunteers. The aim of this study was to assess the effect of FOS administration on disease activity, bifidobacteria concentrations, and mucosal dendritic cell function in patients with moderately active Crohn's disease. Patients and methods Ten patients with active ileocolonic Crohn's disease received 15 g of FOS for three weeks. Disease activity was measured using the Harvey Bradshaw index. Faecal and mucosal bifidobacteria were quantified by fluorescence in situ hybridisation, and mucosal dendritic cell IL‐10 and Toll‐like receptor (TLR) expression were assessed by flow cytometry of dissociated rectal biopsies. Results FOS induced a significant reduction in the Harvey Bradshaw index from 9.8 (SD 3.1) to 6.9 (3.4) (p<0.01). There was a significant increase in faecal bifidobacteria concentration from 8.8 (0.9) log10 to 9.4 (0.9) log10 cells/g dry faeces (p<0.001). The percentage of IL‐10 positive dendritic cells increased from 30 (12)% to 53 (10)% (p = 0.06). Finally, the percentage of dendritic cells expressing TLR2 and TLR4 increased from 1.7 (1.7)% to 36.8 (15.9)% (p = 0.08) and from 3.6 (3.6)% to 75.4 (3.4)% (p<0.001), respectively. Conclusions FOS supplementation increases faecal bifidobacteria concentrations and modifies mucosal dendritic cell function. This novel therapeutic strategy appears to decrease Crohn's disease activity in a small open label trial and therefore warrants further investigation. PMID:16162680

  7. Incidence of tuberculosis and immunological profile of TB/HIV co-infected patients in Nigeria

    PubMed Central

    Musa, Baba Maiyaki; Musa, Babashani; Muhammed, Hamza; Ibrahim, Nashabaru; Musa, Abubakar Garbati

    2015-01-01

    BACKGROUND: We obtained estimates of the incidence of tuberculosis (TB) among patients receiving HIV Treatment. We also modeled the relationship between incident TB and change in CD4 count over the follow-up period. METHODS: We analyzed the incidence of TB over 10 years from initiation of HIV treatment among 345 HIV treatment-naïve persons, who were enrolled in a cohort in Kano, Nigeria. We used Generalized Estimating Equation [GEE] to identify determinants of TB incidence and model the relationship between the occurrences of TB with change in CD4 count over the follow-up period. We created Kaplan-Meier curves stratified by anti-retroviral therapy (ART) treatment failure status to examine the effect of first line ART treatment failure on occurrence of TB. RESULT: During the 10-year period, 47(13.62%) had TB [incidence was 7.43 per (1,000) person year)]. It is associated with decreasing age (OR = 0.98), female gender (OR = 0.83), being on first line ART other than AZT (OR = 0.87), poor adherence (OR = 1.25), change in ART regimen (OR = 2.3) and ART treatment failure (OR = 1.51). Odds of TB occurrence was also associated with CD4 increment at 10 years (OR = 0.99). Those with TB/HIV co-infection tend to have statistically significant shorter time to failing first line ART regimen compared to those with HIV infection alone. CONCLUSION: There was high incidence of TB in the studied HIV cohort with a deleterious effect on the outcome of ART treatment. There is need for early TB screening and re-screening among all HIV patients. PMID:26229561

  8. Clinical and immunological features of patients with atopy and concomitant HTLV-1 infection.

    PubMed

    Gaspar-Sobrinho, F P; Souza-Machado, A; Santos, S B; Orge, G; Lessa, H A; Cruz, A A; Carvalho, E M

    2010-12-01

    Human T-cell lymphotropic virus type 1 (HTLV-1) induces an exacerbated type 1 immune response characterized by high spontaneous IFN-γ and TNF-α production. Allergic rhinitis and asthma are associated with the type 2 immune response, with elevated secretion of IL-4 and IL-5. The aim of this study was to characterize the immune response in atopic HTLV-1 carriers. The cytokine profile of atopic HTLV-1 carriers (N = 10; all females) was compared with that of non-atopic HTLV-1 carriers (N = 14; 9 females and 5 males). Mean patient age of atopic and non-atopic groups was 45 ± 8 and 38 ± 11 years, respectively. All atopic HTLV-1 carriers had rhinitis with or without asthma and a skin prick test positive for Dermatophagoides pteronyssinus antigen 1 (Derp-1). There was no difference in cytokine levels between the two groups in unstimulated peripheral blood mononuclear cell cultures. In cultures stimulated with Derp-1, IFN-γ levels tended to be higher (P = 0.06) and IL-5 levels were higher (P = 0.02) in atopic HTLV-1 patients than in non-atopic subjects. In contrast, IL-10 was lower (P = 0.004) in atopic than in non-atopic HTLV-1-infected subjects. This study shows that HTLV-1 infection with an exaggerated type 1 immune response does not prevent atopy. In this case, the exacerbated type 1 and type 2 immune responses were due to a lack of IL-10 production, a cytokine that plays an important role in down-modulating type 1 and type 2 immune responses and in preventing the development of chronic inflammatory diseases. PMID:21140101

  9. Selected immunological parameters in clinical evaluation of patients with atopic dermatitis

    PubMed Central

    Czarnecka-Operacz, Magdalena; Adamski, Zygmunt

    2016-01-01

    Introduction It has been suggested that soluble immune receptors (SIRs) such as sCD25 and sCD30 may serve as potential biomarkers in evaluation of atopic dermatitis (AD). Previous studies clearly indicated that serum levels of interleukin (IL)-13 and total IgE (tIgE) might be potentially useful in the evaluation of patents with AD. Aim To evaluate whether serum levels of sCD25 and sCD30 are suitable biomarkers of AD. Moreover, we have decided to estimate the usefulness of tIgE and IL-13 serum level determination in the evaluated population. Material and methods A group of 102 AD patients was investigated. Serum concentrations of sCD30, sCD25, IL-13 and tIgE were measured. The clinical phenotype of AD was classified as extrinsic (ADe) or intrinsic (ADi) based on the presence of IgE. Statistical analysis was performed to estimate correlations between obtained results and clinical features of the population such as AD phenotype, age, disease extent and severity. Results Extrinsic AD was diagnosed in 71% of patients, while ADi phenotype was observed in 29% of the investigated population. A negative correlation between serum levels of sCD25 and sCD30 and disease severity as well patients’ age was established. Serum levels of IL-13 did not reach the cut-off point set by the manufacturer. A positive correlation between serum levels of total IgE and disease severity and patients’ age was observed. Conclusions This paper shows that serum levels of sCD25 and sCD30 as well as tIgE are age dependent. Determination of serum levels of sCD25, sCD30 and IL-13 is not useful in everyday practice. PMID:27512357

  10. Immune-related Adverse Events of Dendritic Cell Vaccination Correlate With Immunologic and Clinical Outcome in Stage III and IV Melanoma Patients

    PubMed Central

    Boudewijns, Steve; Westdorp, Harm; Koornstra, Rutger H.T.; Aarntzen, Erik H.J.G.; Schreibelt, Gerty; Creemers, Jeroen H.A.; Punt, Cornelis J.A.; Figdor, Carl G.; Gerritsen, Winald R.; Bol, Kalijn F.

    2016-01-01

    The purpose of this study was to determine the toxicity profile of dendritic cell (DC) vaccination in stage III and IV melanoma patients, and to evaluate whether there is a correlation between side effects and immunologic and clinical outcome. This is a retrospective analysis of 82 stage III and 137 stage IV melanoma patients, vaccinated with monocyte-derived or naturally circulating autologous DCs loaded with tumor-associated antigens gp100 and tyrosinase. Median follow-up time was 54.3 months in stage III patients and 12.9 months in stage IV patients. Treatment-related adverse events occurred in 84% of patients; grade 3 toxicity was present in 3% of patients. Most common adverse events were flu-like symptoms (67%) and injection site reactions (50%), and both correlated with the presence of tetramer-positive CD8+ T cells (both P<0.001). In stage III melanoma patients experiencing flu-like symptoms, median overall survival (OS) was not reached versus 32.3 months in patients without flu-like symptoms (P=0.009); median OS in patients with an injection site reaction was not reached versus 53.7 months in patients without an injection site reaction (P<0.05). In stage IV melanoma patients (primary uveal and mucosal melanomas excluded), median OS in patients with or without flu-like symptoms was 13.1 versus 8.9 months, respectively (P=0.03); median OS in patients with an injection site reaction was 15.7 months versus 9.8 months in patients without an injection site reaction (P=0.003). In conclusion, DC vaccination is safe and tolerable and the occurrence of the immune-related side effects, such as flu-like symptoms and injection site reactions, correlates with immunologic and clinical outcome. PMID:27227325

  11. Immune-related Adverse Events of Dendritic Cell Vaccination Correlate With Immunologic and Clinical Outcome in Stage III and IV Melanoma Patients.

    PubMed

    Boudewijns, Steve; Westdorp, Harm; Koornstra, Rutger H T; Aarntzen, Erik H J G; Schreibelt, Gerty; Creemers, Jeroen H A; Punt, Cornelis J A; Figdor, Carl G; de Vries, I Jolanda M; Gerritsen, Winald R; Bol, Kalijn F

    2016-01-01

    The purpose of this study was to determine the toxicity profile of dendritic cell (DC) vaccination in stage III and IV melanoma patients, and to evaluate whether there is a correlation between side effects and immunologic and clinical outcome. This is a retrospective analysis of 82 stage III and 137 stage IV melanoma patients, vaccinated with monocyte-derived or naturally circulating autologous DCs loaded with tumor-associated antigens gp100 and tyrosinase. Median follow-up time was 54.3 months in stage III patients and 12.9 months in stage IV patients. Treatment-related adverse events occurred in 84% of patients; grade 3 toxicity was present in 3% of patients. Most common adverse events were flu-like symptoms (67%) and injection site reactions (50%), and both correlated with the presence of tetramer-positive CD8 T cells (both P<0.001). In stage III melanoma patients experiencing flu-like symptoms, median overall survival (OS) was not reached versus 32.3 months in patients without flu-like symptoms (P=0.009); median OS in patients with an injection site reaction was not reached versus 53.7 months in patients without an injection site reaction (P<0.05). In stage IV melanoma patients (primary uveal and mucosal melanomas excluded), median OS in patients with or without flu-like symptoms was 13.1 versus 8.9 months, respectively (P=0.03); median OS in patients with an injection site reaction was 15.7 months versus 9.8 months in patients without an injection site reaction (P=0.003). In conclusion, DC vaccination is safe and tolerable and the occurrence of the immune-related side effects, such as flu-like symptoms and injection site reactions, correlates with immunologic and clinical outcome. PMID:27227325

  12. Effect of a clinical decision support system on early action on immunological treatment failure in patients with HIV in Kenya: a cluster randomised controlled trial

    PubMed Central

    Oluoch, Tom; Katana, Abraham; Kwaro, Daniel; Santas, Xenophon; Langat, Patrick; Mwalili, Samuel; Muthusi, Kimeu; Okeyo, Nicky; Ojwang, James K; Cornet, Ronald; Abu-Hanna, Ameen; de Keizer, Nicolette

    2016-01-01

    Summary Background A clinical decision support system (CDSS) is a computer program that applies a set of rules to data stored in electronic health records to offer actionable recommendations. We aimed to establish whether a CDSS that supports detection of immunological treatment failure among patients with HIV taking antiretroviral therapy (ART) would improve appropriate and timely action. Methods We did this prospective, cluster randomised controlled trial in adults and children (aged ≥18 months) who were eligible for, and receiving, ART at HIV clinics in Siaya County, western Kenya. Health facilities were randomly assigned (1:1), via block randomisation (block size of two) with a computer-generated random number sequence, to use electronic health records either alone (control) or with CDSS (intervention). Facilities were matched by type and by number of patients enrolled in HIV care. The primary outcome measure was the difference between groups in the proportion of patients who experienced immunological treatment failure and had a documented clinical action. We used generalised linear mixed models with random effects to analyse clustered data. This trial is registered with ClinicalTrials.gov, number NCT01634802. Findings Between Sept 1, 2012, and Jan 31, 2014, 13 clinics, comprising 41 062 patients, were randomly assigned to the control group (n=6) or the intervention group (n=7). Data collection at each site took 12 months. Among patients eligible for ART, 10 358 (99%) of 10 478 patients were receiving ART at control sites and 10 991 (99%) of 11 028 patients were receiving ART at intervention sites. Of these patients, 1125 (11%) in the control group and 1342 (12%) in the intervention group had immunological treatment failure, of whom 332 (30%) and 727 (54%), respectively, received appropriate action. The likelihood of clinicians taking appropriate action on treatment failure was higher with CDSS alerts than with no decision support system (adjusted odds ratio

  13. Immune Evasion and Recognition of the Syphilis Spirochete in Blood and Skin of Secondary Syphilis Patients: Two Immunologically Distinct Compartments

    PubMed Central

    Cruz, Adriana R.; Ramirez, Lady G.; Zuluaga, Ana V.; Pillay, Allan; Abreu, Christine; Valencia, Carlos A.; La Vake, Carson; Cervantes, Jorge L.; Dunham-Ems, Star; Cartun, Richard; Mavilio, Domenico; Radolf, Justin D.; Salazar, Juan C.

    2012-01-01

    bring to light the extent of the systemic innate and adaptive immunologic abnormalities that define the secondary stage of the disease, which in the skin of patients trends towards a T-cell cytolytic response. PMID:22816000

  14. Immunologically mediated abortion (IMA).

    PubMed

    Giacomucci, E; Bulletti, C; Polli, V; Prefetto, R A; Flamigni, C

    1994-06-01

    Roughly 20% of all clinical pregnancies evolve into "spontaneous abortions". The causes of spontaneous abortion have been determined in under 60% of the total and comprise genetic, infectious, hormonal and immunological factors. In some cases the immune tolerance mechanism may be impaired and the foetus immunologically rejected (IMA, immunologically mediated abortion). The immunological mechanism implicated depends on the time in which pregnancy loss takes place. During preimplantation and up to the end of implantation (13th day) the cell-mediated immune mechanism (potential alloimmune etiologies) is responsible for early abortion. This mechanism involves immunocompetent decidual cells (eGL, endometrial granulated lymphocytes) already present during pre-decidualization (late luteal phase) and their production of soluble factors or cytokines. Once the implantation process is over, after blastocyst penetration of the stroma and the decidual reaction of uterine tissue, IMA could be caused by cell-mediated and humoral mechanism (anti-paternal cytotoxic antibodies or autoantibody etiology), by the production of paternal anti major histocompatibility complex antibodies, or even by an autoimmune disorder leading to the production of autoantibodies (antiphospholipid antibodies, antinuclear antibodies or polyclonal B cell activation). The diagnostic work-up adopted to select IMA patients is crucial and includes primary (karyotype of both partners, toxo-test, hysterosalpingography, endometrial biopsy, thyroid function tests, serum hprolactin, luteal phase dating) and secondary (full hemochromocytometric test, search for LE cells, lupus anticoagulant, anticardiolipin, antinuclear antibodies, Rheumatoid factor, blood complement VDRL) investigations. Therapeutical approaches vary. If autoimmune disorders are demonstrated therapies with different combinations of corticosteroids, aspirin and heparin or intravenous immunoglobulin are administered. Otherwise, therapy with paternal

  15. Evaluating immunologic response and clinical deterioration in treatment-naïve patients initiating first-line therapies infected with HIV-1 CRF01_AE and subtype B

    PubMed Central

    Oyomopito, Rebecca A.; Li, Patrick CK.; Sungkanuparph, Somnuek; Phanuphak, Praphan; Tee, Kok Keng; Sirisanthana, Thira; Kantipong, Pacharee; Oka, Shinichi; Lee, Chris KC.; Kamarulzaman, Adeeba; Choi, Jun Yong; Sohn, Annette H.; Law, Matthew; Chen, Yi-Ming A.

    2012-01-01

    Background HIV-1 group M viruses diverge 25%–35% in envelope, important for viral attachment during infection, and 10–15% in the pol region, under selection pressure from common antiretrovirals. In Asia, subtypes B and CRF01_AE are common genotypes. Our objectives were to determine whether clinical, immunologic or virologic treatment responses differed by genotype in treatment-naïve patients initiating first-line therapy. Methods Prospectively collected, longitudinal data from patients in Thailand, Hong Kong, Malaysia, Japan, Taiwan and South Korea were provided for analysis. Covariates included demographics, hepatitis B and C coinfections, baseline CD4 T lymphocyte count and plasma HIV-1 RNA levels. Clinical deterioration (a new diagnosis of CDC category B/AIDS-defining illness or death) was assessed by proportional hazards models. Surrogate endpoints were 12-month change in CD4 cell count and virologic suppression post-therapy, evaluated by linear and logistic regression, respectively. Results Of 1105 patients, 1036 (93.8%) infected with CRF01_AE or subtype B were eligible for inclusion in clinical deterioration analyses and contributed 1546.7 person-years of follow-up (median:413 days, IQR:169–672 days). Patients >40 years demonstrated smaller immunological increases (p=0.002) and higher risk of clinical deterioration (HR=2.17; p=0.008). Patients with baseline CD4 cell counts >200 cells/μL had lower risk of clinical deterioration (HR=0.373; p=0.003). A total of 532 patients (48.1% of eligible) had CD4 counts available at baseline and 12 months post-therapy for inclusion in immunolgic analyses. Patients infected with subtype B had larger increases in CD4 counts at 12 months (p=0.024). A total of 530 patients (48.0% of eligible) were included in virologic analyses with no differences in response found between genotypes. Conclusions Results suggest that patients infected with CRF01_AE have reduced immunologic response to therapy at 12 months, compared to

  16. Clinical and Immunological Responses in Ocular Demodecosis

    PubMed Central

    Kim, Jae Hoon; Chun, Yeoun Sook

    2011-01-01

    The purpose of this study was to investigate clinical and immunological responses to Demodex on the ocular surface. Thirteen eyes in 10 patients with Demodex blepharitis and chronic ocular surface disorders were included in this study and treated by lid scrubbing with tea tree oil for the eradication of Demodex. We evaluated ocular surface manifestations and Demodex counts, and analyzed IL-1β, IL-5, IL-7, IL-12, IL-13, IL-17, granulocyte colony-stimulating factor, and macrophage inflammatory protein-1β in tear samples before and after the treatment. All patients exhibited ocular surface manifestations including corneal nodular opacity, peripheral corneal vascularization, refractory corneal erosion and infiltration, or chronic conjunctival inflammatory signs before treatment. After treatment, Demodex was nearly eradicated, tear concentrations of IL-1β and IL-17 were significantly reduced and substantial clinical improvement was observed in all patients. In conclusion, we believe that Demodex plays an aggravating role in inflammatory ocular surface disorders. PMID:21935281

  17. Immunological Diagnosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine tuberculosis (TB) is generally considered a slowly progressive disease of extended duration (lasting years) and most cattle do not exhibit readily apparent clinical signs of infection until late in the course of disease. Currently, agent-based strategies for the detection of tuberculous cattl...

  18. A clinical and immunologic phase 2 trial of Wilms tumor gene product 1 (WT1) peptide vaccination in patients with AML and MDS.

    PubMed

    Keilholz, Ulrich; Letsch, Anne; Busse, Antonia; Asemissen, Anne Marie; Bauer, Sandra; Blau, Igor Wolfgang; Hofmann, Wolf-Karsten; Uharek, Lutz; Thiel, Eckhard; Scheibenbogen, Carmen

    2009-06-25

    This study investigated the immunogenicity of Wilms tumor gene product 1 (WT1)-peptide vaccination in WT1-expressing acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients without curative treatment option. Vaccination consisted of granulocyte-macrophage colony-stimulating factor subcutaneously days 1 to 4, and WT1.126-134 peptide and 1 mg keyhole limpet hemocyanin on day 3. The initial 9 patients received 4 vaccinations biweekly, then monthly, and the subsequent 10 patients received continual biweekly vaccination. Seventeen AML patients and 2 refractory anemia with excess blasts patients received a median of 11 vaccinations. Treatment was well tolerated. Objective responses in AML patients were 10 stable diseases (SDs) including 4 SDs with more than 50% blast reduction and 2 with hematologic improvement. An additional 4 patients had clinical benefit after initial progression, including 1 complete remission and 3 SDs. WT1 mRNA levels decreased at least 3-fold from baseline in 35% of patients. In 8 of 18 patients, WT1-tetramer(+) T cells increased in blood and in 8 of 17 patients in bone marrow, with a median frequency in bone marrow of 0.18% at baseline and 0.41% in week 18. This WT1 vaccination study provides immunologic, molecular, and preliminary evidence of potential clinical efficacy in AML patients, warranting further investigations. PMID:19389880

  19. Patients treated with first-generation HCV protease inhibitors exhibit high ribavirin concentrations.

    PubMed

    Bodeau, Sandra; Nguyen-Khac, Eric; Solas, Caroline; Bennis, Youssef; Capron, Dominique; Duverlie, Gilles; Brochot, Etienne

    2015-05-01

    Anemia is a well-known RBV-related event in HCV therapy which is exacerbated by the addition of telaprevir and boceprevir. This retrospective study evaluated and compared ribavirin exposure and parameters able to influence hemoglobin decrease in a large population of patients treated with dual or triple therapy. Patients on triple therapy had higher ribavirin concentrations at week 12 of treatment (3460 ng/mL vs. 1843 ng/mL; P < .0001). An association was also observed between week 12 eGFR and ribavirin concentration only for patients on triple therapy (P = .002). The proportion of patients with a  >20 mL/min/1.73 m(2) decrease in eGFR at week 12 was higher among patients on triple therapy: 32%, 14%, and 5% for boceprevir, telaprevir, and dual therapy, respectively (P = .025 and .026). No correlation was observed between boceprevir and telaprevir concentrations and hemoglobin or eGFR decrease. Exacerbation of anemia in patients on triple therapy is related to higher ribavirin concentrations. We provide an explanation for this increase in plasma RBV concentration. Triple therapy with PEG-IFN, RBV, and telaprevir or boceprevir will remain the only HCV treatment option for many patients. Our data show that the RBV dose can be decreased while maintaining adequate plasma concentrations and reducing anemia. PMID:25535910

  20. Adult medication-free schizophrenic patients exhibit long-chain omega-3 Fatty Acid deficiency: implications for cardiovascular disease risk.

    PubMed

    McNamara, Robert K; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Dwivedi, Yogesh; Pandey, Ghanshyam N

    2013-01-01

    Deficiency in long-chain omega-3 (LCn - 3) fatty acids, eicosapentaenoic acid (EPA, 20:5n - 3) and docosahexaenoic acid (DHA, 22:6n - 3), has been implicated in the pathoetiology of cardiovascular disease, a primary cause of excess premature mortality in patients with schizophrenia (SZ). In the present study, we determined erythrocyte EPA + DHA levels in adult medication-free patients SZ (n = 20) and age-matched healthy controls (n = 24). Erythrocyte EPA + DHA composition exhibited by SZ patients (3.5%) was significantly lower than healthy controls (4.5%, -22%, P = 0.007). The majority of SZ patients (72%) exhibited EPA+DHA levels ≤4.0% compared with 37% of controls (Chi-square, P = 0.001). In contrast, the omega-6 fatty acid arachidonic acid (AA, 20:4n - 6) (+9%, P = 0.02) and the AA:EPA + DHA ratio (+28%, P = 0.0004) were significantly greater in SZ patients. Linoleic acid (18:2n - 6) was significantly lower (-12%, P = 0.009) and the erythrocyte 20:3/18:2 ratio (an index of delta6-desaturase activity) was significantly elevated in SZ patients. Compared with same-gender controls, EPA + DHA composition was significantly lower in male (-19%, P = 0.04) but not female (-13%, P = 0.33) SZ patients, whereas the 20:3/18:2 ratio was significantly elevated in both male (+22%, P = 0.008) and female (+22%, P = 0.04) SZ patients. These results suggest that the majority of SZ patients exhibit low LCn - 3 fatty acid levels which may place them at increased risk for cardiovascular morbidity and mortality. PMID:23533712

  1. Immunological data from cancer patients treated with Ad5/3-E2F-Δ24-GMCSF suggests utility for tumor immunotherapy

    PubMed Central

    Hemminki, Otto; Parviainen, Suvi; Juhila, Juuso; Turkki, Riku; Linder, Nina; Lundin, Johan; Kankainen, Matti; Ristimäki, Ari; Koski, Anniina; Liikanen, Ilkka; Oksanen, Minna; Nettelbeck, Dirk M.; Kairemo, Kalevi; Partanen, Kaarina; Joensuu, Timo; Kanerva, Anna; Hemminki, Akseli

    2015-01-01

    Oncolytic viruses that selectively replicate in tumor cells can be used for treatment of cancer. Accumulating data suggests that virus induced oncolysis can enhance anti-tumor immunity and break immune tolerance. To capitalize on the immunogenic nature of oncolysis, we generated a quadruple modified oncolytic adenovirus expressing granulocyte-macrophage colony-stimulating factor (GMCSF). Ad5/3-E2F-Δ24-GMCSF (CGTG-602) was engineered to contain a tumor specific E2F1 promoter driving an E1 gene deleted at the retinoblastoma protein binding site (“Δ24”). The fiber features a knob from serotype 3 for enhanced gene delivery to tumor cells. The virus was tested preclinically in vitro and in vivo and then 13 patients with solid tumors refractory to standard therapies were treated. Treatments were well tolerated and frequent tumor- and adenovirus-specific T-cell immune responses were seen. Overall, with regard to tumor marker or radiological responses, signs of antitumor efficacy were seen in 9/12 evaluable patients (75%). The radiological disease control rate with positron emission tomography was 83% while the response rate (including minor responses) was 50%. Tumor biopsies indicated accumulation of immunological cells, especially T-cells, to tumors after treatment. RNA expression analyses of tumors indicated immunological activation and metabolic changes secondary to virus replication. PMID:25714011

  2. [Immunological therapy in asthma].

    PubMed

    Matta Campos, Juan José

    2009-01-01

    The goals of pharmacological treatment of asthma is to achieve clinical control and prevent exacerbations with the minimal adverse effects. Pharmacologic therapies are categorized in two general classes: long-term and quick-relief medications. Local or systemic corticosteroids blockade the late phase reaction of the immunological inflammatory response and reduce airway hyperresponsiveness. This reaction can also be diminished by allergen specific immunotherapy, this treatment also create immunological tolerance for the allergen and prevents new sensitizations. Immunosuppressants and immunomodulators such as methotrexate can be used as part of therapy in patients who does not respond to the recommended treatment, these medications should be used only selected patients under the supervision of an asthma specialist, as their potential beneficial effect may not outweigh the risk of serious side effects. Biomolecular therapy medications, such as etarnecept, are not recommended, more studies are required. The anti-IgE monoclonal antibody, omalizumab, is recommended in adults and children over 12, who have allergy as an important cause of their asthma. In reference to childhood immunizations, there is no evidence of influence on the incidence of asthma, possible beneficial effect on asthma exacerbations with anti-influenzae vaccine. Finally we'll see some interesting points about pharmacogenetics. PMID:20873057

  3. Virtual Immunology: Software for Teaching Basic Immunology

    ERIC Educational Resources Information Center

    Berçot, Filipe Faria; Fidalgo-Neto, Antônio Augusto; Lopes, Renato Matos; Faggioni, Thais; Alves, Luiz Anastácio

    2013-01-01

    As immunology continues to evolve, many educational methods have found difficulty in conveying the degree of complexity inherent in its basic principles. Today, the teaching-learning process in such areas has been improved with tools such as educational software. This article introduces "Virtual Immunology," a software program available…

  4. Aphasic Patients Exhibit a Reversal of Hemispheric Asymmetries in Categorical Color Discrimination

    ERIC Educational Resources Information Center

    Paluy, Yulia; Gilbert, Aubrey L.; Baldo, Juliana V.; Dronkers, Nina F.; Ivry, Richard B.

    2011-01-01

    Patients with left hemisphere (LH) or right hemisphere (RH) brain injury due to stroke were tested on a speeded, color discrimination task in which two factors were manipulated: (1) the categorical relationship between the target and the distracters and (2) the visual field in which the target was presented. Similar to controls, the RH patients…

  5. Pediatric Crohn disease patients exhibit specific ileal transcriptome and microbiome signature

    PubMed Central

    Haberman, Yael; Tickle, Timothy L.; Dexheimer, Phillip J.; Kim, Mi-Ok; Tang, Dora; Karns, Rebekah; Baldassano, Robert N.; Noe, Joshua D.; Rosh, Joel; Markowitz, James; Heyman, Melvin B.; Griffiths, Anne M.; Crandall, Wallace V.; Mack, David R.; Baker, Susan S.; Huttenhower, Curtis; Keljo, David J.; Hyams, Jeffrey S.; Kugathasan, Subra; Walters, Thomas D.; Aronow, Bruce; Xavier, Ramnik J.; Gevers, Dirk; Denson, Lee A.

    2014-01-01

    Interactions between the host and gut microbial community likely contribute to Crohn disease (CD) pathogenesis; however, direct evidence for these interactions at the onset of disease is lacking. Here, we characterized the global pattern of ileal gene expression and the ileal microbial community in 359 treatment-naive pediatric patients with CD, patients with ulcerative colitis (UC), and control individuals. We identified core gene expression profiles and microbial communities in the affected CD ilea that are preserved in the unaffected ilea of patients with colon-only CD but not present in those with UC or control individuals; therefore, this signature is specific to CD and independent of clinical inflammation. An abnormal increase of antimicrobial dual oxidase (DUOX2) expression was detected in association with an expansion of Proteobacteria in both UC and CD, while expression of lipoprotein APOA1 gene was downregulated and associated with CD-specific alterations in Firmicutes. The increased DUOX2 and decreased APOA1 gene expression signature favored oxidative stress and Th1 polarization and was maximally altered in patients with more severe mucosal injury. A regression model that included APOA1 gene expression and microbial abundance more accurately predicted month 6 steroid-free remission than a model using clinical factors alone. These CD-specific host and microbe profiles identify the ileum as the primary inductive site for all forms of CD and may direct prognostic and therapeutic approaches. PMID:25003194

  6. Pediatric Crohn disease patients exhibit specific ileal transcriptome and microbiome signature.

    PubMed

    Haberman, Yael; Tickle, Timothy L; Dexheimer, Phillip J; Kim, Mi-Ok; Tang, Dora; Karns, Rebekah; Baldassano, Robert N; Noe, Joshua D; Rosh, Joel; Markowitz, James; Heyman, Melvin B; Griffiths, Anne M; Crandall, Wallace V; Mack, David R; Baker, Susan S; Huttenhower, Curtis; Keljo, David J; Hyams, Jeffrey S; Kugathasan, Subra; Walters, Thomas D; Aronow, Bruce; Xavier, Ramnik J; Gevers, Dirk; Denson, Lee A

    2014-08-01

    Interactions between the host and gut microbial community likely contribute to Crohn disease (CD) pathogenesis; however, direct evidence for these interactions at the onset of disease is lacking. Here, we characterized the global pattern of ileal gene expression and the ileal microbial community in 359 treatment-naive pediatric patients with CD, patients with ulcerative colitis (UC), and control individuals. We identified core gene expression profiles and microbial communities in the affected CD ilea that are preserved in the unaffected ilea of patients with colon-only CD but not present in those with UC or control individuals; therefore, this signature is specific to CD and independent of clinical inflammation. An abnormal increase of antimicrobial dual oxidase (DUOX2) expression was detected in association with an expansion of Proteobacteria in both UC and CD, while expression of lipoprotein APOA1 gene was downregulated and associated with CD-specific alterations in Firmicutes. The increased DUOX2 and decreased APOA1 gene expression signature favored oxidative stress and Th1 polarization and was maximally altered in patients with more severe mucosal injury. A regression model that included APOA1 gene expression and microbial abundance more accurately predicted month 6 steroid-free remission than a model using clinical factors alone. These CD-specific host and microbe profiles identify the ileum as the primary inductive site for all forms of CD and may direct prognostic and therapeutic approaches. PMID:25003194

  7. Patients with type 1 diabetes exhibit altered cerebral metabolism during hypoglycemia

    PubMed Central

    van de Ven, Kim C.C.; Tack, Cees J.; Heerschap, Arend; van der Graaf, Marinette; de Galan, Bastiaan E.

    2013-01-01

    Patients with type 1 diabetes mellitus (T1DM) experience, on average, 2 to 3 hypoglycemic episodes per week. This study investigated the effect of hypoglycemia on cerebral glucose metabolism in patients with uncomplicated T1DM. For this purpose, hyperinsulinemic euglycemic and hypoglycemic glucose clamps were performed on separate days, using [1-13C]glucose infusion to increase plasma 13C enrichment. In vivo brain 13C magnetic resonance spectroscopy was used to measure the time course of 13C label incorporation into different metabolites and to calculate the tricarboxylic acid cycle flux (VTCA) by a one-compartment metabolic model. We found that cerebral glucose metabolism, as reflected by the VTCA, was not significantly different comparing euglycemic and hypoglycemic conditions in patients with T1DM. However, the VTCA was inversely related to the HbA1C and was, under hypoglycemic conditions, approximately 45% higher than that in a previously investigated group of healthy subjects. These data suggest that the brains of patients with T1DM are better able to endure moderate hypoglycemia than those of subjects without diabetes. PMID:23298837

  8. Vitiligo patient-derived keratinocytes exhibit characteristics of normal wound healing via epithelial to mesenchymal transition.

    PubMed

    Banerjee, Poulomi; Venkatachalam, Sandhyaa; Mamidi, Murali Krishna; Bhonde, Ramesh; Shankar, Krupa; Pal, Rajarshi

    2015-05-01

    Vitiligo is an autoimmune disorder that leads to depigmentation of skin via melanocyte dysfunction. Keratinocyte-induced toxicity is one among the several etiological factors implicated for vitiligo, and hence, autologous keratinocyte grafting is projected as one of the primary mode of treatment for vitiligo. However, reports indicate that perilesional keratinocytes not only display signatures of apoptosis but also could secrete cytokines and mediators which have antagonistic effect on proliferation or survival. Therefore, we investigated how vitiligo patients' derived keratinocytes respond to surplus amounts of inflammatory cytokines and whether they recapitulate events that take place during conventional wound healing. The primary objective of our study was to determine whether keratinocytes isolated from a vitiligo patient would undergo epithelial-mesenchymal transition similar to their normal counterparts upon induction with inflammatory cytokines such as TGF-b1 and EGF. We found that these keratinocytes undergo EMT during wound repair accompanied with increase in the levels of mesenchymal markers and ECM proteins; decrease in the levels of epithelial markers and enhanced migratory ability. Besides, we also demonstrated that EMT induction leads to activation of SMAD and MAPK pathways via Ras, Raf, PAI 1, Snail, Slug and ZO1. To our knowledge, this is the first report on the characterization of primary keratinocytes isolated from vitiligo patients with respect to their wound healing capacity. PMID:25690925

  9. Invasive breast carcinoma cells from patients exhibit MenaINV- and macrophage-dependent transendothelial migration.

    PubMed

    Pignatelli, Jeanine; Goswami, Sumanta; Jones, Joan G; Rohan, Thomas E; Pieri, Evan; Chen, Xiaoming; Adler, Esther; Cox, Dianne; Maleki, Sara; Bresnick, Anne; Gertler, Frank B; Condeelis, John S; Oktay, Maja H

    2014-11-25

    Metastasis is a complex, multistep process of cancer progression that has few treatment options. A critical event is the invasion of cancer cells into blood vessels (intravasation), through which cancer cells disseminate to distant organs. Breast cancer cells with increased abundance of Mena [an epidermal growth factor (EGF)-responsive cell migration protein] are present with macrophages at sites of intravasation, called TMEM sites (for tumor microenvironment of metastasis), in patient tumor samples. Furthermore, the density of these intravasation sites correlates with metastatic risk in patients. We found that intravasation of breast cancer cells may be prevented by blocking the signaling between cancer cells and macrophages. We obtained invasive breast ductal carcinoma cells of various subtypes by fine-needle aspiration (FNA) biopsies from patients and found that, in an in vitro transendothelial migration assay, cells that migrated through a layer of human endothelial cells were enriched for the transcript encoding Mena(INV), an invasive isoform of Mena. This enhanced transendothelial migration required macrophages and occurred with all of the breast cancer subtypes. Using mouse macrophages and the human cancer cells from the FNAs, we identified paracrine and autocrine activation of colony-stimulating factor-1 receptor (CSF-1R). The paracrine or autocrine nature of the signal depended on the breast cancer cell subtype. Knocking down Mena(INV) or adding an antibody that blocks CSF-1R function prevented transendothelial migration. Our findings indicate that Mena(INV) and TMEM frequency are correlated prognostic markers and CSF-1 and Mena(INV) may be therapeutic targets to prevent metastasis of multiple breast cancer subtypes. PMID:25429076

  10. Patients with sepsis exhibit increased mitochondrial respiratory capacity in peripheral blood immune cells

    PubMed Central

    2013-01-01

    Introduction In sepsis, mitochondria have been associated with both initial dysfunction and subsequent upregulation (biogenesis). However, the evolvement of mitochondrial function in sepsis over time is largely unknown, and we therefore investigated mitochondrial respiration in peripheral blood immune cells (PBICs) in sepsis patients during the first week after admission to the intensive care unit (ICU). Methods PBICs from 20 patients with severe sepsis or septic shock were analyzed with high-resolution respirometry 3 times after admission to the ICU (within 48 hours, days 3 to 4 and days 6 to 7). Mitochondrial DNA (mtDNA), cytochrome c (Cyt c), and citrate synthase (CS) were measured as indicators of cellular mitochondrial content. Results In intact PBICs with endogenous substrates, a gradual increase in cellular respiration reached 173% of controls after 1 week (P = 0.001). In permeabilized cells, respiration using substrates of complex I, II, and IV were significantly increased days 1 to 2, reaching 137%, 130%, and 173% of controls, respectively. In parallel, higher levels of CS activity, mtDNA, and Cyt c content in PBICs (211%, 243%, and 331% of controls for the respective indicators were found at days 6 to 7; P < 0.0001). No differences in respiratory capacities were noted between survivors and nonsurvivors at any of the time points measured. Conclusions PBICs from patients with sepsis displayed higher mitochondrial respiratory capacities compared with controls, due to an increased mitochondrial content, as indicated by increased mitochondrial DNA, protein content, and enzyme activity. The results argue against mitochondrial respiratory dysfunction in this type of cells in sepsis. PMID:23883738

  11. Hydrogel-forming Microneedle Arrays Exhibit Antimicrobial Properties: Potential for Enhanced Patient Safety

    PubMed Central

    Donnelly, Ryan F.; Singh, Thakur Raghu Raj; Alkilani, Ahlam Zaid; McCrudden, Maelíosa T.C.; O’Mahony, Conor; Armstrong, Keith; McLoone, Nabla; Kole, Prashant; Woolfson, A. David

    2014-01-01

    We describe, for the first time, the microbial characterisation of hydrogel-forming polymeric microneedle arrays and the potential for passage of microorganisms into skin following microneedle penetration. Uniquely, we also present insights into the storage stability of these hydroscopic formulations, from physical and microbiological viewpoints, and examine clinical performance and safety in human volunteers. Experiments employing excised porcine skin and radiolabelled microorganisms showed that microorganisms can penetrate skin beyond the stratum corneum following microneedle puncture. Indeed, the numbers of microorganisms crossing the stratum corneum following microneedle puncture was greater than 105 cfu in each case. However, no microorganisms crossed the epidermal skin. When using a 21G hypodermic needle, more than 104 microorganisms penetrated into the viable tissue and 106 cfu of C. albicans and S. epidermidis completely crossed the epidermal skin in 24 h. The hydrogel-forming materials contained no microorganisms following de-moulding and exhibited no microbial growth during storage, while also maintaining their mechanical strength, apart from when stored at relative humidities of 86%. No microbial penetration through the swelling microneedles was detectable, while human volunteer studies confirmed that skin or systemic infection is highly unlikely when polymeric microneedles are used for transdermal drug delivery. Since no pharmacopoeial standards currently exist for microneedle-based products, the exact requirements for a proprietary product based on hydrogel-forming microneedles are at present unclear. However, we are currently working towards a comprehensive specification set for this microneedle system that may inform future developments in this regard. PMID:23644043

  12. Early-Course Unmedicated Schizophrenia Patients Exhibit Elevated Prefrontal Connectivity Associated with Longitudinal Change

    PubMed Central

    Anticevic, Alan; Hu, Xinyu; Xiao, Yuan; Hu, Junmei; Li, Fei; Bi, Feng; Cole, Michael W.; Savic, Aleksandar; Yang, Genevieve J.; Repovs, Grega; Murray, John D.; Wang, Xiao-Jing; Huang, Xiaoqi; Lui, Su; Krystal, John H.

    2015-01-01

    Strong evidence implicates prefrontal cortex (PFC) as a major source of functional impairment in severe mental illness such as schizophrenia. Numerous schizophrenia studies report deficits in PFC structure, activation, and functional connectivity in patients with chronic illness, suggesting that deficient PFC functional connectivity occurs in this disorder. However, the PFC functional connectivity patterns during illness onset and its longitudinal progression remain uncharacterized. Emerging evidence suggests that early-course schizophrenia involves increased PFC glutamate, which might elevate PFC functional connectivity. To test this hypothesis, we examined 129 non-medicated, human subjects diagnosed with early-course schizophrenia and 106 matched healthy human subjects using both whole-brain data-driven and hypothesis-driven PFC analyses of resting-state fMRI. We identified increased PFC connectivity in early-course patients, predictive of symptoms and diagnostic classification, but less evidence for “hypoconnectivity.” At the whole-brain level, we observed “hyperconnectivity” around areas centered on the default system, with modest overlap with PFC-specific effects. The PFC hyperconnectivity normalized for a subset of the sample followed longitudinally (n = 25), which also predicted immediate symptom improvement. Biologically informed computational modeling implicates altered overall connection strength in schizophrenia. The initial hyperconnectivity, which may decrease longitudinally, could have prognostic and therapeutic implications. PMID:25568120

  13. [Comparative characteristics of clinical and immunologic indicators of various groups of opisthorchiasis patients in a focus. Aboriginal population].

    PubMed

    Parfenov, S B; Ozeretskovskaia, N N; Zolotukhin, V A

    1989-01-01

    Clinical and immunological observations of people belonging to two population groups--aborigens (khanty, mansi, komi) and 40 immigrants--were performed in opisthorchiasis foci of the Tyumen region. Rapid clinical reinvasion of unimmune immigrants (in a 3-4 year period) was established; the aborigens featured subclinical invasion pattern. T-system immunity in immigrants was suppressed, while in the aboriginal group insignificant reduction of the number of T-helpers and significant increase in the number of T-suppressors, lack of apparent mobilization of humoral immunity factors--reduction of the absolute B-lymphocytes number, normal A, G immunoglobulines and CIC levels-were observed. Such T--B immune systems' ratio may indicate immune tolerance of a suppressor type. The observed indicators of aborigens' tolerance to helminths' antigens point to the necessity of differentiated approach to chemotherapy prescription (especially of the repeated courses) in the endemic invasion foci. PMID:2526919

  14. Oligodeoxynucleotide CpG 7909 delivered as intravenous infusion demonstrates immunologic modulation in patients with previously treated non-Hodgkin lymphoma.

    PubMed

    Link, Brian K; Ballas, Zuhair K; Weisdorf, Daniel; Wooldridge, James E; Bossler, Aaron D; Shannon, Mary; Rasmussen, Wendy L; Krieg, Arthur M; Weiner, George J

    2006-01-01

    Oligodeoxynucleotides containing CpG motifs (CpG ODN) can alter various immune cell subsets important in antibody therapy of malignancy. We undertook a phase I trial of CPG 7909 (also known as PF-3512676) in patients with previously treated lymphoma with the primary objective of evaluating safety across a range of doses, and secondary objectives of evaluating immunomodulatory effects and clinical effects. Twenty-three patients with previously treated non-Hodgkin lymphoma received up to 3 weekly 2-hour intravenous (IV) infusions of CPG ODN 7909 at dose levels 0.01 to 0.64 mg/kg. Evaluation of immunologic parameters and clinical endpoints occurred for 6 weeks. Infusion-related toxicity included grade 1 nausea, hypotension, and IV catheter discomfort. Serious adverse hematologic events observed more than once included anemia (2=Gr3, 2=Gr4), thrombocytopenia (4=Gr3), and neutropenia (2=Gr3), and were largely judged owing to progressive disease. Immunologic observations included: (1) The mean ratio of NK-cell concentrations compared with pretreatment at day 2 was 1.44 (95% CI=0.94-1.94) and at day 42 was 1.53 (95% CI=1.14-1.91); (2) NK activity generally increased in subjects; and (3) Antibody-dependent cellular cytotoxicity activity increased in select cohorts. No clinical responses were documented radiographically at day 42. Two subjects demonstrated late response. We conclude CpG 7909 can be safely given as a 2-hour IV infusion to patients with previously treated non-Hodgkin lymphoma at doses that have immunomodulatory effects. PMID:16971811

  15. Effects of opioids on immunologic parameters that are relevant to anti-tumour immune potential in patients with cancer: a systematic literature review

    PubMed Central

    Boland, J W; McWilliams, K; Ahmedzai, S H; Pockley, A G

    2014-01-01

    Background: The immune system has a central role in controlling cancer, and factors that influence protective antitumour immunity could therefore have a significant impact on the course of malignant disease. Opioids are essential for the management of cancer pain, and preclinical studies indicate that opioids have the potential to influence these tumour immune surveillance mechanisms. The aim of this systematic literature review is to evaluate the clinical effects of opioids on the immune system of patients with cancer. Methods: A systematic search of Ovid MEDLINE (PubMed) and Embase, Cochrane database and Web of Knowledge for clinical studies, which evaluated the effects of opioids on the immune system in patients with cancer, was performed. Results: Five human studies, which have assessed the effects of opioids on the immune system in patients with cancer, were identified. Although all of these evaluated the effect of morphine on immunologic end points in patients with cancer, none measured the clinical effects. Conclusions: Evidence from preclinical, healthy volunteer and surgical models suggests that different opioids variably influence protective anti-tumour immunity; however, actual data derived from cancer populations are inconclusive and definitive recommendations cannot be made. Appropriately designed and powered studies assessing clinical outcomes of opioid use in people with cancer are therefore required to inform oncologists and others involved in cancer care about the rational use of opioids in this patient group. PMID:25025960

  16. Detailed analysis of immunologic effects of the cytotoxic T lymphocyte-associated antigen 4-blocking monoclonal antibody tremelimumab in peripheral blood of patients with melanoma

    PubMed Central

    Comin-Anduix, Begoña; Lee, Yohan; Jalil, Jason; Algazi, Alain; de la Rocha, Pilar; Camacho, Luis H; Bozon, Viviana A; Bulanhagui, Cecile A; Seja, Elisabeth; Villanueva, Arturo; Straatsma, Bradley R; Gualberto, Antonio; Economou, James S; Glaspy, John A; Gomez-Navarro, Jesus; Ribas, Antoni

    2008-01-01

    Background CTLA4-blocking antibodies induce tumor regression in a subset of patients with melanoma. Analysis of immune parameters in peripheral blood may help define how responses are mediated. Methods Peripheral blood from HLA-A*0201-positive patients with advanced melanoma receiving tremelimumab (formerly CP-675,206) at 10 mg/kg monthly was repeatedly sampled during the first 4 cycles. Samples were analyzed by 1) tetramer and ELISPOT assays for reactivity to CMV, EBV, MART1, gp100, and tyrosinase; 2) activation HLA-DR and memory CD45RO markers on CD4+/CD8+ cells; and 3) real-time quantitative PCR of mRNA for FoxP3 transcription factor, preferentially expressed by T regulatory cells. The primary endpoint was difference in MART1-specific T cells by tetramer assay. Immunological data were explored for significant trends using clustering analysis. Results Three of 12 patients eligible for immune monitoring had tumor regression lasting > 2 years without relapse. There was no significant change in percent of MART1-specific T cells by tetramer assay. Additionally, there was no generalized trend toward postdosing changes in other antigen-specific CD8+ cell populations, FoxP3 transcripts, or overall changes in surface expression of T-cell activation or memory markers. Unsupervised hierarchical clustering based on immune monitoring data segregated patients randomly. However, clustering according to T-cell activation or memory markers separated patients with clinical response and most patients with inflammatory toxicity into a common subgroup. Conclusion Administration of CTLA4-blocking antibody tremelimumab to patients with advanced melanoma results in a subset of patients with long-lived tumor responses. T-cell activation and memory markers served as the only readout of the pharmacodynamic effects of this antibody in peripheral blood. Clinical trial registration number NCT00086489 PMID:18452610

  17. Elucidating the immunological effects of 5-azacytidine treatment in patients with myelodysplastic syndrome and identifying new conditional ligands and T-cell epitopes of relevance in melanoma.

    PubMed

    Frøsig, Thomas Mørch

    2015-08-01

    This review is focused on research within three different areas of tumor immunology: discovery of new T-cell epitopes and a new immunological antigen (reported in Paper I and II), elucidation of the immunological effects of treatment with a hypomethylating drug (reported in Paper III) and discovery of new conditional ligands (reported in Paper IV). Many melanoma-associated T-cell epitopes have been described, but 45% of these are restricted to human leukocyte antigen (HLA)-A2, leaving the remaining 36 different HLA molecules with only a few described T-cell epitopes each. Therefore we wanted to expand the number of T-cell epitopes restricted to HLA-A1, -A3, -A11 and -B7, all HLA molecules frequently expressed in Caucasians in Western Europe and Northern America. In Paper I we focused on the proteins gp100, Mart1, MAGE-A3, NY-ESO-1, tyrosinase and TRP-2, all melanoma-associated antigens frequently recognized by T cells from HLA-A2 patients. On contrary, in Paper II we wanted to investigate the protein Nodal as a novel immunological target. We took advantage of a T-cell epitope mapping platform in which HLA ligands are predicted by computer-based algorithms, further tested in the laboratory by an ELISA-based method and used for flow cytometry-based detection of specific T-cell responses by use of combinatorial encoded major histocompatibility (MHC) class I multimers. This procedure resulted in 127 (Paper I) and 32 (Paper II) confirmed HLA ligands, respectively, which we used for screening of the T-cell recognition within peripheral blood mononuclear cell samples from melanoma patients. As spontaneous tumor-specific T-cell responses tend to be of very low frequency and probably below the detection threshold of the method, we incorporated a T-cell enrichment step prior to the detection of these responses. Our screening of 39 melanoma patients resulted in 26 (17 different) T-cell responses against the common melanoma-associated antigens and 10 (8 different) T

  18. Characterization of dengue virus infections in a sample of patients suggests unique clinical, immunological, and virological profiles that impact on the diagnosis of dengue and dengue hemorrhagic fever.

    PubMed

    Senaratne, Thamarasi; Wimalaratne, Harith; Alahakoon, D G S; Gunawardane, Nirmali; Carr, Jillian; Noordeen, Faseeha

    2016-10-01

    Dengue virus (DENV) infections are increasing with respect to incidence and severity in the Central Province of Sri Lanka. The objective of this study was to define the clinical, immunological, and virological profiles of patients admitted to the General Hospital, Kandy with clinically apparent dengue. Demographic, clinical, hematological parameters, liver enzymes (ALT and AST), and blood samples were collected from 292 patients with fever <5 days post onset and fulfilling the WHO criteria for the diagnosis of dengue fever/dengue hemorrhagic fever (DF/DHF). Samples were analyzed for, anti-DENV IgM, IgG, and DENV nucleic acid. Myalgia was the commonest complaint by 65% of the patients. Packed cell volume was >45% in 27% of the patients while 42.12% had reduced platelets and 62.67% had reduced white blood cell counts. In contrast to other studies, positive tourniquet test (PTT) and petechiae were not major indicators of DENV infection or severity of the disease. Clinical profiles were significantly different between DF and DHF/DSS and showed many similarities to that reported elsewhere. Altogether, 43 patients (14.73%) were viremic as detected by RT-PCR; 181 patients (62%) were positive for anti-DENV IgM, and 245 (84%) patients were positive for anti-DENV IgG. In combination, anti-DENV IgM and RT-PCR assays detected 224 (77.5%) of DENV infected cases, thus improving the DENV diagnosis rate. Hence, the diagnostic utility of PTT, anti-DENV IgM/IgG serology, or RT-PCR used alone in the early phase of illness is low in Sri Lanka but the diagnostic value can be improved by a combination of serology and RT-PCR. J. Med. Virol. 88:1703-1710, 2016. © 2016 Wiley Periodicals, Inc. PMID:26990973

  19. Immunological characterization of Echinococcus granulosus cyclophilin, an allergen reactive with IgE and IgG4 from patients with cystic echinococcosis

    PubMed Central

    ORTONA, E; VACCARI, S; MARGUTTI, P; DELUNARDO, F; RIGANÒ, R; PROFUMO, E; BUTTARI, B; RASOOL, O; TEGGI, A; SIRACUSANO, A

    2002-01-01

    By immunological screening of a cDNA library derived from protoscoleces of Echinococcus granulosus with IgE from patients with cystic echinococcosis (CE) and allergic manifestations, we isolated a protein identical to E. granulosus cyclophilin. The protein, named EA21, has close homology with Malassezia furfur cyclophilin allergen (Mal f 6) and with human cyclophilin. Using immunoblotting (IB) with a polyclonal antibody specific to EA21, we identified E. granulosus cyclophilin both in protoscoleces and in sheep hydatid fluid. Of the 58 sera from patients with CE, 29 (50%) were IgE positive to EA21, whereas, despite the high sequence homology, none were IgE positive to Mal f 6 or human cyclophilin. Only 26 of the 58 patients (45%) had IgG specific to EA21, whereas all patients (100%) had IgG specific to Mal f 6 and human cyclophilin. IB analysis showed that serum IgE-binding reactivity to EA21 differed significantly in patients with and without allergic reactions (20 of 25, 80%versus nine of 33, 27%; P < 10–4). Conversely, five of the 25 patients who had CE-related allergic manifestations (20%) and 21 of the 33 who did not (63%) had specific IgG4 (P = 10–3) and total IgG to EA21. EA21 induced a proliferative response in 15 of 19 (79%) patients’ PBMC regardless of the allergic manifestations, but it induced no IL-4 production. Overall, these findings suggest that E. granulosus cyclophilin is a conserved, constitutive, parasite protein that does not cross-react with cyclophilins from other organisms and is involved in the allergic symptoms related to CE. PMID:11982600

  20. Prevalence of colorectal diseases in immunological fecal occult blood test (I-FOBT) positive patients in a tertiary care hospital in Bangladesh.

    PubMed

    Mollick, S H; Roy, P K; Bhuiyan, M R; Mia, A R; Alam, M S; Mollick, K A; Pervin, S; Hassan, M Q

    2014-10-01

    Bleeding lesion anywhere in the GI tract can cause positive reaction to Immunological Fecal Occult Blood Test (FOBT). Although any colonic lesion can cause occult lower GI bleeding, relative frequency of this lesion not known. Guaic based tests require prior preparation and dietary restriction and less sensitive and specific than IFOBT for detection of occult bleeding .IFOBT is specific for human hemoglobin and is more sensitive and specific for detection of occult bleeding from any colonic lesion. Aim of this study was to diagnose occult gastrointestinal bleeding with positive IFOBT and the prevalence of colorectal disease in IFOBT positive patients in a tertiary care hospital in Bangladesh. This was a prospective cross sectional study conducted in Department of gastroenterology in collaboration with clinical pathology, BSMMU, Dhaka during the period of January 2009 to December 2009. In this study 200 patients meeting the inclusion criteria were included. Detailed clinical history and physical findings were recorded; FOBT was done on single stool specimen. Positive occult bleeding was confirmed in 90 patients of whom 80 patients underwent colonoscopy. The mean age of study population was 36.73±13.64 (range 16 to 72) years. At colonoscopy lesion were identified in 46(57.50%) patients, of which colonic polyp in12 (15%), colorectal cancer in 11(13.7%), inflammatory bowel disease in 3(3.75%), hemorrhoids and anal fissure in 7(8.75%), tuberculosis in 5(6.25%), and proctitis in 1(1.25%) cases. A positive IFOBT is more sensitive and specific test than other FOBT for detection of occult lower GI bleeding of colonic origin. In this study colorectal diseases were detected in 57.50% of the IFOBT positive patients, so IOBT can be used as an important diagnostic tool for detection of occult lower GI bleeding. PMID:25481598

  1. Extended Evaluation of Virological, Immunological and Pharmacokinetic Endpoints of CELADEN: A Randomized, Placebo-Controlled Trial of Celgosivir in Dengue Fever Patients

    PubMed Central

    Sung, Cynthia; Wei, Yuan; Watanabe, Satoru; Lee, How Sung; Khoo, Yok Moi; Fan, Lu; Rathore, Abhay P. S.; Chan, Kitti Wing-Ki; Choy, Milly M.; Kamaraj, Uma S.; Sessions, October M.; Aw, Pauline; de Sessions, Paola F.; Lee, Bernett; Connolly, John E.; Hibberd, Martin L.; Vijaykrishna, Dhanasekaran; Wijaya, Limin; Ooi, Eng Eong; Low, Jenny Guek-Hong

    2016-01-01

    CELADEN was a randomized placebo-controlled trial of 50 patients with confirmed dengue fever to evaluate the efficacy and safety of celgosivir (A study registered at ClinicalTrials.gov, number NCT01619969). Celgosivir was given as a 400 mg loading dose and 200 mg bid (twice a day) over 5 days. Replication competent virus was measured by plaque assay and compared to reverse transcription quantitative PCR (qPCR) of viral RNA. Pharmacokinetics (PK) correlations with viremia, immunological profiling, next generation sequence (NGS) analysis and hematological data were evaluated as exploratory endpoints here to identify possible signals of pharmacological activity. Viremia by plaque assay strongly correlated with qPCR during the first four days. Immunological profiling demonstrated a qualitative shift in T helper cell profile during the course of infection. NGS analysis did not reveal any prominent signature that could be associated with drug treatment; however the phylogenetic spread of patients’ isolates underlines the importance of strain variability that may potentially confound interpretation of dengue drug trials conducted during different outbreaks and in different countries. Celgosivir rapidly converted to castanospermine (Cast) with mean peak and trough concentrations of 5727 ng/mL (30.2 μM) and 430 ng/mL (2.3 μM), respectively and cleared with a half-life of 2.5 (± 0.6) hr. Mean viral log reduction between day 2 and 4 (VLR2-4) was significantly greater in secondary dengue than primary dengue (p = 0.002). VLR2-4 did not correlate with drug AUC but showed a trend of greater response with increasing Cmin. PK modeling identified dosing regimens predicted to achieve 2.4 to 4.5 times higher Cmin. than in the CELADEN trial for only 13% to 33% increase in overall dose. A small, non-statistical trend towards better outcome on platelet nadir and difference between maximum and minimum hematocrit was observed in celgosivir-treated patients with secondary dengue

  2. Hereditary angioedema. Long-term follow-up of 88 patients. Experience of the Argentine Allergy and Immunology Institute.

    PubMed

    Fabiani, J E; Avigliano, A; Dupont, J C; Fabiana, J E

    2000-01-01

    Since the detection of the first patient with hereditary angioedema (HA) in 1978, 88 new patients belonging to 16 families have been referred to our clinic. Eighty patients had Type I disease, 5 Type II, and 3 Type III (secondary). We describe the clinical onset, frequent complications, diagnostic tests of the complement system, and abnormalities of the coagulation pathway linked to complement activation. Particular attention was paid to family members who could present succedaneum symptoms. The results of danazole and other therapies and protective and preventive treatment for surgery also are discussed. PMID:11270087

  3. The New Cellular Immunology

    ERIC Educational Resources Information Center

    Claman, Henry N.

    1973-01-01

    Discusses the nature of the immune response and traces many of the discoveries that have led to the present state of knowledge in immunology. The new cellular immunology is directing its efforts toward improving health by proper manipulation of the immune mechanisms of the body. (JR)

  4. hiPSC-derived cardiomyocytes from Brugada Syndrome patients without identified mutations do not exhibit clear cellular electrophysiological abnormalities

    PubMed Central

    Veerman, Christiaan C.; Mengarelli, Isabella; Guan, Kaomei; Stauske, Michael; Barc, Julien; Tan, Hanno L.; Wilde, Arthur A. M.; Verkerk, Arie O.; Bezzina, Connie R.

    2016-01-01

    Brugada syndrome (BrS) is a rare cardiac rhythm disorder associated with sudden cardiac death. Mutations in the sodium channel gene SCN5A are found in ~20% of cases while mutations in other genes collectively account for <5%. In the remaining patients the genetic defect and the underlying pathogenic mechanism remain obscure. To provide insight into the mechanism of BrS in individuals without identified mutations, we here studied electrophysiological properties of cardiomyocytes (CMs) generated from human induced pluripotent stem cells (hiPSCs) from 3 BrS patients who tested negative for mutations in the known BrS-associated genes. Patch clamp studies revealed no differences in sodium current (INa) in hiPSC-CMs from the 3 BrS patients compared to 2 unrelated controls. Moreover, action potential upstroke velocity (Vmax), reflecting INa, was not different between hiPSC-CMs from the BrS patients and the controls. hiPSC-CMs harboring the BrS-associated SCN5A-1795insD mutation exhibited a reduction in both INa and Vmax, demonstrating our ability to detect reduced sodium channel function. hiPSC-CMs from one of the BrS lines demonstrated a mildly reduced action potential duration, however, the transient outward potassium current (Ito) and the L-type calcium current (ICa,L), both implicated in BrS, were not different compared to the controls. Our findings indicate that ion channel dysfunction, in particular in the cardiac sodium channel, may not be a prerequisite for BrS. PMID:27485484

  5. Human Cardiosphere-Derived Cells From Advanced Heart Failure Patients Exhibit Augmented Functional Potency in Myocardial Repair

    PubMed Central

    Shen, Deliang; Sun, Baiming; Blusztajn, Agnieszka; Xie, Yucai; Ibrahim, Ahmed; Aminzadeh, Mohammad Amin; Liu, Weixin; Li, Tao-Sheng; De Robertis, Michele A.; Marbán, Linda; Czer, Lawrence S. C.; Trento, Alfredo; Marbán, Eduardo

    2014-01-01

    Objectives This study sought to compare the regenerative potency of cells derived from healthy and diseased human hearts. Background Results from pre-clinical studies and the CADUCEUS (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction) trial support the notion that cardiosphere-derived cells (CDCs) from normal and recently infarcted hearts are capable of regenerating healthy heart tissue after myocardial infarction (MI). It is unknown whether CDCs derived from advanced heart failure (HF) patients retain the same regenerative potency. Methods In a mouse model of acute MI, we compared the regenerative potential and functional benefits of CDCs derived from 3 groups: 1) non-failing (NF) donor: healthy donor hearts post-transplantation; 2) MI: patients who had an MI 9 to 35 days before biopsy; and 3) HF: advanced cardiomyopathy tissue explanted at cardiac transplantation. Results Cell growth and phenotype were identical in all 3 groups. Injection of HF CDCs led to the greatest therapeutic benefit in mice, with the highest left ventricular ejection fraction, thickest infarct wall, most viable tissue, and least scar 3 weeks after treatment. In vitro assays revealed that HF CDCs secreted higher levels of stromal cell-derived factor 1 (SDF-1), which may contribute to the cells’ augmented resistance to oxidative stress, enhanced angiogenesis, and improved myocyte survival. Histological analysis indicated that HF CDCs engrafted better, recruited more endogenous stem cells, and induced greater angiogenesis and cardiomyocyte cell-cycle re-entry. CDC-secreted SDF-1 levels correlated with decreases in scar mass over time in CADUCEUS patients treated with autologous CDCs. Conclusions CDCs from advanced HF patients exhibit augmented potency in ameliorating ventricular dysfunction post-MI, possibly through SDF-1–mediated mechanisms. PMID:24511463

  6. A Very Low Geno2pheno False Positive Rate Is Associated with Poor Viro-Immunological Response in Drug-Naïve Patients Starting a First-Line HAART

    PubMed Central

    Armenia, Daniele; Soulie, Cathia; Di Carlo, Domenico; Fabeni, Lavinia; Gori, Caterina; Forbici, Federica; Svicher, Valentina; Bertoli, Ada; Sarmati, Loredana; Giuliani, Massimo; Latini, Alessandra; Boumis, Evangelo; Zaccarelli, Mauro; Bellagamba, Rita; Andreoni, Massimo; Marcelin, Anne-Geneviève; Calvez, Vincent; Antinori, Andrea; Ceccherini-Silberstein, Francesca; Perno, Carlo-Federico; Santoro, Maria Mercedes

    2014-01-01

    Background We previously found that a very low geno2pheno false positive rate (FPR ≤2%) defines a viral population associated with low CD4 cell count and the highest amount of X4-quasispecies. In this study, we aimed at evaluating whether FPR ≤2% might impact on the viro-immunological response in HIV-1 infected patients starting a first-line HAART. Methods The analysis was performed on 305 HIV-1 B subtype infected drug-naïve patients who started their first-line HAART. Baseline FPR (%) values were stratified according to the following ranges: ≤2; 2–5; 5–10; 10–20; 20–60; >60. The impact of genotypically-inferred tropism on the time to achieve immunological reconstitution (a CD4 cell count gain from HAART initiation ≥150 cells/mm3) and on the time to achieve virological success (the first HIV-RNA measurement <50 copies/mL from HAART initiation) was evaluated by survival analyses. Results Overall, at therapy start, 27% of patients had FPR ≤10 (6%, FPR ≤2; 7%, FPR 2–5; 14%, FPR 5–10). By 12 months of therapy the rate of immunological reconstitution was overall 75.5%, and it was significantly lower for FPR ≤2 (54.1%) in comparison to other FPR ranks (78.8%, FPR 2–5; 77.5%, FPR 5–10; 71.7%, FPR 10–20; 81.8%, FPR 20–60; 75.1%, FPR >60; p = 0.008). The overall proportion of patients achieving virological success was 95.5% by 12 months of therapy. Multivariable Cox analyses showed that patients having pre-HAART FPR ≤2% had a significant lower relative adjusted hazard [95% C.I.] both to achieve immunological reconstitution (0.37 [0.20–0.71], p = 0.003) and to achieve virological success (0.50 [0.26–0.94], p = 0.031) than those with pre-HAART FPR >60%. Conclusions Beyond the genotypically-inferred tropism determination, FPR ≤2% predicts both a poor immunological reconstitution and a lower virological response in drug-naïve patients who started their first-line therapy. This parameter could be useful to identify patients

  7. Immunological features of T cells induced by human telomerase reverse transcriptase-derived peptides in patients with hepatocellular carcinoma.

    PubMed

    Mizukoshi, Eishiro; Nakagawa, Hidetoshi; Kitahara, Masaaki; Yamashita, Tatsuya; Arai, Kuniaki; Sunagozaka, Hajime; Fushimi, Kazumi; Kobayashi, Eiji; Kishi, Hiroyuki; Muraguchi, Atsushi; Kaneko, Shuichi

    2015-08-10

    Human telomerase reverse transcriptase (hTERT) is a catalytic enzyme required for telomere elongation. In this study, we investigated the safety and immunogenicity of an hTERT-derived peptide (hTERT461) as a vaccine and characterized the hTERT-specific T cell responses induced. Fourteen hepatocellular carcinoma (HCC) patients were enrolled in the study. The hTERT-derived peptide was emulsified in incomplete Freund's adjuvant and administered via subcutaneous immunization three times biweekly. The maximum toxicity observed was grade 2 according to the common terminology criteria and mainly consisted of skin reactions at the site of vaccination. The vaccination induced hTERT-specific immunity in 71.4% of patients and 57.1% of patients administered with hTERT461 peptide-specific T cells could prevent HCC recurrence after vaccination. In phenotypic analysis, the post-vaccinated increase in hTERT-specific T cells was due to an increase in cells with the effector memory phenotype, with the potential to produce multiple cytokines. Seven hTERT-specific T cell receptors were obtained from the vaccinated patients, showing their cytotoxic activities to hTERT-derived peptide-bearing cells. In conclusion, the safety and effects of immune boosting by hTERT461 peptide have shown the potential of the peptide to provide clinical benefits in HCC patients. PMID:25982205

  8. Clinical and immunological evaluation after BCG-id vaccine in leprosy patients in a 5-year follow-up study

    PubMed Central

    Zenha, Erika Muller Ramalho; Wambier, Carlos Gustavo; Novelino, Ana Lúcia; de Andrade, Thiago Antônio Moretti; Ferreira, Maria Aparecida Nunes; Frade, Marco Andrey Cipriani; Foss, Norma Tiraboschi

    2012-01-01

    Introduction The use of bacillus Calmette–Guérin (BCG) has long been considered a stimulus for immune reactivity in leprosy household contacts. Probably, the combination of multidrug therapy with BCG could facilitate the clearance of leprosy bacilli in the host, reduce relapse rates, and shorten the duration of skin-smear positivity. Methods To investigate the mechanism of action of BCG, a study involving 19 leprosy patients, eleven multibacillary (MB) and eight paucibacillary, was performed to assess the in vitro production of interleukin (IL)-10, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-6, and IL-17 in the supernatant of peripheral blood mononuclear cells, before and 30 days after inoculation with BCG intradermally (BCG-id). Peripheral blood mononuclear cells isolated by Ficoll–Hypaque gradient were cultivated with Concanavalin-A (Con-A), lipopolysccharides (LPS), or BCG. The supernatant was collected for ELISA quantification of cytokines. The immunohistochemistry of IFN-γ, IL-1, IL-10, IL-12, transforming growth factor (TGF)-β, and TNF-α was carried out in biopsies of skin lesions of leprosy patients before and 30 days after inoculation of BCG-id. These patients were followed up for 5 years to assess the therapeutic response to multidrug therapy, the occurrence of leprosy reactions, and the results of bacterial index and anti-PGL-1 serology after the end of treatment. Results The results showed increased production of cytokines after BCG-id administration in MB and paucibacillary leprosy patients. There was statistically higher levels of TNF-α (P = 0.017) in MB patients and of IL-17 (P = 0.008) and IFN-γ (P = 0.037) in paucibacillary patients. Immunohistochemical staining, especially for TNF-α, was more intense in biopsies of MB leprosy patients taken after BCG-id administration, probably for induction of innate human immunity. The clinical evaluation suggests that BCG-id is able to induce a more effective therapeutic response, with

  9. Low-dose and short-term cyclosporine treatment in patients with chronic idiopathic urticaria: a clinical and immunological evaluation.

    PubMed

    Serhat Inaloz, H; Ozturk, Savas; Akcali, Cenk; Kirtak, Necmettin; Tarakcioglu, Mehmet

    2008-05-01

    The present study aimed to evaluate the effectiveness of 2.5 mg/kg/day cyclosporin (CsA) treatment in patients with severe chronic idiopathic urticaria (CIU) and the impact of CsA treatment on several cytokines involved in the etiopathogenesis of CIU. Twenty-seven CIU patients and 24 healthy control subjects were included in the study. The autologous serum skin test (ASST) for autoantibodies and urticaria activity scoring (UAS) were measured for the evaluation of the clinical severity and the response to therapy, and the serum levels of interleukin (IL)-6, IL-8, IL-2 receptor, IL-1beta, tumor necrosis factor (TNF)-alpha and IL-5 were measured. The mean UAS score was 32.07 +/- 7.05 and 6.22 +/- 3.84 before and after CsA treatment, respectively. The serum IL-2 receptor, TNF-alpha and IL-5 levels of patients before CsA treatment were statistically higher than those of the control group (P = 0.001), and after 4 weeks of CsA therapy the mean IL-2R, TNF-alpha and IL-5 levels were significantly decreased. The data from this study demonstrate that CsA therapy is efficient and safe for CIU patients. Increase in clinical efficacy and marked decreases in serum cytokine levels suggest that inhibition of cytokine generation is involved in the action of the drug in this clinical setting. PMID:18477227

  10. T cells from CLL patients exhibit features of T-cell exhaustion but retain capacity for cytokine production

    PubMed Central

    Davies, Jeffrey K.; McClanahan, Fabienne; Fatah, Rewas; Iqbal, Sameena; Agrawal, Samir; Ramsay, Alan G.; Gribben, John G.

    2013-01-01

    T-cell exhaustion, originally described in chronic viral infections, was recently reported in solid and hematologic cancers. It is not defined whether exhaustion contributes to T-cell dysfunction observed in chronic lymphocytic leukemia (CLL). We investigated the phenotype and function of T cells from CLL patients and age-matched controls. CD8+ and CD4+ T cells from CLL patients had increased expression of exhaustion markers CD244, CD160, and PD1, with expansion of a PD1+BLIMP1HI subset. These molecules were most highly expressed in the expanded population of effector T cells in CLL. CLL CD8+ T cells showed functional defects in proliferation and cytotoxicity, with the cytolytic defect caused by impaired granzyme packaging into vesicles and nonpolarized degranulation. In contrast to virally induced exhaustion, CLL T cells showed increased production of interferon-γ and TNFα and increased expression of TBET, and normal IL2 production. These defects were not restricted to expanded populations of cytomegalovirus (CMV)–specific cells, although CMV seropositivity modulated the distribution of lymphocyte subsets, the functional defects were present irrespective of CMV serostatus. Therefore, although CLL CD8+ T cells exhibit features of T-cell exhaustion, they retain the ability to produce cytokines. These findings also exclude CMV as the sole cause of T-cell defects in CLL. PMID:23247726

  11. A longitudinal cohort study of Finnish patients with primary Sjögren's syndrome: clinical, immunological, and epidemiological aspects

    PubMed Central

    Pertovaara, M; Pukkala, E; Laippala, P; Miettinen, A; Pasternack, A

    2001-01-01

    OBJECTIVE—To evaluate outcome in a cohort of Finnish patients with primary Sjögren's syndrome (pSS).
METHODS—Clinical and laboratory data from the time of diagnosis and follow up were collected from 110 patients with pSS (107 women, three men) diagnosed in 1977-1992 in central Finland. The standardised incidence ratio for cancers was determined as the ratio of the observed number of cases to the expected number based on regional population rates. Eighty one of the 93 patients still alive were interviewed, and clinical and laboratory examinations performed in 1994-1997.
RESULTS—The mean (SD) erythrocyte sedimentation rate (33 (22) v 45 (28) mm/1st h), serum IgG (18.8 (7.4) v 22.5 (8.5) g/l), and serum IgM (1.6 (1.1) v 2.0 (1.2) g/l) at the control visit were significantly (p<0.0001) lower than those at baseline. A similar change was observed in a subgroup of patients never treated with glucocorticosteroids or disease modifying antirheumatic drugs. Three non-Hodgkin's lymphomas were diagnosed (standardised incidence ratio 13; 95% confidence interval 2.7 to 38). In a logistic regression model, the patients with pSS with subsequent lymphoma were found to have higher baseline levels of serum β2 microglobulin than the others (odds ratio 1.9; 95% confidence interval 1.1 to 3.4).
CONCLUSION—The results suggest that mean concentrations of serum IgG and IgM in patients with pSS decline with time, possibly reflecting diminishing inflammatory activity. As in previous studies, the incidence of non-Hodgkin's lymphomas in this cohort of patients with pSS was significantly higher than in the reference population.

 PMID:11302868

  12. The new immunology.

    PubMed

    Siminovitch, K A

    1992-03-01

    Among the biomedical sciences, immunology stands out as a discipline in which knowledge emanating from fundamental research has rapidly been transferred to the clinical paradigm, with consequent improvement in human health. Virtually all medical subspecialties have benefitted from diagnostic reagents and technologies provided by basic immunology. In terms of numbers of lives saved, immunologic-based therapeutic strategies, most notably vaccination, rank among the most effective measures ever achieved by medical intervention. Yet, despite immunology's profound impact on medicine and the longstanding recognition of many of the general principles and cellular components involved in immunity, until relatively recently, the operational workings of the immune system eluded precise definition. The abstract nature of the immune system rendered the field intangible or, at the very least, confusing, to the nonimmunologic medical community. However, in recent years, this situation has changed radically, as cell cloning, hybridoma, and recombinant DNA technologies have provided the means to delineate the precise immunologic cellular structures and interactions. The purpose of this review is to highlight a few of the most significant advances in immunology during the past decade, and to show how they have made possible the translation of abstract concepts of classical immunology into tangible, structural information. Striking gains in the understanding of antigen recognition, one of the most fundamental aspects of immunity, are described as an illustrative case. PMID:1640405

  13. Precision medicine in patients with allergic diseases: Airway diseases and atopic dermatitis-PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology.

    PubMed

    Muraro, Antonella; Lemanske, Robert F; Hellings, Peter W; Akdis, Cezmi A; Bieber, Thomas; Casale, Thomas B; Jutel, Marek; Ong, Peck Y; Poulsen, Lars K; Schmid-Grendelmeier, Peter; Simon, Hans-Uwe; Seys, Sven F; Agache, Ioana

    2016-05-01

    In this consensus document we summarize the current knowledge on major asthma, rhinitis, and atopic dermatitis endotypes under the auspices of the PRACTALL collaboration platform. PRACTALL is an initiative of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology aiming to harmonize the European and American approaches to best allergy practice and science. Precision medicine is of broad relevance for the management of asthma, rhinitis, and atopic dermatitis in the context of a better selection of treatment responders, risk prediction, and design of disease-modifying strategies. Progress has been made in profiling the type 2 immune response-driven asthma. The endotype driven approach for non-type 2 immune response asthma, rhinitis, and atopic dermatitis is lagging behind. Validation and qualification of biomarkers are needed to facilitate their translation into pathway-specific diagnostic tests. Wide consensus between academia, governmental regulators, and industry for further development and application of precision medicine in management of allergic diseases is of utmost importance. Improved knowledge of disease pathogenesis together with defining validated and qualified biomarkers are key approaches to precision medicine. PMID:27155030

  14. Cancer Immunology Miniatures: Immune activation and a 9-year ongoing complete remission following CD40 antibody therapy and metastasectomy in a patient with metastatic melanoma

    PubMed Central

    Bajor, David L.; Xu, Xiaowei; Torigian, Drew A.; Mick, Rosemarie; Garcia, Laura R.; Richman, Lee P.; Desmarais, Cindy; Nathanson, Katherine L.; Schuchter, Lynn M.; Kalos, Michael; Vonderheide, Robert H.

    2014-01-01

    Direct immune activation via agonistic monoclonal antibodies (mAb) is a potentially complementary approach to therapeutic blockade of inhibitory immune receptors in cancer. Here, we provide genetic analysis of the immunological consequences associated with the use of an agonistic CD40 mAb in a patient with metastatic melanoma who responded, underwent a single metastasectomy, and then achieved a complete remission ongoing for more than 9 years after starting therapy. Tumor microenvironment after immunotherapy was associated with pro-inflammatory modulations and emergence of a de novo T-cell repertoire as detected by next-generation sequencing of T-cell receptors (TCR) in the tumor and blood. The de-novo T-cell repertoire identified in the post-treatment metastasectomy sample was also present – and in some cases expanded – in the circulation years after completion of therapy. Comprehensive study of this “exceptional responder” highlights the emerging potential of direct immune agonists in the next wave of cancer immunotherapies and a potential role for TCR deep sequencing in cancer immune assessment. PMID:25252722

  15. Immunological and virological studies of cultured labial biopsy cells from patients with Sjögren's syndrome

    PubMed Central

    Cremer, Natalie E.; Daniels, T. E.; Oshiro, L. S.; Marcus, F.; Claypool, R.; Sylvester, R. A.; Talal, N.

    1974-01-01

    Labial salivary gland tissues from twenty-five patients were cultured in vitro for virus studies and for use as target cells in cellular and antibody-mediated cytotoxicity assays. Fourteen patients had definite Sjögren's Syndrome (SS), four had possible SS and seven did not have SS. No evidence for the presence of a virus in the cultured cells or after chemical treatment of the cultured cells was obtained. Tubuloreticular structures were present in three of the original biopsies but were not seen in the corresponding cultured cells, although in two of these cell lines rare bundles of intranuclear microfibrils occurred. The significance of these structures is unknown. Autologous serum and autologous lymphocytes were not cytotoxic for the cultured cells. ImagesFig. 1Fig. 2 PMID:4468195

  16. The immunological synapse

    PubMed Central

    Dustin, Michael L.

    2015-01-01

    The molecular interactions underlying regulation of the immune response take place in a nano-scale gap between T cells and antigen presenting cells, termed the immunological synapse. If these interactions are regulated appropriately, the host is defended against a wide range of pathogens and deranged host cells. If these interactions are dis-regulated, the host is susceptible to pathogens or tumor escape at one extreme and autoimmunity at the other. Treatments targeting the synapse have helped to establish immunotherapy as a mainstream element in cancer treatment. This Masters primer will cover the basics of the immunological synapse and some of the applications to tumor immunology. PMID:25367977

  17. Ocular diseases: immunological and molecular mechanisms

    PubMed Central

    Song, Jing; Huang, Yi-Fei; Zhang, Wen-Jing; Chen, Xiao-Fei; Guo, Yu-Mian

    2016-01-01

    Many factors, such as environmental, microbial and endogenous stress, antigen localization, can trigger the immunological events that affect the ending of the diverse spectrum of ocular disorders. Significant advances in understanding of immunological and molecular mechanisms have been researched to improve the diagnosis and therapy for patients with ocular inflammatory diseases. Some kinds of ocular diseases are inadequately responsive to current medications; therefore, immunotherapy may be a potential choice as an alternative or adjunctive treatment, even in the prophylactic setting. This article first provides an overview of the immunological and molecular mechanisms concerning several typical and common ocular diseases; second, the functions of immunological roles in some of systemic autoimmunity will be discussed; third, we will provide a summary of the mechanisms that dictate immune cell trafficking to ocular local microenvironment in response to inflammation. PMID:27275439

  18. Gamma irradiation reduces the immunological toxicity of doxorubicin, anticancer drug

    NASA Astrophysics Data System (ADS)

    Kim, Jae-Hun; Sung, Nak-Yun; Raghavendran, H. Balaji; Yoon, Yohan; Song, Beom-Seok; Choi, Jong-il; Yoo, Young-Choon; Byun, Myung-Woo; Hwang, Young-Jeong; Lee, Ju-Woon

    2009-07-01

    Doxorubicin (DOX) is a widely used anticancer agent, but exhibits some immunological toxicity to patients during chemotherapy. The present study was conducted to evaluate the effect of gamma irradiation on the immunological response and the inhibition activity on in vivo tumor mass of DOX. The results showed that DOX irradiated at 10 and 20 kGy reduce the inhibition of mouse peritoneal macrophage proliferation and induce the release of cytokines (TNF-α and IL-6) when compared with non-irradiated DOX. The cytotoxicity against human breast (MCF-7), murine colon adenocarcinoma (Colon 26) and human monocytic (THP-1) tumor cell were not significantly different between non-irradiated and irradiated DOX ( P<0.05). In vivo study on the tumor mass inhibition, gamma-irradiated DOX showed a considerable inhibition of tumor mass and this effect was statistically non-significant as compared with non-irradiated DOX. In conclusion, gamma irradiation could be regarded as a potential method for reducing the immunological toxicity of DOX. Further researches is needed to reveal the formation and activity of radiolysis products by gamma irradiation.

  19. The Clinical Impact of Continuing to Prescribe Antiretroviral Therapy in Patients with Advanced AIDS Who Manifest No Virologic or Immunologic Benefit

    PubMed Central

    Wohl, David A.; Kendall, Michelle A.; Feinberg, Judith; Alston-Smith, Beverly; Owens, Susan; Chafey, Suzette; Marco, Michael; Maxwell, Sharon; Benson, Constance; Keiser, Philip; van der Horst, Charles; Jacobson, Mark A.

    2013-01-01

    Introduction Despite the efficacy and tolerability of modern antiretroviral therapy (ART), many patients with advanced AIDS prescribed these regimens do not achieve viral suppression or immune reconstitution as a result of poor adherence, drug resistance, or both. The clinical outcomes of continued ART prescription for such patients have not been well characterized. Methods We examined the causes and predictors of all-cause mortality, AIDS-defining conditions, and serious non-AIDS-defining events among a cohort of participants in a clinical trial of pre-emptive therapy for CMV disease. We focused on participants who, despite ART had failed to achieve virologic suppression and substantive immune reconstitution. Results 233 ART-receiving participants entered with a median baseline CD4+ T cell count of 30/mm3 and plasma HIV RNA of 5 log10 copies/mL. During a median 96 weeks of follow-up, 24.0% died (a mortality rate of 10.7/100 patient-years); 27.5% reported a new AIDS-defining condition, and 22.3% a new serious non-AIDS event. Of the deaths, 42.8% were due to an AIDS-defining condition, 44.6% were due to a non-AIDS-defining condition, and 12.5% were of unknown etiology. Decreased risk of mortality was associated with baseline CD4+ T cell count ≥25/mm3 and lower baseline HIV RNA. Conclusions Among patients with advanced AIDS prescribed modern ART who achieve neither virologic suppression nor immune reconstitution, crude mortality percentages appear to be lower than reported in cohorts of patients studied a decade earlier. Also, in contrast to the era before modern ART became available, nearly half of the deaths in our modern-era study were caused by serious non-AIDS-defining events. Even among the most advanced AIDS patients who were not obtaining apparent immunologic and virologic benefit from ART, continued prescription of these medications appears to alter the natural history of AIDS—improving survival and shifting the causes of death from AIDS- to non

  20. Psychosocial characteristics and immunological functions in patients with postinfectious chronic fatigue syndrome and noninfectious chronic fatigue syndrome.

    PubMed

    Masuda, Akinori; Munemoto, Takao; Yamanaka, Takao; Takei, Michiko; Tei, Chuwa

    2002-10-01

    Differences between patients with postinfectious chronic fatigue syndrome (CFS, n = 16) and noninfectious CFS (n = 20) were clarified. The noninfectious CFS group had problems in family and developmental history, and had chronic stresses. Members of the postinfectious CFS group were social extroverts while those in the noninfectious CFS group was neurotic and introspective. Natural killer cell activity was suppressed in both groups. These findings suggest that the postinfectious CFS group and the noninfectious CFS group differed in their pathogenesis until the onset of CFS. The latter group should be considered as a variant of psychiatric disorder and treated accordingly. PMID:12442562

  1. Immunologic manifestations of autophagy

    PubMed Central

    Deretic, Vojo; Kimura, Tomonori; Timmins, Graham; Moseley, Pope; Chauhan, Santosh; Mandell, Michael

    2015-01-01

    The broad immunologic roles of autophagy span innate and adaptive immunity and are often manifested in inflammatory diseases. The immune effects of autophagy partially overlap with its roles in metabolism and cytoplasmic quality control but typically expand further afield to encompass unique immunologic adaptations. One of the best-appreciated manifestations of autophagy is protection against microbial invasion, but this is by no means limited to direct elimination of intracellular pathogens and includes a stratified array of nearly all principal immunologic processes. This Review summarizes the broad immunologic roles of autophagy. Furthermore, it uses the autophagic control of Mycobacterium tuberculosis as a paradigm to illustrate the breadth and complexity of the immune effects of autophagy. PMID:25654553

  2. [Comparative estimation of medicinal and complex therapy influence on immunological indexes in the patients with acne disease].

    PubMed

    Davatdarova, M; Kazimov, A

    2008-10-01

    The aim of this work is to study the indexes of immune status and level of endogenous intoxication in patients with acne disease, which have got medicinal and complex treatment with using ozone-oxygen mixture (OOM). After complex course of treatment positive changes have happened in regulatory systems - in indexes of cellular and humoral immunity. The treatment with using OOM enabled earlier normalization of absolute and percentage content of T-lymphocytes, removed immunodeficiency of suppressor and helper population of T-lymphocytes, decreased circulating immune complexes, amount of B-lymphocytes. The latter was accompanied by normalization or increase of the level of the separate classes of immunoglobulines. Using OOM resulted in normalization of nonspecific immunity indexes, its bactericide activity. Under the influence of complex treatment of acne disease, statistically important increase of active neutrophiles amount have been observed in comparison with data before treatment and decrease of spontaneous and stimulated indexes of nitroblue-tetrozolit test. PMID:18997261

  3. [Immunology of pregnancy].

    PubMed

    Barañao, Rosa Inés

    2011-06-01

    One of the phenomena that offers more questions in Immunology is: Why the embryo, behaving like a semialogenic graft, is not rejected by the mother? It is known that the mother produces an active immunological response against the fetus and, nevertheless, in normal conditions, the immunological rejection does not take place. In the present work of revision, some mechanisms are described by means of which the specific immunological tolerance of the mother is generated towards the embryo. All these mechanisms are interdependent and altogether they constitute a safety network to avoid the fetal rejection. Here the effects of female sex hormones on the immunological system, the change of the profile of cytokines, the generation of immunomodulating proteins and blocking antibodies, the effect of the expression of the HLA-G and the paper of some cells, like Regulatory T lymphocytes, dendritic and Natural Killer cells, are detailed. Also other routes by which the embryo defends itself of the maternal immunological attack are described, like the induction of apoptosis in the endometrium and leukocytes, the tryptophan and iron metabolisms, the inhibition of the complement system and the expression of annexins. PMID:21866790

  4. Anorexia, serum zinc, and immunologic response in small cell lung cancer patients receiving chemotherapy and prophylactic cranial radiotherapy.

    PubMed

    Lindsey, A M; Piper, B F

    1986-01-01

    Anorexia is a major clinical problem for patients with certain types of cancer. The specific mechanisms that result in this spontaneous decline in food intake remain unknown. In noncancer populations, zinc has been shown to play a role in maintaining normal appetite, taste acuity, and immunocompetence. One purpose of this prospective, longitudinal study of cachexia in ten males with small cell lung carcinoma was to determine if anorexia (caloric intake), perceived taste changes, zinc intake, and impaired cellular immunity were associated with serum zinc concentrations. The average daily caloric intake declined 490 kcal from time of diagnosis to seven months after diagnosis (mean caloric intake = 72% of RDA). Daily zinc intake ranged from 6.5 to 25.4 mg over the seven months. During this period, the mean serum zinc concentrations, although low (71 micrograms/dl), remained within the normal range. The average weight declined from 81.7 to 74.1 kg. There was no identifiable pattern of perceived taste changes; most of the perceived changes were recorded during the period coinciding with prophylactic cranial radiation. At the initial testing, four of nine subjects were anergic to a battery of skin test antigens (mumps, candida, tuberculin purified protein derivative). The only subject who remained responsive to two antigens throughout the study remained alive at 12 months. Caloric intake was inadequate to maintain weight. While zinc intake was low, low normal serum zinc concentrations were maintained; thus in this sample, serum zinc does not appear to be the anorexigenic factor. PMID:3022247

  5. Evaluation of PIMATM CD4 System for Decentralization of Immunological Monitoring of HIV-Infected Patients in Senegal

    PubMed Central

    Faye, Babacar; Mbow, Moustapha; Camara, Makhtar; Cissé, Cathy; Diouf, Salimata Guèye; Ndao, Babacar; Djibo, Audrey; Sylla Niang, Maguette Dème; Ndiaye, Tandakha; Grillo, Michael P.; Dièye, Alioune

    2016-01-01

    Background HIV infection is a concern in the army troupes because of the risk behaviour of the military population. In order to allow regular access to CD4+ T cell enumeration of military personnel as well as their dependents and civilians living with HIV, the Senegalese Army AIDS program is implementing PIMATM Alere technology in urban and semi-urban military medical centres. Validation such device is therefore required prior their wide implementation. The purpose of this study was to compare CD4+ T cell count measurements between the PIMATM Alere to the BD FACSCountTM. Methodology We selected a total of 200 subjects including 50 patients with CD4+ T-cells below 200/mm3, 50 between 200 and 350/mm3, 50 between 351 and 500/mm3, and 50 above 500/mm3. CD4+ T-cell count was performed on venous blood using the BD FASCountTM as reference method and the PIMATM Point of Care technology. The mean biases and limits of agreement between the PIMATM Alere and BD FACSCountTM were assessed with the Bland-Altman analysis, the linear regression performed using the Passing-Bablok regression analysis, and the percent similarity calculated using the Scott method. Results Our data have shown a mean difference of 22.3 cells/mm3 [95%CI:9.1–35.5] between the BD FACSCountTM and PIMATM Alere CD4 measurements. However, the mean differences of the two methods was not significantly different to zero when CD4+ T-cell count was below 350/mm3 (P = 0.76). The Passing-Bablok regression in categorized CD4 counts has also showed concordance correlation coefficient of 0.89 for CD4+ T cell counts below 350/mm3 whilst it was 0.5 when CD4 was above 350/mm3. Conclusion Overall, our data have shown that for low CD4 counts, the results from the PIMATM Alere provided accurate CD4+ T cell counts with a good agreement compared to the FACSCountTM. PMID:27166955

  6. [The immunology of tuberculosis].

    PubMed

    Tokunaga, T

    1989-02-01

    An introductory overview on the present state and future prospect of the immunology of tuberculosis is presented with the following six chapters. 1. Contribution of tuberculosis immunologists to the modern immunology. When one reminds Koch's phenomenon, Freund's adjuvant, and the findings or new ideas of, for instance, cell-mediated transfer of tuberculin allergy, test of MIF which was first described as "lymphokines", effector macrophages activated with immune lymphocytes against mycobacterial infection, MHC-restriction for presenting tuberculin-antigen from macrophages to T cells, everyone may agree with saying that the tuberculosis immunology contributed greatly to the opening and development of modern immunology. 2. Central dogma of tuberculosis immunology. Tuberculosis immunology possesses a central dogma : infection of tubercle bacilli----phagocytosis----antigen presentation----expansion of specific T cell clone----production of lymphokines----macrophage activation----killing of the bacilli. Recent knowledges from modern immunology have clarified many things in or around this immunological process. However, there remain many important questions. In the following chapters and subtitles, what have been clarified and what are still unsolved will be described. 3. Induction of tuberculosis immunity. (1) Mechanisms of phagocytosis with macrophages, and natural resistance. (2) Antigen presentation and sensitized T cells. 4. Expression of tuberculosis immunity. (1) Lymphokines. (2) Activation of macrophages. (3) Immune suppression. 5. Special characters of tubercle bacilli in relation to the host response. Biochemistry of cellular components of tubercle bacilli and their biological activities have been reported by many investigators already in this journal. Therefore, the following items only are discussed here. (1) Mycobacterial proteins produced by gene-technology. (2) Adjuvant active derivatives of MDP. (3) DNA from BCG and its biological activities. (4

  7. Immunology and cartilage regeneration.

    PubMed

    Smith, Benjamin; Sigal, Ian R; Grande, Daniel A

    2015-12-01

    The intrinsic regenerative capacity of avascular cartilage is limited. Cartilage injuries result in chronic, non-healing lesions requiring surgical management. Frequently, these surgical techniques make use of allogeneic cells and tissues. This review discusses the immune status of these materials. Cartilage allografts, often used in orthopedic and plastic surgeries, have rarely provoked a significant immune response. In whole cartilage transplants, the dense matrix produced by chondrocytes inhibits lymphocyte migration, preventing immune detection rendering them "antigen sequestered." It is unclear whether isolated chondrocytes are immune-privileged; chondrocytes express immune inhibitory B7 molecules, indicating that they have some ability to modulate immune reactions. Allogeneic cartilage grafts often involve a bony portion often retaining immunogenic cells and proteins-to facilitate good surgical attachment and concern that this may enhance inflammation and immune rejection. However, studies of failed cartilage grafts have not found immune responses to be a contributing factor. Meniscus allografts, which also retain a bony portion, raise similar concerns as cartilage allografts. Despite this, the plugs improved patient outcomes, indicating that the immunological effects were not clinically significant. Finally, allogeneic mesenchymal stromal cells (MSCs) also are being investigated as a treatment for cartilage damage. MSCs have been demonstrated to have unique immunomodulatory properties including their ability to reduce immune cell infiltration and to modulate inflammation. In summary, the immunogenic properties of cartilage vary with the type of allograft used: Cartilage allografts demonstrate active immune-suppressive mechanisms as evidenced by lack of allograft rejection, while MSC allografts appear to be safe for transplantation. PMID:26481914

  8. Outdoor Exhibits

    NASA Technical Reports Server (NTRS)

    1996-01-01

    The National Data Buoy Center (NDBC) at the John C. Stennis Space Center has exhibits located in front of the Visitors Center. These boat-shaped buoys are moored in areas of the ocean that experience hostile environmental conditions. The instruments installed gather information and relay it to the National Weather Service by satellite. Nomad buoys are 20 feet long and weigh 13,900 pounds. They provide information on wind speed and direction, humidity levels, air and sea surface temperature and air pressure. U.S. Coast Guard ships transport buoys to their mooring sites.

  9. Immunological memory is associative

    SciTech Connect

    Smith, D.J.; Forrest, S.; Perelson, A.S.

    1996-12-31

    The purpose of this paper is to show that immunological memory is an associative and robust memory that belongs to the class of sparse distributed memories. This class of memories derives its associative and robust nature by sparsely sampling the input space and distributing the data among many independent agents. Other members of this class include a model of the cerebellar cortex and Sparse Distributed Memory (SDM). First we present a simplified account of the immune response and immunological memory. Next we present SDM, and then we show the correlations between immunological memory and SDM. Finally, we show how associative recall in the immune response can be both beneficial and detrimental to the fitness of an individual.

  10. Medical immunology: two-way bridge connecting bench and bedside.

    PubMed

    Rijkers, Ger T; Damoiseaux, Jan G M C; Hooijkaas, Herbert

    2014-12-01

    Medical immunology in The Netherlands is a laboratory specialism dealing with immunological analyses as well as pre- and post-analytical consultation to clinicians (clinical immunologists and other specialists) involved in patients with immune mediated diseases. The scope of medical immunology includes immunodeficiencies, autoimmune diseases, allergy, transfusion and transplantation immunology, and lymphoproliferative disorders plus the monitoring of these patients. The training, professional criteria, quality control of procedures and laboratories is well organized. As examples of the bridge function of medical immunology between laboratory (bench) and patient (bedside) the contribution of medical immunologists to diagnosis and treatment of primary immunodeficiency diseases (in particular: humoral immunodeficiencies) as well as autoantibodies (anti-citrullinated proteins in rheumatoid arthritis) are given. PMID:25455599

  11. Do patients with lactose intolerance exhibit more frequent comorbidities than patients without lactose intolerance? An analysis of routine data from German medical practices

    PubMed Central

    Schiffner, Rebecca; Kostev, Karel; Gothe, Holger

    2016-01-01

    Background The increase in food intolerances poses a burgeoning problem in our society. Food intolerances not only lead to physical impairment of the individual patient but also result in a high socio-economic burden due to factors such as the treatment required as well as absenteeism. The present study aimed to explore whether lactose intolerant (LI) patients exhibit more frequent comorbidities than non-LI patients. Methods The study was conducted on a case-control basis and the results were determined using routine data analysis. Routine data from the IMS Disease Analyzer database were used for this purpose. A total of 6,758 data records were processed and analyzed. Results There were significant correlations between LI and the incidence of osteoporosis, changes in mental status, and the presence of additional food intolerances. Comparing 3,379 LI vs. 3,379 non-LI patients, 34.5% vs. 17.7% (P<0.0001) suffered from abdominal pain; 30.6% vs. 17.2% (P<0.0001) from gastrointestinal infections; and 20.9% vs. 16.0% (P=0.0053) from depression. Adjusted odds ratios (OR) were the highest for fructose intolerance (n=229 LI vs. n=7 non-LI; OR 31.06; P<0.0001), irritable bowel syndrome (n=247 LI vs. n=44 non-LI; OR 5.23; P<0.0001), and bloating (n=351 LI vs. n=68 non-LI; OR 4.94; P<0.0001). Conclusion The study confirms that LI should not be regarded as an isolated illness but considered a possible trigger for further diseases. Additional research is necessary to assert more precise statements. PMID:27065730

  12. Immunologically Mediated Dementias

    PubMed Central

    Rosenbloom, Michael H.; Smith, Sallie; Akdal, Gulden; Geschwind, Michael D.

    2009-01-01

    Although most dementias are due to neurodegenerative or vascular disease, it is important to diagnose immunologically mediated dementias quickly because they can be both rapidly progressive and readily treatable. They usually affect function of limbic and cortical structures, but subcortical involvement can also occur. Because of the variety of symptoms and the rapid course, these dementias present a particular challenge to the clinician and may require evaluation and intervention in the inpatient setting. Diagnostic workup typically reveals evidence of an autoimmune process and, in some cases, cancer. In contrast to the neurodegenerative processes, many of the immunologically mediated dementias respond to immunomodulatory therapy. PMID:19664365

  13. Immunologic lung disease

    SciTech Connect

    Harman, E.M.

    1985-07-01

    The term immunologic lung disease comprises a broad spectrum of disease. The authors have covered a few entities in which recent studies have been particularly helpful in elucidating pathophysiology though not in uncovering the inciting cause. Common to all of these entities is the problem of finding appropriate methods of defining disease activity and response to treatment. As exemplified by the improved outlook for Goodpasture's syndrome with elucidation of its underlying immunopathology, it is likely that better understanding of the immunologic basis of sarcoid and interstitial disease may be helpful in planning more effective treatment strategies. 44 references.

  14. Patients with pancreatic adenocarcinoma exhibit elevated levels of myeloid-derived suppressor cells upon progression of disease

    PubMed Central

    Markowitz, Joseph; Brooks, Taylor R.; Duggan, Megan C.; Paul, Bonnie K.; Pan, Xueliang; Wei, Lai; Abrams, Zachary; Luedke, Eric; Lesinski, Gregory B.; Mundy-Bosse, Bethany; Bekaii-Saab, Tanios

    2015-01-01

    Elevated levels of myeloid-derived suppressor cells (MDSCs) induced by tumor-derived factors are associated with inhibition of immune responses in patients with gastrointestinal malignancies. We hypothesized that pro-MDSC cytokines and levels of MDSC in the peripheral blood would be elevated in pancreatic adenocarcinoma patients with progressive disease. Peripheral blood mononuclear cells (PBMCs) were isolated from 16 pancreatic cancer patients undergoing chemotherapy and phenotyped for MDSC using a five antigen panel (CD33, HLA-DR, CD11b, CD14, CD15). Patients with stable disease had significantly lower MDSC levels in the peripheral blood than those with progressive disease (1.41 ± 1.12 vs. 5.14 ± 4.58 %, p = 0.013, Wilcoxon test). A cutoff of 2.5 % MDSC identified patients with progressive disease. Patients with ECOG performance status ≥2 had a weaker association with increased levels of MDSC. Plasma was obtained from 15 chemonaive patients, 13 patients undergoing chemotherapy and 9 normal donors. Increases in the levels of pro-MDSC cytokines were observed for pancreatic cancer patients versus controls, and the pro-MDSC cytokine IL-6 was increased in those patients undergoing chemotherapy. This study suggests that MDSC in peripheral blood may be a predictive biomarker of chemotherapy failure in pancreatic cancer patients. PMID:25305035

  15. Immunological Treatments for Autism.

    ERIC Educational Resources Information Center

    Gupta, Sudhir

    2000-01-01

    This article discusses research findings that indicate immunological abnormalities in children with autism, including the dysregulation of the immune system, and concludes that there are sufficient data to suggest a role of the immune system in the pathogenesis of autism. Various biological therapies are analyzed, including intravenous…

  16. Basic and clinical immunology

    NASA Technical Reports Server (NTRS)

    Chinen, Javier; Shearer, William T.

    2003-01-01

    Progress in immunology continues to grow exponentially every year. New applications of this knowledge are being developed for a broad range of clinical conditions. Conversely, the study of primary and secondary immunodeficiencies is helping to elucidate the intricate mechanisms of the immune system. We have selected a few of the most significant contributions to the fields of basic and clinical immunology published between October 2001 and October 2002. Our choice of topics in basic immunology included the description of T-bet as a determinant factor for T(H)1 differentiation, the role of the activation-induced cytosine deaminase gene in B-cell development, the characterization of CD4(+)CD25(+) regulatory T cells, and the use of dynamic imaging to study MHC class II transport and T-cell and dendritic cell membrane interactions. Articles related to clinical immunology that were selected for review include the description of immunodeficiency caused by caspase 8 deficiency; a case series report on X-linked agammaglobulinemia; the mechanism of action, efficacy, and complications of intravenous immunoglobulin; mechanisms of autoimmunity diseases; and advances in HIV pathogenesis and vaccine development. We also reviewed two articles that explore the possible alterations of the immune system caused by spaceflights, a new field with increasing importance as human space expeditions become a reality in the 21st century.

  17. Immunology & Human Health.

    ERIC Educational Resources Information Center

    Dawson, Jeffrey R.; And Others

    This monograph was designed for the high school biology curriculum. The first section reviews the major areas of importance in immunology. Section three contains six instructional activities for the high school classroom and the second section contains teacher's materials for those activities. The activities address for students some of the major…

  18. Embracing rejection: Immunologic trends in brain metastasis.

    PubMed

    Farber, S Harrison; Tsvankin, Vadim; Narloch, Jessica L; Kim, Grace J; Salama, April K S; Vlahovic, Gordana; Blackwell, Kimberly L; Kirkpatrick, John P; Fecci, Peter E

    2016-07-01

    Brain metastases represent the most common type of brain tumor. These tumors offer a dismal prognosis and significantly impact quality of life for patients. Their capacity for central nervous system (CNS) invasion is dependent upon induced disruptions to the blood-brain barrier (BBB), alterations to the brain microenvironment, and mechanisms for escaping CNS immunosurveillance. In the emerging era of immunotherapy, understanding how metastases are influenced by the immunologic peculiarities of the CNS will be crucial to forging therapeutic advances. In this review, the immunology of brain metastasis is explored. PMID:27622023

  19. Proteus syndrome: evaluation of the immunological profile.

    PubMed

    Lougaris, Vassilios; Salpietro, Vincenzo; Cutrupi, Maricia; Baronio, Manuela; Moratto, Daniele; Pizzino, M R; Mankad, Kshitij; Briuglia, Silvana; Salpietro, Carmelo; Plebani, Alessandro

    2016-01-01

    Proteus syndrome (PS) is an extremely rare and complex disease characterized by malformations and overgrowth of different tissues. Prognosis of affected patients may be complicated by premature death, mostly due to pulmonary embolism and respiratory failure. To date, immunological data in Proteus syndrome are scarse.We report on the novel immunologic findings of a 15 years old girl affected with PS. Detailed T and B cell evaluation revealed maturational alterations for both subsets and functional hyperactivation for the latter. Such findings have not been reported previously in PS and may be the spy of more complex immune abnormalities in this syndrome. PMID:26758562

  20. [Some immunologic aspects in postoperative peritonitis].

    PubMed

    Perfil'ev, D F

    1998-01-01

    Examination of blood serum and cellular elements of 45 patients with postoperative diffuse purulent peritonitis shows that in the majority of examined persons before and in the first days after the operation immunodepression exists. The dynamics of immunologic disturbances (antibody titers, phagocytosis, immunoglobulines, T- and B-lymphocytes) are sufficiently informative and as a rule, correlate with clinical course of peritonitis. Adequate reaction of the organism to infection resulted in a favourable outcome. Low values of immunologic indices in postoperative period necessitate the use of stimulant therapy in combined treatment of this complication. PMID:9916429

  1. HIV Molecular Immunology 2014

    SciTech Connect

    Yusim, Karina; Korber, Bette Tina Marie; Barouch, Dan; Koup, Richard; de Boer, Rob; Moore, John P.; Brander, Christian; Haynes, Barton F.; Walker, Bruce D.

    2015-02-03

    HIV Molecular Immunology is a companion volume to HIV Sequence Compendium. This publication, the 2014 edition, is the PDF version of the web-based HIV Immunology Database (http://www.hiv.lanl.gov/content/immunology/). The web interface for this relational database has many search options, as well as interactive tools to help immunologists design reagents and interpret their results. In the HIV Immunology Database, HIV-specific B-cell and T-cell responses are summarized and annotated. Immunological responses are divided into three parts, CTL, T helper, and antibody. Within these parts, defined epitopes are organized by protein and binding sites within each protein, moving from left to right through the coding regions spanning the HIV genome. We include human responses to natural HIV infections, as well as vaccine studies in a range of animal models and human trials. Responses that are not specifically defined, such as responses to whole proteins or monoclonal antibody responses to discontinuous epitopes, are summarized at the end of each protein section. Studies describing general HIV responses to the virus, but not to any specific protein, are included at the end of each part. The annotation includes information such as crossreactivity, escape mutations, antibody sequence, TCR usage, functional domains that overlap with an epitope, immune response associations with rates of progression and therapy, and how specific epitopes were experimentally defined. Basic information such as HLA specificities for T-cell epitopes, isotypes of monoclonal antibodies, and epitope sequences are included whenever possible. All studies that we can find that incorporate the use of a specific monoclonal antibody are included in the entry for that antibody. A single T-cell epitope can have multiple entries, generally one entry per study. Finally, maps of all defined linear epitopes relative to the HXB2 reference proteins are provided.

  2. Han Chinese patients with dopa-responsive dystonia exhibit a low frequency of exonic deletion in the GCH1 gene.

    PubMed

    Shi, W T; Cai, C Y; Li, M S; Ling, C; Li, W D

    2015-01-01

    We identified three novel mutations of the GTP cyclohydrolase 1 (GCH1) gene in patients with familial dopa-responsive dystonia (DRD), but were unable to identify meaningful sporadic mutations in patients with no obvious family DRD background. To investigate whether GCH1 regional deletions account for the etiology of DRD, we screened for heterozygous exonic deletions in DRD families and in patients with sporadic DRD. Multiple ligation-dependent probe amplification analysis and quantitative real-time polymerase chain reaction amplification was performed in all members of our DRD cohort and in controls to detect exonic deletions in GCH1, tyrosine hydroxylase, and the epsilon-sarcoglycan-encoding (SGCE) genes. Using these techniques, we detected a GCH1 exon 1 heterozygous deletion in 1 of 10 patients with sporadic DRD. Therefore, we concluded that exonic deletion in the GCH1 gene only accounted for the etiology in a small percentage of patients with sporadic DRD in our Han Chinese cohort. PMID:26400349

  3. Olmsted syndrome: exploration of the immunological phenotype

    PubMed Central

    2013-01-01

    Background Olmsted syndrome is a rare congenital skin disorder presenting with periorifical hyperkeratotic lesions and mutilating palmoplantar keratoderma, which is often associated with infections of the keratotic area. A recent study identified de novo mutations causing constitutive activation of TRPV3 as a cause of the keratotic manifestations of Olmsted syndrome. Methods Genetic, clinical and immunological profiling was performed on a case study patient with the clinical diagnosis of Olmsted syndrome. Results The patient was found to harbour a previously undescribed 1718G-C transversion in TRPV3, causing a G573A point mutation. In depth clinical and immunological analysis found multiple indicators of immune dysregulation, including frequent dermal infections, inflammatory infiltrate in the affected skin, hyper IgE production and elevated follicular T cells and eosinophils in the peripheral blood. Conclusions These results provide the first comprehensive assessment of the immunological features of Olmsted syndrome. The systemic phenotype of hyper IgE and persistent eosinophilia suggest a primary or secondary role of immunological processes in the pathogenesis of Olmsted syndrome, and have important clinical consequences with regard to the treatment of Olmsted syndrome patients. PMID:23692804

  4. Hematology and immunology studies

    NASA Technical Reports Server (NTRS)

    Kimzey, S. L.; Fischer, C. L.; Johnson, P. C.; Ritzmann, S. E.; Mengel, C. E.

    1975-01-01

    The hematology and immunology program conducted in support of the Apollo missions was designed to acquire specific laboratory data relative to the assessment of the health status of the astronauts prior to their commitment to space flight. A second objective was to detect and identify any alterations in the normal functions of the immunohematologic systems which could be attributed to space flight exposure, and to evaluate the significance of these changes relative to man's continuing participation in space flight missions. Specific changes observed during the Gemini Program formed the basis for the major portion of the hematology-immunology test schedule. Additional measurements were included when their contribution to the overall interpretation of the flight data base became apparent.

  5. Immunology in Pittsburgh.

    PubMed

    Finn, Olivera J; Salter, Russell D

    2006-01-01

    The University of Pittsburgh School of Medicine has a long tradition of excellence in immunology research and training. Faculty, students, and postdoctoral fellows walk through hallways that are pictorial reminders of the days when Dr. Jonas Salk worked here to develop the polio vaccine, or when Dr. Niels Jerne chaired the Microbiology Department and worked on perfecting the Jerne Plaque Assay for antibody-producing cells. Colleagues and postdoctoral fellows of Professor Salk are still on the faculty of the University of Pittsburgh Medical School as are graduate students of Professor Jerne. A modern research building, the 17 story high Biomedical Science Tower, is a vivid reminder of the day when Dr. Thomas Starzl arrived in Pittsburgh and started building the most prominent solid-organ-transplant program in the world. The immunology research that developed around the problem of graft rejection and tolerance induction trained numerous outstanding students and fellows. Almost 20 yr ago, the University of Pittsburgh founded the University of Pittsburgh Cancer Institute (UPCI) with the renowned immunologist Dr. Ronald Herberman at its helm. This started a number of new research initiatives in cancer immunology and immunotherapy. A large number of outstanding young investigators, as well as several well-established tumor immunologists, were recruited to Pittsburgh at that time. PMID:17337760

  6. Cosmos-1989 immunology studies

    NASA Technical Reports Server (NTRS)

    Sonnenfeld, Gerald

    1991-01-01

    Evidence from both human and rodent studies has indicated that alterations in immunological parameters occur after space flight. The number of flight experiments has been small, and the full breadth of immunological alterations occurring after space flight remains to be established. Among the major effects on immune responses after space flight that have been reported are: alterations in lymphocyte blastogenesis and natural killer cell activity, alterations in production of cytokines, changes in leukocyte sub-population distribution, and decreases in the ability in the ability of bone marrow cells to respond to colony stimulating factors. Changes have been reported in immunological parameters of both humans and rodents. The significance of these alterations in relation to resistance to infection remains to be established. The current study involved a determination of the effects of flight on Cosmos mission 2044 on leukocyte subset distribution and the sensitivity of bone marrow cells to colony stimulating factor-GM. A parallel study with antiorthostatic suspension was also carried out. The study involved repetition and expansion of studies carried out on Cosmos 1887.

  7. Cross-trial analysis of immunologic and clinical data resulting from phase I and II trials of MVA-5T4 (TroVax) in colorectal, renal, and prostate cancer patients.

    PubMed

    Harrop, Richard; Shingler, William; Kelleher, Michelle; de Belin, Jackie; Treasure, Peter

    2010-01-01

    The attenuated vaccinia virus MVA has been engineered to deliver the tumor antigen 5T4 (MVA-5T4; TroVax), a surface glycoprotein expressed by most solid tumors. MVA-5T4 has been tested in 2 phase I/II and 7 phase II clinical trials in colorectal (4 trials), renal (4 trials), and prostate (1 trial) advanced cancer patients. Data have been collated from all 9 studies and used to investigate the magnitude and kinetics of 5T4-specific antibody responses after vaccination and to identify potential associations between the immune response and patient survival. Antibody responses specific for the 5T4 tumor antigen and the MVA viral vector were quantified in plasma samples taken from cancer patients before and after the treatment with MVA-5T4. Immunologic and survival data were analyzed using proportional hazards regression adjusting for age and gender. Both survival and immunologic response data were available for 189 patients with colorectal (n=73), renal (n=89), and prostate (n=27) cancer. Before the treatment with MVA-5T4, 5T4-specific antibody levels were significantly elevated in cancer patients compared with healthy donors. After MVA-5T4 administration, 5T4-specific antibody responses increased significantly and peaked after 3 to 4 vaccinations. Exploratory analyses showed significant associations between 5T4 antibody responses and overall survival across all 9 trials and in patients with colorectal cancer. The 5T4-specific antibodies were present at higher levels in cancer patients compared with healthy donors and increased significantly after treatment with MVA-5T4. Although the studies were uncontrolled, there were encouraging signs of activity which is associated with the magnitude of 5T4-specific antibody responses. PMID:20948436

  8. PTCH1+/− Dermal Fibroblasts Isolated from Healthy Skin of Gorlin Syndrome Patients Exhibit Features of Carcinoma Associated Fibroblasts

    PubMed Central

    Robert, Thomas; Ripoche, Hugues; Brellier, Florence; Chevallier-Lagente, Odile; Avril, Marie-Françoise; Magnaldo, Thierry

    2009-01-01

    Gorlin's or nevoid basal cell carcinoma syndrome (NBCCS) causes predisposition to basal cell carcinoma (BCC), the commonest cancer in adult human. Mutations in the tumor suppressor gene PTCH1 are responsible for this autosomal dominant syndrome. In NBCCS patients, as in the general population, ultraviolet exposure is a major risk factor for BCC development. However these patients also develop BCCs in sun-protected areas of the skin, suggesting the existence of other mechanisms for BCC predisposition in NBCCS patients. As increasing evidence supports the idea that the stroma influences carcinoma development, we hypothesized that NBCCS fibroblasts could facilitate BCC occurence of the patients. WT (n = 3) and NBCCS fibroblasts bearing either nonsense (n = 3) or missense (n = 3) PTCH1 mutations were cultured in dermal equivalents made of a collagen matrix and their transcriptomes were compared by whole genome microarray analyses. Strikingly, NBCCS fibroblasts over-expressed mRNAs encoding pro-tumoral factors such as Matrix Metalloproteinases 1 and 3 and tenascin C. They also over-expressed mRNA of pro-proliferative diffusible factors such as fibroblast growth factor 7 and the stromal cell-derived factor 1 alpha, known for its expression in carcinoma associated fibroblasts. These data indicate that the PTCH1+/− genotype of healthy NBCCS fibroblasts results in phenotypic traits highly reminiscent of those of BCC associated fibroblasts, a clue to the yet mysterious proneness to non photo-exposed BCCs in NBCCS patients. PMID:19287498

  9. Patients with obstructive sleep apnea exhibit genioglossus dysfunction that is normalized after treatment with continuous positive airway pressure.

    PubMed

    Carrera, M; Barbé, F; Sauleda, J; Tomás, M; Gómez, C; Agustí, A G

    1999-06-01

    Obstructive sleep apnea syndrome (OSAS) is characterized by repetitive episodes of pharyngeal closure during sleep. The pathogenesis of OSAS is unclear. We hypothesized that the genioglossus (GG), the most important pharyngeal dilator muscle, would be abnormal in patients with OSAS. Further, because treatment with continuous positive airway pressure (CPAP) is very effective clinically in these patients, we investigated the effects of CPAP upon the structure and function of the GG. We studied 16 patients with OSAS (nine of them at diagnosis and seven after having been under treatment with CPAP for at least 1 yr) and 11 control subjects in whom OSAS was excluded clinically. A biopsy of the GG was obtained in each subject, mounted in a tissue bath, and stimulated through platinum electrodes. The following measurements were obtained: maximal twitch tension, contraction time, half-relaxation time, the force-frequency relationship, and the response to a fatiguing protocol. The percentage of type I ("slow twitch") and type II ("fast twitch") fibers was also quantified. Patients with OSAS showed a greater GG fatigability than did control subjects (ANOVA, p < 0.001). Interestingly, this abnormality was entirely corrected by CPAP. Likewise, the percentage of type II fibers was significantly higher in patients with OSAS (59 +/- 4%) than in control subjects (39 +/- 4%, p < 0.001) and, again, these structural changes were corrected by CPAP (40 +/- 3%, p < 0.001). These results show that the function and structure of the GG is abnormal in patients with OSAS. Because these abnormalities are corrected by CPAP, we suggest that they are likely a consequence, not a cause, of the disease. PMID:10351945

  10. Immunologic hemorrhagic pneumonia caused by isocyanates.

    PubMed

    Patterson, R; Nugent, K M; Harris, K E; Eberle, M E

    1990-01-01

    The occurrence of hemoptysis, dyspnea, and bilateral pulmonary opacities progressed to respiratory failure in a 34-yr-old man. Recovery occurred with corticosteroid therapy. In the absence of evidence for an infectious etiology, the possibility of immunologic trimellitic anhydride (TMA) hemorrhagic pneumonitis was considered when the lung biopsy excluded Goodpasture's and other diseases and because the patient was a spray painter. Serologic evaluation for antibodies against TMA was requested. Because the immunologic studies for TMA were negative, and because the patient was a spray painter, immunoassays for three isocyanates conjugated to human serum albumin (HSA) were carried out although there was no specific history of isocyanate exposure at that time. High levels of IgG and IgE antibodies were detected against hexamethylene diisocyanate (HDI)-HSA and toluene diisocyanate (TDI)-HSA. Further investigation documented exposure to spray paint that contained HDI and another isocyanate. The paint was sprayed on warm metal, and subsequently the worker developed an acute illness. Further plant studies were not possible. We propose that the pathogenesis of this case of hemorrhagic pneumonitis is immunologic because of uncontrolled exposure to HDI and TDI, is analogous to the immunologic hemorrhagic pneumonia caused by TMA, and should be considered as a possible cause of a similar acute lung disease after isocyanate exposure. PMID:2153356

  11. Platelets in Patients with Premature Coronary Artery Disease Exhibit Upregulation of miRNA340* and miRNA624*

    PubMed Central

    Sondermeijer, Brigitte M.; Bakker, Annemieke; Halliani, Amalia; de Ronde, Maurice W. J.; Marquart, Arnoud A.; Tijsen, Anke J.; Mulders, Ties A.; Kok, Maayke G. M.; Battjes, Suzanne; Maiwald, Steffi; Sivapalaratnam, Suthesh; Trip, Mieke D.; Moerland, Perry D.; Meijers, Joost C. M.; Creemers, Esther E.; Pinto-Sietsma, Sara-Joan

    2011-01-01

    Background Coronary artery disease (CAD) is the leading cause of human morbidity and mortality worldwide, underscoring the need to improve diagnostic strategies. Platelets play a major role, not only in the process of acute thrombosis during plaque rupture, but also in the formation of atherosclerosis itself. MicroRNAs are endogenous small non-coding RNAs that control gene expression and are expressed in a tissue and disease-specific manner. Therefore they have been proposed to be useful biomarkers. It remains unknown whether differences in miRNA expression levels in platelets can be found between patients with premature CAD and healthy controls. Methodology/Principal Findings In this case-control study we measured relative expression levels of platelet miRNAs using microarrays from 12 patients with premature CAD and 12 age- and sex-matched healthy controls. Six platelet microRNAs were significantly upregulated (miR340*, miR451, miR454*, miR545:9.1. miR615-5p and miR624*) and one miRNA (miR1280) was significantly downregulated in patients with CAD as compared to healthy controls. To validate these results, we measured the expression levels of these candidate miRNAs by qRT-PCR in platelets of individuals from two independent cohorts; validation cohort I consisted of 40 patients with premature CAD and 40 healthy controls and validation cohort II consisted of 27 patients with artery disease and 40 healthy relatives. MiR340* and miR624* were confirmed to be upregulated in patients with CAD as compared to healthy controls in both validation cohorts. Conclusion/Significance Two miRNAs in platelets are significantly upregulated in patients with CAD as compared to healthy controls. Whether the two identified miRNAs can be used as biomarkers and whether they are cause or consequence of the disease remains to be elucidated in a larger prospective study. PMID:22022480

  12. Immunological response and overall survival in a subset of advanced renal cell carcinoma patients from a randomized phase 2/3 study of naptumomab estafenatox plus IFN-α versus IFN-α

    PubMed Central

    Elkord, Eyad; Burt, Deborah J.; Sundstedt, Anette; Nordle, Örjan; Hedlund, Gunnar; Hawkins, Robert E.

    2015-01-01

    Naptumomab estafenatox/ABR-217620/ANYARA (Nap) has been evaluated in clinical phase 1 and 2/3 studies. RCC patients in the phase 2/3 trial were randomized 1:1 in an open label study to receive Nap+IFN-α or IFN-α. In this study, we analyzed the UK patients for their immunological response in relation to prolonged overall survival (OS). We found that Nap-specific T cells were reduced after 3 treatment days in patients' peripheral blood. Levels of both Nap-specific CD4+ and CD8+ T cells were significantly higher 8 days after the first treatment. Patients with such pattern of reduction and expansion of Nap-binding T cells also showed increased levels of IL-2 and IFN-γ in plasma 3 hours after the first Nap treatment. In addition, Nap caused an increase of IL-6, IL-10 and TNF-α. The patients in the UK subset showed a tendency of OS benefit after Nap treatment. Most Nap treated patients with long OS had low baseline IL-6 and normal levels of anti-SEA/E-120 antibodies. Furthermore, patients with pronounced Nap induced IL-2 and T cell expansion had long OS. In conclusion, patients with low baseline IL-6 and normal anti-SEA/E-120 may respond well to Nap by T cell activation and expansion paving the way for anti-tumour effects. PMID:25669986

  13. Cerebrospinal fluid of newly diagnosed amyotrophic lateral sclerosis patients exhibits abnormal levels of selenium species including elevated selenite

    PubMed Central

    Vinceti, Marco; Solovyev, Nikolay; Mandrioli, Jessica; Crespi, Catherine M.; Bonvicini, Francesca; Arcolin, Elisa; Georgoulopoulou, Eleni; Michalke, Bernhard

    2013-01-01

    Exposure to selenium, and particularly to its inorganic forms, has been hypothesized as a risk factor for amyotrophic lateral sclerosis (ALS), a fast progressing motor neuron disease with poorly understood etiology. However, no information is known about levels of inorganic and some organic selenium species in the central nervous system of ALS patients, and recent observations suggest that peripheral biomarkers of exposure are unable to predict these levels for several Se species including the inorganic forms. Using a hospital-referred cases-control series and advanced selenium speciation methods, we compared the chemical species of selenium in cerebrospinal fluid from thirty-eight ALS patients to those of thirty-eight reference neurological patients matched on age and gender. We found that higher concentrations of inorganic selenium in the form of selenite and of human serum albumin-bound selenium were associated with increased ALS risk (relative risks 3.9 (95% confidence interval 1.2–11.0) and 1.7 (1.0–2.9) for 0.1µg/l increase). Conversely, lower concentrations of selenoprotein P-bound selenium were associated with increased risk (relative risk 0.2 for 1µg/l increase, 95% confidence interval 0.04–0.8). The associations were stronger among cases age 50 years or older, who are postulated to have lower rates of genetic disease origin. These results suggest that excess selenite and human serum albumin bound-selenium and low levels of selenoprotein P-bound selenium in the central nervous system, which may be related, may play a role in ALS etiology. PMID:23732511

  14. Sterility: an immunologic disorder?

    PubMed

    Rümke, P; Hekman, A

    1977-09-01

    Immunologic aspects of infertility are discussed. The autoantigenic and isoantigenic nature of spermatozoa is reviewed. Sperm antibodies may form in males by extravasation of spermatozoa following vasectomy and as a result of testicular lesions. Although little is known about the formation of isoantibidies to spermatozoa in females, they may arise as a result of epithelial lesions of the genital tract. Clinical findings of sperm agglutination and immobilizing antibodies in males and sperm antibodies in females in association with infertility are discussed along with some therapeutic approaches. A rare condition, allergy to seminal plasma, is noted. PMID:891061

  15. Mathematics in modern immunology

    PubMed Central

    Castro, Mario; Lythe, Grant; Molina-París, Carmen; Ribeiro, Ruy M.

    2016-01-01

    Mathematical and statistical methods enable multidisciplinary approaches that catalyse discovery. Together with experimental methods, they identify key hypotheses, define measurable observables and reconcile disparate results. We collect a representative sample of studies in T-cell biology that illustrate the benefits of modelling–experimental collaborations and that have proven valuable or even groundbreaking. We conclude that it is possible to find excellent examples of synergy between mathematical modelling and experiment in immunology, which have brought significant insight that would not be available without these collaborations, but that much remains to be discovered. PMID:27051512

  16. Hematology and immunology studies

    NASA Technical Reports Server (NTRS)

    Kimzey, S. L.

    1977-01-01

    A coordinated series of experiments were conducted to evaluate immunologic and hemotologic system responses of Skylab crewmen to prolonged space flights. A reduced PHA responsiveness was observed on recovery, together with a reduced number of T-cells, with both values returning to normal 3 to 5 days postflight. Subnormal red cell count, hemoglobin concentration, and hematocrit values also returned gradually to preflight limits. Most pronounced changes were found in the shape of red blood cells during extended space missions with a rapid reversal of these changes upon reentry into a normal gravitational environment.

  17. Monocyte Subpopulations from Pre-Eclamptic Patients Are Abnormally Skewed and Exhibit Exaggerated Responses to Toll-Like Receptor Ligands

    PubMed Central

    Al-ofi, Ebtisam

    2012-01-01

    The leading cause of pregnancy-associated mortality and morbidity is pre-eclampsia (PE). Although information regarding the etiology of this disease is scant, its pathophysiology is characterized by abnormal placentation, endothelial dysfunction as well as an exaggerated inflammatory response. Clinical evidence also indicates that the abundance of many immune cells at the feto-maternal interface and in the circulation of PE patients is abnormal, when compared with normal pregnant (NP) controls. In addition, the phenotype and function of some of these cells is altered. To further characterize the systemic effects of PE on circulating cells, we analyzed monocytic subpopulations in NP and PE patients by flow cytometry. We found that non-classical CD14lowCD16+ monocytes are significantly increased in women with PE and they display irregular expression of several chemokine receptors and antigen presentation molecules. The most striking phenotypic difference among the cell surface molecules was the marked upregulation of TLR4 expression, where both CD14highCD16+ and CD14lowCD16+ monocytes demonstrated higher levels than their NP counterparts. Stimulation of PE monocytes with TLR ligands resulted in profound secretion of various cytokines in comparison with NP controls. These data suggest that PE monocytes are hyper-responsive to TLR ligands and this may contribute to exacerbation of the disease. PMID:22848746

  18. Monocyte subpopulations from pre-eclamptic patients are abnormally skewed and exhibit exaggerated responses to Toll-like receptor ligands.

    PubMed

    Al-ofi, Ebtisam; Coffelt, Seth B; Anumba, Dilly O

    2012-01-01

    The leading cause of pregnancy-associated mortality and morbidity is pre-eclampsia (PE). Although information regarding the etiology of this disease is scant, its pathophysiology is characterized by abnormal placentation, endothelial dysfunction as well as an exaggerated inflammatory response. Clinical evidence also indicates that the abundance of many immune cells at the feto-maternal interface and in the circulation of PE patients is abnormal, when compared with normal pregnant (NP) controls. In addition, the phenotype and function of some of these cells is altered. To further characterize the systemic effects of PE on circulating cells, we analyzed monocytic subpopulations in NP and PE patients by flow cytometry. We found that non-classical CD14(low)CD16(+) monocytes are significantly increased in women with PE and they display irregular expression of several chemokine receptors and antigen presentation molecules. The most striking phenotypic difference among the cell surface molecules was the marked upregulation of TLR4 expression, where both CD14(high)CD16(+) and CD14(low)CD16(+) monocytes demonstrated higher levels than their NP counterparts. Stimulation of PE monocytes with TLR ligands resulted in profound secretion of various cytokines in comparison with NP controls. These data suggest that PE monocytes are hyper-responsive to TLR ligands and this may contribute to exacerbation of the disease. PMID:22848746

  19. Clinical and Immunological Studies of 332 Japanese Patients Tentatively Diagnosed as Anti-BP180-type Mucous Membrane Pemphigoid: A Novel BP180 C-terminal Domain Enzyme-linked Immunosorbent Assay.

    PubMed

    Yasukochi, Atsushi; Teye, Kwesi; Ishii, Norito; Hashimoto, Takashi

    2016-08-23

    Diagnosis of anti-BP180-type mucous membrane pemphigoid (BP180-MMP) is frustrated by the difficulty of detecting BP180 reactivity. A total of 721 patients with suspected MMP, selected from a cohort of 4,698 patients with autoimmune bullous disease (AIBD), were included in this study. Of these, 332 patients were tentatively diagnosed as BP180-MMP if they showed IgG/IgA reactivity with the epidermal side of 1M NaCl-split-skin and/or positive reactivity with BP180 in at least one of our antigen detection methods. Clinically, a predominance of female patients was found. Oral mucosal and cutaneous lesions were found in 85.5% and 41.0% of patients, respectively, and frequent treatments were systemic steroids, tetracycline/minocycline and diaminodiphenyl sulfone. Various immunological methods, including a newly developed BP180 C-terminal domain enzyme-linked immunosorbent assay (ELISA), revealed frequent reactivity with BP180 C-terminal and NC16a domains. Some patients reacted with BP180 and other antigens, indicating that BP180-MMP tends to concur with other AIBDs. This large study of patients with suspected BP180-MMP indicates the difficulty of diagnosis of BP180-MMP and the diagnostic usefulness of BP180 C-terminal domain ELISA. PMID:26984589

  20. OCRL-mutated fibroblasts from patients with Dent-2 disease exhibit INPP5B-independent phenotypic variability relatively to Lowe syndrome cells.

    PubMed

    Montjean, Rodrick; Aoidi, Rifdat; Desbois, Pierrette; Rucci, Julien; Trichet, Michaël; Salomon, Rémi; Rendu, John; Fauré, Julien; Lunardi, Joël; Gacon, Gérard; Billuart, Pierre; Dorseuil, Olivier

    2015-02-15

    OCRL mutations are associated with both Lowe syndrome and Dent-2 disease, two rare X-linked conditions. Lowe syndrome is an oculo-cerebro-renal disorder, whereas Dent-2 patients mainly present renal proximal tubulopathy. Loss of OCRL-1, a phosphoinositide-5-phosphatase, leads in Lowe patients' fibroblasts to phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) accumulation, with defects in F-actin network, α-actinin distribution and ciliogenesis, whereas fibroblasts of Dent-2 patients are still uncharacterized. To search for mechanisms linked to clinical variability observed between these two OCRL mutation-associated pathologies, we compared dermal fibroblasts from independent patients, four affected by Dent-2 disease and six with Lowe syndrome. For the first time, we describe that Dent-2 fibroblasts with OCRL loss-of-function (LOF) mutations exhibit decrease in actin stress fibers, appearance of punctate α-actinin signals and alteration in primary cilia formation. Interestingly, we quantified these phenotypes as clearly intermediate between Lowe and control fibroblasts, thus suggesting that levels of these defects correlate with clinical variations observed between patients with OCRL mutations. In addition, we show that Lowe and Dent-2 fibroblasts display similar PI(4,5)P2 accumulation levels. Finally, we analyzed INPP5B, a paralogous gene already reported to exhibit functional redundancy with OCRL, and report neither differences in its expression at RNA or protein levels, nor specific allelic variations between fibroblasts of patients. Altogether, we describe here differential phenotypes between fibroblasts from Lowe and Dent-2 patients, both associated with OCRL LOF mutations, we exclude direct roles of PI(4,5)P2 and INPP5B in this phenotypic variability and we underline potential key alterations leading to ocular and neurological clinical features in Lowe syndrome. PMID:25305077

  1. Studies on immunological paralysis

    PubMed Central

    Miranda, J. J.

    1972-01-01

    The immunological response to native levan (a fructose homopolymer with molecular weight 2×107) has been studied in (DBA/1×CBA-T6T6)F1 mice by passive haemagglutination and plaque-forming cell (PFC) assays. It resembles type-specific pneumococcal polysaccharide (SSS) in eliciting a prolonged humoral antibody response over a wide dose range (0.0001–100 μg) and in inducing longlasting `high zone' tolerance with a single injection (1 mg or more). Other similarities include an exclusively IgM response, independence of synergy with thymus-derived lymphocytes and absence of immunological memory. On the other hand, parallelism between serum haemagglutinin and PFC levels following all doses of antigen implies that higher immunizing doses of levan, unlike SSS, do not engage in peripheral neutralization of antibody. It was concluded from studying the fate of 14C-labelled levan that this was attributable to more rapid elimination from the circulation and subsequent slow metabolism of this polysaccharide. Levan also differs from SSS in inducing tolerance directly, without a detectable prior immune phase. PMID:4405409

  2. Principles of immunology.

    PubMed

    Lentz, Ashley K; Feezor, Robert J

    2003-12-01

    The immune system, composed of innate and acquired immunity, allows an organism to fight off foreign pathogens. Healthy immunity accomplishes four essential principles: (1) ability to detect and fight off infection; (2) ability to recognize a host's own cells as "self," thereby protecting them from attack; (3) a memory from previous foreign infections; and (4) ability to limit the response after the pathogen has been removed. In an unaltered state, the intricate network of immunologic organs and cells creates an environment for proper host defense. Without adequate execution of immunologic mechanisms, a host is rendered defenseless against pathogens. Conversely, an unchecked immune response can be self-destructive. As a result of either of these untoward sequelae, immune dysfunction can elicit disease states in the host. The goal of this review is to elucidate the characteristics of a healthy immune system, focusing on the principles of immunity and the cells that participate in host protection. We also briefly discuss the clinical ramifications of immune dysfunction. PMID:16215081

  3. Immunology of leishmaniasis*

    PubMed Central

    Heyneman, D.

    1971-01-01

    Knowledge of the immunological basis of the leishmaniases and of the host's response is fragmentary and largely pragmatic. This paper reviews certain conceptual and clinical aspects of the immunology of these diseases. Consideration is given to man's natural resistance and his ability to acquire resistance from natural infections and from vaccination. The age-distribution of infection in different populations is discussed in relation to the effects that interaction between the parasite and its intermediate host may have on its infection characteristics and virulence. Studies in the USSR of differences in virulence among 30 human strains and 39 rodent strains are reported. The rodent strains showed a broader range of virulence than did the human isolates. Serological tests for determining species relationships among the leishmaniae are generally nonspecific, but work concerned with the development of the antiserum—culture test is reviewed. Species identification and the recognition of new forms, perhaps with different infection characteristics, is, nevertheless, of the utmost importance in the prevention and treatment of the disease. The review concludes with a discussion of functional immunity and hypotheses of the immune process in leishmaniasis. PMID:5316252

  4. Immunological results in myocardial diseases.

    PubMed Central

    Bolte, H. D.; Schultheiss, P.

    1978-01-01

    Immunological studies have shown new diagnostically important changes in alcoholic and viral myocarditis, as well as in congestive cardiomyopathy. Increased heart size correlated with the degree of congestive heart failure, as well as with negative immunofluorescence and an increased IgA concentration in the serum. These findings may serve as a diagnostic aid in patients with myocardial disease due to alcohol abuse. Viral heart disease is characterized by a variety of symptoms and nuclear antibodies (IgM) can be of help in the differential diagnosis. Heart muscle tissue of patients with congestive cardiomyopathy preferentially binds IgG and IgA. In addition to the other changes these findings are of diagnostic importance. It seems likely that results similar to those obtained for humoral antibodies in congestive cardiomyopathy will apply in the correlation of the haemodynamic status of the patients. The pathophysiological implication of these findings is not clear at present, but the evolution of congestive cardiomyopathy appears to be associated with binding of immunoglobulin to the myocardium, as well as with humoral antiheart antibodies. PMID:704517

  5. Leukemia patient-derived lymphoblastoid cell lines exhibit increased induction of leukemia-associated transcripts following high-dose irradiation.

    PubMed

    Spencer, A; Granter, N

    1999-09-01

    Improvement in diagnostic cytogenetic techniques has led to the recognition of an increasing number of leukemia-associated chromosomal translocations and inversions. These genetic lesions frequently are associated with the disruption of putative transcription factors and the production of hybrid transcripts that are implicated in leukemogenesis. Epidemiologic evidence suggests that some, but not all, individuals with a history of gamma-irradiation exposure are at increased risk of developing chronic myeloid leukemia (CML). CML is characterized by the Philadelphia chromosome and transcription of the resulting hybrid BCR-ABL gene. Utilizing the leukemia-associated BCR-ABL p210 transcript as a marker, we sought differences in the induction of illegitimate genetic recombination following high-dose gamma-irradiation of karyotypically normal lymphoblastoid cell lines (LCL) derived from individuals with and without a history of myeloid leukemias. Six LCL [4 leukemia patient derived [2 acute myeloid leukemia and 2 CML] and 2 from normal individuals were analyzed with reverse transcriptase polymerase chain reaction for BCR-ABL under stringent conditions following exposure to 0, 50, or 100 Gy of LET gamma-irradiation delivered via a Varian linear accelerator at 4 MV. Transcripts identical to disease-associated b2a2 and b3a2 transcripts were detected both spontaneously (background illegitimate genetic recombination) and following gamma-irradiation. Background BCR-ABL positivity was demonstrable in 4 of the 6 LCL, with no significant difference in detection between leukemic- and nonleukemic-derived LCL. Overall, increasing gamma-irradiation dose resulted in an increased frequency of BCR-ABL transcript detection (0 Gy vs 50 Gy vs 100 Gy,p = 0.0023, Chi-square test). Within the leukemic- but not the nonleukemic-derived LCL there was significantly greater BCR-ABL positivity after gamma-irradiation compared to unirradiated equivalents. Furthermore, the BCR-ABL positivity of both

  6. Intensification of antiretroviral therapy through addition of enfuvirtide in naive HIV-1-infected patients with severe immunosuppression does not improve immunological response: results of a randomized multicenter trial (ANRS 130 Apollo).

    PubMed

    Joly, Véronique; Fagard, Catherine; Grondin, Carine; Descamps, Diane; Yazdanpanah, Yazdan; Charpentier, Charlotte; Colin de Verdiere, Nathalie; Tabuteau, Sophie; Raffi, François; Cabie, André; Chene, Geneviève; Yeni, Patrick

    2013-02-01

    We studied whether addition of enfuvirtide (ENF) to a background combination antiretroviral therapy (cART) would improve the CD4 cell count response at week 24 in naive patients with advanced HIV disease. ANRS 130 Apollo is a randomized study, conducted in naive HIV-1-infected patients, either asymptomatic with CD4 counts of <100/mm(3) or stage B/C disease with CD4 counts of <200/mm(3). Patients received tenofovir-emtricitabine with lopinavir-ritonavir (LPV/r) or efavirenz and were randomized to receive ENF for 24 weeks (ENF arm) or not (control arm). The primary endpoint was the proportion of patients with CD4 counts of ≥ 200/mm(3) at week 24. A total of 195 patients were randomized: 73% had stage C disease, 78% were male, the mean age was 44 years, the median CD4 count was 30/mm(3), and the median HIV-1 RNA load was 5.4 log(10) copies/ml. Eighty-one percent of patients received LPV/r. One patient was lost to follow-up, and eight discontinued the study (four in each arm). The proportions of patients with CD4 counts of ≥ 200/mm(3) at week 24 were 34% and 38% in the ENF and control arms, respectively (P = 0.53). The proportions of patients with HIV-1 RNA loads of <50 copies/ml were 74% and 58% at week 24 in the ENF and control arms, respectively (P < 0.02), and the proportion reached 79% in both arms at week 48. Twenty (20%) and 12 patients (13%) in the ENF and control arms, respectively, experienced at least one AIDS event during follow-up (P = 0.17). Although inducing a more rapid virological response, addition of ENF to a standard cART does not improve the immunological outcome in naive HIV-infected patients with severe immunosuppression. PMID:23165467

  7. Intensification of Antiretroviral Therapy through Addition of Enfuvirtide in Naive HIV-1-Infected Patients with Severe Immunosuppression Does Not Improve Immunological Response: Results of a Randomized Multicenter Trial (ANRS 130 Apollo)

    PubMed Central

    Fagard, Catherine; Grondin, Carine; Descamps, Diane; Yazdanpanah, Yazdan; Charpentier, Charlotte; Colin de Verdiere, Nathalie; Tabuteau, Sophie; Raffi, François; Cabie, André; Chene, Geneviève; Yeni, Patrick

    2013-01-01

    We studied whether addition of enfuvirtide (ENF) to a background combination antiretroviral therapy (cART) would improve the CD4 cell count response at week 24 in naive patients with advanced HIV disease. ANRS 130 Apollo is a randomized study, conducted in naive HIV-1-infected patients, either asymptomatic with CD4 counts of <100/mm3 or stage B/C disease with CD4 counts of <200/mm3. Patients received tenofovir-emtricitabine with lopinavir-ritonavir (LPV/r) or efavirenz and were randomized to receive ENF for 24 weeks (ENF arm) or not (control arm). The primary endpoint was the proportion of patients with CD4 counts of ≥200/mm3 at week 24. A total of 195 patients were randomized: 73% had stage C disease, 78% were male, the mean age was 44 years, the median CD4 count was 30/mm3, and the median HIV-1 RNA load was 5.4 log10 copies/ml. Eighty-one percent of patients received LPV/r. One patient was lost to follow-up, and eight discontinued the study (four in each arm). The proportions of patients with CD4 counts of ≥200/mm3 at week 24 were 34% and 38% in the ENF and control arms, respectively (P = 0.53). The proportions of patients with HIV-1 RNA loads of <50 copies/ml were 74% and 58% at week 24 in the ENF and control arms, respectively (P < 0.02), and the proportion reached 79% in both arms at week 48. Twenty (20%) and 12 patients (13%) in the ENF and control arms, respectively, experienced at least one AIDS event during follow-up (P = 0.17). Although inducing a more rapid virological response, addition of ENF to a standard cART does not improve the immunological outcome in naive HIV-infected patients with severe immunosuppression. PMID:23165467

  8. 21 CFR 866.5220 - Cohn fraction II immunolog-ical test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cohn fraction II immunolog-ical test system. 866.5220 Section 866.5220 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5220 Cohn fraction II immunolog-ical...

  9. The evolution of mathematical immunology.

    PubMed

    Louzoun, Yoram

    2007-04-01

    The types of mathematical models used in immunology and their scope have changed drastically in the past 10 years. Classical models were based on ordinary differential equations (ODEs), difference equations, and cellular automata. These models focused on the 'simple' dynamics obtained between a small number of reagent types (e.g. one type of receptor and one type of antigen or two T-cell populations). With the advent of high-throughput methods, genomic data, and unlimited computing power, immunological modeling shifted toward the informatics side. Many current applications of mathematical models in immunology are now focused around the concepts of high-throughput measurements and system immunology (immunomics), as well as the bioinformatics analysis of molecular immunology. The types of models have shifted from mainly ODEs of simple systems to the extensive use of Monte Carlo simulations. The transition to a more molecular and more computer-based attitude is similar to the one occurring over all the fields of complex systems analysis. An interesting additional aspect in theoretical immunology is the transition from an extreme focus on the adaptive immune system (that was considered more interesting from a theoretical point of view) to a more balanced focus taking into account the innate immune system also. We here review the origin and evolution of mathematical modeling in immunology and the contribution of such models to many important immunological concepts. PMID:17367331

  10. Studies in cryo-immunology

    PubMed Central

    Yantorno, C.; Soanes, W. A.; Gonder, M. J.; Shulman, S.

    1967-01-01

    Experimental cryosurgery has been found to result in the formation of circulating antibodies, directed against antigenic material of the tissue frozen. These antibodies were detected by passive haemagglutination and immunodiffusion. The tissue that was subjected to destructive freezing by means of this surgical procedure was the coagulating gland and seminal vesicle of rabbit. A probe carrying liquid nitrogen and a thermocouple assembly for measuring temperature changes was utilized. Control rabbits were manipulated in the same way but with no freezing. A large number of rabbits subjected to tissue freezing exhibited the development of a rapid antibody response, achieving a maximum titre in 7–10 days, followed by a decline. This antibody response has been compared to that seen following isoimmunization by injection. As an additional comparison, several rabbits were autoimmunized by injection of homogenate from their own accessory tissue; these rabbits also produced antibodies. It was found that the time sequence in the antibody production was quite similar for auto- and isoimmunization, but was quite distinctive for cryo-stimulation. By several means of evaluation, it was shown that the antibody response to the freezing of tissue was an autoantibody. It was not, however, an antibody against serum γ-globulin. The consequences of the freezing of tissue are thus seen to simulate the effects of incorporating adjuvant. This method of producing autoantibodies and investigating the nature of the response has been termed cryo-immunology. ImagesFIG. 4 PMID:4960713

  11. The Immunological Functions of Saposins

    PubMed Central

    Darmoise, Alexandre; Maschmeyer, Patrick; Winau, Florian

    2014-01-01

    Saposins or sphingolipid activator proteins (SAPs) are small, nonenzymatic glycoproteins that are ubiquitously present in lysosomes. SAPs comprise the five molecules saposins A–D and the GM2 activator protein. Saposins are essential for sphingolipid degradation and membrane digestion. On the one hand, they bind the respective hydrolases required to catabolize sphingolipid molecules; on the other hand, saposins can interact with intralysosomal membrane structures to render lipids accessible to their degrading enzymes. Thus, saposins bridge the physicochemical gap between lipid substrate and hydrophilic hydrolases. Accordingly, defects in saposin function can lead to lysosomal lipid accumulation. In addition to their specific functions in sphingolipid metabolism, saposins have membrane-perturbing properties. At the low pH of lysosomes, saposins get protonated and exhibit a high binding affinity for anionic phospholipids. Based on their universal principle to interact with membrane bilayers, we present the immunological functions of saposins with regard to lipid antigen presentation to CD1-restricted T cells, processing of apoptotic bodies for antigen delivery and cross-priming, as well as their potential antimicrobial impact. PMID:20510729

  12. 7. Immunologic lung disease.

    PubMed

    Greenberger, Paul A

    2008-02-01

    The lung is an extremely complex organ and participates in initial responses to inhaled antigens, infectious agents, and irritants or as a response to exposure through the oral, parenteral, or transdermal routes. There can be constriction of the airways or involvement or even destruction of the lung parenchyma, depending on the condition. This review focuses on selected aspects of the pulmonary innate and adaptive immune responses; the new condition World Trade Center cough, which can cause an asthma-like presentation and resemble reactive airways dysfunction syndrome; and the diagnosis and treatment of various immunologic lung conditions. Innate immune responses occur in the acute respiratory distress syndrome and in transfusion-related acute lung injury. Adaptive immune responses involve specialized mucosal and systemic immune responses, lymphocytes, and antibodies and can result in CD4+ TH1 and TH2 phenotypes, such as TH1 for tuberculosis and TH2 for asthma. PMID:18241689

  13. Immunology of vaccination.

    PubMed

    Beverley, P C L

    2002-01-01

    An ideal vaccine is relatively easy to define, but few real vaccines approach the ideal and no vaccines exist for many organisms, for which a vaccine is the only realistic protective strategy in the foreseeable future. Many difficulties account for the failure to produce these vaccines. All micro-organisms deploy evasion mechanisms that interfere with effective immune responses and, for many organisms, it is not clear which immune responses provide effective protection. However, recent advances in methods for studying immune response to pathogens have provided a better understanding of immune mechanisms, including immunological memory, and led to the realisation that the initiation of immune responses is a key event requiring triggering through 'danger' signals. Based on these findings, the development of novel adjuvants, vectors and vaccine formulations allowing stimulation of optimal and prolonged protective immunity should lead to the introduction of vaccines for previously resistant organisms. PMID:12176847

  14. Hepatocytes as Immunological Agents.

    PubMed

    Crispe, Ian N

    2016-01-01

    Hepatocytes are targeted for infection by a number of major human pathogens, including hepatitis B virus, hepatitis C virus, and malaria. However, hepatocytes are also immunological agents in their own right. In systemic immunity, they are central in the acute-phase response, which floods the circulation with defensive proteins during diverse stresses, including ischemia, physical trauma, and sepsis. Hepatocytes express a variety of innate immune receptors and, when challenged with pathogen- or damage-associated molecular patterns, can deliver cell-autonomous innate immune responses that may result in host defense or in immunopathology. Important human pathogens have evolved mechanisms to subvert these responses. Finally, hepatocytes talk directly to T cells, resulting in a bias toward immune tolerance. PMID:26685314

  15. The Ambiguity in Immunology

    PubMed Central

    Barnaba, Vincenzo; Paroli, Marino; Piconese, Silvia

    2012-01-01

    In the present article, we discuss the various ambiguous aspects of the immune system that render this complex biological network so highly flexible and able to defend the host from different external invaders. This ambiguity stems mainly from the property of the immune system to be both protective and harmful. Immunity cannot be fully protective without producing a certain degree of damage (immunopathology) to the host. The balance between protection and tissue damage is, therefore, critical for the establishment of immune homeostasis and protection. In this review, we will consider as ambiguous, various immunological tactics including: (a) the opposing functions driving immune responses, immune-regulation, and contra-regulation, as well as (b) the phenomenon of chronic immune activation as a result of a continuous cross-presentation of apoptotic T cells by dendritic cells. All these plans participate principally to maintain a state of chronic low-level inflammation during persisting infections, and ultimately to favor the species survival. PMID:22566903

  16. Prevalence of Anti–Adeno-Associated Virus Serotype 8 Neutralizing Antibodies and Arylsulfatase B Cross-Reactive Immunologic Material in Mucopolysaccharidosis VI Patient Candidates for a Gene Therapy Trial

    PubMed Central

    Ferla, Rita; Claudiani, Pamela; Savarese, Marco; Kozarsky, Karen; Parini, Rossella; Scarpa, Maurizio; Donati, Maria Alice; Sorge, Giovanni; Hopwood, John J.; Parenti, Giancarlo; Fecarotta, Simona; Nigro, Vincenzo; Sivri, Hatice Serap; Van Der Ploeg, Ans; Andria, Generoso; Brunetti-Pierri, Nicola

    2015-01-01

    Abstract Recombinant vectors based on adeno-associated virus serotype 8 (AAV8) have been successfully used in the clinic and hold great promise for liver-directed gene therapy. Preexisting immunity against AAV8 or the development of antibodies against the therapeutic transgene product might negatively affect the outcomes of gene therapy. In the prospect of an AAV8-mediated, liver-directed gene therapy clinical trial for mucopolysaccharidosis VI (MPS VI), a lysosomal storage disorder caused by arylsulfatase B (ARSB) deficiency, we investigated in a multiethnic cohort of MPS VI patients the prevalence of neutralizing antibodies (Nab) to AAV8 and the presence of ARSB cross-reactive immunologic material (CRIM), which will either affect the efficacy of gene transfer or the duration of phenotypic correction. Thirty-six MPS VI subjects included in the study harbored 45 (62.5%) missense, 13 (18%) nonsense, 9 (12.5%) frameshift (2 insertions and 7 deletions), and 5 (7%) splicing ARSB mutations. The detection of ARSB protein in 24 patients out of 34 (71%) was predicted by the type of mutations. Preexisting Nab to AAV8 were undetectable in 19/33 (58%) analyzed patients. Twelve out of 31 patients (39%) tested were both negative for Nab to AAV8 and CRIM-positive. In conclusion, this study allows estimating the number of MPS VI patients eligible for a gene therapy trial by intravenous injections of AAV8. PMID:25654180

  17. Monocytes from tuberculosis patients that exhibit cleaved caspase 9 and denaturalized cytochrome c are more susceptible to death mediated by Toll-like receptor 2

    PubMed Central

    Chávez-Galán, Leslie; Sada-Ovalle, Isabel; Baez-Saldaña, Renata; Chávez, Raúl; Lascurain, Ricardo

    2012-01-01

    Experimental models have shown that lipoproteins from Mycobacterium tuberculosis induce apoptosis via Toll-like receptor 2 (TLR2) in the THP-1 cell line and in monocyte-derived macrophages from healthy volunteers. We found an increased percentage of circulating monocytes in patients with tuberculosis (TB) in comparison to healthy controls. Patients with TB showed a higher TLR2 and TLR4 expression density on monocytes, and a higher proportion of TLR2+ monocytes, as well as increased serum tumour necrosis factor-α level. In culture, monocytes from TB patients were more susceptible to death than monocytes from healthy controls. Moreover, death-susceptible monocytes were positive to both TLR2 and TLR4 at the start of culture. Freshly obtained monocytes from TB patients exhibited cleaved caspase 9 and denaturalized cytochrome c. For levels of caspase 8, apoptosis-regulating signal kinase 1, and phospho-p38 mitogen-activated protein kinase there was no difference between samples from TB patients and from healthy controls. The culture filtrate antigen extract from M. tuberculosis H37Rv strain induced the death of monocytes from patient with TB after a 4-hr incubation, which was abrogated by neutralizing antibodies for TLR2 but not TLR4. Similarly, Pam3CSK4, a synthetic agonist triacylated ligand to TLR2, also induced the death of monocytes, although it did not increase levels of cleaved caspase 9. Our findings suggest that monocytes from TB patients are more susceptible to death, probably through mitochondrial damage, and that cell death increases in the presence of mycobacterial antigen by a TLR2-dependent pathway. PMID:22133266

  18. Citizens unite for computational immunology!

    PubMed Central

    Belden, Orrin S.; Baker, Sarah Catherine; Baker, Brian M.

    2016-01-01

    Crowdsourcing by recruiting volunteers who can provide computational time, programming expertise, or puzzle-solving talent has emerged as a powerful tool for biomedical research. Recent projects demonstrate the potential for crowdsourcing in immunology. Tools for developing applications, new funding, and an eager public make crowdsourcing a serious option for creative solutions for computationally-challenging immunological problems. Expanded uses of crowdsourcing in immunology will allow for more efficient large-scale data collection and analysis. It will also involve, inspire, educate, and engage the public in a variety of meaningful ways. The benefits are real – it’s time to jump in! PMID:26139599

  19. Functional assessment of chronic illness therapy—the fatigue scale exhibits stronger associations with clinical parameters in chronic dialysis patients compared to other fatigue-assessing instruments

    PubMed Central

    Chao, Chia-Ter; Huang, Jenq-Wen

    2016-01-01

    Background. Patients with end-stage renal disease (ESRD) have a high symptom burden, among which fatigue is highly prevalent. Many fatigue-assessing instruments exist, but comparisons among instruments in this patient population have yet to be investigated. Methods. ESRD patients under chronic hemodialysis were prospectively enrolled and seven types of fatigue instruments were administered: Brief Fatigue Inventory (BFI), Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F), Fatigue Severity Scale (FSS), Lee Fatigue Scale (LFS), Fatigue Questionnaire (FQ), Fatigue Symptom Inventory (FSI), and Short-Form 36-Vitality (SF36-V). Using these instruments, we investigated the correlation between fatigue severity and clinical/biochemical parameters, including demographic/comorbidity profile, dialysis-related complications, and frailty severity. We used regression analysis with serum albumin and frailty severity as the dependent variables to investigate the independent correlations. Results. A total of 46 ESRD patients were enrolled (average age of 67 ± 11.6 years), and 50% of them had type 2 diabetes mellitus. Results from the seven tested instruments showed high correlation with each other. We found that the fatigue severity by FACIT-F was significantly associated with age (p = 0.03), serum albumin (p = 0.003) and creatinine (p = 0.02) levels, while SF36-V scores were also significantly associated with age (p = 0.02) and serum creatinine levels (p = 0.04). However, the fatigue severity measured by the FSS, FSI, FQ, BFI, and LFS did not exhibit these associations. Moreover, regression analysis showed that only FACIT-F scores were independently associated with serum albumin levels and frailty severity in ESRD patients. Conclusion. Among the seven fatigue-assessing instruments, only the FACIT-F yielded results that demonstrated significant and independent associations with important outcome-related features in ESRD patients. PMID:26998414

  20. Immunology of lymphatic filariasis

    PubMed Central

    Babu, Subash; Nutman, Thomas B.

    2013-01-01

    The immune responses to filarial parasites encompass a complex network of innate and adaptive cells whose interaction with the parasite underlies a spectrum of clinical manifestations. The predominant immunological feature of lymphatic filariasis is an antigen - specific Th2 response and an expansion of IL-10 producing CD4+ T cells that is accompanied by a muted Th1 response. This antigen specific T cell hypo-responsiveness appears to be crucial for the maintenance of the sustained, long-standing infection often with high parasite densities. While the correlates of protective immunity to lymphatic filariasis are still incompletely understood, primarily due to the lack of suitable animal models to study susceptibility, it is clear that T cells and to a certain extent B cells are required for protective immunity. Host immune responses, especially CD4+ T cell responses clearly play a role in mediating pathological manifestations of LF, including lymphedema, hydrocele and elephantiasis. The main underlying defect in the development of clinical pathology appears to be a failure to induce T cell hypo-responsiveness in the face of antigenic stimulation. Finally, another intriguing feature of filarial infections is their propensity to induce bystander effects on a variety of immune responses, including responses to vaccinations, allergens and to other infectious agents. The complexity of the immune response to filarial infection therefore provides an important gateway to understanding the regulation of immune responses to chronic infections, in general. PMID:24134686

  1. Immunology of schistosomiasis*

    PubMed Central

    1974-01-01

    This Memorandum, after summarizing the life cycle of the different species of human schistosome, reviews the present knowledge of the immunology of schistosomiasis. Each stage of the parasite contains antigen that may stimulate an immune response. However, at the moment there are no accepted serological in vitro tests that correlate with protection; this develops only after the host has experienced a living infection, which suggests that the stimulation of immunity is due to some metabolic process involving the release of protective antigen. The adult worm, however, seems to be able to escape the immune mechanism of the host. Specific antigens are also released by the eggs, and the immune response against these antigens seems to cause granuloma formation around the egg itself. The granuloma is the main lesion found in schistosomiasis. Evidence for protective immunity in experimental animals and man is reviewed, together with the possible mechanism by which the adult worm escapes the immune response of the host. A review of methods used for the diagnosis of schistosomiasis and a list of recommendations for further research are also included. PMID:4219757

  2. Mucosal Immunology of HIV Infection

    PubMed Central

    Xu, Huanbin; Wang, Xiaolei; Veazey, Ronald S.

    2013-01-01

    Summary Recent advances in the immunology, pathogenesis, and prevention of human immunodeficiency virus (HIV) infection continue to reveal clues to the mechanisms involved in the progressive immunodeficiency attributed to infection but more importantly have shed light on the correlates of immunity to infection and disease progression. HIV selectively infects, eliminates, and/or dysregulates several key cells of the human immune system, thwarting multiple arms of the host immune response, and inflicting severe damage to mucosal barriers, resulting in tissue infiltration of ‘symbiotic’ intestinal bacteria and viruses that essentially become opportunistic infections promoting systemic immune activation. This leads to activation and recruitment or more target cells for perpetuating HIV infection, resulting in persistent, high level viral replication in lymphoid tissues, rapid evolution of resistant strains, and continued evasion of immune responses. However, vaccine studies and studies of spontaneous controllers are finally providing correlates of immunity from protection and disease progression, including virus-specific CD4+ T-cell responses, binding antibodies, innate immune responses, and generation of antibodies with potent antibody-dependent cell-mediated cytotoxicity activity. Emerging correlates of immunity indicate that prevention of HIV infection may be possible through effective vaccine strategies that protect and stimulate key regulatory cells and immune responses in susceptible hosts. Further, immune therapies specifically directed towards boosting specific aspects of the immune system may eventually lead to a cure for HIV-infected patients. PMID:23772612

  3. Immunological memory to viral infection.

    PubMed

    Slifka, Mark K

    2004-08-01

    Immunological memory is defined by the ability of a host to remember a past encounter with a specific pathogen and to respond to it in an effective manner upon re-exposure. How long immunological memory can be maintained in the absence of re-infection continues to be a subject of great controversy. Recent studies on immunity following smallpox vaccination demonstrate that T-cell memory declines steadily with a half-life of 8-15 years, whereas antiviral antibody responses are maintained for up to 75 years without appreciable decline. By combining recent advances in quantitative immunology with historical accounts of protection against smallpox dating back to the time of Edward Jenner, we are gaining a better understanding of the duration and magnitude of immunological memory and how it relates to protective immunity. PMID:15245737

  4. Actin engine in immunological synapse.

    PubMed

    Piragyte, Indre; Jun, Chang-Duk

    2012-06-01

    T cell activation and function require physical contact with antigen presenting cells at a specialized junctional structure known as the immunological synapse. Once formed, the immunological synapse leads to sustained T cell receptor-mediated signalling and stabilized adhesion. High resolution microscopy indeed had a great impact in understanding the function and dynamic structure of immunological synapse. Trends of recent research are now moving towards understanding the mechanical part of immune system, expanding our knowledge in mechanosensitivity, force generation, and biophysics of cell-cell interaction. Actin cytoskeleton plays inevitable role in adaptive immune system, allowing it to bear dynamic and precise characteristics at the same time. The regulation of mechanical engine seems very complicated and overlapping, but it enables cells to be very sensitive to external signals such as surface rigidity. In this review, we focus on actin regulators and how immune cells regulate dynamic actin rearrangement process to drive the formation of immunological synapse. PMID:22916042

  5. Advances in cancer immunology and cancer immunotherapy.

    PubMed

    Voena, Claudia; Chiarle, Roberto

    2016-02-01

    After decades of setbacks, cancer immunology is living its Golden Age. Recent advances in cancer immunology have provided new therapeutic approaches to treat cancer. The objective clinical response observed in patients treated with antibodies that block the immune checkpoints, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell-death protein 1 (PD-1)/programmed cell-death 1 ligand 1 (PD-L1) pathways, has led to their FDA approval for the treatment of melanoma in 2011 and in 2014, respectively. The anti-PD-1 antibody nivolumab has received the FDA-approval in March 2015 for squamous lung cancer treatment. In addition, antibodies targeting PD-1 or PD-L1 have demonstrated their efficacy and safety in additional tumors, including non-small cell lung carcinoma (NSCLC), renal cell carcinoma (RCC), bladder cancer, and Hodgkin's lymphoma. Almost at the same time, the field of adoptive cell transfer has exploded. The chimeric antigen receptor (CAR) T technology has provided strong evidence of efficacy in the treatment of B cell malignancies, and different T cell based treatments are currently under investigation for different types of tumors. In this review we will discuss the latest advances in cancer immunology and immunotherapy as well as new treatments now under development in the clinic and potential strategies that have shown promising results in preclinical models. PMID:27011048

  6. Resistin and interleukin-6 exhibit racially-disparate expression in breast cancer patients, display molecular association and promote growth and aggressiveness of tumor cells through STAT3 activation.

    PubMed

    Deshmukh, Sachin K; Srivastava, Sanjeev K; Bhardwaj, Arun; Singh, Ajay P; Tyagi, Nikhil; Marimuthu, Saravanakumar; Dyess, Donna L; Dal Zotto, Valeria; Carter, James E; Singh, Seema

    2015-05-10

    African-American (AA) women with breast cancer (BC) are diagnosed with more aggressive disease, have higher risk of recurrence and poorer prognosis as compared to Caucasian American (CA) women. Therefore, it is imperative to define the factors associated with such disparities to reduce the unequal burden of cancer. Emerging data suggest that inherent differences exist in the tumor microenvironment of AA and CA BC patients, however, its molecular bases and functional impact have remained poorly understood. Here, we conducted cytokine profiling in serum samples from AA and CA BC patients and identified resistin and IL-6 to be the most differentially-expressed cytokines with relative greater expression in AA patients. Resistin and IL-6 exhibited positive correlation in serum levels and treatment of BC cells with resistin led to enhanced production of IL-6. Moreover, resistin also enhanced the expression and phosphorylation of STAT3, and treatment of BC cells with IL-6-neutralizing antibody prior to resistin stimulation abolished STAT3 phosphorylation. In addition, resistin promoted growth and aggressiveness of BC cells, and these effects were mediated through STAT3 activation. Together, these findings suggest a crucial role of resistin, IL-6 and STAT3 in BC racial disparity. PMID:25868978

  7. Resistin and interleukin-6 exhibit racially-disparate expression in breast cancer patients, display molecular association and promote growth and aggressiveness of tumor cells through STAT3 activation

    PubMed Central

    Bhardwaj, Arun; Singh, Ajay P.; Tyagi, Nikhil; Marimuthu, Saravanakumar; Dyess, Donna L.; Zotto, Valeria Dal; Carter, James E.; Singh, Seema

    2015-01-01

    African-American (AA) women with breast cancer (BC) are diagnosed with more aggressive disease, have higher risk of recurrence and poorer prognosis as compared to Caucasian American (CA) women. Therefore, it is imperative to define the factors associated with such disparities to reduce the unequal burden of cancer. Emerging data suggest that inherent differences exist in the tumor microenvironment of AA and CA BC patients, however, its molecular bases and functional impact have remained poorly understood. Here, we conducted cytokine profiling in serum samples from AA and CA BC patients and identified resistin and IL-6 to be the most differentially-expressed cytokines with relative greater expression in AA patients. Resistin and IL-6 exhibited positive correlation in serum levels and treatment of BC cells with resistin led to enhanced production of IL-6. Moreover, resistin also enhanced the expression and phosphorylation of STAT3, and treatment of BC cells with IL-6-neutralizing antibody prior to resistin stimulation abolished STAT3 phosphorylation. In addition, resistin promoted growth and aggressiveness of BC cells, and these effects were mediated through STAT3 activation. Together, these findings suggest a crucial role of resistin, IL-6 and STAT3 in BC racial disparity. PMID:25868978

  8. Clinical and biochemical investigation of male patients exhibiting membranous cytoplasmic bodies in biopsied kidney tissues; a pitfall in diagnosis of Fabry disease

    PubMed Central

    Sakuraba, Hitoshi; Tsukimura, Takahiro; Tanaka, Toshie; Togawa, Tadayasu; Takahashi, Naoki; Mikami, Daisuke; Wakai, Sachiko; Akai, Yasuhiro

    2015-01-01

    Background: The existence of membranous cytoplasmic bodies in biopsied kidney tissues is one of the important findings when considering Fabry disease as the first choice diagnosis. However, there are possible acquired lysosomal diseases associated with pharmacological toxicity, although less attention has been paid to them. Case Presentation: We experienced 3 male patients presenting with proteinuria and specific pathological changes strongly suggesting Fabry disease. We sought detailed clinical and biochemical information to avoid a wrong diagnosis. The patients were examined clinically and pathologically, and plasma α-galactosidase A (GLA) activity and the globotriaosylsphingosine (lyso-Gb3) concentrations were measured. Electron microscopic examination revealed numerous membranous inclusion bodies in podocytes, and biochemical analysis revealed normal GLA activity and a normal lyso-Gb3 level in plasma, showing that they did not have Fabry disease. They suffered from hyperlipidemia, myeloma, or lupus nephritis. They had received pitavastatin calcium, clarithromycin, loxoprofen and/or prednisolone, and there was no medication history of cationic amphiphilic drugs. Conclusions: In this case series, the etiology of the inclusions was not clarified. However, these cases indicate that careful attention should be paid on diagnosis of patients exhibiting inclusion bodies in kidney cells, and it is important to confirm their past and present illnesses, and medication history as well as to measure the GLA activity and lyso-Gb3 level. PMID:26312237

  9. Immunological responses induced by the combination of phototherapy and immunotherapy in the treatment of metastatic tumors

    NASA Astrophysics Data System (ADS)

    Chen, Wei R.; Naylor, Mark F.; Nordquist, Robert E.; Teague, T. Kent; Liu, Hong

    2008-02-01

    Combination therapy using laser photothermal interaction and immunological stimulation has demonstrated its ability to induce immunological responses. Glycated chitosan (GC), an immunological stimulant, and imiquimod, a new type of immune response modifier (IRM), when used in conjunction with laser phototherapy, have shown to have a great immunological stimulation function. Specifically, imiquimod can help release cytokines from immunocompetent cells, stimulate TH1 lymphocyte responses (CD8+ T-cells), and recruit additional dendritic cells. To study the effects of immunoadjuvnats in combination of laser photo-irradiation, we treated animal tumors with laser-ICG-GC combination and late-stage melanoma patients with laser-ICG-imiquimod combination. At designated times, tumors, blood, and spleens in both treated and untreated animals were colleted for analysis. The major immunological indicators, such as IL-6, IL-12, IFN-gamma, CD4, and CD8 were analyzed. The same immunological analysis was also performed for melanoma patients treated by the laser-imiquimod combination.

  10. Immunologic Evaluation of Drug Allergy

    PubMed Central

    Gómez, Enrique; Torres, Maria Jose; Mayorga, Cristobalina

    2012-01-01

    Hypersensitivity drug reactions (HDR) consist of an individual abnormal response with the involvement of the immunological system. In addition to specific immunological mechanisms where specific antibodies or sensitised T cells participate, release of inflammatory mediators by non-specific immunological recognition may also occur. Within this category are one of the most common groups of drugs, the non-steroidal anti-inflammatory drugs. In addition to chemical drugs new emerging ones with an increasing protagonism are biological agents like humanised antibodies and others. For IgE dependent reactions both in vivo and in vitro tests can be used for the immunological evaluation. Sensitivity of these is not optimal and very often a drug provocation test must be considered for knowing the mechanism involved and/or establishing the diagnosis. For non-immediate reactions also both in vivo and in vitro tests can be used. Sensitivity for in vivo tests is generally low and in vitro tests may be needed for the immunological evaluation. Immunohistochemical studies of the affected tissue enable a more precise classification of non-immediate reactions. The monitorization of the acute response of the reactions has given clues for understanding these reactions and has promising results for the future of the immunological evaluation of HDR. PMID:22950030

  11. Immunological complications of blood transfusions.

    PubMed

    Brand, Anneke

    2016-01-01

    Most adverse blood transfusion (BT) events are immune-mediated and in the majority of severe reactions antibodies can be identified as causal factors. Alloimmunization not only causes symptomatic reactions, transfused cells can also be (silently) destroyed. Immunization by BT can contribute to hemolytic disease of the newborn as well as to allograft rejection after transplantation. Reversely, pregnancy and transplantation may evoke immunity hampering transfusion therapy. Besides causing mortality and morbidity, alloimmunization has a huge economic impact. Transfusion reactions prolong hospital stay, require diagnostic tests and complex donor selection procedures and create the need for typed donor registries. In the 1970s, Opeltz and colleagues described that pre-transplantation BT impaired rejection of renal transplants. Leukocytes were essential for this immunosuppressive BT effect that raised concern about negative effects on cancer growth and resistance against infections. Studies on the mechanism were however preliminary abandoned when calcineurin inhibitors for prevention of graft rejection became available and since all blood products underwent leukoreduction in most countries as precautionary measure against transmission of variant Creutzfeldt-Jacob disease. Whether current leukoreduced BT are immunosuppressive and for which patients or circumstances this may contribute to worse outcome, is unknown. The last decades of the previous century, leukoreduction of cellular blood products for leukemia patients significantly reduced the incidence of immunological platelet transfusion refractoriness. The first decade of this century the avoidance of plasma- and platelet-products from females, that may contain donor-derived leukocyte antibodies, decreased transfusion related acute lung injury (TRALI) by more than 30%. These were major achievements. Challenge for the near future is to further reduce alloimmunization in particular against red blood cells (RBC) as a

  12. Immunology of infertility.

    PubMed

    Jones, W R

    1981-12-01

    Recent research on immunological infertility in men and women is reviewed and the possibilities for therapeutic success in this area are assessed. Surface antigens of the acrosome and main tail piece appear to provoke antibodies of special relevance to male and female infertility and are recognized by circulating sperm-immobilizing antibodies in women and by immobilizing and agglutinizing antibodies in men. Assessment methods have focused on the development of tests of local immunity to sperm. Antisperm antibodies have been tested via sperm microagglutination, the gelatin agglutination test, the sperm immobilization test, and immunofluorescence techniques. In addition, measurement has focused on antibodies in cervical mucus, antibodies in seminal plasma, and cell-mediated immunity. Methods involving both partners include postcoital test, the sperm-cervical mucus penetration test, and the sperm-cervical mucus contact test. There remains a need for the development of specific radioimmunoassys for the precise detection and quantitation of antibodies to sperm antigens, especially those of cell membrane origin. In males, autoimmunity to sperm antigens can be related to infertility by 2 main pathogenic mechanisms: 1) the adverse effects of antibodies directly on spermatozoa, and 2) the association with disordered spermatogenesis resulting in oligospermia and azoospermia. In women, the effector pathways of local immunization mediate both systemic and cell-mediated immune responses. Local antibodies can interfere with the reproductive process by arming macrophages and enhancing phagocytic clearance of spermatozoa from the genital tract, mediating cytotoxic effects on sperm, preventing sperm from adequately penetrating cervical mucus, intefering with sperm capacitation, and influencing sperm selection within the female genital tract. Between 5-10% of infertile men and women show evidence of anitbodies to sperm. Treatment has included occlusion therapy, intrauterine

  13. 21 CFR 866.5590 - Lipoprotein X immunolog-ical test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Lipoprotein X immunolog-ical test system. 866.5590... Lipoprotein X immunolog-ical test system. (a) Identification. A lipoprotein X immunological test system is a device that consists of the reagents used to measure by immunochemical techniques lipoprotein X (a...

  14. Immunological studies in sickle cell-beta zero thalassemia. Comparison with sickle cell anemia.

    PubMed

    Donadi, E A; Falcao, R P

    1989-01-01

    Despite genetic differences, patients with S-beta zero thalassemia or sickle cell anemia present several clinical and hematological similarities. In this study we present evidence that they can also show similar immunological profiles. Both hemoglobinopathies exhibited increased total lymphocyte counts as well as B, CD4 and CD8 lymphocyte subset counts. The CD4/CD8 ratio and the determination of the activity of antibody-dependent cellular cytotoxicity were within the normal range for patients with both diseases. The levels of IgG and IgA were also increased for both conditions, but the amount of factor B of the complement system was elevated only in sickle cell anemia patients. PMID:2628234

  15. Immunological perspectives of temporal lobe seizures.

    PubMed

    Liimatainen, Suvi; Lehtimäki, Kai; Kai, Lehtimäki; Palmio, Johanna; Johanna, Palmio; Alapirtti, Tiina; Tiina, Alapirtti; Peltola, Jukka; Jukka, Peltola

    2013-10-15

    The temporal lobes are affected in many different neurological disorders, such as neurodegenerative diseases, viral and immunological encephalitides, and epilepsy. Both experimental and clinical evidence suggests a different inflammatory response to seizures in patients with temporal lobe epilepsy (TLE) in comparison to those with extra-TLE (XTLE). Proinflammatory cytokines and several autoantibodies have been shown to be associated with TLE compared to other epilepsy types suggesting the specific role and structure of the temporal lobe. Abundant experience suggests that activation of both innate and adaptive immunity is associated with epilepsy, particularly refractory focal epilepsy. Limbic encephalitis often triggers temporal lobe seizures, and a proportion of these disorders are immune-mediated. Histological evidence shows activation of specific inflammatory pathways in resected temporal lobes of epileptic patients, and certain epileptic disorders have shown increased incidence in patients with autoimmune diseases. Rapid activation of proinflammatory cytokines is observed after single seizures, but there is also evidence of chronic overproduction of cytokines and other inflammatory mediators in patients with TLE, suggesting a neuromodulatory role of inflammation in epilepsy. In this review we summarize current data on the presence and the role of immunological factors in temporal lobe seizures, and their possible involvement in epileptogenesis. PMID:23998423

  16. CD4+FOXP3+ Regulatory T Cells Exhibit Impaired Ability to Suppress Effector T Cell Proliferation in Patients with Turner Syndrome

    PubMed Central

    Lee, Young Ah; Kim, Hang-Rae; Lee, Jeong Seon; Jung, Hae Woon; Kim, Hwa Young; Lee, Gyung Min; Lee, Jieun; Sim, Ji Hyun; Oh, Sae Jin; Chung, Doo Hyun; Shin, Choong Ho; Yang, Sei Won

    2015-01-01

    Objective We investigated whether the frequency, phenotype, and suppressive function of CD4+FOXP3+ regulatory T cells (Tregs) are altered in young TS patients with the 45,X karyotype compared to age-matched controls. Design and Methods Peripheral blood mononuclear cells from young TS patients (n = 24, 17.4–35.9 years) and healthy controls (n = 16) were stained with various Treg markers to characterize their phenotypes. Based on the presence of thyroid autoimmunity, patients were categorized into TS (–) (n = 7) and TS (+) (n = 17). Tregs sorted for CD4+CD25bright were co-cultured with autologous CD4+CD25− target cells in the presence of anti-CD3 and -CD28 antibodies to assess their suppressive function. Results Despite a lower frequency of CD4+ T cells in the TS (-) and TS (+) patients (mean 30.8% and 31.7%, vs. 41.2%; P = 0.003 and P < 0.001, respectively), both groups exhibited a higher frequency of FOXP3+ Tregs among CD4+ T cells compared with controls (means 1.99% and 2.05%, vs. 1.33%; P = 0.029 and P = 0.004, respectively). There were no differences in the expression of CTLA-4 and the frequency of Tregs expressing CXCR3+, and CCR4+CCR6+ among the three groups. However, the ability of Tregs to suppress the in vitro proliferation of autologous CD4+CD25− T cells was significantly impaired in the TS (–) and TS (+) patients compared to controls (P = 0.003 and P = 0.041). Meanwhile, both the TS (–) and TS (+) groups had lower frequencies of naïve cells (P = 0.001 for both) but higher frequencies of effector memory cells (P = 0.004 and P = 0.002) than did the healthy control group. Conclusions The Tregs of the TS patients could not efficiently suppress the proliferation of autologous effector T cells, despite their increased frequency in peripheral CD4+ T cells. PMID:26709833

  17. Immunogenetics and immunology of transplantation in Leiden.

    PubMed

    Heidt, Sebastiaan; Eikmans, Michael; Roelen, Dave L; van Kooten, Cees; Claas, Frans H J

    2014-10-01

    The historical observation of Jon van Rood that pregnancy can lead to the induction of HLA antibodies (1) was the start of a long history of research on immunogenetics and immunology of transplantation in Leiden. Some of the current research topics are presented in this mini-review. These include amongst others the differential immunogenicity of HLA mismatches in clinical transplantation, a special strategy to transplant highly sensitized patients, new tools to monitor donor specific memory B cells, new parameters for risk assessment in transplant recipients and the importance of the innate immune response in transplantation. PMID:25251513

  18. [Immunological aspects of depressive disorders].

    PubMed

    Müller, N; Schwarz, M J

    2007-11-01

    Beside the monoaminergic deficiency concept as a pathophysiological correlate of depressive disorder, the role of increased glutamatergic neurotransmission is increasingly being discussed. Causes and interactions of these neurotransmitter disturbances are not fully understood to date. This review presents a concept integrating actual findings of the neurotransmitter dysregulations with immunological and morphological findings in depressive disorder. Several intertwined mechanisms seem to be important: The common cause of serotonin deficiency and increased glutamatergic neurotransmission seems to be the increase of proinflammatory cytokines. Immune activation with increased production of proinflammatory cytokines activate the tryptophan- and serotonin-degradating enzyme indolamine-2,3-dioxygenase (IDO). The increased consumption of serotonin and its precursor tryptophan due to IDO activation may explain the reduced availability of serotonin in depression. In inflammatory somatic disorders, depressive mood is associated with an increase of proinflammatory cytokines and increased consumption of tryptophan. This activation of IDO by proinflammatory cytokines leads to the production of glutamatergic agonists. In the CNS, IDO is activated during inflammatory processes primarily in microglial cells. Therefore the astrocyte:microglial balance in depression is important. The observed decrease of astrocytes in the CNS of depressive patients may contribute to a regulatory fault in the activity of IDO in microglial cells but also can cause an alteration of the glutamatergic neurotransmission. By this mechanism, the dysbalance of the immune response and the astrocyte:microglia dysbalance may contribute to serotonergic deficiency and glutamatergic overproduction in depression. The further search for new antidepressant therapeutic mechanisms should take into regard anti-inflammatory substances, e.g. cyclo-oxygenase-2 (COX-2)-inhibitors. PMID:17928982

  19. Immunological effects in patients with steroid-refractory graft-versus-host disease following treatment with basiliximab, a CD25 monoclonal antibody.

    PubMed

    Chakupurakal, Geothy; García-Márquez, María Alejandra; Shimabukuro-Vornhagen, Alexander; Theurich, Sebastian; Holtick, Udo; Hallek, Michael; Scheid, Christof; von Bergwelt-Baildon, Michael

    2016-08-01

    Steroid-refractory graft-versus-host disease (GvHD) is a complication following an allogeneic stem cell transplantation with limited therapeutic options. Studies have shown a response in up to 80% of patients with this condition after treatment with the CD25 monoclonal antibody, basiliximab. Despite the good responses to treatment, around 50% of the patients experience recurrence of their GvHD symptoms 4-6 wk following cessation of therapy. The in vivo changes in the following treatment with this antibody have not been elucidated so far. We treated 14 patients with severe steroid-refractory GvHD with basiliximab weekly for 4 wk and monitored the changes in the T-, B-, NK- and dendritic cell subsets over this time period. The overall response to treatment was 92% (13/14) with 50% (7/14) achieving a complete response. Fifty four percentage (7/13) of the patients who responded showed recurrence of their GvHD symptoms. Contrary to expectations, our observations showed a significant depletion of the regulatory T-cell subset following treatment. Our findings suggest that the undesirable depletion of the regulatory T cells along with the CD25(+) acute inflammatory cells might be responsible for the high incidence of GvHD recurrence in this cohort of patients. PMID:26492560

  20. The immunological and clinical effects of mutated ras peptide vaccine in combination with IL-2, GM-CSF, or both in patients with solid tumors

    PubMed Central

    2014-01-01

    Background Mutant Ras oncogenes produce proteins that are unique to cancer cells and represent attractive targets for vaccine therapy. We have shown previously that vaccinating cancer patients with mutant ras peptides is feasible and capable of inducing a specific immune response against the relevant mutant proteins. Here, we tested the mutant ras peptide vaccine administered in combination with low dose interleukin-2 (IL-2) or/and granulocyte-macrophage colony-stimulating factor (GM-CSF) in order to enhance the vaccine immune response. Methods 5000μg of the corresponding mutant ras peptide was given subcutaneously (SQ) along with IL-2 (Arm A), GM-CSF (Arm B) or both (Arm C). IL-2 was given SQ at 6.0 million IU/m2/day starting at day 5, 5 days/week for 2 weeks. GM-CSF was given SQ in a dose of 100μg/day one day prior to each ras peptide vaccination for 4 days. Vaccines were repeated every 5 weeks on arm A and C, and every 4 weeks on arm B, for a maximum of 15 cycles or until disease progression. Results We treated 53 advanced cancer patients (38 with colorectal, 11 with pancreatic, 1 with common bile duct and 3 with lung) on 3 different arms (16 on arm A, 18 on arm B, and 19 on arm C). The median progression free survival (PFS) and overall survival (OS) was 3.6 and 16.9 months, respectively, for all patients evaluable for clinical response (n = 48). There was no difference in PFS or OS between the three arms (P = 0.73 and 0.99, respectively). Most adverse events were grade 1-2 toxicities and resolved spontaneously. The vaccine induced an immune response to the relevant ras peptide in a total of 20 out of 37 evaluable patients (54%) by ELISPOT, proliferative assay, or both. While 92.3% of patients on arm B had a positive immune response, only 31% of patients on arm A and 36% of patients on arm C had positive immune responses (P = 0.003, Fisher’s exact test). Conclusions The reported data showed that IL-2 might have a negative effect on the specific

  1. Noncoding RNAs in Cancer Immunology.

    PubMed

    Li, Qian; Liu, Qiang

    2016-01-01

    Cancer immunology is the study of interaction between cancer cells and immune system by the application of immunology principle and theory. With the recent approval of several new drugs targeting immune checkpoints in cancer, cancer immunology has become a very attractive field of research and is thought to be the new hope to conquer cancer. This chapter introduces the aberrant expression and function of noncoding RNAs, mainly microRNAs and long noncoding RNAs, in tumor-infiltrating immune cells, and their significance in tumor immunity. It also illustrates how noncoding RNAs are shuttled between tumor cells and immune cells in tumor microenvironments via exosomes or other microvesicles to modulate tumor immunity. PMID:27376738

  2. Sarcoidosis: Immunopathogenesis and Immunological Markers

    PubMed Central

    Loke, Wei Sheng Joshua; Herbert, Cristan; Thomas, Paul S.

    2013-01-01

    Sarcoidosis is a multisystem granulomatous disorder invariably affecting the lungs. It is a disease with noteworthy variations in clinical manifestation and disease outcome and has been described as an “immune paradox” with peripheral anergy despite exaggerated inflammation at disease sites. Despite extensive research, sarcoidosis remains a disease with undetermined aetiology. Current evidence supports the notion that the immune response in sarcoidosis is driven by a putative antigen in a genetically susceptible individual. Unfortunately, there currently exists no reliable biomarker to delineate the disease severity and prognosis. As such, the diagnosis of sarcoidosis remains a vexing clinical challenge. In this review, we outline the immunological features of sarcoidosis, discuss the evidence for and against various candidate etiological agents (infective and noninfective), describe the exhaled breath condensate, a novel method of identifying immunological biomarkers, and suggest other possible immunological biomarkers to better characterise the immunopathogenesis of sarcoidosis. PMID:26464848

  3. [Biochemical and immunological markers of autoimmune thyroiditis].

    PubMed

    Biktagirova, E M; Sattarova, L I; Vagapova, G R; Skibo, Y V; Chuhlovina, E N; Kravtsova, O A; Abramova, Z I

    2016-05-01

    Correlations between biochemical and immunological markers of programmed cell death (apoptosis), and the functional state of the thyroid gland (hyperthyroidism, euthyroidism, hypothyroidism) have been investigated in autoimmune thyroiditis (AT) (also known as chronic autoimmune thyroiditis). Annexin V, TRAIL and TNF-a, as well as DNA-hydrolyzing antibodies were used as the main markers. Increased levels of TRAIL were found in the serum of AT patients (hyperthyroidism>hypothyroidism>euthyroidism) compared with healthy individuals. The highest frequency of antibodies to denatured DNA (Abs-dDNA) had the highest frequency in AT patients (97%) compared with healthy controls. Among these patients, 75% had hyperthyroidism, 85% had hypothyroidism, and 84.7% had euthyroidism. Abs hydrolyzing activity demonstrated correlation dependence with symptoms of the thyroid dysfunction. PMID:27563001

  4. Citizens unite for computational immunology!

    PubMed

    Belden, Orrin S; Baker, Sarah Catherine; Baker, Brian M

    2015-07-01

    Recruiting volunteers who can provide computational time, programming expertise, or puzzle-solving talent has emerged as a powerful tool for biomedical research. Recent projects demonstrate the potential for such 'crowdsourcing' efforts in immunology. Tools for developing applications, new funding opportunities, and an eager public make crowdsourcing a serious option for creative solutions for computationally-challenging problems. Expanded uses of crowdsourcing in immunology will allow for more efficient large-scale data collection and analysis. It will also involve, inspire, educate, and engage the public in a variety of meaningful ways. The benefits are real - it is time to jump in! PMID:26139599

  5. Lung Fibroblasts from Patients with Idiopathic Pulmonary Fibrosis Exhibit Genome-Wide Differences in DNA Methylation Compared to Fibroblasts from Nonfibrotic Lung

    PubMed Central

    Huang, Steven K.; Scruggs, Anne M.; McEachin, Richard C.; White, Eric S.; Peters-Golden, Marc

    2014-01-01

    Excessive fibroproliferation is a central hallmark of idiopathic pulmonary fibrosis (IPF), a chronic, progressive disorder that results in impaired gas exchange and respiratory failure. Fibroblasts are the key effector cells in IPF, and aberrant expression of multiple genes contributes to their excessive fibroproliferative phenotype. DNA methylation changes are critical to the development of many diseases, but the DNA methylome of IPF fibroblasts has never been characterized. Here, we utilized the HumanMethylation 27 array, which assays the DNA methylation level of 27,568 CpG sites across the genome, to compare the DNA methylation patterns of IPF fibroblasts (n = 6) with those of nonfibrotic patient controls (n = 3) and commercially available normal lung fibroblast cell lines (n = 3). We found that multiple CpG sites across the genome are differentially methylated (as defined by P value less than 0.05 and fold change greater than 2) in IPF fibroblasts compared to fibroblasts from nonfibrotic controls. These methylation differences occurred both in genes recognized to be important in fibroproliferation and extracellular matrix generation, as well as in genes not previously recognized to participate in those processes (including organ morphogenesis and potassium ion channels). We used bisulfite sequencing to independently verify DNA methylation differences in 3 genes (CDKN2B, CARD10, and MGMT); these methylation changes corresponded with differences in gene expression at the mRNA and protein level. These differences in DNA methylation were stable throughout multiple cell passages. DNA methylation differences may thus help to explain a proportion of the differences in gene expression previously observed in studies of IPF fibroblasts. Moreover, significant variability in DNA methylation was observed among individual IPF cell lines, suggesting that differences in DNA methylation may contribute to fibroblast heterogeneity among patients with IPF. These

  6. Citrate Anticoagulation in Tandem Membrane Plasma-Exchange or Immunoadsorption and Hemodialysis in Patients With Immunological Diseases and Dialysis-Dependence.

    PubMed

    Ponikvar, Rafael; Gubenšek, Jakob; Ponikvar, Jadranka Buturović

    2016-06-01

    In 1996 we performed tandem membrane plasma exchange-hemodialysis in a 3-year-old girl and tandem immunoadsorption-hemodialysis with citrate as the only anticoagulant in a patient with Goodpasture's syndrome. In the present study, we evaluated the feasibility, efficacy and safety of 24 tandem plasma exchange/immunoadsorption hemodialysis procedures in four different circuit setups with citrate as the only anticoagulant. In two setups, the tandem procedures were connected in series (plasma exchange hemodialysis and immunoadsorption hemodialysis), while in the other two setups they were in parallel (plasma exchange hemodialysis with independent blood circuits and plasma exchange hemodialysis with independent arterial blood lines, but with a common return line). All tandem procedures were feasible, efficient and safe. No serious side-effects were recorded. The most elegant setup was the procedure with independent, parallel blood circuits. However, serial tandem procedures provided for the elimination of citrate and normalization of electrolytes before blood was returned to the patient. PMID:27312909

  7. Serum cytokine profiling and enrichment analysis reveal the involvement of immunological and inflammatory pathways in stable patients with chronic obstructive pulmonary disease

    PubMed Central

    Bade, Geetanjali; Khan, Meraj Alam; Srivastava, Akhilesh Kumar; Khare, Parul; Solaiappan, Krishna Kumar; Guleria, Randeep; Palaniyar, Nades; Talwar, Anjana

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) is a major global health problem. It results from chronic inflammation and causes irreversible airway damage. Levels of different serum cytokines could be surrogate biomarkers for inflammation and lung function in COPD. We aimed to determine the serum levels of different biomarkers in COPD patients, the association between cytokine levels and various prognostic parameters, and the key pathways/networks involved in stable COPD. In this study, serum levels of 48 cytokines were examined by multiplex assays in 30 subjects (control, n=9; COPD, n=21). Relationships between serum biomarkers and forced expiratory volume in 1 second, peak oxygen uptake, body mass index, dyspnea score, and smoking were assessed. Enrichment pathways and network analyses were implemented, using a list of cytokines showing differential expression between healthy controls and patients with COPD by Cytoscape and GeneGo Metacore™ software (Thomson-Reuters Corporation, New York, NY, USA). Concentrations of cutaneous T-cell attracting chemokine, eotaxin, hepatocyte growth factor, interleukin 6 (IL-6), IL-16, and stem cell factor are significantly higher in COPD patients compared with in control patients. Notably, this study identifies stem cell factor as a biomarker for COPD. Multiple regression analysis predicts that cutaneous T-cell-attracting chemokine, eotaxin, IL-6, and stem cell factor are inversely associated with forced expiratory volume in 1 second and peak oxygen uptake change, whereas smoking is related to eotaxin and hepatocyte growth factor changes. Enrichment pathways and network analyses reveal the potential involvement of specific inflammatory and immune process pathways in COPD. Identified network interaction and regulation of different cytokines would pave the way for deeper insight into mechanisms of the disease process. PMID:25125975

  8. Nonrandom development of immunologic abnormalities after infection with human immunodeficiency virus: implications for immunologic classification of the disease.

    PubMed Central

    Zolla-Pazner, S; Des Jarlais, D C; Friedman, S R; Spira, T J; Marmor, M; Holzman, R; Mildvan, D; Yancovitz, S; Mathur-Wagh, U; Garber, J

    1987-01-01

    Blood specimens from 165 intravenous drug users who were seropositive for the human immunodeficiency virus (HIV), from 158 seropositive homosexual men with lymphadenopathy, and from 77 patients with acquired immunodeficiency syndrome (AIDS) were assessed immunologically. Immunologic parameters were analyzed by the Guttman scalogram technique to determine if immunologic abnormalities occurred in a nonrandom pattern. The following four patterns emerged: (i) seropositivity for HIV with no immunologic abnormalities; (ii) seropositivity for HIV with a depressed T4/T8 cell ratio; (iii) seropositivity with a depressed T4/T8 cell ratio and T4-cell depletion; and (iv) seropositivity with a depressed T4/T8 cell ratio, T4-cell depletion, and lymphopenia. Ninety-two to 100% of subjects in each of the three groups of patients were found "to scale" because the abnormalities occurred in the cumulative, ordered fashion described. This nonrandom occurrence of abnormalities indicates an ordered progression of immunologic abnormalities in individuals infected with HIV, a finding useful in the staging of both symptomatic and asymptomatic HIV-seropositive subjects. PMID:3496603

  9. [THE DYNAMICS OF IMMUNOLOGICAL RESULTS OF PATIENTS WITH T-CELL SKIN LYMPHOMAS AND PSORIASIS BY THE THERAPY OF ACTIVATION MECHANISMS SANOGENESIS METHODS].

    PubMed

    Kurgan, D M; Kokoruz, M V; Kurgan, M G; Novak, V L

    2015-01-01

    The therapy T-cell skin lymphoma and psoriasis by the application of activation mechanisms sanogenesis methods, such as: original--a treatment plasmapheresis, a standard heparin infusion; used for the first time--wobenzym; solutions of acid acetic food and sodium bicarbonate; known--the basic sanitations of concomitant diseases, photopheresis caused remissions in 79.6% patients with different stages T-cell skin lymphoma (observed over an 8-year span), and in 67% of patients with psoriasis (observed over an 6-year span). Depuration reactions (phagocytosis, pinocytosis, toxin neutralization) has been activated by detoxication of treatment plasmapheresis and heparin infusions. The topical therapy with wobenzym, solutions of acid acetic food and sodium bicarbonate renewed natural immune barrier of skin. Basic therapy of concomitant diseases enhanced of patient state of health and mobilized compensatory resources. Photopheresis initiated autoimmunization processes by malignant CD4+ lymphocytes. When remission was achieved, the parameters of cellular and humoral immunity returned to normal levels, or the parameters made worse in the absence of remission. PMID:26827436

  10. A different immunologic profile characterizes patients with HER-2-overexpressing and HER-2-negative locally advanced breast cancer: implications for immune-based therapies

    PubMed Central

    2011-01-01

    Introduction The clinical efficacy of trastuzumab and taxanes is at least partly related to their ability to mediate or promote antitumor immune responses. On these grounds, a careful analysis of basal immune profile may be capital to dissect the heterogeneity of clinical responses to these drugs in patients with locally advanced breast cancer undergoing neoadjuvant chemotherapy. Methods Blood samples were collected from 61 locally advanced breast cancers (36 HER2- and 25 HER2+) at diagnosis and from 23 healthy women. Immunophenotypic profiling of circulating and intratumor immune cells, including regulatory T (Treg) cells, was assessed by flow cytometry and immunohistochemistry, respectively. Serum levels of 10 different cytokines were assessed by multiplex immunoassays. CD8+ T cell responses to multiple tumor-associated antigens (TAA) were evaluated by IFN-γ-enzyme-linked immunosorbent spot (ELISPOT). The Student's t test for two tailed distributions and the Wilcoxon two-sample test were used for the statistical analysis of the data. Results The proportion of circulating immune effectors was similar in HER2+ patients and healthy donors, whereas higher percentages of natural killer and Treg cells and a lower CD4+/CD8+ T cell ratio (with a prevalence of naïve and central memory CD8+ T cells) were observed in HER2- cases. Higher numbers of circulating CD8+ T cells specific for several HLA-A*0201-restricted TAA-derived peptides were observed in HER2+ cases, together with a higher prevalence of intratumor CD8+ T cells. Serum cytokine profile of HER2+ patients was similar to that of controls, whereas HER2- cases showed significantly lower cytokine amounts compared to healthy women (IL-2, IL-8, IL-6) and HER2+ cases (IL-2, IL-1β, IL-8, IL-6, IL-10). Conclusions Compared to HER2- cases, patients with HER2-overexpressing locally advanced breast cancer show a more limited tumor-related immune suppression. This may account for the clinical benefit achieved in this subset

  11. Atypical Strain of Toxoplasma gondii Causing Fatal Reactivation after Hematopoietic Stem Cell Transplantion in a Patient with an Underlying Immunological Deficiency

    PubMed Central

    Štajner, Tijana; Vasiljević, Zorica; Vujić, Dragana; Marković, Marija; Ristić, Goran; Mićić, Dragan; Pašić, Srdjan; Ivović, Vladimir; Ajzenberg, Daniel

    2013-01-01

    In immunocompromized patients, including hematopoietic stem cell transplant (HSCT) recipients, life-threatening toxoplasmosis may result from reactivation of previous infection. We report a case of severe disseminated toxoplasmosis that developed early after allogeneic HSCT for T-cell lymphoblastic leukemia/lymphoma in a 15-year-old Toxoplasma gondii-seropositive boy with Nijmegen breakage syndrome, a rare genetic DNA repair disorder associated with immunodeficiency. The donor was the patient's HLA-identical brother. Prophylaxis with cotrimoxazole was discontinued a day before the HSCT procedure. Signs of lung infection appeared as early as day 14 post-HSCT. The presence of tachyzoite-like structures on Giemsa-stained bronchoalveolar lavage (BAL) fluid smears suggested toxoplasmosis. Real-time PCR targeted at the T. gondii AF146527 gene revealed extremely high parasite burdens in both blood and BAL fluid. Although immediate introduction of specific treatment resulted in a marked reduction of the parasite load and transient clinical improvement, the patient deteriorated and died of multiple organ failure on day 39 post-HSCT. Direct genotyping of T. gondii DNA from blood and BAL fluid with the PCR-restriction fragment length polymorphism method revealed type II alleles with SAG1, SAG2, and GRA6 markers but alleles of both type I and type II with GRA7. Additional analysis with 15 microsatellite markers showed that the T. gondii DNA was atypical and genetically divergent from that of the clonal type I, II, and III strains. This is the first report of increased clinical severity of toxoplasmosis associated with an atypical strain in the setting of immunosuppression, which emphasizes the need to diagnose and monitor toxoplasmosis by quantitative molecular methods in cases of reactivation risk. PMID:23761151

  12. Importance of the association of molecular and immunological diagnosis in immunocompetent patient with Histoplasma capsulatum and Cryptoccocus neoformans infection: a case report

    PubMed Central

    2014-01-01

    This case reports an immunocompetent 29-year-old woman with suspected pneumonia, suggestive of fungal infection. Immunoblotting analysis reactivity against Histoplasma capsulatum and Paracoccidioides brasiliensis were observed. Nested-PCR in blood employing species-specific primers was positive for H. capsulatum and Cryptococcus neoformans. The evaluation of paucisymptomatic patients with positive results for H. capsulatum and C. neoformans could be relevant for the prevention as well as the possible evaluation of the reactivated quiescent foci. In conclusion, the associated methodology may have contributed to the monitoring endogenous reactivation of these diseases. PMID:25180029

  13. The double helix and immunology

    NASA Astrophysics Data System (ADS)

    Nossal, Gustav J. V.

    2003-01-01

    The immune system can recognize and produce antibodies to virtually any molecule in the Universe. This enormous diversity arises from the ingenious reshuffling of DNA sequences encoding components of the immune system. Immunology is an example of a field completely transformed during the past 50 years by the discovery of the structure of DNA and the emergence of DNA technologies that followed.

  14. American College of Allergy, Asthma & Immunology

    MedlinePlus

    ... an Allergist American College of Allergy, Asthma, and Immunology Seeking Relief? Find an Allergist ACAAI Members Members ... Find an Allergist American College of Allergy, Asthma & Immunology © 2014 Contact US

  15. Immunology beats cancer: a blueprint for successful translation

    PubMed Central

    Pardoll, Drew M

    2015-01-01

    Immunology offers an unprecedented opportunity for the science-driven development of therapeutics. The successes of antibodies to the immunomodulatory receptor CTLA-4 and blockade of the immunoinhibitory receptor PD-1 in cancer immunotherapy, from gene discovery to patient benefit, have created a paradigm for driving such endeavors. PMID:23160205

  16. [Evaluation of a telemedicine system for the transmission of morpho/immunological data at the inclusion of patients in a therapeutic trial (Goelams LLC 98)].

    PubMed

    Lesesve, J-F; Palmiéri, A; Brion, A; Feugier, P; Mahé, B; Garand, R

    2007-01-01

    The performances of the images digitalization and teletransmission systems make them more and more used. Applied to cellular haematology, they contribute to confrontations of diagnosis mostly within the framework of therapeutic trials. We present one of the first approaches of the use of telehematology for the inclusion of patients in the Goelams Chronic Lymphocytic Leukaemia 98 trial. The advantages were the constitution of a protected data bank, conveniently consultable; expertise on identical documents; facility of the exchanges between experts. We were able to set new standards of images sampling for CLL, solve the semantic divergences, to point out the inter-observer variability for the morphology. The limiting factors were the personal investment of the experts, but mainly the implication of first line morphologists which should benefit from adequate tools to apprehend this system of second reading like a quality control. PMID:17353168

  17. Implementing Mass Cytometry at the Bedside to Study the Immunological Basis of Human Diseases: Distinctive Immune Features in Patients with a History of Term or Preterm Birth.

    PubMed

    Gaudillière, Brice; Ganio, Edward A; Tingle, Martha; Lancero, Hope L; Fragiadakis, Gabriela K; Baca, Quentin J; Aghaeepour, Nima; Wong, Ronald J; Quaintance, Cele; El-Sayed, Yasser Y; Shaw, Gary M; Lewis, David B; Stevenson, David K; Nolan, Garry P; Angst, Martin S

    2015-09-01

    Single-cell technologies have immense potential to shed light on molecular and biological processes that drive human diseases. Mass cytometry (or Cytometry by Time Of Flight mass spectrometry, CyTOF) has already been employed in clinical studies to comprehensively survey patients' circulating immune system. As interest in the "bedside" application of mass cytometry is growing, the delineation of relevant methodological issues is called for. This report uses a newly generated dataset to discuss important methodological considerations when mass cytometry is implemented in a clinical study. Specifically, the use of whole blood samples versus peripheral blood mononuclear cells (PBMCs), design of mass-tagged antibody panels, technical and analytical implications of sample barcoding, and application of traditional and unsupervised approaches to analyze high-dimensional mass cytometry datasets are discussed. A mass cytometry assay was implemented in a cross-sectional study of 19 women with a history of term or preterm birth to determine whether immune traits in peripheral blood differentiate the two groups in the absence of pregnancy. Twenty-seven phenotypic and 11 intracellular markers were simultaneously analyzed in whole blood samples stimulated with lipopolysaccharide (LPS at 0, 0.1, 1, 10, and 100 ng mL(-1)) to examine dose-dependent signaling responses within the toll-like receptor 4 (TLR4) pathway. Complementary analyses, grounded in traditional or unsupervised gating strategies of immune cell subsets, indicated that the prpS6 and pMAPKAPK2 responses in classical monocytes are accentuated in women with a history of preterm birth (FDR<1%). The results suggest that women predisposed to preterm birth may be prone to mount an exacerbated TLR4 response during the course of pregnancy. This important hypothesis-generating finding points to the power of single-cell mass cytometry to detect biologically important differences in a relatively small patient cohort. PMID

  18. Immunology of Chagas' disease*

    PubMed Central

    1974-01-01

    After reviewing present knowledge of the morphology, multiplication, and transmission of Trypanosoma cruzi, this Memorandum discusses the animal models that may be of value in understanding the immune mechanisms operating in Chagas' disease. The role of both circulating antibody and cell-mediated immunity in protection against the parasite is discussed, together with the possibility that immunopathological mechanisms may be responsible for some of the lesions found in patients with Chagas' disease. The immunodiagnostic methods at present available are also reviewed, and the possibility of producing a vaccine for human use is considered in the light of recent findings in experimental animals. A series of recommendations for further research is included. PMID:4218137

  19. 42 CFR 493.927 - General immunology.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false General immunology. 493.927 Section 493.927 Public... Proficiency Testing Programs by Specialty and Subspecialty § 493.927 General immunology. (a) Program content and frequency of challenge. To be approved for proficiency testing for immunology, the annual...

  20. 42 CFR 493.927 - General immunology.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 5 2014-10-01 2014-10-01 false General immunology. 493.927 Section 493.927 Public... Proficiency Testing Programs by Specialty and Subspecialty § 493.927 General immunology. (a) Program content and frequency of challenge. To be approved for proficiency testing for immunology, the annual...

  1. 42 CFR 493.927 - General immunology.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 5 2012-10-01 2012-10-01 false General immunology. 493.927 Section 493.927 Public... Proficiency Testing Programs by Specialty and Subspecialty § 493.927 General immunology. (a) Program content and frequency of challenge. To be approved for proficiency testing for immunology, the annual...

  2. 42 CFR 493.921 - Diagnostic immunology.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 5 2013-10-01 2013-10-01 false Diagnostic immunology. 493.921 Section 493.921... Testing Proficiency Testing Programs by Specialty and Subspecialty § 493.921 Diagnostic immunology. The subspecialties under the specialty of immunology for which a program may offer proficiency testing are...

  3. 42 CFR 493.921 - Diagnostic immunology.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 5 2012-10-01 2012-10-01 false Diagnostic immunology. 493.921 Section 493.921... Testing Proficiency Testing Programs by Specialty and Subspecialty § 493.921 Diagnostic immunology. The subspecialties under the specialty of immunology for which a program may offer proficiency testing are...

  4. 42 CFR 493.927 - General immunology.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 5 2013-10-01 2013-10-01 false General immunology. 493.927 Section 493.927 Public... Proficiency Testing Programs by Specialty and Subspecialty § 493.927 General immunology. (a) Program content and frequency of challenge. To be approved for proficiency testing for immunology, the annual...

  5. 42 CFR 493.927 - General immunology.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false General immunology. 493.927 Section 493.927 Public... Proficiency Testing Programs by Specialty and Subspecialty § 493.927 General immunology. (a) Program content and frequency of challenge. To be approved for proficiency testing for immunology, the annual...

  6. 42 CFR 493.921 - Diagnostic immunology.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Diagnostic immunology. 493.921 Section 493.921... Testing Proficiency Testing Programs by Specialty and Subspecialty § 493.921 Diagnostic immunology. The subspecialties under the specialty of immunology for which a program may offer proficiency testing are...

  7. 42 CFR 493.921 - Diagnostic immunology.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 5 2014-10-01 2014-10-01 false Diagnostic immunology. 493.921 Section 493.921... Testing Proficiency Testing Programs by Specialty and Subspecialty § 493.921 Diagnostic immunology. The subspecialties under the specialty of immunology for which a program may offer proficiency testing are...

  8. 42 CFR 493.921 - Diagnostic immunology.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Diagnostic immunology. 493.921 Section 493.921... Testing Proficiency Testing Programs by Specialty and Subspecialty § 493.921 Diagnostic immunology. The subspecialties under the specialty of immunology for which a program may offer proficiency testing are...

  9. [Clinico-immunologic indices of various patient contingents in a focus of chronic opisthorchiasis. 3. Dynamics of the indices following praziquantel treatment].

    PubMed

    Parfenov, S B; Ozeretskovskaia, N N; Pomigalov, A Iu; Chistiakova, I V

    1989-01-01

    Studies of the time course of the immune status characteristics after praziquantel treatment and of the nature of its side-effects on various groups of opisthorchiasis patients in the focus established significant differences in their immune response to specific treatment. The lack of alterations in the T- and B-immunity systems in aboriginal population of the focus may suggest its tolerance to helminthic antigens. The trend towards cellular immunity stimulation and a significant increase in the levels of circulating immune complexes and specific antibodies in the serum were observed in aboriginal population of the focus. The comers showed significant initial alterations of the immunity status before treatment, pointing to their sensitization to parasitic antigens. Suppression of the infection normalizes several cellular and humoral immunity characteristics--the number of T-helpers, T-lymphocytes, B-lymphocytes, Th/Tc indices, T-lymphocyte functional activity, thus eliminating immune depression. The increased IgG, CIC and specific antibody levels significantly exceeding the normal level, occurrence or enhancement of allergic reactions point to the necessity of performing a desensitizing therapy and using effective cholagogic drugs in the multimodality treatment to rapidly eliminate the parasitic antigen. PMID:2811752

  10. Evaluation of a telemedicine system for the transmission of morpho/immunological data aiming at the inclusion of patients in a therapeutic trial.

    PubMed

    Lesesve, Jean-François; Garand, Richard

    2009-01-01

    Due to their high levels of achievement and efficiency, image digitalization and teletransmission tools are more and more frequently used. Applied to cellular haematology, these tools often contribute to diagnosis confrontation, sometimes within the framework of therapeutic trials. We present one of the first approaches of the use of telehaematology for the inclusion of patients in the GOELAMS chronic lymphocytic leukaemia 98 trial. The advantages were (1) the creation of a unique, protected, stable data bank that could be remotely consulted, (2) the use of digitized pictures which made expertise on identical documents possible, (3) the facility of computer exchanges between experts, in terms of reception as well as replying time delays. We were able to set out new standards of image sampling for CLL, solve the semantic divergences, and point out interobserver variability as regards morphology. The limiting factors were the important need for expert investment, but they more importantly concerned the first line morphologists who should benefit from adequate tools, in terms of computer equipment as well as members of staff, so as to apprehend this second reading system as a quality control procedure. PMID:19190767

  11. Highlights of 10 years of immunology in Nature Reviews Immunology

    PubMed Central

    Medzhitov, Ruslan; Shevach, Ethan M.; Trinchieri, Giorgio; Mellor, Andrew L.; Munn, David H.; Gordon, Siamon; Libby, Peter; Hansson, Göran K.; Shortman, Ken; Dong, Chen; Gabrilovich, Dmitry; Gabryšová, Leona; Howes, Ashleigh; O’Garra, Anne

    2013-01-01

    As Nature Reviews Immunology reaches its 10th anniversary, we’ve asked the authors of one of the top-cited articles of each year to look back on the state of research at the time their Review was published, to consider why the article has had the impact it has and to discuss the future directions of their field. This Viewpoint article provides an interesting snapshot of some of the fundamental advances in the field of immunology over the past 10 years — including Toll-like receptor signalling, immune regulation mediated by regulatory T cells, indoleamine 2,3-dioxygenase, myeloid-derived suppressor cells and interleukin-10, the development and heterogeneity of macrophages, dendritic cells and T helper cells, and the immune processes involved in diseases such as atherosclerosis — and looks forward to what the next 10 years may bring. PMID:21941295

  12. Perioperative period: immunological modifications.

    PubMed

    Cardinale, F; Chinellato, I; Caimmi, S; Peroni, D G; Franceschini, F; Miraglia Del Giudice, M; Bernardini, R

    2011-01-01

    Surgical stress induces complex modifications in the hemodynamic, metabolic, neuro-hormonal and immune response of the individual. The magnitude of these alterations depends on preoperative events leading to surgery, the severity of surgical trauma, and also on post-operative/post-traumatic complications (multiple hit hypothesis). As in other conditions of tissue damage, surgery trauma is followed by an immune-inflammatory response, initiated at the site of injury by the innate immune system, followed by a compensatory anti-inflammatory (or immunosuppressive) response (CARS), involving mainly cells of the adaptive immune system, which predispose the host to septic complications. The up-regulated inflammatory response, together with a profound impairment of macrophage and cell-mediated immunity, appear to be the cause for patients' increased susceptibility in developing subsequent sepsis after major surgery. PMID:22014920

  13. Immunologically mediated oral diseases.

    PubMed

    Jimson, Sudha; Balachader, N; Anita, N; Babu, R

    2015-04-01

    Immune mediated diseases of oral cavity are uncommon. The lesions may be self-limiting and undergo remission spontaneously. Among the immune mediated oral lesions the most important are lichen planus, pemphigus, erythema multiformi, epidermolysis bullosa, systemic lupus erythematosis. Cellular and humoral mediated immunity play a major role directed against epithelial and connective tissue in chronic and recurrent patterns. Confirmatory diagnosis can be made by biopsy, direct and indirect immunoflouresence, immune precipitation and immunoblotting. Therapeutic agents should be selected after thorough evaluation of immune status through a variety of tests and after determining any aggravating or provoking factors. Early and appropriate diagnosis is important for proper treatment planning contributing to better prognosis and better quality of life of patient. PMID:26015713

  14. Implementing Mass Cytometry at the Bedside to Study the Immunological Basis of Human Diseases: Distinctive Immune Features in Patients with a History of Term or Preterm Birth

    PubMed Central

    Gaudillière, Brice; Ganio, Edward A.; Tingle, Martha; Lancero, Hope L.; Fragiadakis, Gabriela K.; Baca, Quentin J.; Aghaeepour, Nima; Wong, Ronald J.; Quaintance, Cele; El-Sayed, Yasser Y.; Shaw, Gary M.; Lewis, David B.; Stevenson, David K.; Nolan, Garry P.; Angst, Martin S.

    2016-01-01

    Single-cell technologies have immense potential to shed light on molecular and biological processes that drive human diseases. Mass cytometry (or Cytometry by Time Of Flight mass spectrometry, CyTOF) has already been employed in clinical studies to comprehensively survey patients’ circulating immune system. As interest in the “bedside” application of mass cytometry is growing, the delineation of relevant methodological issues is called for. This report uses a newly generated dataset to discuss important methodological considerations when mass cytometry is implemented in a clinical study. Specifically, the use of whole blood samples versus peripheral blood mononuclear cells (PBMCs), design of mass-tagged antibody panels, technical and analytical implications of sample barcoding, and application of traditional and unsupervised approaches to analyze high-dimensional mass cytometry datasets are discussed. A mass cytometry assay was implemented in a cross-sectional study of 19 women with a history of term or preterm birth to determine whether immune traits in peripheral blood differentiate the two groups in the absence of pregnancy. Twenty-seven phenotypic and 11 intracellular markers were simultaneously analyzed in whole blood samples stimulated with lipopolysaccharide (LPS at 0, 0.1, 1, 10, and 100 ng mL−1) to examine dose-dependent signaling responses within the toll-like receptor 4 (TLR4) pathway. Complementary analyses, grounded in traditional or unsupervised gating strategies of immune cell subsets, indicated that the prpS6 and pMAPKAPK2 responses in classical monocytes are accentuated in women with a history of preterm birth (FDR<1%). The results suggest that women predisposed to preterm birth may be prone to mount an exacerbated TLR4 response during the course of pregnancy. This important hypothesis-generating finding points to the power of single-cell mass cytometry to detect biologically important differences in a relatively small patient cohort. PMID

  15. Hypersensitivity to pollen of four different species of Brassica: a clinico-immunologic evaluation in patients of respiratory allergy in India

    PubMed Central

    Shahi, Shipra; Katiyar, Raj Kishore; Gaur, Shailendra; Jain, Vikram

    2014-01-01

    Background Rapeseed-mustard is the second most important source of edible oil in India. Several species of Brassica are grown in different parts of country for its oilseeds. Objective The objective was to investigate allergenicity to antigenic extracts of pollen of 4 species of Brassica. Methods Brassica campestris, Brassica juncea, Brassica nigra, and Brassica napus were selected for the detailed investigation. Pollen samples from each of the four species were collected from the polliniferous materials. The antigenic and allergenic profiles of these extracts were evaluated by means of sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Skin prick test, enzyme linked immuno sorbent assay and Western blot on atopic individuals. Results Out of the 159 atopic subjects tested, 21.38% were positive to at least one or other species of Brassica pollen, with highest skin positivity (13.20%) to B. campestris extract. Raised IgE with significant linear correlation with intensity of skin reactions was obtained. Protein fractions of 20, 25, 32, 37, 56, and 90 kDa were recognized by B. campestris and B. juncea whereas 56, 76, 87, and 90 kDa were recognized by B. nigra and B. napus as major IgE binding protein fractions. The patients also showed positivity to other inhalant pollen allergens tested. Conclusion IgE mediated hypersensitivity varied from 4.40% to 13.20% in Indian atopic subjects to pollen of one or the other species of Brassica. Protein fractions of 47, 56, 76, 87, and 90 kDa were identified as IgE binding by all the four species, however individual heterogeneity exists. Thus a local species may be more pertinent for immunotherapy. The major allergen needs to be further characterized. PMID:25379479

  16. Adverse immunologic effects of antithyroid drugs.

    PubMed Central

    Wing, S S; Fantus, I G

    1987-01-01

    Propylthiouracil and methimazole are frequently used in the management of hyperthyroidism. Two patients in whom adverse immunologic effects other than isolated agranulocytosis developed during treatment with propylthiouracil are described. A review of the literature revealed 53 similar cases over a 35-year period. Rash, fever, arthralgias and granulocytopenia were the most common manifestations. Vasculitis, particularly with cutaneous manifestations, occurs and may be fatal. The clinical evidence suggests that an immunologic mechanism is involved. A number of different autoantibodies were reported, but antinuclear antibodies were infrequent, and none of the cases met the criteria for a diagnosis of systemic lupus erythematosus. Thus, the reactions do not represent a true drug-induced lupus syndrome. Current hypotheses and experimental data regarding the cause of the reactions are reviewed. No specific clinical subgroup at high risk can be identified, and manifestations may occur at any dosage and at any time during therapy. Cross-reactivity between the two antithyroid drugs can be expected. Except for minor symptoms (e.g., mild arthralgias or transient rash), such reactions are an indication for withdrawal of the drug and the use of alternative methods to control the hyperthyroidism. In rare cases of severe vasculitis a short course of high-dose glucocorticoid therapy may be helpful. PMID:3539299

  17. [Cerebrovascular complications of immunologically mediated heparin-induced thrombocytopenia].

    PubMed

    Macha, K; Kloska, S; Dörfler, A; Raaz-Schrauder, D; Schwab, S; Köhrmann, M; Seifert, F

    2014-03-01

    Immunologically mediated heparin-induced thrombocytopenia (HIT) is a thrombotic disease caused by antibodies occurring after heparin exposure. Thrombocytopenia occurs within a few days after heparin exposure, about half of HIT-patients develop venous or arterial thrombotic complications. Neurological complications of HIT are mainly ischaemic stroke and sinus vein thrombosis. To ensure the primary clinical diagnosis functional and immunological assays for antibody detection are available. The probability for the occurrence of HIT depends on the nature of heparin employed (LMWH vs. UFH) and individual patient characteristics such as gender and primary disease (medical vs. surgical patients). In the case of suspected HIT heparin administration should be discontinued immediately and replaced by an alternative anticoagulation to prevent the expansion or development of further thrombotic complications. Herein we report a case of a patient suffering from HIT-associated embolic cerebral ischaemic stroke. PMID:24615586

  18. [Immunological mechanisms involved in pregnancy].

    PubMed

    Rico-Rosillo, María Guadalupe; Vega-Robledo, Gloria Bertha

    2012-05-01

    Pregnancy progresses through mechanisms that allow the embryo implantation and its development during gestation. Those mechanisms involve the immune cells that participate in the regulation of immune tolerance and response, as well as the protection conferred by Th2 cytokines and molecules expressed on trophoblast cells. Local factors expressed in the fetal interface as HLA-G, which inhibits the cytotoxicity of uterine natural killer cells and induces apoptosis of activated CD8 cells; transforming growth factor-beta, that induces tolerance, and uterine natural killer cells that are functionally different to the peripheral, as well as circulating progesterone and the glicodeline molecules that are important regulators of the immune response, also intervene in the process. From the conventional immunological point of view, pregnancy is a unique immune condition in which the fetus, semiallogenic, avoids being rejected immunologically by the mother, apparently by inducing a tolerance more than a sensitization PMID:23301425

  19. Immunological Aspects of Malignant Gliomas.

    PubMed

    Cohen-Inbar, Or; Zaaroor, Menashe

    2016-07-01

    Glioblastoma Multiforme (GBM) is the most common malignant primary brain neoplasm having a mean survival time of <24 months. This figure remains constant, despite significant progress in medical research and treatment. The lack of an efficient anti-tumor immune response and the micro-invasive nature of the glioma malignant cells have been explained by a multitude of immune-suppressive mechanisms, proven in different models. These immune-resistant capabilities of the tumor result in a complex interplay this tumor shares with the immune system. We present a short review on the immunology of GBM, discussing the different unique pathological and molecular features of GBM, current treatment modalities, the principles of cancer immunotherapy and the link between GBM and melanoma. Current knowledge on immunological features of GBM, as well as immunotherapy past and current clinical trials, is discussed in an attempt to broadly present the complex and formidable challenges posed by GBM. PMID:27324313

  20. Systems immunology: Beyond antibody titers.

    PubMed

    Cao, Raquel; Mejias, Asuncion; Ramilo, Octavio

    2016-07-01

    Despite the evident success of currently available vaccines to prevent infectious diseases, we still lack a full understanding of the mechanisms by which vaccines induce protective immune responses. Systems immunology applies multifaceted analytical tools to better understand the immune responses to vaccines by deep characterization of the cellular components, regulatory pathways, antibody responses and immune gene profiles with the ultimate goal of identifying the complex cellular, genetic and regulatory factors and mechanisms that contribute to effective and protective immune responses. PMID:27180310

  1. Ethics on Exhibit

    ERIC Educational Resources Information Center

    Vick, Randy M.

    2011-01-01

    This article discusses ethical questions raised by an exhibition of work by an artist with a history of mental illness and the exhibition's relevance to art therapy and “outsider art” discourse on the subject. Considerations for how such an exhibit could be handled had the circumstances included an art therapist and art therapy client are…

  2. Clinical and immunological aspects and outcome of a Brazilian cohort of 414 patients with systemic lupus erythematosus (SLE): comparison between childhood-onset, adult-onset, and late-onset SLE.

    PubMed

    das Chagas Medeiros, M M; Bezerra, M Campos; Braga, F N Holanda Ferreira; da Justa Feijão, M R Melo; Gois, A C Rodrigues; Rebouças, V C do Rosário; de Carvalho, T M Amorim Zaranza; Carvalho, L N Solon; Ribeiro, Át Mendes

    2016-04-01

    The clinical expression of systemic lupus erythematosus (SLE) is influenced by genetic and environmental factors and therefore varies between ethnicities. Information on the epidemiology of SLE in Brazil is scarce and practically limited to studies conducted in socioeconomically developed regions (South and Southeast). The objective of this study was to describe the clinical and immunological aspects and outcome of a cohort of patients with SLE treated at a university hospital in northeastern Brazil and compare patterns related to age at onset: childhood (cSLE), adult (aSLE), and late (lSLE). A random sample of 414 records (women: 93.5%) were reviewed. The mean age at SLE onset and the mean disease duration were 28.9 ± 10.9 years and 10.2 ± 6.6 years, respectively. Most patients had aSLE (n = 338; 81.6%), followed by cSLE (n = 60; 14.5%) and lSLE (n = 16; 3.9%). The female/male ratio was 6.5:1 in cSLE and 16.8:1 in aSLE; in lSLE, all patients were female (p = 0.05). During follow-up, the cSLE group presented higher rates of nephritis (70% vs. 52.9% vs. 12.5%; p = 0.0001) and leuko/lymphopenia (61.7% vs. 43.8% vs. 56.2%; p = 0.02). No significant differences were found for anti-dsDNA, anti-Sm, and antiphospholipid antibodies. Treatment with immunosuppressants was significantly more common, and higher doses of prednisone were used, in cSLE. The prevalence of cardiovascular diseases were more frequent in lSLE (p = 0.03). No significant differences were found between the three groups with regard to mean damage accrual (SDI), remission, and mortality. Although cSLE presented higher rates of nephritis and leuko/lymphopenia, more frequent use of immunosuppressants and higher prednisone doses than aSLE and lSLE, the three groups did not differ significantly with regard to damage accrual, remission, and mortality. PMID:26405022

  3. Immunology of Gut Mucosal Vaccines

    PubMed Central

    Pasetti, Marcela F.; Simon, Jakub K.; Sztein, Marcelo B.; Levine, Myron M.

    2011-01-01

    Summary Understanding the mechanisms underlying the induction of immunity in the gastrointestinal mucosa following oral immunization and the cross-talk between mucosal and systemic immunity should expedite the development of vaccines to diminish the global burden caused by enteric pathogens. Identifying an immunological correlate of protection in the course of field trials of efficacy, animal models (when available), or human challenge studies is also invaluable. In industrialized country populations, live attenuated vaccines (e.g. polio, typhoid, and rotavirus) mimic natural infection and generate robust protective immune responses. In contrast, a major challenge is to understand and overcome the barriers responsible for the diminished immunogenicity and efficacy of the same enteric vaccines in underprivileged populations in developing countries. Success in developing vaccines against some enteric pathogens has heretofore been elusive (e.g. Shigella). Different types of oral vaccines can selectively or inclusively elicit mucosal secretory immunoglobulin A and serum immunoglobulin G antibodies and a variety of cell-mediated immune responses. Areas of research that require acceleration include interaction between the gut innate immune system and the stimulation of adaptive immunity, development of safe yet effective mucosal adjuvants, better understanding of homing to the mucosa of immunologically relevant cells, and elicitation of mucosal immunologic memory. This review dissects the immune responses elicited in humans by enteric vaccines. PMID:21198669

  4. [Immunological reactivity of rats exposed on the Kosmos-605 and 690 biosatellites].

    PubMed

    Ivanov, A A; Shvets, V N

    1979-01-01

    Immunological reactivity of rats flown aboard the biosatellites Cosmos-605 and Cosmos-690 was compared with respect to the complementary activity of serum and frequency antibodies to sheep red blood cells. Cosmos-605 rats showed changes that rapidly returned to the normal whereas Cosmos-690 rats irradiated inflight with a dose of 800 rad exhibited significant and stable changes in immunological reactivity. Those latter seemed to be associated with the combined effect of ionizing radiation and other space flight factors. PMID:582191

  5. An Exhibit for Touching.

    ERIC Educational Resources Information Center

    Hunt, Susan

    1979-01-01

    An exhibit designed for visually handicapped persons presented by the Kalamazoo (Michigan) Institute of Art included bronze sculptures and oil paintings from the institute's permanent collection. (CL)

  6. Dysbiosis of Salivary Microbiota in Inflammatory Bowel Disease and Its Association With Oral Immunological Biomarkers

    PubMed Central

    Said, Heba S.; Suda, Wataru; Nakagome, Shigeki; Chinen, Hiroshi; Oshima, Kenshiro; Kim, Sangwan; Kimura, Ryosuke; Iraha, Atsushi; Ishida, Hajime; Fujita, Jiro; Mano, Shuhei; Morita, Hidetoshi; Dohi, Taeko; Oota, Hiroki; Hattori, Masahira

    2014-01-01

    Analysis of microbiota in various biological and environmental samples under a variety of conditions has recently become more practical due to remarkable advances in next-generation sequencing. Changes leading to specific biological states including some of the more complex diseases can now be characterized with relative ease. It is known that gut microbiota is involved in the pathogenesis of inflammatory bowel disease (IBD), mainly Crohn's disease and ulcerative colitis, exhibiting symptoms in the gastrointestinal tract. Recent studies also showed increased frequency of oral manifestations among IBD patients, indicating aberrations in the oral microbiota. Based on these observations, we analyzed the composition of salivary microbiota of 35 IBD patients by 454 pyrosequencing of the bacterial 16S rRNA gene and compared it with that of 24 healthy controls (HCs). The results showed that Bacteroidetes was significantly increased with a concurrent decrease in Proteobacteria in the salivary microbiota of IBD patients. The dominant genera, Streptococcus, Prevotella, Neisseria, Haemophilus, Veillonella, and Gemella, were found to largely contribute to dysbiosis (dysbacteriosis) observed in the salivary microbiota of IBD patients. Analysis of immunological biomarkers in the saliva of IBD patients showed elevated levels of many inflammatory cytokines and immunoglobulin A, and a lower lysozyme level. A strong correlation was shown between lysozyme and IL-1β levels and the relative abundance of Streptococcus, Prevotella, Haemophilus and Veillonella. Our data demonstrate that dysbiosis of salivary microbiota is associated with inflammatory responses in IBD patients, suggesting that it is possibly linked to dysbiosis of their gut microbiota. PMID:24013298

  7. Dysbiosis of salivary microbiota in inflammatory bowel disease and its association with oral immunological biomarkers.

    PubMed

    Said, Heba S; Suda, Wataru; Nakagome, Shigeki; Chinen, Hiroshi; Oshima, Kenshiro; Kim, Sangwan; Kimura, Ryosuke; Iraha, Atsushi; Ishida, Hajime; Fujita, Jiro; Mano, Shuhei; Morita, Hidetoshi; Dohi, Taeko; Oota, Hiroki; Hattori, Masahira

    2014-02-01

    Analysis of microbiota in various biological and environmental samples under a variety of conditions has recently become more practical due to remarkable advances in next-generation sequencing. Changes leading to specific biological states including some of the more complex diseases can now be characterized with relative ease. It is known that gut microbiota is involved in the pathogenesis of inflammatory bowel disease (IBD), mainly Crohn's disease and ulcerative colitis, exhibiting symptoms in the gastrointestinal tract. Recent studies also showed increased frequency of oral manifestations among IBD patients, indicating aberrations in the oral microbiota. Based on these observations, we analyzed the composition of salivary microbiota of 35 IBD patients by 454 pyrosequencing of the bacterial 16S rRNA gene and compared it with that of 24 healthy controls (HCs). The results showed that Bacteroidetes was significantly increased with a concurrent decrease in Proteobacteria in the salivary microbiota of IBD patients. The dominant genera, Streptococcus, Prevotella, Neisseria, Haemophilus, Veillonella, and Gemella, were found to largely contribute to dysbiosis (dysbacteriosis) observed in the salivary microbiota of IBD patients. Analysis of immunological biomarkers in the saliva of IBD patients showed elevated levels of many inflammatory cytokines and immunoglobulin A, and a lower lysozyme level. A strong correlation was shown between lysozyme and IL-1β levels and the relative abundance of Streptococcus, Prevotella, Haemophilus and Veillonella. Our data demonstrate that dysbiosis of salivary microbiota is associated with inflammatory responses in IBD patients, suggesting that it is possibly linked to dysbiosis of their gut microbiota. PMID:24013298

  8. Macrophages from IBD patients exhibit defective tumour necrosis factor-α secretion but otherwise normal or augmented pro-inflammatory responses to infection.

    PubMed

    Campos, Nair; Magro, Fernando; Castro, Ana Rita; Cabral, Joana; Rodrigues, Pedro; Silva, Ricardo; Appelberg, Rui; Rodrigues, Susana; Lopes, Susana; Macedo, Guilherme; Sarmento, Amélia

    2011-08-01

    Defects in macrophage function have been implicated in the establishment of Crohn's disease (CD). However, the response of macrophages from CD patients to live bacteria, particularly Mycobacterium avium subsp. paratuberculosis (MAP), has not been addressed. Considering MAP has long been associated to CD, our objective was to assess whether macrophages from CD patients showed impaired inflammatory response to infection by MAP comparing to M. avium subsp. avium (MA) and other live intestinal commensal bacteria. Human peripheral blood monocyte-derived macrophages were obtained from CD patients, ulcerative colitis (UC) patients and controls. Following in vitro infection with MAP, MA, Escherichia coli or Enterococcus faecalis, cytokine levels and cell surface receptor expression were evaluated at different time points. Macrophages from CD patients showed impaired TNF-α secretion in response to bacterial challenge, but augmented IL-23 secretion and preserved IL-12 secretion and CD-40 expression. In addition, CD macrophages showed low IL-10 secretion. Macrophages from IBD patients showed increased expression of TLR-2 and -4, unaffected by infection. Differences in cytokine secretion observed after bacterial challenge were not MAP-specific, as other bacteria (E. coli and MA) showed similar effects. Macrophages from UC patients showed a less compromised TNF-α synthesis in response to mycobacterial infection than CD macrophages, with increased constitutive IL-12 secretion, and preserved IL-10 secretion. The increased IL-23 levels in response to infection and decreased IL-10 production observed in macrophages from CD patients may contribute to the inflammatory exacerbation observed in those patients. PMID:21269730

  9. The laboratory mouse and wild immunology.

    PubMed

    Viney, M; Lazarou, L; Abolins, S

    2015-05-01

    The laboratory mouse, Mus musculus domesticus, has been the workhorse of the very successful laboratory study of mammalian immunology. These studies--discovering how the mammalian immune system can work--have allowed the development of the field of wild immunology that is seeking to understand how the immune responses of wild animals contributes to animals' fitness. Remarkably, there have hardly been any studies of the immunology of wild M. musculus domesticus (or of rats, another common laboratory model), but the general finding is that these wild animals are more immunologically responsive, compared with their laboratory domesticated comparators. This difference probably reflects the comparatively greater previous exposure to antigens of these wild-caught animals. There are now excellent prospects for laboratory mouse immunology to make major advances in the field of wild immunology. PMID:25303494

  10. Historical Overview of Immunological Tolerance

    PubMed Central

    Schwartz, Ronald H.

    2012-01-01

    A fundamental property of the immune system is its ability to mediate self-defense with a minimal amount of collateral damage to the host. The system uses several different mechanisms to achieve this goal, which is collectively referred to as the “process of immunological tolerance.” This article provides an introductory historical overview to these various mechanisms, which are discussed in greater detail throughout this collection, and then briefly describes what happens when this process fails, a state referred to as “autoimmunity.” PMID:22395097

  11. San Rafael Schools Exhibit.

    ERIC Educational Resources Information Center

    San Rafael City Schools, CA.

    The San Rafael City Schools' exhibit which was displayed at the 1983 Marin County Fair (California) is described. The exhibit, entitled "Education - A Real Winner," consisted of 12 display panels illustrating the following aspects of the school system: (1) early history from 1861; (2) present board and administration; (3) present schools and…

  12. A Teaching Aids Exhibition.

    ERIC Educational Resources Information Center

    Mahanja, Salah

    1985-01-01

    Describes an exhibition for the benefit of teachers of English in Arab Primary Schools, which was prepared by third-year students at the Teachers College for Arab Teachers. The exhibition included games, songs, audiovisual aids, crossword puzzles, vocabulary, spelling booklets, preposition aids, and worksheet and lesson planning aids. (SED)

  13. Visitors Center Exhibits

    NASA Technical Reports Server (NTRS)

    1997-01-01

    A child enjoys building his own LEGO model at a play table which was included in the exhibit 'Travel in Space' World Show. The exhibit consisted of 21 displays designed to teach children about flight and space travel from the Wright brothers to future generations of space vehicles.

  14. Immunology in Malaysia--a review.

    PubMed

    Bosco, J

    1988-04-01

    Immunology is a discipline that traverses all branches of clinical medicine. Thus since about ten years ago major hospitals in Malaysia established routine clinical immunology services particularly in the diagnosis of autoimmune/connective tissue disorders. More recently these laboratories have ventured into basic research in Dengue Haemorrhagic Fever, Leukaemia Immunology, Nasopharyngeal Cancer and Leprosy. The rationale for these projects together with early results from them are discussed. PMID:3044263

  15. The Safety and Immunological Effects of rAd5-EBV-LMP2 Vaccine in Nasopharyngeal Carcinoma Patients: A Phase I Clinical Trial and Two-Year Follow-Up.

    PubMed

    Si, Yongfeng; Deng, Zhuoxia; Lan, Guiping; Du, Haijun; Wang, Yongli; Si, Jinyuan; Wei, Jiazhang; Weng, Jingjin; Qin, Yangda; Huang, Bo; Yang, Yong; Qin, Ying

    2016-01-01

    Epstein-Barr virus (EBV)-encoded latent membrane protein 2 (LMP2) promotes nasopharyngeal carcinoma (NPC) progression. Previously, we reported that the dendritic cells (DCs) transfected with EBV-LMP2 recombinant serotype 5 adenoviruses (rAd5) induced anti-tumor effect by eliciting cytotoxic T lymphocytes (CTLs)-mediated immune response in vitro and the adenoviral vaccine of EBV-LMP2 (rAd5-EBV-LMP2) stimulated antigen-specific cellular immunity in mice. However, the safety and immunological effect of rAd5-EBV-LMP2 vaccine in human still remained unknown. Here we conducted a single-center, non-randomized, open-label, single-arm phase I clinical trial to clarify this unsolved issue. A total of 24 patients with regional advanced NPC were sequentially enrolled into three dose level groups (2×10(9), 2×10(10), 2×10(11) vp). The rAd5-EBV-LMP2 vaccines were intramuscularly injected for four times within 28 d (D0, D7, D14, D28). Blood samples were harvested immediately before every vaccination, one week and one month after the last vaccination (D0, D7, D14, D28, D35, D58). All the vaccine inoculation-related toxicities presented as grade I/II adverse events. The most frequent systemic adverse reactions were fatigue (33.0%, 8/24), myalgia (29.2%, 7/24) and cough (29.2%, 7/24), while the most common regional adverse reaction was tenderness in the inoculation site (54.2%, 13/24). In addition, proportion of CD(3+)CD(4+) cells in peripheral blood was significantly increased in the high dose group (2×10(11) vp). The rAd5-EBV-LMP2 vaccine was generally well-tolerated and the high dose (2×10(11) vp) is recommended to be adopted in phase II studies. The long-term outcome of rAd5-EBV-LMP2 vaccine inoculation is required to be determined in following placebo-controlled trials. PMID:27477649

  16. Communicating Science through Exhibitions

    NASA Astrophysics Data System (ADS)

    Dusenbery, P.; Harold, J.; Morrow, C.

    It is critically important for the public to better understand the scientific process. Museum exhibitions are an important part of informal science education that can effectively reach public audiences as well as school groups. They provide an important gateway for the public to learn about compelling scientific endeavors. There are many ways for scientists to help develop science exhibitions. The Space Science Institute (SSI) is a national leader in producing traveling science exhibitions and their associated educational programming (i.e. interactive websites, educator workshops, public talks, instructional materials). Two of its exhibitions, Space Weather Center and MarsQuest, are currently on tour. Another exhibition, Alien Earths, is in development. The Space Weather Center was developed in partnership with various research missions at NASA's Goddard Space Flight Center. MarsQuest is a 5000 square-foot traveling exhibition. The exhibit's second 3-year tour began this January at the Detroit Science Center. It is enabling millions of Americans to share in the excitement of the scientific exploration of Mars and to learn more about their own planet in the process. The 3,000 square-foot traveling exhibition, called Alien Earths, will bring origins-related research and discoveries to students and the American public. Alien Earths has four interrelated exhibit areas: Our Place in Space, Star Birth, PlanetQuest, and Search for Life. Exhibit visitors will explore the awesome events surrounding the birth of stars and planets; they will join scientists in the hunt for planets outside our solar system including those that may be in ``habitable zones'' around other stars; and finally they will be able to learn about how scientists are looking for signs of life beyond Earth. Besides the exhibits, SSI is also developing interactive web sites based on exhibit themes. New technologies are transforming the Web from a static medium to an interactive environment with tremendous

  17. Overview of spaceflight immunology studies.

    PubMed

    Taylor, G R

    1993-09-01

    The effects of spaceflight and analogues of spaceflight are discussed here and in nine accompanying articles. In this summary we present spaceflight studies with human subjects, animal subjects, and cell cultures and we review ground-based systems used to model the observed effects of spaceflight on the immune system. Human paradigms include bed rest, academic or psychological stress, physical stress, hypobaric or high altitude stress, and confinement. Animal models include antiorthostatic and orthostatic suspension, hypobarism, and confinement. The ten manuscripts in this collection were selected to provide a summary that should give the reader an overview of the various activities of spaceflight immunology researchers throughout the history of space travel. This manuscript identifies the major contributors to the study of spaceflight immunology, explains what types of studies have been conducted, and how they have changed over the years. Also presented is a discussion of the unusual limitations associated with spaceflight research and the efforts to develop appropriate ground-based surrogate model systems. Specific details, data, and mechanistic speculations will be held to a minimum, because they will be discussed in depth in the other articles in the collection. PMID:8371047

  18. The immunology of smallpox vaccines.

    PubMed

    Kennedy, Richard B; Ovsyannikova, Inna G; Jacobson, Robert M; Poland, Gregory A

    2009-06-01

    In spite of the eradication of smallpox over 30 years ago; orthopox viruses such as smallpox and monkeypox remain serious public health threats both through the possibility of bioterrorism and the intentional release of smallpox and through natural outbreaks of emerging infectious diseases such as monkeypox. The eradication effort was largely made possible by the availability of an effective vaccine based on the immunologically cross-protective vaccinia virus. Although the concept of vaccination dates back to the late 1800s with Edward Jenner, it is only in the past decade that modern immunologic tools have been applied toward deciphering poxvirus immunity. Smallpox vaccines containing vaccinia virus elicit strong humoral and cellular immune responses that confer cross-protective immunity against variola virus for decades after immunization. Recent studies have focused on: establishing the longevity of poxvirus-specific immunity, defining key immune epitopes targeted by T and B cells, developing subunit-based vaccines, and developing genotypic and phenotypic immune response profiles that predict either vaccine response or adverse events following immunization. PMID:19524427

  19. Overview of spaceflight immunology studies

    NASA Technical Reports Server (NTRS)

    Taylor, G. R.

    1993-01-01

    The effects of spaceflight and analogues of spaceflight are discussed here and in nine accompanying articles. In this summary we present spaceflight studies with human subjects, animal subjects, and cell cultures and we review ground-based systems used to model the observed effects of spaceflight on the immune system. Human paradigms include bed rest, academic or psychological stress, physical stress, hypobaric or high altitude stress, and confinement. Animal models include antiorthostatic and orthostatic suspension, hypobarism, and confinement. The ten manuscripts in this collection were selected to provide a summary that should give the reader an overview of the various activities of spaceflight immunology researchers throughout the history of space travel. This manuscript identifies the major contributors to the study of spaceflight immunology, explains what types of studies have been conducted, and how they have changed over the years. Also presented is a discussion of the unusual limitations associated with spaceflight research and the efforts to develop appropriate ground-based surrogate model systems. Specific details, data, and mechanistic speculations will be held to a minimum, because they will be discussed in depth in the other articles in the collection.

  20. New Hurricane Exhibit

    NASA Technical Reports Server (NTRS)

    2007-01-01

    A new exhibit in StenniSphere depicting NASA's role in hurricane prediction and research and SSC's role in helping the region recover from Hurricane Katrina. The cyclone-shaped exhibit focuses on the effects of the Aug. 29, 2005 storm and outlines how NASA is working to improve weather forecasting. Through photos, 3-D models and digital animations, the exhibit tells the story of what happened inside the storm and how NASA's scientific research can increase the accuracy of hurricane tracking and modeling.

  1. 21 CFR 866.5170 - Breast milk immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Breast milk immunological test system. 866.5170... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5170 Breast milk immunological test system. (a) Identification. A breast milk immunological test system is a...

  2. 21 CFR 866.5170 - Breast milk immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Breast milk immunological test system. 866.5170... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5170 Breast milk immunological test system. (a) Identification. A breast milk immunological test system is a...

  3. 21 CFR 866.5040 - Albumin immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Albumin immunological test system. 866.5040... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5040 Albumin immunological test system. (a) Identification. An albumin immunological test system is a device that consists...

  4. Immunological monitoring of anticancer vaccines in clinical trials

    PubMed Central

    Ogi, Chizuru; Aruga, Atsushi

    2013-01-01

    Therapeutic anticancer vaccines operate by eliciting or enhancing an immune response that specifically targets tumor-associated antigens. Although intense efforts have been made for developing clinically useful anticancer vaccines, only a few Phase III clinical trials testing this immunotherapeutic strategy have achieved their primary endpoint. Here, we report the results of a retrospective research aimed at clarifying the design of previously completed Phase II/III clinical trials testing therapeutic anticancer vaccines and at assessing the value of immunological monitoring in this setting. We identified 17 anticancer vaccines that have been investigated in the context of a completed Phase II/III clinical trial. The immune response of patients receiving anticancer vaccination was assessed for only 8 of these products (in 15 distinct studies) in the attempt to identify a correlation with clinical outcome. Of these studies, 13 were supported by a statistical correlation study (Log-rank test), and no less than 12 identified a positive correlation between vaccine-elicited immune responses and disease outcome. Six trials also performed a Cox proportional hazards analysis, invariably demonstrating that vaccine-elicited immune responses have a positive prognostic value. However, despite these positive results in the course of early clinical development, most therapeutic vaccines tested so far failed to provide any clinical benefit to cancer patients in Phase II/III studies. Our research indicates that evaluating the immunological profile of patients at enrollment might constitute a key approach often neglected in these studies. Such an immunological monitoring should be based not only on peripheral blood samples but also on bioptic specimens, whenever possible. The evaluation of the immunological profile of cancer patients enrolled in early clinical trials will allow for the identification of individuals who have the highest chances to benefit from anticancer vaccination

  5. [Allergy to drugs and contrast media--recommendations of the Israeli Allergy and Clinical Immunology Association].

    PubMed

    Agmon-Levin, Nancy; Tal, Yuval; Broides, Arnon; Asher, Ilan; Hersheko, Alon; Staubers, Tali; Confino-Cohen, Ronit

    2013-09-01

    Drug hypersensitivity is an adverse reaction that was brought about by a specific immunologic response, not related to the pharmacological components of the drug. Additionally, drug related pseudoallergic and anaphylactoid reactions have been encompassed under the umbrella of hypersensitivity. Some of these reactions are linked with significant morbidity and mortality. Nowadays, the hypersensitivity reactions of most drugs can be well defined and recurrence risk following exposure to the culprit drug and/or related drugs can be assessed. Medical history skin, blood and challenge tests, conducted in an allergy clinic, enable prediction and prevention of repeated events as well as unnecessary avoidance of certain compounds. For instance, most patients who report a prior reaction to penicillin are not allergic to beta-lactams upon allergic evaluation, while avoidance of penicillin based on self-reporting alone often leads to the use of an alternate antibiotic with greater cost or side effect profile. On the other hand, for patients who previously exhibited hypersensitivity to a compound which is currently required, premedication or a desensitization protocol can be recommended to allow the use of this compound. Drug hypersensitivity is most commonly attributed to beta-lactams antibiotics, contrast media reagents and non-steroidal anti-inflammatory drugs (NSAID). Hence, in the current review the recommendations of the Israeli Association for Allergy and Clinical Immunology for the evaluation and treatment of patients suspected to have hypersensitivity to beta-lactams and contrast media reagents are detailed. Recommendations regarding the evaluation of NSAID hypersensitivity will be published on the IMA website, together with those explicated herein. PMID:24364087

  6. [Immunologic findings in homosexual males with generalized lymphadenopathy. Prodromal state of acquired immunodeficiency syndrome?].

    PubMed

    Kalden, J R; Burmester, G R; Manger, B; Coester, C H; Bienzle, U

    1983-11-01

    Peripheral blood of 6 homosexual men with lymphadenopathy associated with fever, weight loss and night sweat, 13 homosexuals with lymphadenopathy without further clinical symptoms, 13 healthy homosexuals and 20 healthy hetero-sexual blood donors was evaluated for different lymphocyte subpopulation, mitogen induced T-cell proliferation and Gamma-interferon production. In the six patients with lymphadenopathy lymphocyte subpopulations were also analysed in lymph node-biopsies. delayed type hypersensitivity was established by skin test's using different recall antigens. Sera of all homosexual men were screened for immunoglobulin levels, complement activity, presence of immunocomplexes and autoantibodies. Most of the homosexuals with lymphadenopathy but without clinical symptoms and all patients with lymphadenopathy associated with clinical symptoms had a significantly decreased helper-(OKT 4) suppressor- (OKT 8) cell ratio. In contrast, the OKT 4/OKT 8 ratio was found to be normal in lymphocyte suspension from lymph node-biopsy from the 6 patients with lymphadenopathy and clinical symptoms. Within the group of healthy homosexuals this ratio exhibited a rather large variation, in three of the tested persons the ratio was below 1. No functional abnormalities of T-cell immunity were observed in the homosexual men as compared to the control group, with the exception of a significantly increased LAG- and PWM-induced lymphocyte proliferation in the group of healthy homosexual men. Likewise no significant differences were obtained with regard to the further analysed immunological parameters. It is concluded that the obtained immunological results do not provide the possibility to define persons at immediate risk for the development of AIDS. PMID:6227767

  7. Communicating Science through Exhibitions

    NASA Astrophysics Data System (ADS)

    Dusenbery, Paul

    2005-04-01

    It is critically important for the public to better understand the scientific process. Museum exhibitions are an important part of informal science education that can effectively reach public audiences as well as school groups. They provide an important gateway for the public to learn about compelling scientific endeavors. Science exhibitions also provide a marvelous opportunity for scientists to become engaged in the exhibit development process. The Space Science Institute (SSI) is a national leader in producing traveling science exhibitions and their associated educational programming (i.e. interactive websites, educator workshops, public talks, instructional materials). The focus of this presentation will be on two of its exhibit projects: MarsQuest (on tour for four years) and Alien Earths (its tour began early in 2005). MarsQuest is enabling millions of Americans to share in the excitement of the scientific exploration of Mars and to learn more about their own planet in the process. Alien Earths will bring origins-related research and discoveries to students and the American public. It has four interrelated exhibit areas: Our Place in Space, Star Birth, Planet Quest, and Search for Life. Exhibit visitors will explore the awesome events surrounding the birth of stars and planets; they will join scientists in the hunt for planets outside our solar system including those that may be in ``habitable zones'' around other stars; and finally they will be able to learn about how scientists are looking for signs of life beyond Earth. SSI is also developing interactive web sites based on exhibit themes. New technologies are transforming the Web from a static medium to an interactive environment with tremendous potential for informal education and inquiry-based investigations. This talk will focus on the role informal science projects play in effectively communicating science to a broad, public audience.

  8. Test Control Center exhibit

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Have you ever wondered how the engineers at John C. Stennis Space Center in Hancock County, Miss., test fire a Space Shuttle Main Engine? The Test Control Center exhibit at StenniSphere can answer your questions by simulating the test firing of a Space Shuttle Main Engine. A recreation of one of NASA's test control centers, the exhibit explains and portrays the 'shake, rattle and roar' that happens during a real test firing.

  9. Evolution and conservation of immunological activity.

    PubMed

    Vaz, N M

    2006-12-01

    Paraphrasing what Gregory Bateson says on evolution, we might say that: "Immunology has long been badly taught. In particular, students--and even professional immunologists--acquire theories of immunological activity without any deep understanding of what problems these theories attempt to solve." PMID:17160260

  10. The ninth international veterinary immunology symposium

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This Introduction to the special issue of Veterinary Immunology and Immunopathology summarizes the Proceedings of the 9th International Veterinary Immunology Symposium (9th IVIS) held August, 2010, in Tokyo, Japan. Over 340 delegates from 30 countries discussed research progress analyzing the immune...

  11. Immunological characterization of plant ornithine transcarbamylases

    NASA Technical Reports Server (NTRS)

    Slocum, R. D.; Williamson, C. L.; Poggenburg, C. A.; Lynes, M. A.

    1990-01-01

    Pea (Pisum sativum L.) ornithine transcarbamylase (OTC) antisera were used to investigate the immunological relatedness of several plant and animal OTC enzymes. The antisera immunoprecipitated OTC activity in all monocot and dicot species tested, and sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis of immunoprecipitated protein revealed monomeric proteins ranging from 35,200 to 36,800 daltons in size. Pea OTC antisera did not recognize mammalian OTC protein. OTC activity and protein levels detected on sodium dodecyl sulfate polyacrylamide gel electrophoresis immunoblots from homogenates of green leaf, etiolated epicotyl and cotyledon, and root tissues of pea were poorly correlated. This might result from differences in amounts of enzymatically active OTC protein in the homogenates. Alternatively, the antisera may fail to recognize different isozyme forms of OTC, which have been reported for some plant species. A putative cytosolic precursor OTC (pOTC) polypeptide exhibiting and Mr = 39,500 to 40,000 daltons was immunoprecipitated from in vitro translation mixtures of total pea leaf poly(A)+ RNA. The size of the pOTC polypeptide, as compared with mature OTC monomer (36,000 daltons), suggests that a 4 kilodalton N-terminal leader sequence, like that responsible for mitochondrial targeting of the mammalian enzyme, may be involved in organellar import of the plant enzyme.

  12. The immunology of mycobacterial infections.

    PubMed

    Chaparas, S D

    1982-01-01

    Mycobacteria are endowed with substances that profoundly affect the immune system. Leprosy and tuberculosis exemplify broad spectra of useful and detrimental immune responses of mycobacterial infections that range from intense potentiation to severe specific adn nonspecific suppression of humoral and cellular immune elements. The cellular hypersensitivity induced by mycobacteria serves as a classical model for the analysis of specific and nonspecific immune mechanisms. Mycobacterial disease are prevalent worldwide and rank among the most important bacterial diseases. The kaleidoscope of immunologic events induced by injected mycobacteria and during infections will be reviewed from the standpoint of pathogenesis, pathology, in vitro and in vivo effects on cellular and humoral arms of the immune response, diagnosis, classification, potentiation and suppression. PMID:7042210

  13. Ratio of Circulating IFNγ+ “Th17 Cells” in Memory Th Cells Is Inversely Correlated with the Titer of Anti-CCP Antibodies in Early-Onset Rheumatoid Arthritis Patients Based on Flow Cytometry Methods of the Human Immunology Project

    PubMed Central

    Kotake, Shigeru; Nanke, Yuki; Yago, Toru; Kawamoto, Manabu; Kobashigawa, Tsuyoshi; Yamanaka, Hisashi

    2016-01-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic joint inflammation characterized by activated T cells. IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. However, it remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we validated the methods of the Human Immunology Project using only the cell-surface marker through measuring the actual expression of IL-17 and IFNγ. We also evaluated the expression of CD161 in human Th17 cells. We then tried to identify Th17 cells, IL-17+Th17 cells, and IFNγ+Th17 cells in the peripheral blood of early-onset RA patients using the standardized method of the Human Immunology Project. Our findings validated the method and the expression of CD161. The ratio of IFNγ+Th17 cells in memory T cells was inversely correlated to the titers of anti-CCP antibodies in the early-onset RA patients. These findings suggest that Th17 cells play important roles in the early phase of RA and that anti-IL-17 antibodies should be administered to patients with early phase RA, especially those with high titers of CCP antibodies. PMID:27294146

  14. Split Immunological Tolerance to Trophoblast

    PubMed Central

    de Mestre, Amanda; Noronha, Leela; Wagner, Bettina; Antczak, Douglas F.

    2010-01-01

    Split immunological tolerance refers to states in which an individual is capable of mounting certain types of immune responses to a particular antigenic challenge, but is tolerant of the same antigen in other compartments of the immune system. This concept is applicable to the immunological relationship between mother and fetus, and particularly relevant in equine pregnancy. In pregnant mares, antibody responses to paternal foreign Major Histocompatibility Complex class I antigens are robust, while anti-paternal cytotoxic T cell responses are diminished compared to those mounted by non-pregnant mares. Here we compared the distribution of the major lymphocyte subsets, the percentage of lymphocytes expressing Interferon Gamma (IFNG) and Interleukin 4 (IL4) and the level of expression of the immunoregulatory transcription factor FOXP3 between pregnant and non-pregnant mares, and between peripheral blood and the endometrium during pregnancy. In a cohort of mares in which peripheral blood lymphocytes were tested during early pregnancy and in the non-pregnant state, there were only slight changes observed during pregnancy. In contrast, comparison of peripheral blood lymphocytes with lymphocytes isolated from the endometrial cups of pregnant mares revealed striking differences in lymphocyte sub-populations. The endometrial cups contained higher numbers of IFNG+ lymphocytes, and lower numbers of lymphocytes expressing IL4. The endometrial cup lymphocytes also had higher numbers of FOXP3+ cells compared to peripheral blood lymphocytes. Taken together, these results strengthen the evidence for a state of split tolerance to trophoblast, and furthermore define sharp differences in immune reactivity during equine pregnancy between peripheral blood lymphocytes and lymphocytes at the maternal-fetal interface. PMID:19876828

  15. Immunologic methods for monitoring carcinogen exposure

    NASA Astrophysics Data System (ADS)

    Santella, Regina M.; Perera, Frederica P.; Zhang, Yu J.; Chen, Chen J.; Young, Tie L.

    1993-03-01

    Immunologic methods have been developed for monitoring human exposure to environmental and occupational carcinogens. These methods involve the development of monoclonal and polyclonal antisera which specifically recognize the carcinogens themselves or their DNA or protein adducts. Antisera recognizing the DNA adducts of several polycyclic aromatic hydrocarbon diol epoxides have been used in competitive enzyme-linked immunosorbent assays to monitor adducts in tissue or blood samples. Elevated levels of DNA adducts have been seen in mononuclear cells of smokers and in total white blood cells of foundry and coke oven workers. Environmental exposure to PAH has been measured in individuals living in a highly polluted region of Poland. Antisera recognizing PAH-DNA adducts have also been used in immunohistochemical studies to monitor adducts in specific cells of biopsy samples. The DNA adducts of aflatoxin B1 have been monitored in liver tissue of hepatocellular carcinoma patients in Taiwan. Detectable adducts were seen in 50 - 70% of the patients suggesting that dietary exposure to this carcinogen may be a risk factor for cancer induction. Thus, immunoassays for monitoring exposure to carcinogens are an important tool in epidemiologic studies.

  16. Development of the discipline of exercise immunology.

    PubMed

    Shephard, Roy J

    2010-01-01

    Interest in the influence of exercise upon the human white cell population dates back more than a 100 years. Thus, when introducing the third meeting of the International Society of Exercise Immunology in Brussels, Dr. Bente Klarlund-Pedersen noted that Schulte had already described an exercise-induced leukocytosis as early as 1893. However, for much of the following century interest remained strictly clinical, with physicians assessing the possible changes in vulnerability to bacterial and viral diseases that were induced by various forms of physical activity. In the absence of specific remedies, bed rest was a common medical recommendation for infectious disease, and if the patient recovered from the immediate infection there was often a substantial residual loss of physical condition. Army hospitals in particular were thus anxious to know whether recovery would be compromised if physical activity were to be encouraged during convalescence. Prominent concerns of this era were the influence of exercise upon anterior poliomyelitis and viral hepatitis. The paralysis resulting from the anterior poliomyelitis virus was generally localized to body parts that had been active, and it seemed most likely to develop in those who continued to engage in vigorous exercise in the face of early symptoms (46, 57, 119, 120). Data on viral hepatitis also suggested a need for rest in the acute phase of the disease (1, 65, 115, 128), although most authors concluded that in this condition exercise could be resumed during convalescence, provided that the patient was no longer severely jaundiced (5, 32, 136). PMID:20839500

  17. Swamp to Space exhibit

    NASA Technical Reports Server (NTRS)

    2000-01-01

    The menacing-looking alligator is really harmless. It is one of the realistic props to help convince visitors that the feel of the swamp is real in StenniSphere's Swamp to Space exhibit at John C. Stennis Space Center in Hancock County, Miss. The historical section of the Swamp to Space exhibit tells the story of why and how Stennis Space Center came to be. It also pays tribute to the families who moved their homes to make way for the space age in Mississippi.

  18. Immunologic profiles of multiple sclerosis treatments reveal shared early B cell alterations

    PubMed Central

    Dooley, James; Pauwels, Ine; Franckaert, Dean; Smets, Ide; Garcia-Perez, Josselyn E.; Hilven, Kelly; Danso-Abeam, Dina; Terbeek, Joanne; Nguyen, Anh T.L.; De Muynck, Louis; Decallonne, Brigitte; Dubois, Bénédicte

    2016-01-01

    Objective: We undertook a systems immunology approach of the adaptive immune system in multiple sclerosis (MS), overcoming tradeoffs between scale and level of detail, in order to identify the immunologic signature of MS and the changes wrought by current immunomodulatory treatments. Methods: We developed a comprehensive flow cytometry platform measuring 38 immunologic cell types in the peripheral blood of 245 individuals in a routine clinical setting. These include patients with MS, untreated or receiving any of 4 current immunomodulatory treatments (interferon-β, glatiramer acetate, natalizumab, or fingolimod), patients with autoimmune thyroid disease, and healthy controls. Results: An increase in memory CD8+ T cells and B cells was observed in untreated patients with MS. Interferon-β and fingolimod induce significant changes upon multiple aspects of the peripheral immune system, with an unexpectedly prominent alteration of B cells. Overall, both treatments push the immune system in different directions, with only 2 significant effects shared across these treatments—an increase in transitional B cells and a decrease in class-switched B cells. We further identified heightened B cell-activating factor (BAFF) levels as regulating this shared B cell pathway. Conclusions: A systems immunology approach established different immunologic profiles induced by current immunomodulatory MS treatments, offering perspectives for personalized medicine. Pathways shared between the immunologic architecture of existing efficacious treatments identify targets for future treatment design. PMID:27231713

  19. Comparative expression profiles of microRNA in left and right atrial appendages from patients with rheumatic mitral valve disease exhibiting sinus rhythm or atrial fibrillation

    PubMed Central

    2014-01-01

    Background The atrial fibrillation (AF) associated microRNAs (miRNAs) were found in the right atrium (RA) and left atrium (LA) from patients with rheumatic mitral valve disease (RMVD). However, most studies only focus on the RA; and the potential differences of AF-associated miRNAs between the RA and LA are still unknown. The aim of this study was to perform miRNA expression profiles analysis to compare the potential differences of AF-associated miRNAs in the right atrial appendages (RAA) and left atrial appendages (LAA) from RMVD patients. Methods Samples tissues from the RAA and LAA were obtained from 18 RMVD patients (10 with AF) during mitral valve replacement surgery. From these tissues, miRNA expression profiles were created and analyzed using a human miRNA microarray. Then, the results were validated using qRT-PCR analysis for 12 selected miRNAs. Finally, potential targets of 10 validated miRNAs were predicted and their functions and potential pathways were analyzed using the miRFocus database. Results In RAA, 65 AF-associated miRNAs were found and significantly dysregulated (i.e. 28 miRNAs were up-regulated and 37 were down-regulated). In LAA, 42 AF-associated miRNAs were found and significantly dysregulated (i.e. 22 miRNAs were up-regulated and 20 were down-regulated). Among these AF-associated miRNAs, 23 of them were found in both RAA and LAA, 45 of them were found only in RAA, and 19 of them were found only in LAA. Finally, 10 AF-associated miRNAs validated by qRT-PCR were similarly distributed in RAA and LAA; 3 were found in both RAA and LAA, 5 were found only in RAA, and 2 were found only in LAA. Potential miRNA targets and molecular pathways were identified. Conclusions We have found the different distributions of AF-associated miRNAs in the RAA and LAA from RMVD patients. This may reflect different miRNA mechanisms in AF between the RA and LA. These findings may provide new insights into the underlying mechanisms of AF in RMVD patients. PMID:24708751

  20. Patients undergoing elective coronary artery bypass grafting exhibit poor pre-operative intakes of fruit, vegetables, dietary fibre, fish and vitamin D.

    PubMed

    Ruiz-Núñez, B; van den Hurk, G H A M; de Vries, J H M; Mariani, M A; de Jongste, M J L; Dijck-Brouwer, D A J; Muskiet, F A J

    2015-05-14

    CHD may ensue from chronic systemic low-grade inflammation. Diet is a modifiable risk factor for both, and its optimisation may reduce post-operative mortality, atrial fibrillation and cognitive decline. In the present study, we investigated the usual dietary intakes of patients undergoing elective coronary artery bypass grafting (CABG), emphasising on food groups and nutrients with putative roles in the inflammatory/anti-inflammatory balance. From November 2012 to April 2013, we approached ninety-three consecutive patients (80% men) undergoing elective CABG. Of these, fifty-five were finally included (84% men, median age 69 years; range 46-84 years). The median BMI was 27 (range 18-36) kg/m(2). The dietary intake items were fruits (median 181 g/d; range 0-433 g/d), vegetables (median 115 g/d; range 0-303 g/d), dietary fibre (median 22 g/d; range 9-45 g/d), EPA+DHA (median 0.14 g/d; range 0.01-1.06 g/d), vitamin D (median 4.9 μg/d; range 1.9-11.2 μg/d), saturated fat (median 13.1% of energy (E%); range 9-23 E%) and linoleic acid (LA; median 6.3 E%; range 1.9-11.3 E%). The percentages of patients with dietary intakes below recommendations were 62% (fruits; recommendation 200 g/d), 87 % (vegetables; recommendation 150-200 g/d), 73% (dietary fibre; recommendation 30-45 g/d), 91% (EPA+DHA; recommendation 0.45 g/d), 98% (vitamin D; recommendation 10-20 μg/d) and 13% (LA; recommendation 5-10 E%). The percentages of patients with dietary intakes above recommendations were 95% (saturated fat; recommendation < 10 E%) and 7% (LA). The dietary intakes of patients proved comparable with the average nutritional intake of the age- and sex-matched healthy Dutch population. These unbalanced pre-operative diets may put them at risk of unfavourable surgical outcomes, since they promote a pro-inflammatory state. We conclude that there is an urgent need for intervention trials aiming at rapid improvement of their diets to reduce peri-operative risks. PMID:25827177

  1. Zika virus infections imported to Italy: clinical, immunological and virological findings, and public health implications.

    PubMed

    Zammarchi, Lorenzo; Stella, Giulia; Mantella, Antonia; Bartolozzi, Dario; Tappe, Dennis; Günther, Stephan; Oestereich, Lisa; Cadar, Daniel; Muñoz-Fontela, César; Bartoloni, Alessandro; Schmidt-Chanasit, Jonas

    2015-02-01

    We report the first two cases of laboratory confirmed Zika virus (ZIKV) infections imported into Italy from French Polynesia. Both patients presented with low grade fever, malaise, conjunctivitis, myalgia, arthralgia, ankle oedema, and axillary and inguinal lymphadenopathy. One patient showed leukopenia with relative monocytosis and thrombocytopenia. The diagnosis was based on ZIKV seroconversion in both cases and on ZIKV RNA detection in one patient from acute serum sample. Sera from both patients exhibited cross-reactivity with dengue virus antigens. Our immunological analysis demonstrated that recovery from ZIKV infection is associated with restoration of normal numbers of immune cells in the periphery as well as with normal function of antigen-presenting cells. ZIKV is an emerging arbovirus, which has recently spread extensively in tourist destinations on several West Pacific islands. Returning viremic travelers may ignite autochthonous infections in countries like Italy, which are infested by Aedes albopictus, a suitable vector for ZIKV. The role of clinicians is crucial and includes early diagnosis and timely notification of public health authorities in order to quickly implement adequate focal vector control measurements. PMID:25600600

  2. Effect of endosulfan on immunological competence of layer birds

    PubMed Central

    Singh, P. P.; Kumar, Ashok; Chauhan, R. S.; Pankaj, P. K.

    2016-01-01

    Aim: The present study was aimed to investigate the immunological competence of endosulfan insecticide after limited oral administration in White Leghorn layer chickens. Materials and Methods: A total of 20 White Leghorn birds were given endosulfan in drinking water at 30 ppm/bird/day (no observable effect level dose) for a period of 3-months. Immune competence status of layer birds and chicks hatched from endosulfan offered birds were estimated at 15-day interval in layer birds and at monthly interval in chicks using immunological, biochemical parameters, and teratological estimates. Results: There was a significant decrease in levels of total leukocytes count, absolute lymphocyte count, absolute heterophil count, total serum protein, serum albumin, serum globulin, and serum gamma globulin in the birds fed with endosulfan as compared to control. Similarly, immune competence tests such as lymphocyte stimulation test, oxidative burst assay, and enzyme-linked immunosorbent assay tests indicated lower immunity in birds treated with endosulfan as compared to control. Subsequently, chicks produced from endosulfan-treated birds were also examined for immune competence, but no significant difference was observed between chicks of both the groups. Conclusion: The exposure to endosulfan in limited oral dosage was able to exhibit hemo-biochemical and other changes that could be correlated with changes in the immunological profile of layer chickens suggesting cautious usage of endosulfan insecticide in poultry sheds. PMID:27536042

  3. 1989 Architectural Exhibition Winners.

    ERIC Educational Resources Information Center

    School Business Affairs, 1990

    1990-01-01

    Winners of the 1989 Architectural Exhibition sponsored annually by the ASBO International's School Facilities Research Committee include the Brevard Performing Arts Center (Melbourne, Florida), the Capital High School (Santa Fe, New Mexico), Gage Elementary School (Rochester, Minnesota), the Lakewood (Ohio) High School Natatorium, and three other…

  4. Exhibitions in Sight

    ERIC Educational Resources Information Center

    Wasserman, Burton

    1978-01-01

    During this past year a vast number of art shows have been exhibited across the United States. Their most striking features were their range and diversity. Here are some comments on Ben Shahn's paintings and photography focusing on social realism, some works by the Polish Constructivists, interested in redefining form in relation to space, the…

  5. 21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... derived from fungal or animal protein sources. When these antibodies react with such dusts in the lung... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological...

  6. 21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... derived from fungal or animal protein sources. When these antibodies react with such dusts in the lung... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological...

  7. 21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... derived from fungal or animal protein sources. When these antibodies react with such dusts in the lung... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological...

  8. 21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... derived from fungal or animal protein sources. When these antibodies react with such dusts in the lung... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological...

  9. Immunologic cross-reactivity among various strains of Sarcoptes scabiei.

    PubMed

    Arlian, L G; Morgan, M S; Arends, J J

    1996-02-01

    Varieties of Sarcoptes scabiei from different hosts are highly host specific but they are morphologically indistinguishable. The purpose of this study was to investigate the immunologic cross-reactivity among several varieties of scabies mites using serum from a human scabies patient and from several other species of infested hosts. Homologous and heterologous crossed-immunoelectrophoretic (CIE) analysis of extracts prepared from var. canis (dog) and var. suis (pig) mites yielded very similar antigen profiles. Serum from a human patient infested with var. hominis had circulating IgE that bound to antigens present in extracts prepared from each animal mite variety. Antigen homology was further confirmed by fused peaks on tandem CIE. Additionally, sodium dodecyl sulfate polyacrylamide gel electrophoresis/immunoblot analysis showed that the 2 extracts contained proteins that bound antibody in serum from a var. suis-infested pig, a var. canis-infested dog, var. canis-infested rabbits, and a var. hominis-infested human. The results of this study clearly indicate that different varieties of scabies mites, though host specific, introduce some immunologically cross-reactive molecules into the host. However, each serum from the 4 scabies-infested hosts also contained antibody that was specific for proteins in extract from only 1 variety of mite. These data indicated that each variety of scabies introduced some unique molecules into the host, each strain produced some similar molecules, or both, but different hosts responded immunologically to different sets of these. PMID:8627503

  10. Immunologic Changes Implicated in the Pathogenesis of Focal Segmental Glomerulosclerosis

    PubMed Central

    Kronbichler, Andreas; Leierer, Johannes; Oh, Jun; Meijers, Björn; Shin, Jae Il

    2016-01-01

    Focal segmental glomerulosclerosis is a histological pattern on renal biopsy caused by diverse mechanisms. In its primary form, a circulatory factor is implicated in disease onset and recurrence. The natural history of primary FSGS is unpredictable, since some patients are unresponsive towards immunosuppressive measures. Immunologic changes, leading to a proinflammatory or profibrotic milieu, have been implicated in disease progression, namely, glomerular scarring, eventually leading to end-stage renal disease. Among these, interleukin-1ß, tumor-necrosis factor-α (TNF-α), and transforming growth factor-ß1 (TGF-ß1) have emerged as important factors. Translating these findings into clinical practice dampened the enthusiasm, since both TNF-α and TGF-ß1 blockade failed to achieve significant control of the disease. More recently, a role of the complement system has been demonstrated which in fact may be another attractive target in clinical practice. Rituximab, blocking CD20-bearing cells, demonstrated conflicting data regarding efficacy in FSGS. Finally, the T-cell costimulating molecule B7-1 (CD80) is implicated in development of proteinuria in general. Blockade of this target demonstrated significant benefits in a small cohort of resistant patients. Taken together, this review focuses on immunology of FSGS, attributable to either the disease or progression, and discusses novel therapeutic approaches aiming at targeting immunologic factors. PMID:26989679

  11. The immunology of human and animal cysticercosis: a review

    PubMed Central

    Flisser, A.; Pérez-Montfort, R.; Larralde, C.

    1979-01-01

    In this review of the literature concerning the immunology of animal and human cysticercosis, emphasis is placed on whether previous exposure to the antigen confers protection to the host. Statistical analysis of the published data indicates that immunized animals have a lower risk than non-immunized animals of contracting cysticercosis, there being large variations within and between different host—cysticercus relationships. There is no indication as to which antigen is best for immunization but, although live parasites in all stages of development, or extracts, appear to give protection, embryos, eggs, and excretions are most frequently used. Antibodies appear to be the principal mediators of resistance, but the action seems to be only upon very young larvae, while fully grown cysticerci are unharmed. Several immunological methods are valuable in the diagnosis of cysticercosis, the choice depending more on the purpose of the study than on differences in their ability to discriminate between healthy and sick. The presence of anticysticercus antibodies in the serum of up to 50% of human patients indicates that human vaccination may be possible in high-risk areas; the remaining patients pose an interesting problem open to speculation and research on immunological evasion, immunodepression, and the existence of serotypes. ImagesFig. 3Fig. 4Fig. 4(Contd.) PMID:396058

  12. Blastocystis Isolates from Patients with Irritable Bowel Syndrome and from Asymptomatic Carriers Exhibit Similar Parasitological Loads, but Significantly Different Generation Times and Genetic Variability across Multiple Subtypes

    PubMed Central

    Ramirez-Guerrero, Celedonio; Vargas-Hernandez, Ines; Ramirez-Miranda, Maria Elena; Martinez-Ocaña, Joel; Valadez, Alicia; Ximenez, Cecilia; Lopez-Escamilla, Eduardo; Hernandez-Campos, Maria Elena; Villalobos, Guiehdani; Martinez-Hernandez, Fernando; Maravilla, Pablo

    2015-01-01

    Blastocystis spp is a common intestinal parasite of humans and animals that has been associated to the etiology of irritable bowel syndrome (IBS); however, some studies have not found this association. Furthermore, many biological features of Blastocystis are little known. The objective of present study was to assess the generation times of Blastocystis cultures, from IBS patients and from asymptomatic carriers. A total of 100 isolates were obtained from 50 IBS patients and from 50 asymptomatic carriers. Up to 50 mg of feces from each participant were cultured in Barret’s and in Pavlova’s media during 48 h. Initial and final parasitological load were measured by microscopy and by quantitative PCR. Amplicons were purified, sequenced and submitted to GenBank; sequences were analysed for genetic diversity and a Bayesian inference allowed identifying genetic subtypes (ST). Generation times for Blastocystis isolates in both media, based on microscopic measures and molecular assays, were calculated. The clinical symptoms of IBS patients and distribution of Blastocystis ST 1, 2 and 3 in both groups was comparable to previous reports. Interestingly, the group of cases showed scarce mean nucleotide diversity (π) as compared to the control group (0.011±0.016 and 0.118±0.177, respectively), whilst high gene flow and small genetic differentiation indexes between different ST were found. Besides, Tajima’s D test showed negative values for ST1-ST3. No statistical differences regarding parasitological load between cases and controls in both media, as searched by microscopy and by qPCR, were detected except that parasites grew faster in Barret’s than in Pavlova’s medium. Interestingly, slow growth of isolates recovered from cases in comparison to those of controls was observed (p<0.05). We propose that generation times of Blastocystis might be easily affected by intestinal environmental changes due to IBS probably because virulent strains with slow growth may be

  13. The 9th International Veterinary Immunology Symposium.

    PubMed

    Lunney, Joan K; Kai, Chieko; Inumaru, Shigeki; Onodera, Takashi

    2012-07-15

    This special issue of Veterinary Immunology and Immunopathology summarizes the Proceedings of the 9th International Veterinary Immunology Symposium (9th IVIS) held August 2010, in Tokyo, Japan. Over 340 delegates from 30 countries discussed research progress analyzing the immune systems of numerous food animals and wildlife, probing basic immunity and the influence of stress, genetics, nutrition, endocrinology and reproduction. Major presentations addressed defense against pathogens and alternative control and prevention strategies including vaccines, adjuvants and novel biotherapeutics. A special Organisation for Economic Co-operation and Development (OECD) Co-operative Research Programme Sponsored Conference on "Vaccination and Diagnosis for Food Safety in Agriculture" highlighted the particular issue of "Immunology in Bovine Paratuberculosis". In April 2010 there was an outbreak of foot-and-mouth disease (FMD) in the southern part of Japan. This stimulated a special 9th IVIS session on FMD, sponsored by the World Organization for Animal Health (OIE) and the Ministry of Agriculture, Forestry and Fisheries (MAFF) of Japan, to discuss improvements of FMD vaccines, their use in FMD control, and risk assessment for decision management. The 9th IVIS was supported by the Veterinary Immunology Committee (VIC) of the International Union of Immunological Societies (IUIS) and included workshops for its MHC and Toolkit Committees. Finally VIC IUIS presented its 2010 Distinguished Service Award to Dr. Kazuya Yamanouchi for "outstanding contributions to the veterinary immunology community" and its 2010 Distinguished Veterinary Immunologist Award to Dr. Douglas F. Antczak for "outstanding research on equine immunology". PMID:22766039

  14. Skylab Exhibit Ribbon Cutting

    NASA Technical Reports Server (NTRS)

    1976-01-01

    A metal strap became tangled over one of the folded solar array panels when Skylab lost its micro meteoroid shield during its launch. Cutters like the ones used to free the solar array were used to cut the ribbon opening to the public a new full-scale Skylab cluster exhibit at the Alabama Space and Rocket Center in Huntsville, Alabama. Wielding the cutters are (left to right): Alabama Senator James B. Allen; Marshall Space Flight Center director, Dr. William R. Lucas, Huntsville Mayor, Joe Davis; Madison County Commission Chairman, James Record (standing behind Mayor Davis); and chairman of the Alabama Space Science Exhibit Commission, Jack Giles. Astronauts Conrad and Kerwin used the same type of tool in Earth orbit to cut the aluminum strap which jammed the Skylab solar array.

  15. Schistosoma mansoni in a low-prevalence area in Brazil: the importance of additional methods for the diagnosis of hard-to-detect individual carriers by low-cost immunological assays

    PubMed Central

    Grenfell, Rafaella Fortini Queiroz; Martins, Watson; Enk, Martin; Almeida, Áureo; Siqueira, Liliane; Silva-Moraes, Vanessa; Oliveira, Edward; Carneiro, Nídia Francisca de Figueiredo; Coelho, Paulo Marcos Zech

    2013-01-01

    Schistosomiasis diagnosis is based on the detection of eggs in the faeces, which is laborious and lacks sensitivity, especially for patients with a low parasite burden. Immunological assays for specific antibody detection are available, but they usually demonstrate low sensitivity and/or specificity. In this study, two simple immunological assays were evaluated for the detection of soluble Schistosoma mansoni adult worm preparation (SWAP) and egg-specific IgGs. These studies have not yet been evaluated for patients with low parasite burdens. Residents of an endemic area in Brazil donated sera and faecal samples for our study. The patients were initially diagnosed by a rigorous Kato-Katz analysis of 18 thick smears from four different stool samples. The ELISA-SWAP was successful for human diagnosis with 90% sensitivity and specificity, confirming the Kato-Katz diagnosis with nearly perfect agreement, as seen by the Kappa index (0.85). Although the ELISA-soluble S. mansoni egg antigen was 85% sensitive, it exhibited low specificity (80%; Kappa index: 0.75) and was more susceptible to cross-reactivity. We believe that immunological assays should be used in conjunction with Kato-Katz analysis as a supplementary tool for the diagnosis of schistosomiasis for patients with low infection burdens, which are usually hard to detect. PMID:23778663

  16. WASp-dependent actin cytoskeleton stability at the dendritic cell immunological synapse is required for extensive, functional T cell contacts.

    PubMed

    Malinova, Dessislava; Fritzsche, Marco; Nowosad, Carla R; Armer, Hannah; Munro, Peter M G; Blundell, Michael P; Charras, Guillaume; Tolar, Pavel; Bouma, Gerben; Thrasher, Adrian J

    2016-05-01

    The immunological synapse is a highly structured and molecularly dynamic interface between communicating immune cells. Although the immunological synapse promotes T cell activation by dendritic cells, the specific organization of the immunological synapse on the dendritic cell side in response to T cell engagement is largely unknown. In this study, confocal and electron microscopy techniques were used to investigate the role of dendritic cell actin regulation in immunological synapse formation, stabilization, and function. In the dendritic cell-restricted absence of the Wiskott-Aldrich syndrome protein, an important regulator of the actin cytoskeleton in hematopoietic cells, the immunological synapse contact with T cells occupied a significantly reduced surface area. At a molecular level, the actin network localized to the immunological synapse exhibited reduced stability, in particular, of the actin-related protein-2/3-dependent, short-filament network. This was associated with decreased polarization of dendritic cell-associated ICAM-1 and MHC class II, which was partially dependent on Wiskott-Aldrich syndrome protein phosphorylation. With the use of supported planar lipid bilayers incorporating anti-ICAM-1 and anti-MHC class II antibodies, the dendritic cell actin cytoskeleton organized into recognizable synaptic structures but interestingly, formed Wiskott-Aldrich syndrome protein-dependent podosomes within this area. These findings demonstrate that intrinsic dendritic cell cytoskeletal remodeling is a key regulatory component of normal immunological synapse formation, likely through consolidation of adhesive interaction and modulation of immunological synapse stability. PMID:26590149

  17. Starship 2040 Exhibit

    NASA Technical Reports Server (NTRS)

    2002-01-01

    This photograph shows Justin Varnadore, son of a Marshall TV employee, at the controls of one of the many displays within the Starship 2040 exhibit on display at Joe Davis Stadium in Huntsville, Alabama. Developed by the Space Transportation Directorate at Marshall Space Flight Center (MSFC), the Starship 2040 exhibit is housed in a 48-ft (14.6-m) tractor and trailer rig, permitting it to travel around the Nation, demonstrating NASA's vision of what commercial spaceflight might be like 40 years from now. All the irnovations suggested aboard the exhibit (automated vehicle health monitoring systems, high-energy propulsion drive, navigational aids, and emergency and safety systems) are based on concepts and technologies now being studied at NASA Centers and partner institutions around the Nation. NASA is the Nation's premier agency for development of the space transportation system, including future-generation reusable launch vehicles. Such systems, the keys to a 'real' Starship 2040, require revolutionary advances in critical aerospace technologies, from thermal, magnetic, chemical, and propellantless propulsion systems to new energy sources such as space solar power or antimatter propulsion. These and other advances are now being studied, developed, and tested at NASA field centers and partner institutions all over the Nation.

  18. The immunology of parasite infections in immunocompromised hosts

    PubMed Central

    Evering, T.; Weiss, L. M.

    2011-01-01

    Summary Immune compromise can modify the severity and manifestation of some parasitic infections. More widespread use of newer immnosuppressive therapies, the growing population of individuals with immunocompromised states as well as the prolonged survival of these patients have altered the pattern of parasitic infection. This review article discusses the burden and immunology of parasitic infections in patients who are immunocompromised secondary to congenital immunodeficiency, malnutrition, malignancy, and immunosuppressive medications. This review does not address the literature on parasitic infections in the setting of HIV-1 infection. PMID:17042927

  19. Online Exhibits & Concept Maps

    NASA Astrophysics Data System (ADS)

    Douma, M.

    2009-12-01

    Presenting the complexity of geosciences to the public via the Internet poses a number of challenges. For example, utilizing various - and sometimes redundant - Web 2.0 tools can quickly devour limited time. Do you tweet? Do you write press releases? Do you create an exhibit or concept map? The presentation will provide participants with a context for utilizing Web 2.0 tools by briefly highlighting methods of online scientific communication across several dimensions. It will address issues of: * breadth and depth (e.g. from narrow topics to well-rounded views), * presentation methods (e.g. from text to multimedia, from momentary to enduring), * sources and audiences (e.g. for experts or for the public, content developed by producers to that developed by users), * content display (e.g. from linear to non-linear, from instructive to entertaining), * barriers to entry (e.g. from an incumbent advantage to neophyte accessible, from amateur to professional), * cost and reach (e.g. from cheap to expensive), and * impact (e.g. the amount learned, from anonymity to brand awareness). Against this backdrop, the presentation will provide an overview of two methods of online information dissemination, exhibits and concept maps, using the WebExhibits online museum (www.webexhibits.org) and SpicyNodes information visualization tool (www.spicynodes.org) as examples, with tips on how geoscientists can use either to communicate their science. Richly interactive online exhibits can serve to engage a large audience, appeal to visitors with multiple learning styles, prompt exploration and discovery, and present a topic’s breadth and depth. WebExhibits, which was among the first online museums, delivers interactive information, virtual experiments, and hands-on activities to the public. While large, multidisciplinary exhibits on topics like “Color Vision and Art” or “Calendars Through the Ages” require teams of scholars, user interface experts, professional writers and editors

  20. Immunologic Evaluation of Immediate Hypersensitivity to Cefaclor

    PubMed Central

    Yoo, Hye-Soo; Kim, Seung-Hyun; Kwon, Hyouk-Soo; Kim, Tae-Bum; Nam, Young-Hee; Ye, Young-Min

    2014-01-01

    Purpose Cefaclor is widely prescribed for various infectious diseases. As its consumption increases, the number of hypersensitivity reactions to cefaclor has increased. This study aimed to evaluate the immunologic findings of immediate hypersensitivity to cefaclor. Materials and Methods We enrolled 47 patients with immediate hypersensitivity to cefaclor from Ajou University Hospital and Asan Medical Center. Serum specific IgE, IgG1, and IgG4 antibodies to cefaclor-human serum albumin (HSA) conjugate were measured by enzyme-linked immunosorbent assay (ELISA). Results The most common phenotype was anaphylaxis (Group I, 78.7%), followed by urticaria (Group II, 21.3%). The detection of specific IgE, IgG1, and IgG4 to cefaclor-HSA conjugate by ELISA tended to be higher in Group I (40.5%, 41.7%, 21.6%) than in Group II (20.0%, 20.0%, 0%) with no statistical significance. Significant associations were found between specific IgE and IgG1 or IgG4 (p<0.001, p=0.019). ELISA inhibition tests showed significant inhibitions by both free cefaclor and cefaclor-HSA conjugate. For basophil activation tests in patients having no specific IgE antibody, the CD63 expression level on basophils increased with incubations of free cefaclor. Conclusion The most common manifestation of immediate hypersensitivity to cefaclor was anaphylaxis, most of which was mediated by IgE; however, a non-IgE mediated direct basophil activation mechanism was suggested in a subset of anaphylaxis patients. PMID:25323882

  1. Immunological aspects of corneal transplant.

    PubMed

    Kumar, Vijay; Kumar, Asha

    2014-01-01

    Corneal transplant is the most common solid tissue transplant in humans. Advances in microsurgical techniques, eye banking and the use of corticosteroids have improved the success of corneal transplants. Over 65,000 corneal transplants are being performed worldwide annually. Most of these transplants are performed in developed countries. Cornea is considered an immune privileged site. Despite this, immune mediated graft rejection is the most single cause of cornea graft failure and is one of the major postoperative complications. Incidences from as low as 2% to as high as 50% have been reported depending upon the degree of vascularization. Rejection involves donor tissue recognition and various factors may influence this rejection. Major factors include the antigenic load of the donor tissue; other factors include death to enucleation time, methods and temperature of preserving the tissue. Host factors that may impact the graft include ocular surface diseases such as dry eye, chemical burns and autoimmune diseases such as mucous membrane pemphigoid. Following infection, surgery or trauma, cells of the innate immune system invade the cornea as a result of up-regulation of cytokines, cellular adhesion molecules and growth and angiogenic factors. These factors results in neoangiogenesis and lymphoangiogenesis, leading to immune activation and graft rejection. The various immunological mechanisms that may play a role in the corneal transplant are discussed. PMID:25296240

  2. Instructive selection and immunological theory.

    PubMed

    Lederberg, Joshua

    2002-07-01

    The turning point of modern immunological theory was the advent of the clonal selection theory (Burnet, Talmage - 1957). A useful heuristic in the classification of theoretical models was the contrast of 'instructive' with 'selective' models of the acquisition of information by biological systems. The neo-Darwinian synthesis of the 1940s had consolidated biologists' model of evolution based on prior random variation and natural selection, viz. differential fecundity. While evolution in the large was by then pretty well settled, controversy remained about examples of cellular adaptation to chemical challenges, like induced drug-resistance, enzyme formation and the antibody response. While instructive theories have been on the decline, some clear cut examples can be found of molecular imprinting in the abiotic world, leading, e.g. to the production of specific sorbents. Template-driven assembly, as in DNA synthesis, has remained a paradigm of instructive specification. Nevertheless, the classification may break down with more microscopic scrutiny of the processes of molecular fit of substrates with enzymes, of monomers to an elongating polymer chain, as the reactants often traverse a state space from with activated components are appropriately selected. The same process may be 'instructive' from a holistic, 'selective' from an atomic perspective. PMID:12190921

  3. Pulmonary Surfactant: An Immunological Perspective

    PubMed Central

    Chroneos, Zissis C.; Sever-Chroneos, Zvjezdana; Shepherd, Virginia L.

    2009-01-01

    Pulmonary surfactant has two crucial roles in respiratory function; first, as a biophysical entity it reduces surface tension at the air water interface, facilitating gas exchange and alveolar stability during breathing, and, second, as an innate component of the lung's immune system it helps maintain sterility and balance immune reactions in the distal airways. Pulmonary surfactant consists of 90% lipids and 10% protein. There are four surfactant proteins named SP-A, SP-B, SP-C, and SP-D; their distinct interactions with surfactant phospholipids are necessary for the ultra-structural organization, stability, metabolism, and lowering of surface tension. In addition, SP-A and SP-D bind pathogens, inflict damage to microbial membranes, and regulate microbial phagocytosis and activation or deactivation of inflammatory responses by alveolar macrophages. SP-A and SP-D, also known as pulmonary collectins, mediate microbial phagocytosis via SP-A and SP-D receptors and the coordinated induction of other innate receptors. Several receptors (SP-R210, CD91/calreticulin, SIRPα, and toll-like receptors) mediate the immunological functions of SP-A and SP-D. However, accumulating evidence indicate that SP-B and SP-C and one or more lipid constituents of surfactant share similar immuno-regulatory properties as SP-A and SP-D. The present review discusses current knowledge on the interaction of surfactant with lung innate host defense. PMID:20054141

  4. Immunological and Hematopoietic Biotechnology Studies

    NASA Technical Reports Server (NTRS)

    Fernandez-Botran, Rafael; Sonnenfeld, Gerald

    1996-01-01

    The purpose of the work carried under this interchanges was to support the development of space flight biotechnology experiments in the areas of immunology and hematopoiesis to facilitate the commercial development of space. The studies involved the interaction and development of experiments with biotechnology companies for necessary ground-based studies to allow the development of flight studies. The thrust of the work was to develop experiments with the Chiron Corporation and Bioserve involving the use of interleukin-2 to modulate the effects of spaceflight on immune responses. Spaceflight has been shown to have multiple effects on immune responses (1). lnterleukin-2 is an immuno-regulator that could have potential to counter some of the alterations induced in immune responses by spaceflight (1). To test this possibility before flight, rats were suspended antiorthostatically (2) and treated with interleukin-2. Antiorthostatic suspension is a model for some of the effects of spaceflight on immune responses (2). The interleukin-2 was given to see if it could alter some of the effects of suspension. This was achieved. As a result of these studies, two flight experiments were developed and flown with the Chiron Corp. And Bioserve to determine if use of interleukin-2 could prevent or attenuate the effects of space flight on immune responses.

  5. Immunological Response to Biodegradable Magnesium Implants

    NASA Astrophysics Data System (ADS)

    Pichler, Karin; Fischerauer, Stefan; Ferlic, Peter; Martinelli, Elisabeth; Brezinsek, Hans-Peter; Uggowitzer, Peter J.; Löffler, Jörg F.; Weinberg, Annelie-Martina

    2014-04-01

    The use of biodegradable magnesium implants in pediatric trauma surgery would render surgical interventions for implant removal after tissue healing unnecessary, thereby preventing stress to the children and reducing therapy costs. In this study, we report on the immunological response to biodegradable magnesium implants—as an important aspect in evaluating biocompatibility—tested in a growing rat model. The focus of this study was to investigate the response of the innate immune system to either fast or slow degrading magnesium pins, which were implanted into the femoral bones of 5-week-old rats. The main alloying element of the fast-degrading alloy (ZX50) was Zn, while it was Y in the slow-degrading implant (WZ21). Our results demonstrate that degrading magnesium implants beneficially influence the immune system, especially in the first postoperative weeks but also during tissue healing and early bone remodeling. However, rodents with WZ21 pins showed a slightly decreased phagocytic ability during bone remodeling when the degradation rate reached its maximum. This may be due to the high release rate of the rare earth-element yttrium, which is potentially toxic. From our results we conclude that magnesium implants have a beneficial effect on the innate immune system but that there are some concerns regarding the use of yttrium-alloyed magnesium implants, especially in pediatric patients.

  6. Immunological and Psychological Benefits of Aromatherapy Massage

    PubMed Central

    2005-01-01

    This preliminary investigation compares peripheral blood cell counts including red blood cells (RBCs), white blood cells (WBCs), neutrophils, peripheral blood lymphocytes (PBLs), CD4+, CD8+ and CD16+ lymphocytes, CD4+/CD8+ ratio, hematocrit, humoral parameters including serum interferon-γ and interleukin-6, salivary secretory immunoglobulin A (IgA). Psychological measures including the State–Trait Anxiety Inventory (STAI) questionnaire and the Self-rating Depression Scale (SDS) between recipients (n = 11) of carrier oil massage and aromatherapy massage, which includes sweet almond oil, lavender oil, cypress oil and sweet marjoram oil. Though both STAI and SDS showed a significant reduction (P < 0.01) after treatment with aromatherapy and carrier massage, no difference between the aromatherapy and control massage was observed for STAI and SDS. Aromatherapy, in contrast to control massage, did not significantly reduce RBC count or hematocrit. However, aromatherapy massage showed a significant (P > 0.05) increase in PBLs, possibly due to an increase in CD8+ and CD16+ lymphocytes, which had significantly increased post-treatment (P < 0.01). Consequently, the CD4+/CD8+ ratio decreased significantly (P < 0.01). The paucity of such differences after carrier oil massage suggests that aromatherapy massage could be beneficial in disease states that require augmentation of CD8+ lymphocytes. While this study identifies the immunological benefits of aromatherapy massage, there is a need to validate the findings prospectively in a larger cohort of patients. PMID:15937558

  7. Space Shuttle Cockpit exhibit

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Want to sit in the cockpit of the Space Shuttle and watch astronauts work in outer space? At StenniSphere, you can do that and much more. StenniSphere, the visitor center at John C. Stennis Space Center in Hancock County, Miss., presents 14,000-square-feet of interactive exhibits that depict America's race for space as well as a glimpse of the future. StenniSphere is open free of charge from 9 a.m. to 5 p.m. daily.

  8. Pathogen evolution and the immunological niche

    PubMed Central

    Cobey, Sarah

    2014-01-01

    Host immunity is a major driver of pathogen evolution and thus a major determinant of pathogen diversity. Explanations for pathogen diversity traditionally assume simple interactions between pathogens and the immune system, a view encapsulated by the susceptible–infected–recovered (SIR) model. However, there is growing evidence that the complexity of many host–pathogen interactions is dynamically important. This revised perspective requires broadening the definition of a pathogen's immunological phenotype, or what can be thought of as its immunological niche. After reviewing evidence that interactions between pathogens and host immunity drive much of pathogen evolution, I introduce the concept of a pathogen's immunological phenotype. Models that depart from the SIR paradigm demonstrate the utility of this perspective and show that it is particularly useful in understanding vaccine-induced evolution. This paper highlights questions in immunology, evolution, and ecology that must be answered to advance theories of pathogen diversity. PMID:25040161

  9. Modeling-Enabled Systems Nutritional Immunology

    PubMed Central

    Verma, Meghna; Hontecillas, Raquel; Abedi, Vida; Leber, Andrew; Tubau-Juni, Nuria; Philipson, Casandra; Carbo, Adria; Bassaganya-Riera, Josep

    2016-01-01

    This review highlights the fundamental role of nutrition in the maintenance of health, the immune response, and disease prevention. Emerging global mechanistic insights in the field of nutritional immunology cannot be gained through reductionist methods alone or by analyzing a single nutrient at a time. We propose to investigate nutritional immunology as a massively interacting system of interconnected multistage and multiscale networks that encompass hidden mechanisms by which nutrition, microbiome, metabolism, genetic predisposition, and the immune system interact to delineate health and disease. The review sets an unconventional path to apply complex science methodologies to nutritional immunology research, discovery, and development through “use cases” centered around the impact of nutrition on the gut microbiome and immune responses. Our systems nutritional immunology analyses, which include modeling and informatics methodologies in combination with pre-clinical and clinical studies, have the potential to discover emerging systems-wide properties at the interface of the immune system, nutrition, microbiome, and metabolism. PMID:26909350

  10. Pathogen evolution and the immunological niche.

    PubMed

    Cobey, Sarah

    2014-07-01

    Host immunity is a major driver of pathogen evolution and thus a major determinant of pathogen diversity. Explanations for pathogen diversity traditionally assume simple interactions between pathogens and the immune system, a view encapsulated by the susceptible-infected-recovered (SIR) model. However, there is growing evidence that the complexity of many host-pathogen interactions is dynamically important. This revised perspective requires broadening the definition of a pathogen's immunological phenotype, or what can be thought of as its immunological niche. After reviewing evidence that interactions between pathogens and host immunity drive much of pathogen evolution, I introduce the concept of a pathogen's immunological phenotype. Models that depart from the SIR paradigm demonstrate the utility of this perspective and show that it is particularly useful in understanding vaccine-induced evolution. This paper highlights questions in immunology, evolution, and ecology that must be answered to advance theories of pathogen diversity. PMID:25040161

  11. Multiscale modelling in immunology: a review.

    PubMed

    Cappuccio, Antonio; Tieri, Paolo; Castiglione, Filippo

    2016-05-01

    One of the greatest challenges in biomedicine is to get a unified view of observations made from the molecular up to the organism scale. Towards this goal, multiscale models have been highly instrumental in contexts such as the cardiovascular field, angiogenesis, neurosciences and tumour biology. More recently, such models are becoming an increasingly important resource to address immunological questions as well. Systematic mining of the literature in multiscale modelling led us to identify three main fields of immunological applications: host-virus interactions, inflammatory diseases and their treatment and development of multiscale simulation platforms for immunological research and for educational purposes. Here, we review the current developments in these directions, which illustrate that multiscale models can consistently integrate immunological data generated at several scales, and can be used to describe and optimize therapeutic treatments of complex immune diseases. PMID:25810307

  12. Modeling-Enabled Systems Nutritional Immunology.

    PubMed

    Verma, Meghna; Hontecillas, Raquel; Abedi, Vida; Leber, Andrew; Tubau-Juni, Nuria; Philipson, Casandra; Carbo, Adria; Bassaganya-Riera, Josep

    2016-01-01

    This review highlights the fundamental role of nutrition in the maintenance of health, the immune response, and disease prevention. Emerging global mechanistic insights in the field of nutritional immunology cannot be gained through reductionist methods alone or by analyzing a single nutrient at a time. We propose to investigate nutritional immunology as a massively interacting system of interconnected multistage and multiscale networks that encompass hidden mechanisms by which nutrition, microbiome, metabolism, genetic predisposition, and the immune system interact to delineate health and disease. The review sets an unconventional path to apply complex science methodologies to nutritional immunology research, discovery, and development through "use cases" centered around the impact of nutrition on the gut microbiome and immune responses. Our systems nutritional immunology analyses, which include modeling and informatics methodologies in combination with pre-clinical and clinical studies, have the potential to discover emerging systems-wide properties at the interface of the immune system, nutrition, microbiome, and metabolism. PMID:26909350

  13. Obese First-Degree Relatives of Patients with Type 2 Diabetes with Elevated Triglyceride Levels Exhibit Increased β-Cell Function

    PubMed Central

    Torres-Rasgado, Enrique; Porchia, Leonardo M.; Ruiz-Vivanco, Guadalupe; Gonzalez-Mejia, M. Elba; Báez-Duarte, Blanca G.; Pulido-Pérez, Patricia; Rivera, Alicia; Romero, Jose R.

    2015-01-01

    Abstract Background: Type 2 diabetes mellitus (T2DM) is characterized as a disease continuum that is marked by metabolic changes that are present for several years, sometimes well before frank diagnosis of T2DM. Genetic predisposition, ethnicity, geography, alterations in BMI, and lipid profile are considered important markers for the pathogenesis of T2DM through mechanisms that remain unresolved and controversial. The aim of this study was to investigate the relationship between triglycerides (TGs) and β-cell function, insulin resistance (IR), and insulin sensitivity (IS) in obese first-degree relatives of patients with T2DM (FDR-T2DM) among subjects from central Mexico with normal glucose tolerance (NGT). Methods: We studied 372 FDR-T2DM subjects (ages,18–65) and determined body mass index (BMI), fasting plasma glucose (FPG), oral glucose tolerance test (OGTT), insulin, and TGs levels. Subjects were categorized based on glycemic control [NGT, prediabetes (PT2DM), or T2DM]. NGT subjects were further categorized by BMI [normal weight (Ob−) or obese (Ob+)] and TGs levels (TG−, <150 mg/dL, or TG+, ≥150 mg/dL). β-cell function, IR, and IS were determined by the homeostasis model assessment of β-cell function (HOMA2-β), homeostasis model assessment of insulin resistance (HOMA2-IR), and Quantitative Insulin Sensitivity Check Index (QUICKI) indices, respectively. Results: The obese subjects with elevated TGs levels had 21%–60% increased β-cell function when compared to all groups (P<0.05). In addition, this group had insulin levels, IS, and IR similar to PT2DM. Furthermore, only in obese subjects did TGs correlate with β-cell function (ρ=0.502, P<0.001). Conclusion: We characterized FDR-T2DM subjects from central Mexico with NGT and revealed a class of obese subjects with elevated TGs and β-cell function, which may precede PT2DM. PMID:25423015

  14. Communication, the centrosome and the immunological synapse

    PubMed Central

    Stinchcombe, Jane C.; Griffiths, Gillian M.

    2014-01-01

    Recent findings on the behaviour of the centrosome at the immunological synapse suggest a critical role for centrosome polarization in controlling the communication between immune cells required to generate an effective immune response. The features observed at the immunological synapse show parallels to centrosome (basal body) polarization seen in cilia and flagella, and the cellular communication that is now known to occur at all of these sites. PMID:25047617

  15. 21 CFR 866.5715 - Plasminogen immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Plasminogen immunological test system. 866.5715 Section 866.5715 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5715 Plasminogen immunological test system....

  16. 21 CFR 866.5735 - Prothrombin immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Prothrombin immunological test system. 866.5735 Section 866.5735 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5735 Prothrombin immunological test system....

  17. 21 CFR 866.5735 - Prothrombin immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Prothrombin immunological test system. 866.5735 Section 866.5735 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5735 Prothrombin immunological test system....

  18. 21 CFR 866.5715 - Plasminogen immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Plasminogen immunological test system. 866.5715 Section 866.5715 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5715 Plasminogen immunological test system....

  19. 21 CFR 866.5490 - Hemopexin immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Hemopexin immunological test system. 866.5490 Section 866.5490 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5490 Hemopexin immunological test system....

  20. 21 CFR 866.5490 - Hemopexin immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Hemopexin immunological test system. 866.5490 Section 866.5490 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5490 Hemopexin immunological test system....

  1. 21 CFR 866.5560 - Lactic dehydrogenase immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Lactic dehydrogenase immunological test system. 866.5560 Section 866.5560 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5560 Lactic dehydrogenase immunological...

  2. 21 CFR 866.5460 - Haptoglobin immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Haptoglobin immunological test system. 866.5460 Section 866.5460 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5460 Haptoglobin immunological test system....

  3. 21 CFR 866.5230 - Colostrum immunological test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Colostrum immunological test system. 866.5230 Section 866.5230 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5230 Colostrum immunological test system....

  4. 21 CFR 866.5230 - Colostrum immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Colostrum immunological test system. 866.5230 Section 866.5230 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5230 Colostrum immunological test system....

  5. 21 CFR 866.5230 - Colostrum immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Colostrum immunological test system. 866.5230 Section 866.5230 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5230 Colostrum immunological test system....

  6. 21 CFR 866.5230 - Colostrum immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Colostrum immunological test system. 866.5230 Section 866.5230 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5230 Colostrum immunological test system....

  7. 21 CFR 866.5230 - Colostrum immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Colostrum immunological test system. 866.5230 Section 866.5230 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5230 Colostrum immunological test system....

  8. First major museum exhibit on the science of AIDS.

    PubMed

    Nary, G

    1995-05-01

    The Chicago Museum of Science and Industry recently opened its 4,000-square-foot permanent exhibit on the science of AIDS. The exhibit is designed to educate visitors about immunology and virology by presenting AIDS as an example of an immune system breakdown and showing advances made in research and prevention of diseases caused by viruses. The exhibit also seeks to engage preteens with compelling graphics and interactive displays in the hope of motivating them to pursue careers in science. One exhibit, called Frontline, allows visitors to question several physicians and researchers specializing in HIV/AIDS through a touch-screen video program. The exhibit allows these professionals to reveal their commitment and explain their views on the future of the pandemic. PMID:11362508

  9. Utilizing social networks, blogging and YouTube in allergy and immunology practices.

    PubMed

    Dimov, Ves; Eidelman, Frank

    2015-01-01

    Online social networks are used to connect with friends and family members, and increasingly, to stay up-to-date with the latest news and developments in allergy and immunology. As communication is a central part of healthcare delivery, the utilization of such networking channels in allergy and immunology will continue to grow. There are inherent risks to online social networks related to breaches of patient confidentiality, professionalism and privacy. Malpractice and liability risks should also be considered. There is a paucity of information in the literature on how social network interventions affect patient outcomes. The allergy and immunology community should direct future studies towards investigating how the use of social networks and other technology tools and services can improve patient care. PMID:26163316

  10. The immunology of respiratory allergies.

    PubMed

    Frew, A J

    1996-08-01

    The main function of the respiratory tract is to provide a large surface area of thin epithelium for gas exchange. At the same time, this exposed surface and the conducting airways have to be defended against airborne irritants and infectious agents. The principal defence is the barrier formed by airway mucus and the mucociliary escalator. Agents which penetrate the initial defences may be destroyed by phagocytic cells, and may initiate an immune response. Respiratory allergy results when airborne allergens penetrate these defences and elicit and unhelpful immunological response. The nature of the airway immune response depends on the nature of the allergen, the antigen-processing pathway, and the microenvironment which dictates the phenotype of available T lymphocytes. Most allergens elicit IgE antibodies which then bind to mast cells and, when cross-linked, the mast cell releases inflammatory mediators which cause bronchospasm and mucus formation. Some chemical allergens appear able to trigger this pathway without involving IgE. In both cases, other inflammatory cells, especially eosinophils, are then recruited. These cells appear to be responsible for the epithelial damage and increased airways reactivity that characterise asthma. Similar histological patterns are found in atopic asthma, non-atopic asthma, occupational asthma due to low molecular weight chemicals and even in the reactive airways dysfunction syndrome (RADS)/irritant-induced asthma syndrome. Allergic airway inflammation and clinical asthma appear to be common histological and clinical consequences of a variety of specific and non-specific insults to the airways epithelium, airways mast cells and airways T lymphocytes. PMID:8711778

  11. Immunology of Corneal Allografts: Insights from Animal Models

    PubMed Central

    Niederkorn, Jerry Y.

    2015-01-01

    Corneal transplantation stands alone as the most common and successful form of solid organ transplantation. Even though HLA matching and systemic antirejection drugs are not routinely used, 90% of the first time corneal allografts will succeed. By contrast, all other major categories of organ transplantation require HLA matching and the use of systemically administered immunosuppressive drugs. This remarkable success of corneal transplants under these conditions is an example of “immune privilege” and is the primary reason for the extraordinary success of corneal transplantation. A number of dogmas have emerged over the past century to explain immune privilege and the immunobiology of corneal transplantation. Many of these dogmas have been based largely on inferences from clinical observations on keratoplasty patients. The past 30 years have witnessed a wealth of rodent studies on corneal transplantation that have tested hypotheses and dogmas that originated from clinical observations on penetrating keratoplasty patients. Rodent models allow the application of highly sophisticated genetic and immunological tools for testing these hypotheses in a controlled environment and with experiments designed prospectively. These studies have validated some of the widely held assumptions based on clinical observations and in other cases, previous dogmas have been replaced with new insights that could only come from prospective studies performed under highly controlled conditions. This review highlights some of the key dogmas and these widely held assumptions that have been scrutinized through the use of rodent models of penetrating keratoplasty. This review also makes note of new immunological principles of corneal immunology that have emerged from rodent studies on corneal transplantation that most likely would not have been revealed in studies on corneal transplantation patients. PMID:26301126

  12. [Prevalence of caries and its correlation with clinical and immunological classification in HIV-infected children].

    PubMed

    Castro, G F; de Souza, I P; e Oliveira, R H; Portela, M B; Esteves, C

    2001-01-01

    This research aims to determine the relationship between the prevalence of caries and clinical and immunological classification in HIV-infected children. Ninety-two outpatients (42 male and 50 female subjects) with definitive diagnosis of HIV infection took part in this research. The patients were examined in order to determine the prevalence of caries (dmf and DMFT indexes), and medical data were collected from their medical records. The mean age of the subjects was 5.77 years. Although no statistical differences were found, young patients (up to 5 years old) had more caries when they were more clinically and immunologically compromised. The same fact was observed regarding older children. PMID:11705204

  13. 21 CFR 866.5160 - Beta-globulin immunolog-ical test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Beta-globulin immunolog-ical test system. 866.5160 Section 866.5160 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... protein) in serum and other body fluids. Beta-globulin proteins include beta-lipoprotein,...

  14. SPECIAL ISSUE VETERINARY IMMUNOLOGY IMMUNOPATHOLOGY: PROCEEDINGS 8TH INTERNATIONAL VETERINARY IMMUNOLOGY SYMPOSIUM

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This is the Special Issue of Vet. Immunol. Immunopathol. that summarizes the 8th International Veterinary Immunology Symposium (8 th IVIS) held August 15th-19th, 2007, in Ouro Preto, Brazil. The 8 th IVIS highlighted the importance of veterinary immunology for animal health, vaccinology, reproducti...

  15. 21 CFR 866.5210 - Ceruloplasmin immunolog-ical test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ceruloplasmin immunolog-ical test system. 866.5210 Section 866.5210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... aid in the diagnosis of copper metabolism disorders. (b) Classification. Class II...

  16. 21 CFR 866.5210 - Ceruloplasmin immunolog-ical test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Ceruloplasmin immunolog-ical test system. 866.5210 Section 866.5210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... (copper-transporting serum protein) in serum, other body fluids, or tissues. Measurements of...

  17. 21 CFR 866.5210 - Ceruloplasmin immunolog-ical test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Ceruloplasmin immunolog-ical test system. 866.5210 Section 866.5210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... (copper-transporting serum protein) in serum, other body fluids, or tissues. Measurements of...

  18. 21 CFR 866.5210 - Ceruloplasmin immunolog-ical test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Ceruloplasmin immunolog-ical test system. 866.5210 Section 866.5210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... (copper-transporting serum protein) in serum, other body fluids, or tissues. Measurements of...

  19. 21 CFR 866.5160 - Beta-globulin immunolog-ical test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Beta-globulin immunolog-ical test system. 866.5160 Section 866.5160 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... protein) in serum and other body fluids. Beta-globulin proteins include beta-lipoprotein,...

  20. 21 CFR 866.5590 - Lipoprotein X immunolog-ical test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Lipoprotein X immunolog-ical test system. 866.5590 Section 866.5590 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...-density lipoprotein) in serum and other body fluids. Measurement of lipoprotein X aids in the diagnosis...

  1. 21 CFR 866.5160 - Beta-globulin immunolog-ical test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Beta-globulin immunolog-ical test system. 866.5160 Section 866.5160 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... protein) in serum and other body fluids. Beta-globulin proteins include beta-lipoprotein,...

  2. 21 CFR 866.5590 - Lipoprotein X immunolog-ical test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Lipoprotein X immunolog-ical test system. 866.5590 Section 866.5590 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...-density lipoprotein) in serum and other body fluids. Measurement of lipoprotein X aids in the diagnosis...

  3. 21 CFR 866.5160 - Beta-globulin immunolog-ical test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Beta-globulin immunolog-ical test system. 866.5160 Section 866.5160 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... protein) in serum and other body fluids. Beta-globulin proteins include beta-lipoprotein,...

  4. 21 CFR 866.5590 - Lipoprotein X immunolog-ical test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Lipoprotein X immunolog-ical test system. 866.5590 Section 866.5590 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...-density lipoprotein) in serum and other body fluids. Measurement of lipoprotein X aids in the diagnosis...

  5. 21 CFR 866.5590 - Lipoprotein X immunolog-ical test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Lipoprotein X immunolog-ical test system. 866.5590 Section 866.5590 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...-density lipoprotein) in serum and other body fluids. Measurement of lipoprotein X aids in the diagnosis...

  6. 21 CFR 866.5210 - Ceruloplasmin immunolog-ical test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Ceruloplasmin immunolog-ical test system. 866.5210 Section 866.5210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... (copper-transporting serum protein) in serum, other body fluids, or tissues. Measurements of...

  7. 21 CFR 866.5160 - Beta-globulin immunolog-ical test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Beta-globulin immunolog-ical test system. 866.5160 Section 866.5160 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... protein) in serum and other body fluids. Beta-globulin proteins include beta-lipoprotein,...

  8. Refractory Immunological Thrombocytopenia Purpura and Splenectomy in Pregnancy

    PubMed Central

    Bernal-Macías, Santiago; Fino-Velásquez, Laura-Marcela; Vargas-Barato, Felipe E.; Guerra-Galue, Lucio; Reyes-Beltrán, Benjamín; Rojas-Villarraga, Adriana

    2015-01-01

    Thrombocytopenia is defined as a platelet count of less than 100,000 platelets per microlitre (mcL). Thrombocytopenia develops in approximately 6-7% of women during pregnancy and at least 3% of these cases are caused by immunological platelet destruction. Herein, we present a pregnant woman who develops at the first trimester autoimmune thrombocytopenia purpura associated with positive antiphospholipid antibodies. The disease was refractory to pharmacological treatments but had a favourable response to splenectomy. The patient carried the pregnancy to term without complication and gave birth to a healthy baby girl. PMID:26798527

  9. Modification of soluble immunological parameters during treatment with interleukin-2.

    PubMed

    Abbate, I; Correale, M; Musci, M D; Guida, M; Dragone, C D; De Santis, M; De Lena, M

    1993-01-01

    In the present study we tested numerous soluble immunological parameters (soluble Interleukin 2 receptor, Beta 2 microglobulin, Neopterin, soluble CD8 antigen, gamma Interferon and alpha Tumor Necrosis Factor) in sera obtained from 18 advanced cancer patients during subcutaneous treatment with recombinant Interleukin 2. The treatment cycles consisted of a dose of 9 x 10(6) IU/m2 twice daily for 2 days followed by 1.8 x 10(6) IU/m2 twice daily for 5 days/week during 6 weeks. Even before therapy, neoplastic patients had higher levels of soluble Interleukin 2 receptor than a group of healthy subjects. Moreover, basal soluble CD8 antigen levels showed significant differences (p < 0.01) in patients with different clinical responses (responders and non-responders). During treatment we observed a fast increase (in the first or second week) of all parameters considered; soluble Interleukin 2 receptor and soluble CD8 antigen were the markers that were best related to the course of immunotherapy. In conclusion, monitoring recombinant Interleukin 2 immunotherapy with immunological parameters in serum seems to be of interest. However, more data are necessary to confirm the real value of the single markers. PMID:8138662

  10. Immunological Challenges and Therapies in Xenotransplantation

    PubMed Central

    Vadori, Marta; Cozzi, Emanuele

    2014-01-01

    Xenotransplantation, or the transplantation of cells, tissues, or organs between different species, was proposed a long time ago as a possible solution to the worldwide shortage of human organs and tissues for transplantation. In this setting, the pig is currently seen as the most likely candidate species. In the last decade, progress in this field has been remarkable and includes a better insight into the immunological mechanisms underlying the rejection process. Several immunological hurdles nonetheless remain, such as the strong antibody-mediated and innate or adaptive cellular immune responses linked to coagulation derangements, precluding indefinite xenograft survival. This article reviews our current understanding of the immunological mechanisms involved in xenograft rejection and the potential strategies that may enable xenotransplantation to become a clinical reality in the not-too-distant future. PMID:24616201

  11. Comparative Anatomy of Phagocytic and Immunological Synapses

    PubMed Central

    Niedergang, Florence; Di Bartolo, Vincenzo; Alcover, Andrés

    2016-01-01

    The generation of phagocytic cups and immunological synapses are crucial events of the innate and adaptive immune responses, respectively. They are triggered by distinct immune receptors and performed by different cell types. However, growing experimental evidence shows that a very close series of molecular and cellular events control these two processes. Thus, the tight and dynamic interplay between receptor signaling, actin and microtubule cytoskeleton, and targeted vesicle traffic are all critical features to build functional phagosomes and immunological synapses. Interestingly, both phagocytic cups and immunological synapses display particular spatial and temporal patterns of receptors and signaling molecules, leading to the notion of “phagocytic synapse.” Here, we discuss both types of structures, their organization, and the mechanisms by which they are generated and regulated. PMID:26858721

  12. [Immunological surrogate endpoints to evaluate vaccine efficacy].

    PubMed

    Jin, Pengfei; Li, Jingxin; Zhou, Yang; Zhu, Fengcai

    2015-12-01

    An immunological surrogate endpoints is a vaccine-induced immune response (either humoral or cellular immune) that predicts protection against clinical endpoints (infection or disease), and can be used to evaluate vaccine efficacy in clinical vaccine trials. Compared with field efficacy trials observing clinical endpoints, immunological vaccine trials could reduce the sample size or shorten the duration of a trial, which promote the license and development of new candidate vaccines. For these reasons, establishing immunological surrogate endpoints is one of 14 Grand Challenges of Global Health of the National Institutes of Health (NIH) and the Bill and Melinda Gates Foundation. From two parts of definition and statistical methods for evaluation of surrogate endpoints, this review provides a more comprehensive description. PMID:26887309

  13. Systemic lupus erythematosus in men: clinical and immunological characteristics.

    PubMed Central

    Font, J; Cervera, R; Navarro, M; Pallarés, L; López-Soto, A; Vivancos, J; Ingelmo, M

    1992-01-01

    Although systemic lupus erythematosus (SLE) has traditionally been considered a disease of women, men may also be affected. Thirty of 261 patients (12%) with SLE seen in this hospital were men. Arthritis was less common as a first symptom in the men, although this group of patients had discoid lesions and serositis more often than the women. During the follow up a lower incidence of arthritis and malar rash and a higher incidence of other skin complications including discoid lesions and subcutaneous lupus erythematosus was found in the men. The incidence of nephropathy, neurological disease, thrombocytopenia, vasculitis, and serositis, was similar in the two groups. No significant immunological differences were found between men and women. These features indicate that several gender associated clinical differences may be present in patients with SLE. PMID:1417135

  14. What Can Vampires Teach Us about Immunology?

    PubMed

    Schneider, David S

    2016-04-01

    Speculative fiction examines the leading edge of science and can be used to introduce ideas into the classroom. For example, most students are already familiar with the fictional infectious diseases responsible for vampire and zombie outbreaks. The disease dynamics of these imaginary ailments follow the same rules we see for real diseases and can be used to remind students that they already understand the basic rules of disease ecology and immunology. By engaging writers of this sort of fiction in an effort to solve problems in immunology we may be able to perform a directed evolution experiment where we follow the evolution of plots rather than genetic traits. PMID:26968492

  15. Molecular Programming of Immunological Memory in Natural Killer Cells.

    PubMed

    Beaulieu, Aimee M; Madera, Sharline; Sun, Joseph C

    2015-01-01

    Immunological memory is a hallmark of the adaptive immune system. Although natural killer (NK) cells have traditionally been classified as a component of the innate immune system, they have recently been shown in mice and humans to exhibit certain features of immunological memory, including an ability to undergo a clonal-like expansion during virus infection, generate long-lived progeny (i.e. memory cells), and mediate recall responses against previously encountered pathogens--all characteristics previously ascribed only to adaptive immune responses by B and T cells in mammals. To date, the molecular events that govern the generation of NK cell memory are not completely understood. Using a mouse model of cytomegalovirus infection, we demonstrate that individual pro-inflammatory IL-12, IL-18, and type I-IFN signaling pathways are indispensible and play non-redundant roles in the generation of virus-specific NK cell memory. Furthermore, we discovered that antigen-specific proliferation and protection by NK cells is mediated by the transcription factor Zbtb32, which is induced by pro-inflammatory cytokines and promotes a cell cycle program in activated NK cells. A greater understanding of the molecular mechanisms controlling NK cell responses will provide novel strategies for tailoring vaccines to target infectious disease. PMID:26324348

  16. Novel immunologic tolerance of human cancer cell xenotransplants in zebrafish.

    PubMed

    Zhang, Beibei; Shimada, Yasuhito; Hirota, Tomokazu; Ariyoshi, Michiko; Kuroyanagi, Junya; Nishimura, Yuhei; Tanaka, Toshio

    2016-04-01

    Immune deficiency or suppression in host animals is an essential precondition for the success of cancer cell xenotransplantation because the host immune system has a tendency to reject implanted cells. However, in such animals, the typical tumor microenvironment seen in cancer subjects does not form because of the lack of normal immunity. Here, we developed a novel zebrafish (Danio rerio) model based on 2 rounds of cancer cell xenotransplantation that achieved cancer-specific immunologic tolerance without immunosuppression. We irradiated human cancer cells (PC-3, K562 and HepG2) to abolish their proliferative abilities and implanted them into zebrafish larvae. These cells survived for 2 weeks in the developing host. Three months after the first implantation, the zebrafish were implanted with the same, but nonirradiated, cell lines. These cancer cells proliferated and exhibited metastasis without immune suppression. To reveal the transcriptional mechanism of this immune tolerance, we conducted dual RNA-seq of the tumor with its surrounding tissues and identified several regulatory zebrafish genes that are involved in immunity; the expression of plasminogen activator, urokinase, and forkhead box P3 was altered in response to immunologic tolerance. In conclusion, this xenograft method has potential as a platform for zebrafish-based anticancer drug discovery because it can closely mimic human clinical cancers without inducing immune suppression. PMID:26746804

  17. [Experimental, clinical and immunologic assessment of acellular staphylococcal vaccine "Staphylovac"].

    PubMed

    Egorova, N B; Efremova, V N; Kurbatova, E A; Gruber, I M

    2008-01-01

    Results of experimental, clinical and immunological effects of acellular dry staphylococcal vaccine "Staphylovac" developed in Mechnikov Research Institute of Vaccines and Sera are presented. Original mildly virulent strains of Staphylococcus aureus having high immunogenicity, and intra- and interspecies protective activity against different representatives of opportunistic microflora were used for construction of the preparation. Low-toxicity and weak anapylactogenicity of the vaccine were established. In experiments on mice, guinea pigs and rabbits significant protective, antigenic and immunomodulate activity of the preparation was revealed with low sensitization of animals. Clinical trials performed in different centers showed that inclusion of vaccinotherapy in complex treatment of chronic staphylococcal infections (chronic pyodermia, lung abscess etc.) resulted in prolonged pathologic locus, decrease of number and severity of exacerbations, prolongation of remission, and complete recovery in significant number of patients. Activation of innate and adaptive immunity was revealed in the same patients. It was shown on the large group of athletes that administration of the vaccine by aerosol route prevents disruption of immunologic adaptation occurring due to excess physical activity and stress situations during competitions. PMID:19186558

  18. Immunological risk assessment: The key to individualized immunosuppression after kidney transplantation.

    PubMed

    Pratschke, Johann; Dragun, Duska; Hauser, Ingeborg A; Horn, Sabine; Mueller, Thomas F; Schemmer, Peter; Thaiss, Friedrich

    2016-04-01

    The wide range of immunosuppressive therapies and protocols permits tailored planning of the initial regimen according to the immunological risk status of individual patients. Pre-transplant risk assessment can include many factors, but there is no clear consensus on which parameters to take into account, and their relative importance. In general younger patients are known to be at higher risk for acute rejection, compounded by higher rates of non-adherence in adolescents. Donor age and recipient gender do not appear to exert a meaningful effect on risk of rejection per se, but black recipient ethnicity remains a well-established risk factor even under modern immunosuppression regimens. Little difference in risk is now observed between deceased- and living-donor recipients. Immunological risk assessment has developed substantially in recent years. Cross-match testing with cytotoxic analysis has long been supplemented by flow cytometry, but development of solid-phase single-bead antigen testing of solubilized human leukocyte antigens (HLA) to detect donor-specific antibodies (DSA) permits a far more nuanced stratification of immunological risk status, including the different classes and intensities of HLA antibodies Class I and/or II, including HLA-DSA. Immunologic risk evaluation is now often based on a combination of these tests, but other assessments are becoming more widely introduced, such as measurement of non-HLA antibodies against angiotensin type 1 (AT1) receptors or T-cell ELISPOT assay of alloantigen-specific donor. Targeted densensitization protocols can improve immunological risk, notably for DSA-positive patients with negative cytotoxicity and flow cross-match. HLA mismatch remains an important and undisputed risk factor for rejection. Delayed graft function also increases the risk of subsequent acute rejection, and the early regimen can be modified in such cases. Overall, there is a shift towards planning the immunosuppressive regimen based on pre

  19. Immunological effects of the anti-programmed death-1 antibody on human peripheral blood mononuclear cells.

    PubMed

    Akiyama, Yasuto; Nonomura, Chizu; Kondou, Ryota; Miyata, Haruo; Ashizawa, Tadashi; Maeda, Chie; Mitsuya, Koichi; Hayashi, Nakamasa; Nakasu, Yoko; Yamaguchi, Ken

    2016-09-01

    Immune checkpoint antibody-mediated blockade has gained attention as a new cancer immunotherapy strategy. Accumulating evidence suggests that this therapy imparts a survival benefit to metastatic melanoma and non-small cell lung cancer patients. A substantial amount of data on immune checkpoint antibodies has been collected from clinical trials; however, the direct effect of the antibodies on human peripheral blood mononuclear cells (PBMCs) has not been exclusively investigated. In this study, we developed an anti-programmed death-1 (PD-1) antibody (with biosimilarity to nivolumab) and examined the effects of the antibody on PBMCs derived from cancer patients. Specifically, we investigated the effects of the anti-PD-1 antibody on proliferation, cytokine production, cytotoxic T lymphocytes (CTL) and regulatory T cells. These investigations yielded several important results. First, the anti-PD-1 antibody had no obvious effect on resting PBMCs; however, high levels of the anti-PD-1 antibody partly stimulated PBMC proliferation when accompanied by an anti-CD3 antibody. Second, the anti-PD-1 antibody restored the growth inhibition of anti-CD3 Ab-stimulated PBMCs mediated by PD-L1. Third, the anti-PD-1 antibody exhibited a moderate inhibitory effect on the induction of myeloid-derived suppressor cells (MDSCs) by anti-CD3 antibody stimulation. Additionally, the presence of the anti-PD-1 antibody promoted antigen-specific CTL induction, which suggests that combining anti-PD-1 antibody and conventional immunotherapy treatments may have beneficial effects. These results indicate that specific cellular immunological mechanisms are partly responsible for the antitumor effect exhibited by the anti-PD-1 antibody against advanced cancers in clinical trials. PMID:27573705

  20. The Porcine Immunology and Nutrition Resource Database

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Diverse genomics-based databases have been developed to facilitate research with human and rodent models. Current porcine gene databases, however, lack the nutritional and immunological orientation and robust annotation to design effective molecular tools to study relevant pig models. To address t...

  1. Immunology of Paratuberculosis Infection and Disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The study of host immune responses to Mycobacterium avium subsp. paratuberculosis (MAP) is complicated by a number of factors, including the protracted nature of the disease and the stealthy nature of the pathogen. Improved tools for the measurement of immunologic responses in ruminant species, par...

  2. Immunology of Archaebacteria that produce methane gas

    SciTech Connect

    Conway de Macario, E.; Wolin, M.J.; Macario, A.J.L.

    1981-10-02

    The antigenic map of 17 methanogenic bacteria representing the entire range of available species was determined by multiple assay with antibody probes. Four major clusters of antigenically related strains coincide with the families proposed on the basis of 16S ribosomal RNA analysis. Immunological mapping uncovered relationships not yet shown by other methods and allowed identification and classification of two new bacterial isolates.

  3. Pros and cons of immunological methods

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The International regulatory agencies Codex Alimentarius, European Commission Regulation and the U.S. Food and Drug Administration have set 20 mg/kg (ppm) as the maximum limit of gluten allowed in foods labeled as “gluten-free”. Immunological approaches appear to be, so far, the most suitable method...

  4. What's so special about chicken immunology?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    What’s so special about chickens? Firstly, chickens are not only an invaluable model for studying immunology, they also provide the world’s main source of meat and will be a key protein source needed to feed the growing human population into the future. Poultry meat production is highly efficient ...

  5. 21 CFR 866.5090 - Antimitochondrial antibody immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test... immunochemical techniques the antimitochondrial antibodies in human serum. The measurements aid in the diagnosis of diseases that produce a spectrum of autoantibodies (antibodies produced against the body's...

  6. 21 CFR 866.5090 - Antimitochondrial antibody immunological test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test... immunochemical techniques the antimitochondrial antibodies in human serum. The measurements aid in the diagnosis of diseases that produce a spectrum of autoantibodies (antibodies produced against the body's...

  7. 21 CFR 866.5090 - Antimitochondrial antibody immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test... immunochemical techniques the antimitochondrial antibodies in human serum. The measurements aid in the diagnosis of diseases that produce a spectrum of autoantibodies (antibodies produced against the body's...

  8. 21 CFR 866.5090 - Antimitochondrial antibody immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test... immunochemical techniques the antimitochondrial antibodies in human serum. The measurements aid in the diagnosis of diseases that produce a spectrum of autoantibodies (antibodies produced against the body's...

  9. Immunologic Aging in Adults with Congenital Heart Disease: Does Infant Sternotomy Matter?

    PubMed

    Elder, Robert W; George, Roshan P; McCabe, Nancy M; Rodriguez Iii, Fred H; Book, Wendy M; Mahle, William T; Kirk, Allan D

    2015-10-01

    Thymectomy is performed routinely in infants undergoing cardiothoracic surgery. Children post-sternotomy have decreased numbers of T lymphocytes, although the mechanisms involved and long-term consequences of this have not been defined. We hypothesized that lymphopenia in patients with adult congenital heart disease (ACHD) would be reflective of premature T cell maturation and exhaustion. Adults with ACHD who had sternotomy to repair congenital heart disease as infants (<1 year) and age-matched ACHD patients without prior sternotomy were studied using polychromatic flow cytometry interrogating markers of lymphocyte maturation, exhaustion and senescence. Group differences were analyzed using Mann-Whitney U and Fisher's exact tests. Eighteen ACHD patients aged 21-40 years participated: 10 cases and 8 controls. Median age at sternotomy for cases was 52 days. Cases and controls were matched for age (28.9 vs. 29.1 years; p = 0.83), gender (p = 0.15) and race (p = 0.62) and had similar case complexity. Cases had a lower mean percentage of cytotoxic CD8 lymphocytes compared to controls (26.8 vs. 33.9 %; p = 0.016), with fewer naive, undifferentiated CD8 T cells (31.0 vs. 53.6 %; p = 0.027). CD8 cells expressing PD1, a marker of immune exhaustion, trended higher in cases versus controls (25.6 vs. 19.0 %; p = 0.083). Mean percentage of CD4 cells was higher in cases versus controls (65.6 vs. 59.6 %; p = 0.027), without differences in CD4 T cell maturation subtype. In summary, ACHD patients who undergo sternotomy as infants exhibit differences in T lymphocyte composition compared to ACHD controls, suggesting accelerated immunologic exhaustion. Investigation is warranted to assess the progressive nature and clinical impact of this immune phenotypic change. PMID:25916315

  10. Hypersensitivity Pneumonitis by a Cool-Mist Vaporizer a Detailed Microbiologic and Immunologic Study

    PubMed Central

    Chung, Jae Chun; Choi, Jin Myung; Lee, Hyun Woo; Hong, Suhk; Kim, Chung Sook

    1989-01-01

    A patient with hypersensitivity pneumonitis caused by a contaminated cool-mist vaporizer was evaluated. A detailed microbiologic and immunologic study was done, and a Pseudomonas species was isolated as the possible causative organism by inhalational provocative and serologic tests. PMID:2486849

  11. 21 CFR 866.6010 - Tumor-associated antigen immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Tumor-associated antigen immunological test system. 866.6010 Section 866.6010 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN..., plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for...

  12. 21 CFR 866.6010 - Tumor-associated antigen immunological test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Tumor-associated antigen immunological test system. 866.6010 Section 866.6010 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN..., plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for...

  13. 21 CFR 866.6010 - Tumor-associated antigen immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Tumor-associated antigen immunological test system. 866.6010 Section 866.6010 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN..., plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for...

  14. 21 CFR 866.6010 - Tumor-associated antigen immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Tumor-associated antigen immunological test system. 866.6010 Section 866.6010 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN..., plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for...

  15. Antitumor vaccines, immunotherapy and the immunological constant of rejection

    PubMed Central

    Wang, Ena; Monaco, Alessandro; Monsurró, Vladia; Sabatino, Marianna; Pos, Zoltan; Uccellini, Lorenzo; Wang, Jeanne; Worschech, Andrea; Stroncek, David F

    2012-01-01

    Anti-cancer vaccines have not matched the clinical expectations projected from their ability to induce consistently systemic anti-cancer T-cell responses. Thus, a dichotomy is observed between the immunological and clinical endpoints of anti-cancer immunization. Anti-cancer vaccines have clearly demonstrated that highly specific T-cell responses can be induced that can recognize autologous cancer antigens in patients with cancer. This ability is an outstanding achievement of modern biotechnology, yielding one of the most specific types of potential anti-cancer reagents. However, systemic, vaccine-induced anti-cancer responses exemplify a broader immunological paradox: cytotoxic T-cells can coexist within the same organism with their target cells not only in the context of cancer, but also in the context of chronic infections, well-controlled allo-transplant reactions and autoimmunity. According to this view, anti-cancer immune responses are a facet of a tissue-specific autoimmune phenomenon specific for cancer tissue that may or may not result in the successful immune-destruction of target cells, depending on an assortment of genetic factors related to the background of the host or evolving phenotypes of a heterogeneous cancer environment. This feature article summarizes the current understanding of the mechanisms leading to tumor rejection in humans as well as in experimental models, in the context of the broader immunological phenomenon leading to tissue-specific destruction. Anti-cancer vaccines that may not induce clinically significant anti-cancer responses independently could function as a unique tool to enhance the specificity of the response of the host against cancer, provided that strategies are implemented to amplify the immune reaction initiated by vaccine-induced antibodies and/or T-cells. PMID:19431094

  16. Anti-tumor response with immunologically modified carbon nanotubes and phototherapy

    NASA Astrophysics Data System (ADS)

    Acquaviva, Joseph T.; Zhou, Feifan; Boarman, Ellen; Chen, Wei R.

    2013-02-01

    While successes of different cancer therapies have been achieved in various degrees a systemic immune response is needed to effectively treat late-stage, metastatic cancers, and to establish long-term tumor resistance in the patients. A novel method for combating metastatic cancers has been developed using immunologically modified carbon nanotubes in conjunction with phototherapy. Glycated chitosan (GC) is a potent immunological adjuvant capable of increasing host immune responses, including antigen presentation by activation of dendritic cells (DCs) and causing T cell proliferation. GC is also an effective surfactant for nanomaterials. By combining single-walled carbon nanotubes (SWNTs) and GC, immunologically modified carbon nanotubes (SWNT-GC) were constructed. The SWNT-GC suspension retains the enhanced light absorption properties in the near infrared (NIR) region and the ability to enter cells, which are characteristic of SWNTs. The SWNT-GC also retains the immunological properties of GC. Cellular SWNT-GC treatments increased macrophage activity, DC activation and T cell proliferation. When cellular SWNT-GC was irradiated with a laser of an appropriate wavelength, these immune activities could be enhanced. The combination of laser irradiation and SWNT-GC induced cellular toxicity in targeted tumor cells, leading to a systemic antitumor response. Immunologically modified carbon nanotubes in conjunction with phototherapy is a novel and promising method to produce a systemic immune response for the treatment of metastatic cancers.

  17. 21 CFR 866.5170 - Breast milk immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Breast milk immunological test system. 866.5170... milk immunological test system. (a) Identification. A breast milk immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the breast milk proteins....

  18. 21 CFR 866.5170 - Breast milk immunological test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Breast milk immunological test system. 866.5170... milk immunological test system. (a) Identification. A breast milk immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the breast milk proteins....

  19. 21 CFR 866.5470 - Hemoglobin immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Hemoglobin immunological test system. 866.5470... Hemoglobin immunological test system. (a) Indentification. A hemoglobin immunological test system is a device... hemoglobin (the oxygen-carrying pigment in red blood cells) in blood, urine, plasma, or other body...

  20. 21 CFR 866.5640 - Infectious mononucleosis immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Infectious mononucleosis immunological test system. 866.5640 Section 866.5640 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5640 Infectious...

  1. 21 CFR 866.5750 - Radioallergosorbent (RAST) immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Radioallergosorbent (RAST) immunological test system. 866.5750 Section 866.5750 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological...

  2. 21 CFR 866.5750 - Radioallergosorbent (RAST) immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Radioallergosorbent (RAST) immunological test system. 866.5750 Section 866.5750 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological...

  3. 21 CFR 866.5750 - Radioallergosorbent (RAST) immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Radioallergosorbent (RAST) immunological test system. 866.5750 Section 866.5750 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5750 Radioallergosorbent...

  4. 21 CFR 866.5750 - Radioallergosorbent (RAST) immunological test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Radioallergosorbent (RAST) immunological test system. 866.5750 Section 866.5750 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5750 Radioallergosorbent...

  5. 21 CFR 866.5750 - Radioallergosorbent (RAST) immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Radioallergosorbent (RAST) immunological test system. 866.5750 Section 866.5750 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological...

  6. 21 CFR 866.5090 - Antimitochondrial antibody immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Antimitochondrial antibody immunological test... Systems § 866.5090 Antimitochondrial antibody immunological test system. (a) Identification. An antimitochondrial antibody immunological test system is a device that consists of the reagents used to measure...

  7. 21 CFR 866.5170 - Breast milk immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Breast milk immunological test system. 866.5170... milk immunological test system. (a) Identification. A breast milk immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the breast milk proteins....

  8. 42 CFR 493.1208 - Condition: General immunology.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 5 2012-10-01 2012-10-01 false Condition: General immunology. 493.1208 Section 493....1208 Condition: General immunology. If the laboratory provides services in the subspecialty of General immunology, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, and §§...

  9. 42 CFR 493.833 - Condition: Diagnostic immunology.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 5 2014-10-01 2014-10-01 false Condition: Diagnostic immunology. 493.833 Section..., Or Any Combination of These Tests § 493.833 Condition: Diagnostic immunology. The specialty of diagnostic immunology includes for purposes of proficiency testing the subspecialties of syphilis...

  10. 42 CFR 493.1208 - Condition: General immunology.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: General immunology. 493.1208 Section 493....1208 Condition: General immunology. If the laboratory provides services in the subspecialty of General immunology, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, and §§...

  11. 42 CFR 493.1208 - Condition: General immunology.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 5 2013-10-01 2013-10-01 false Condition: General immunology. 493.1208 Section 493....1208 Condition: General immunology. If the laboratory provides services in the subspecialty of General immunology, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, and §§...

  12. 42 CFR 493.833 - Condition: Diagnostic immunology.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 5 2012-10-01 2012-10-01 false Condition: Diagnostic immunology. 493.833 Section..., Or Any Combination of These Tests § 493.833 Condition: Diagnostic immunology. The specialty of diagnostic immunology includes for purposes of proficiency testing the subspecialties of syphilis...

  13. 42 CFR 493.833 - Condition: Diagnostic immunology.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Condition: Diagnostic immunology. 493.833 Section..., Or Any Combination of These Tests § 493.833 Condition: Diagnostic immunology. The specialty of diagnostic immunology includes for purposes of proficiency testing the subspecialties of syphilis...

  14. 42 CFR 493.1208 - Condition: General immunology.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Condition: General immunology. 493.1208 Section 493....1208 Condition: General immunology. If the laboratory provides services in the subspecialty of General immunology, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, and §§...

  15. 42 CFR 493.833 - Condition: Diagnostic immunology.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Diagnostic immunology. 493.833 Section..., Or Any Combination of These Tests § 493.833 Condition: Diagnostic immunology. The specialty of diagnostic immunology includes for purposes of proficiency testing the subspecialties of syphilis...

  16. 42 CFR 493.833 - Condition: Diagnostic immunology.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 5 2013-10-01 2013-10-01 false Condition: Diagnostic immunology. 493.833 Section..., Or Any Combination of These Tests § 493.833 Condition: Diagnostic immunology. The specialty of diagnostic immunology includes for purposes of proficiency testing the subspecialties of syphilis...

  17. 42 CFR 493.1208 - Condition: General immunology.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 5 2014-10-01 2014-10-01 false Condition: General immunology. 493.1208 Section 493....1208 Condition: General immunology. If the laboratory provides services in the subspecialty of General immunology, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, and §§...

  18. Structural and immunological relationships among mammalian arylsulfatase A enzymes.

    PubMed

    Waheed, A; Risley, J M; Van Etten, R L

    1985-01-01

    Structural and immunological properties of numerous arylsulfatase A enzymes (EC 3.1.6) were examined in order to assess the relationships among these enzymes in animals. Arylsulfatase A enzymes from all animals bind to a Concanavalin A-Sepharose column, consistent with the conclusion that they are all glycoproteins. At pH 7.5 the apparent mol. wts of the enzymes are 80-182 kDa, while at pH 4.5 the mammalian arylsulfatase A enzymes dimerize and exhibit apparent mol. wts in the range of 297-348 kDa, but the enzymes from opossum and other lower classes of animals do not aggregate at pH 4.5. The mammalian arylsulfatase A enzymes, which aggregate at pH 4.5, also bind to rabbit liver arylsulfatase A monomers immobilized on an Affi-Gel 10 matrix. The arylsulfatase A enzymes that were studied all exhibit the anomalous kinetic behavior regarded as characteristic of these enzymes. However, not all of the inactivated enzymes are reactivated by sulfate ions. Goat antiserum raised against homogeneous rabbit liver arylsulfatase A cross-reacts with all of the mammalian enzymes in Ouchterlony gel diffusion experiments, whereas the enzymes from lower classes of animals do not cross-react. Quantitative immunoprecipitation experiments demonstrate that the mammalian enzymes are very similar to each other, with greater than 60% primary sequence homology indicated, while arylsulfatase A from opossum and other lower classes of animals show only a partial immunological similarity with the mammalian enzymes. Taken together, the data suggest that the active site of the enzyme and the structural features of the protein are highly conserved during the evolution of the enzyme molecule.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2868837

  19. Immunological synapse arrays: Patterned protein surfaces that modulate immunological synapse structure formation in T cells

    PubMed Central

    Doh, Junsang; Irvine, Darrell J.

    2006-01-01

    T cells are activated by recognition of foreign peptides displayed on the surface of antigen presenting cells (APCs), an event that triggers assembly of a complex microscale structure at the T cell–APC interface known as the immunological synapse (IS). It remains unresolved whether the unique physical structure of the synapse itself impacts the functional response of T cells, independent of the quantity and quality of ligands encountered by the T cell. As a first step toward addressing this question, we created multicomponent protein surfaces presenting lithographically defined patterns of tethered T cell receptor (TCR) ligands (anti-CD3 “activation sites”) surrounded by a field of tethered intercellular adhesion molecule-1 (ICAM-1), as a model substrate on which T cells could be seeded to mimic T cell–APC interactions. CD4+ T cells seeded on these surfaces polarized and migrated; on contact with activation sites, T cells assembled an IS with a structure modulated by the physical pattern of ligand encountered. On surfaces patterned with focal spots of TCR ligand, T cells stably interacted with activation sites, proliferated, and secreted cytokines. In contrast, T cells interacting with activation sites patterned to preclude centralized clustering of TCR ligand failed to form stable contacts with activation sites, exhibited aberrant PKC-θ clustering in a fraction of cells, and had significantly reduced production of IFN-γ. These results suggest that focal clustering of TCR ligand characteristic of the “mature” IS may be required under some conditions for full T cell activation. PMID:16585528

  20. Surgical implications of tumour immunology.

    PubMed Central

    Somers, S. S.

    1996-01-01

    The presence of immune infiltration of tumour deposits and the existence of effective in vitro anti-tumour immune responses would suggest the possibility of therapeutic manipulation against tumour cells. However, clinical immunotherapy has shown little promise as a cancer treatment. Numerous explanations for this inefficacy have been proposed, one of which involves the elaboration of immunosuppressive moieties from tumour cells. The results of studies presented below show that serum from patients with gastrointestinal and other tumours have immunosuppressive influences on normal lymphocytes. The degree of this in vitro inhibition is related to tumour 'bulk' and may reflect a systemic immunosuppressive influence of the tumour. Isolation and culture of lymphocytes from gastrointestinal tumour deposits demonstrated that these immune cells are functionally inert, suggesting the existence of an immunosuppressive tumour microenvironment. The isolation and partial purification of an immunosuppressive moiety from conditioned culture medium of a variety of human tumour cell lines further supports the hypothesis of tumour-mediated immunosuppression. A number of protein tumour cell products have been described with potent immunosuppressive properties. These include transforming growth factor-beta, interleukin-10, and the retroviral envelope protein p15E. The surgical implications of the proposed tumour-host immune relationship includes the hypothesis that clinically apparent disease may not be amenable to immune attack owing to tumour-mediated immune suppression. The use of immunostimulatory strategies as adjuvant perioperative therapy would seem a more effective environment for the activation of antitumour immune responses in the surgical patient. PMID:8678441

  1. Immunologic findings, thrombocytopenia and disease activity in lupus nephritis.

    PubMed Central

    Clark, W. F.; Linton, A. L.; Cordy, P. E.; Keown, P. E.; Lohmann, R. C.; Lindsay, R. M.

    1978-01-01

    Twenty patients with nephritis due to systemic lupus erythematosus were followed up for a mean of 34 months after renal biopsy with serial determinations of total serum complement and C3 and C4 concentrations, binding of deoxyribonucleic acid (DNA), antinuclear antibody pattern and platelet count. There were 25 episodes of nonhematologic observed disease activity in 16 of the 20 patients; elevated DNA binding and thrombocytopenia correlated well with these episodes. The mean platelet count during episodes of observed disease activity was 96 +/- 42 X 10(9)/L, which was significantly different from the mean count of 248 +/- 90 X 10(9)/L during disease quiescence. The proportion of false-positive results with the immunologic tests varied from 25% to 67% and with platelet counts it was 11%. It is suggested that thrombocytopenia may be a simple and accurate index of disease activity in lupus nephritis. PMID:350367

  2. Immunological aspects of sport nutrition.

    PubMed

    Gleeson, Michael

    2016-02-01

    Prolonged bouts of exercise and heavy training regimens are associated with depression of immune system functions that can increase the risk of picking up opportunistic infections such as the common cold and influenza. Some common sport nutrition practices including high-carbohydrate diets and carbohydrate ingestion during exercise, training with low-glycogen stores, intentional dieting for weight loss, ingestion of high-dose antioxidant supplements and protein ingestion post exercise may influence immune system status in athletes. In order to maintain robust immunity, athletes need to consume a well-balanced diet that is sufficient to meet their requirements for energy, carbohydrate, protein and micronutrients. Dietary deficiencies of protein and specific micronutrients are well known to be potential causes of immune dysfunction and an adequate intake of some essential minerals including iron and zinc and the vitamins A, D, E, B6 and B12 are important to maintain a healthy immune function. Vitamin D may be a particular concern as recent studies have emphasised its importance in limiting infection episode incidence and duration in both the general population and in athletes and many individuals exhibit inadequate vitamin D status during the winter months. There is only limited evidence that individual amino acids, β-glucans, herbal extracts and zinc are capable of boosting immunity or reducing infection risk in athletes. The ingestion of carbohydrate during exercise and daily consumption of probiotics, vitamin D3, bovine colostrum and plant polyphenol containing supplements or foodstuffs currently offer the best chance of success, particularly for those individuals who are prone to illness. PMID:26634839

  3. Immunological Characteristics of Recurrent Echinococcosis-Induced Anaphylactic Shock.

    PubMed

    Ye, Jianrong; Zhang, Qin; Ma, Long; Zheng, Hong

    2016-02-01

    Anaphylactic shock represents a serious complication of echinococcosis as up to 4.6% of patients die as a result of its severity and improper handling. Once a definite diagnosis is made, effective treatments need to be immediately initiated. Here, we report the immunological characteristics and management of two patients with recurrent anaphylactic shock concurrent with the surgical removal of hydatid cysts. Both patients had systemic echinococcosis classified as cystic echinococcosis type 2 (CE2) with multiple, immature cysts (absence of calcification and necrosis). In addition, both patients had increased eosinophils and basophils before surgery, as well as elevated crude hydatid cyst fluid antigen (anti-EgCF) and hydatid cyst fluid native antigen B (anti-EgB) antibodies and high IgG levels. Although we cannot definitively predict which patients are at risk for cyst fluid leakage or anaphylactic shock at present, clinicians may consider taking precautions before surgery on encountering patients with a similar profile to prevent the occurrence of anaphylactic shock and the likelihood of a second incident. However, these observations need to be confirmed in further studies with a larger number of patients. PMID:26711523

  4. Immunological treatment of multiple sclerosis.

    PubMed

    Diebold, Martin; Derfuss, Tobias

    2016-04-01

    Treatment of multiple sclerosis (MS) has been a challenge since its first description by Charcot. The advent of immunomodulatory drugs in the mid 1990s brought the first big change in the treatment of MS patients. During the last 10 years there has been an ongoing tremendous evolution of novel treatment options for relapsing-remitting MS. These options include monoclonal antibodies, which inhibit migration of lymphocytes (natalizumab), deplete lymphocytes (alemtuzumab), or block the cytokine receptor interleukin (IL)-2 (daclizumab), teriflunomide that inhibits proliferation of activated lymphocytes, fingolimod that modulates the sphingosine-receptor system, and dimethylfumarate that combines features of immunomodulatory and immunosuppressive drugs. The topic of this review is to discuss currently available treatments and provide an outlook into the near future. PMID:27312167

  5. Immunologic testing and immunotherapy in recurrent spontaneous abortion.

    PubMed

    McIntyre, J A; Faulk, W P; Nichols-Johnson, V R; Taylor, C G

    1986-02-01

    One hundred sixty-one couples with clinical histories of unexplained recurrent spontaneous abortions were analyzed in part for human leukocyte antigens, antibodies to paternal lymphocytes, and mixed lymphocyte culture reactions. All sera with antipaternal antibodies were investigated on a cell panel and absorbed with various tissues and heparin to help define antigenic specificities, and the couples were categorized as primary or secondary aborters. Primary but not secondary aborters were found to share more human leukocyte antigens with their mates than did 103 control fertile couples. Lymphocytotoxins were rarely identified in primary but were commonly present in secondary aborter sera. Results of mixed lymphocyte culture reactions with primary aborting couples showed an intrinsic cellular inability for the wives to recognize their husbands' cells. Secondary aborting couples' mixed lymphocyte culture reactions also were depressed but as a result of an inhibiting substance in the wives' sera. Thirty-three primary aborting women were treated by immunotherapy with leukocyte infusions as a prophylactic source of trophoblast-lymphocyte cross reactive antigen stimulation to immunologically protect their pregnancies. Eighty-nine percent of primary aborting patients delivered successfully. Six secondary aborting women were treated with heparin therapy; two of these delivered normal infants, two are pregnant, and two have aborted. Clinical implications for immunologic testing and immunotherapy in pregnancy failures are discussed. PMID:2935759

  6. [Immunologic reconstruction after antiretroviral treatment].

    PubMed

    Tubiana, R; Carcelain, G; Mohand, H A; Li, T S; Renaud, M; Blanc, C; Calvez, V; Debré, P; Agut, H; Katlama, C; Autran, B; Bricaire, F

    1999-02-27

    DATA FAVORING IMMUNE RECONSTITUTION: Multiple drug therapies for HIV infection have enabled a major reduction in the viral load, higher CD4 counts, and a lower incidence of opportunistic infections and tumor formations, and subsequently lower hospitalization rates and mortality. TWO STAGES OF CD4 RECONSTITUTION: In HIV-positive patients with advanced stage disease treated with a protease inhibitor associated with 2 nucleoside analog reverse transcriptase inhibitors and followed prospectively, it has been observed that CD4 counts rise considerably, with a rapid increase during the first 2 months followed by a slower but still positive slope over a period of 18 months. Discordant results have however also been observed suggesting an ineffective anti-viral effect or a retarded immune reconstitution. SEVERAL MECHANISMS: The lymphocyte amplification observed during the early phase corresponds to re-circulation of CD4 and CD8 lymphocytes which had been sequestered in lymphoid organs; most of these CD4 lymphocytes are memory cells. A second phase corresponds to a more moderate and progressive rise in naive CD4 cells which originate from an unknown source. This biphasic reconstitution of CD4 lymphocytes is associated with a correction of the chronic lymphocyte overactivation. PARTIAL IMMUNE RECONSTITUTION: With treatment, the capacity to respond to known antigens reappears. This restored capacity is secondary to the amplification of CD4 memory cells and appears prior to the expansion phase of naive cells. The response remains moderate and is only observed against antigens from microorganisms highly prevalent during advanced stage infection. PMID:10093603

  7. A novel point mutation in a 3{prime} splice site of the NADH-cytochrome b{sub 5} reductase gene results in immunologically undetectable enzyme and impaired NADH-dependent ascorbate regeneration in cultured fibroblasts of a patient with type II hereditary methemoglobinemia

    SciTech Connect

    Shirabe, Komie; Takeshita, Masazumi; Landi, M.T.

    1995-08-01

    Hereditary methemoglobinemia with generalized deficiency of NADH-cytochrome b{sub 5} reductase (b{sub 5}R) (type II) is a rare disease characterized by severe developmental abnormalities, which often lead to premature death. Although the molecular relationship between the symptoms of this condition and the enzyme deficit are not understood, it is thought that an important cause is the loss of the lipid metabolizing activities of the endoplasmic reticulum-located reductase. However, the functions of the form located on outer mitochondrial membranes have not been considered previously. In this study, we have analyzed the gene of an Italian patient and identified a novel G{r_arrow}T transversion at the splice-acceptor site of the 9th exon, which results in the complete absence of immunologically detectable b{sub 5}R in blood cells and skin fibroblasts. In cultured fibroblasts of the patient, NADH-dependent cytochrome c reductase, ferricyanide reductase, and semidehydroascorbate reductase activities were severely reduced. The latter activity is known to be due to b{sub 5}R located on outer mitochondrial membranes. Thus, our results demonstrate that the reductase in its two membrane locations, endoplasmic reticulum and outer mitochondrial membranes, is the product of the same gene and suggest that a defect in ascorbate regeneration may contribute to the phenotype of hereditary methemoglobinemia of generalized type. 37 refs., 5 figs., 2 tabs.

  8. [Immunological background and pathomechanisms of food allergies].

    PubMed

    Schülke, Stefan; Scheurer, Stephan

    2016-06-01

    Recent advances in immunology have greatly improved our understanding of the pathomechanisms of food allergies. Food allergies are caused and maintained by complex interactions of the innate and adaptive immune system involving antigen-presenting cells (APC), T cells, group 2 innate lymphoid cells (ILC2), epithelial cells (EC) and effectors cells. Additionally, epigenetic factors, the intestinal microbiome and nutritional factors modulating the gastrointestinal lymphatic tissue probably have a significant impact on allergy development. However, why certain individuals develop tolerance while others mount allergic responses, the factors defining the allergenicity of food proteins, as well as the immunological mechanisms triggering allergy development have yet to be analyzed in detail. PMID:27177897

  9. Understanding liver immunology using intravital microscopy.

    PubMed

    Marques, Pedro Elias; Oliveira, André Gustavo; Chang, Lynne; Paula-Neto, Heitor Affonso; Menezes, Gustavo Batista

    2015-09-01

    The liver has come a long way since it was considered only a metabolic organ attached to the gastrointestinal tract. The simultaneous ascension of immunology and intravital microscopy evidenced the liver as a central axis in the immune system, controlling immune responses to local and systemic agents as well as disease tolerance. The multiple hepatic cell populations are organized in a vascular environment that promotes intimate cellular interactions, including initiation of innate and adaptive immune responses, rapid leukocyte recruitment, pathogen clearance and production of a variety of immune mediators. In this review, we focus on the advances in liver immunology supported by intravital microscopy in diseases such as isquemia/reperfusion, acute liver injury and infections. PMID:26055800

  10. [Metaphors of immunology: war and peace].

    PubMed

    Löwy, I

    1996-01-01

    Immunology has always relied on metaphorical language. In its early beginnings, it varied between bellicose images and images that stressed the interaction of immunity mechanisms with the organism's physiological functions overall. In the late nineteenth century, white blood globules were not only compared to 'border police' assigned to rebuffing intruders -- an army formed to combat the invaders -- but were also described as a physiological mechanism for eliminating aged, dead cells, at times exterminators of foreign bodies. Antibodies were described as very powerful, deadly weapons but also as an integral part of mechanisms that allowed cells to assimilate food. This duality of images holds true today. The article analyzes the emergence and development of these images, relating them to the redefinition of immunology as a science of the self and non-self and dissecting them in light of recent events, such as the Aids epidemic. PMID:11625247

  11. Immunological features underlying viral hemorrhagic fevers.

    PubMed

    Messaoudi, Ilhem; Basler, Christopher F

    2015-10-01

    Several enveloped RNA viruses of the arenavirus, bunyavirus, filovirus and flavivirus families are associated with a syndrome known as viral hemorrhagic fever (VHF). VHF is characterized by fever, vascular leakage, coagulation defects and multi organ system failure. VHF is currently viewed as a disease precipitated by viral suppression of innate immunity, which promotes systemic virus replication and excessive proinflammatory cytokine responses that trigger the manifestations of severe disease. However, the mechanisms by which immune dysregulation contributes to disease remain poorly understood. Infection of nonhuman primates closely recapitulates human VHF, notably Ebola and yellow fever, thereby providing excellent models to better define the immunological basis for this syndrome. Here we review the current state of our knowledge and suggest future directions that will better define the immunological mechanisms underlying VHF. PMID:26163194

  12. Immunological effects of ayahuasca in humans.

    PubMed

    dos Santos, Rafael Guimarães

    2014-01-01

    Ayahuasca is a botanical hallucinogen traditionally used by indigenous groups of the northwest Amazon. In the last decade, the use of ayahuasca has spread from Brazil, Colombia, Ecuador, and Peru to the U.S., Europe, Asia, and Africa. Despite acute and long-term evidence of good tolerability and safety for ayahuasca administered in the laboratory or ritually consumed in religious contexts, little is known about the immunological impact of ayahuasca on humans. Since ayahuasca is used by an increasing number of consumers, and considering its therapeutic potential, more information is needed regarding ayahuasca potential risks. This article presents a brief overview of the available data regarding the immunological impact of ayahuasca in humans. PMID:25364989

  13. Engineering antigen-specific immunological tolerance.

    SciTech Connect

    Kontos, Stephan; Grimm, Alizee J.; Hubbell, Jeffrey A.

    2015-05-01

    Unwanted immunity develops in response to many protein drugs, in autoimmunity, in allergy, and in transplantation. Approaches to induce immunological tolerance aim to either prevent these responses or reverse them after they have already taken place. We present here recent developments in approaches, based on engineered peptides, proteins and biomaterials, that harness mechanisms of peripheral tolerance both prophylactically and therapeutically to induce antigenspecific immunological tolerance. These mechanisms are based on responses of B and T lymphocytes to other cells in their immune environment that result in cellular deletion or ignorance to particular antigens, or in development of active immune regulatory responses. Several of these approaches are moving toward clinical development, and some are already in early stages of clinical testing.

  14. Immunologic and Neurodevelopmental Susceptibilities of Autism

    PubMed Central

    Pessah, Isaac N.; Seegal, Richard F.; Lein, Pamela J.; LaSalle, Janine; Yee, Benjamin K.; Van De Water, Judy; Berman, Robert F.

    2008-01-01

    Symposium 5 focused on research approaches that are aimed at understanding common patterns of immunological and neurological dysfunction contributing to neurodevelopmental disorders such as autism and ADHD. The session focused on genetic, epigenetic, and environmental factors that might act in concert to influence autism risk, severity and co-morbidities, and immunological and neurobiological targets as etiologic contributors. The immune system of children at risk of autism may be therefore especially susceptible to psychological stressors, exposure to chemical triggers, and infectious agents. Identifying early biomarkers of risk provides tangible approaches toward designing studies in animals and humans that yield a better understanding of environmental risk factors, and can help identify rational intervention strategies to mitigate these risks. PMID:18394707

  15. Demographical, Viro-Immunological, Clinical and Therapeutical Characteristics of HIV-Infected Patients in an “Epidemiologically Unexplored” Region of Italy (Calabria Region): the CalabrHIV Cohort

    PubMed Central

    Postorino, Maria Concetta; Luciani, Filippo; Mangano, Carmelo; Carpentieri, Maria Stella; Scerbo, Paolo; Priamo, Armando; Berardelli, Giuseppina; Marino, Roberto; Vallone, Alfredo; Serrao, Nicola; Pisani, Vincenzo; Costa, Chiara; Terremoto, Albano; Foti, Giuseppe; Cosco, Lucio; Calderazzo, Massimo; Corigliano, Domenico; Scordo, Preziosa; Strazzulla, Alessio; Torti, Carlo

    2015-01-01

    Background and Objectives HIV epidemics may differ among epidemiological contexts. We aimed at constructing an HIV clinical cohort whose main epidemiological, clinical and therapeutical characteristics are described (the CalabrHIV cohort, Calabria Region, Southern Italy). Methods The CalabrHIV Cohort includes all HIV patients on active follow-up in all infectious disease centers in the Calabria Region as at October 2014. All information was recorded in a common electronic database. Not-infectious co-morbidities (such as cardiovascular diseases, bone fractures, diabetes, renal failure and hypertension) were also studied. Results 548 patients (68% males; 59% aged <50 years) were included in the CalabrHIV cohort. Major risk factors were: sexual transmission (49%) and intravenous drug use (34%). 39% patients had HCV and/or HBV co-infection. Amongst 404 patients who had a complete clinical history, 34% were AIDS presenters and 49.3% had CD4 count ≤350/mm3 at HIV diagnosis. 83% patients on HAART had undetectable HIV-RNA. Hypertension was the most frequent co-morbidity (21.5%). Multimorbidity was more frequent in >50 years old patients than in <50 years old ones (30% vs. 6%; p<0.0001). Co-morbidity was more frequent in HCV and/or HBV co-infected than in HIV mono-infected patients (46.6% vs. 31.7%: p=0.0006). Conclusion This cohort presentation study sheds light, for the first time, on HIV patients’ characteristics in the Calabria Region. We showed that HIV-infected patients with chronic hepatitis were affected by concomitant not-infectious co-morbidities more than the HIV mono-infected individuals. New HCV treatments are therefore to be implemented in the co-infected population. PMID:26543523

  16. The Promised Land of Human Immunology

    PubMed Central

    Su, Laura F.; Han, Arnold; McGuire, Helen M.; Furman, David; Newell, Evan W.; Davis, Mark M.

    2016-01-01

    Advances in technology and data analysis have made it possible to take a new look at human immunology. These advances run the gamut from systems biology approaches, which are likely in the vanguard of how we can start “to put the pieces together” of immune function, to a deeper understanding of specific diseases and vaccines and the immune repertoire. In our own experience, we have also found that asking simple questions about human immunity has often given us very surprising answers, causing a rethink of established dogma. Thus, we have developed a new perspective on the nature of the αβ TCR repertoire and also the likely role of T-cell repertoire (TCR) cross-reactivity in generating T memory independent of specific antigen interactions. These findings show that human immunology is not just a necessary step for “translating” basic immunology to treat diseases or develop better vaccines, but is also an important complement to the inbred mouse model. PMID:24638855

  17. Chapter 17: Occupational immunologic lung disease.

    PubMed

    Sabin, Bradley R; Grammer, Leslie C

    2012-01-01

    Occupational immunologic lung disease is characterized by an immunologic response in the lung to an airborne agent inhaled in the work environment and can be subdivided into immunologically mediated occupational asthma (OA) and hypersensitivity pneumonitis (HP). Irritant-induced OA, a separate nonimmunologic entity, can be caused by chronic exposure to inhaled irritants or reactive airways dysfunction syndrome, defined as an asthma-like syndrome that persists for >3 months and occurs abruptly after a single exposure to a high concentration of an irritating industrial agent. High-risk fields for OA include farmers, printers, woodworkers, painters, plastic workers, cleaners, spray painters, electrical workers, and health care workers. OA can be triggered by high molecular weight (HMW) proteins that act as complete allergens or low molecular weight (LMW) sensitizers that act as haptens. HMW proteins (>10 kDa) are generally derived from microorganisms (such as molds and bacteria, including thermophilic actinomycetes), plants (such as latex antigens and flour proteins), or animals (such as animal dander, avian proteins, and insect scales) and are not specifically regulated by the Occupational Safety and Health Administration (OSHA). LMW haptens that bind to proteins in the respiratory mucosa include some OSHA-regulated substances such as isocyanates, anhydrides, and platinum. HP can present in an acute, a chronic, or a subacute form. The acute, subacute, and early chronic form is characterized by a CD4(+) T(H)1 and CD8(+) lymphocyte alveolitis. Classically, the bronchoalveolar lavage will show a CD4/CD8 ratio of <1. PMID:22794690

  18. Panel 5: Microbiology and Immunology Panel

    PubMed Central

    Murphy, Timothy F.; Chonmaitree, Tasnee; Barenkamp, Stephen; Kyd, Jennelle; Nokso-Koivisto, Johanna; Patel, Janak A.; Heikkinen, Terho; Yamanaka, Noboru; Ogra, Pearay; Swords, W. Edward; Sih, Tania; Pettigrew, Melinda M.

    2014-01-01

    Objective The objective is to perform a comprehensive review of the literature from January 2007 through June 2011 on the virology, bacteriology, and immunology related to otitis media. Data Sources PubMed database of the National Library of Medicine. Review Methods Three subpanels with co-chairs comprising experts in the virology, bacteriology, and immunology of otitis media were formed. Each of the panels reviewed the literature in their respective fields and wrote draft reviews. The reviews were shared with all panel members, and a second draft was created. The entire panel met at the 10th International Symposium on Recent Advances in Otitis Media in June 2011 and discussed the review and refined the content further. A final draft was created, circulated, and approved by the panel. Conclusion Excellent progress has been made in the past 4 years in advancing an understanding of the microbiology and immunology of otitis media. Advances include laboratory-based basic studies, cell-based assays, work in animal models, and clinical studies. Implications for Practice The advances of the past 4 years formed the basis of a series of short-term and long-term research goals in an effort to guide the field. Accomplishing these goals will provide opportunities for the development of novel interventions, including new ways to better treat and prevent otitis media. PMID:23536533

  19. Immunologic reactions triggered during irritant contact dermatitis.

    PubMed

    Nickoloff, B J

    1998-06-01

    This article discusses a novel approach to the understanding of human skin barrier function with particular emphasis on the immunologic consequences of barrier perturbation. Clearly, the most important homeostatic function of the skin is to restrict the ebb and flow of water molecules to maintain a physiological balance with respect to hydration between the inside of the body and the external environment. The early investigators of barrier function initially focused on defining the biophysical properties of the stratum corneum and integrating the concepts of Singer and Nicholson1 into various models such as the brick and mortar concept by Elias2 and the domain mosaic model by Forslind.3 Rather than examining lipids, cholesterol, and free fatty acids in the stratum corneum, the authors have been interested in characterizing the types of specialized proteins termed cytokines that are intimately linked to the barrier structure and function of human and rodent skin.4 Cytokines are key mediators of inflammatory and immunologic reactions throughout the body; how these cytokines are modulated in response to changes in barrier function provides new insights that pass beyond the physical/mechanical protective nature of skin into the immunologic sphere of influence for barrier function and cutaneous homeostasis. PMID:9601898

  20. The parallel evolution of immunology and pharmacology.

    PubMed

    Conti, A A

    2010-01-01

    Immunology is the systematic evaluation of the means through which human beings protect themselves and respond to the attack of internal and external agents, and Edward Jenner (1749-1823) and Louis Pasteur (1822-1895) are considered pioneers of this field. Jenner observed the protective effect of cowpox against smallpox and inoculated the cowpox in human beings to protect them from the often lethal smallpox. Pasteur developed in his laboratory a vaccine against rabies and elaborated methods for attenuating the virulence of pathogenic microorganisms while maintaining their immunogenicity. Pharmacology is the area of medical science dealing with drugs and their uses, and it was during the nineteenth century that it assumed its status of scientific specialty, mainly in German-speaking Europe, through the establishment of pharmacological institutes and dedicated laboratories. The discovery and the synthesis of drugs and the systematic evaluation of their activity have constituted through time a scientific field in which immunology and pharmacology have met and given origin to notable progress in the history of science. The development of chemotherapy, as well as of organ and tissue transplantation, in the twentieth century has been decisively promoted by both immunology and pharmacology. In the last three decades the relationship between these two scientific branches has become increasingly closer in basic research, clinical science, medical education and also editorial scientific activity, as documented by the Journal hosting this paper. PMID:20646363

  1. Immunological dysfunction, vaccination and Gulf War illness

    PubMed Central

    Peakman, Mark; Skowera, Ania; Hotopf, Matthew

    2006-01-01

    One candidate cause of Gulf War illness is vaccination against infectious diseases including medical counter-measures against biological weapons. One influential theory has suggested that such mass-vaccination caused a shift in immune response to a Type 2 cytokine pattern (Th2), which it was suggested was accompanied by a chronic fatigue syndrome-like illness. This article critically appraises this theory. We start by examining epidemiological evidence, which indicates that single vaccines are unlikely to be a substantial cause of Gulf War illness, but that there was a modest relationship with multiple vaccines, which was strongest in those vaccinated while deployed to the Gulf. These relationships may be affected by recall bias. We conclude by examining the results of immunological studies carried out in veterans or in a relevant setting in vitro. The balance of evidence from immunological studies on veterans returning from the War, including those developing multi-symptom illness, is that the immune response has not become polarized towards Th2. In summary, the epidemiological evidence for a multiple vaccine effect on Gulf War-related illness remains a potentially important aetiological lead, but mechanistic studies available at this stage do not identify any immunological basis for it. PMID:16687270

  2. Photothermal effects of immunologically modified carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Griswold, Ryan T.; Henderson, Brock; Goddard, Jessica; Tan, Yongqiang; Hode, Tomas; Liu, Hong; Nordquist, Robert E.; Chen, Wei R.

    2013-02-01

    Carbon nanotubes have a great potential in the biomedical applications. To use carbon nanotubes in the treatment of cancer, we synthesized an immunologically modified single-walled carbon nanotube (SWNT) using a novel immunomodifier, glycated chitosan (GC), as an effective surfactant for SWNT. This new composition SWNT-GC was stable due to the strong non-covalent binding between SWNT and GC. The structure of SWNT-GC is presented in this report. The photothermal effect of SWNT-GC was investigated under irradiation of a near-infrared laser. SWNT-GC retained the optical properties of SWNT and the immunological properties of GC. Specifically, the SWNT-GC could selectively absorb a 980-nm light and induce desirable thermal effects in tissue culture and in animals. It could also induce tumor cell destruction, controlled by the laser settings and the doses of SWNT and GC. Laser+SWNT-GC treatment could also induce strong expression of heat shock proteins on the surface of tumor cells. This immunologically modified carbon nanotube could be used for selective photothermal interactions in noninvasive tumor treatment.

  3. Immunological Approaches to Biomass Characterization and Utilization

    PubMed Central

    Pattathil, Sivakumar; Avci, Utku; Zhang, Tiantian; Cardenas, Claudia L.; Hahn, Michael G.

    2015-01-01

    Plant biomass is the major renewable feedstock resource for sustainable generation of alternative transportation fuels to replace fossil carbon-derived fuels. Lignocellulosic cell walls are the principal component of plant biomass. Hence, a detailed understanding of plant cell wall structure and biosynthesis is an important aspect of bioenergy research. Cell walls are dynamic in their composition and structure, varying considerably among different organs, cells, and developmental stages of plants. Hence, tools are needed that are highly efficient and broadly applicable at various levels of plant biomass-based bioenergy research. The use of plant cell wall glycan-directed probes has seen increasing use over the past decade as an excellent approach for the detailed characterization of cell walls. Large collections of such probes directed against most major cell wall glycans are currently available worldwide. The largest and most diverse set of such probes consists of cell wall glycan-directed monoclonal antibodies (McAbs). These McAbs can be used as immunological probes to comprehensively monitor the overall presence, extractability, and distribution patterns among cell types of most major cell wall glycan epitopes using two mutually complementary immunological approaches, glycome profiling (an in vitro platform) and immunolocalization (an in situ platform). Significant progress has been made recently in the overall understanding of plant biomass structure, composition, and modifications with the application of these immunological approaches. This review focuses on such advances made in plant biomass analyses across diverse areas of bioenergy research. PMID:26579515

  4. Immunological characterization of pulmonary intravascular macrophages

    NASA Technical Reports Server (NTRS)

    Chitko-McKown, C. G.; Reddy, D. N.; Chapes, S. K.; McKown, R. D.; Blecha, F.; Spooner, B. S. (Principal Investigator)

    1992-01-01

    Pulmonary intravascular macrophages (PIMs) are lung macrophages found apposed to the endothelium of pulmonary capillaries. In many species, they are responsible for the clearance of blood-borne particulates and pathogens; however, little else is known about their roles as immunologic effector cells. We compared PIMs with pulmonary alveolar macrophages (PAMs) to determine the relative immunological activities of these two cell populations. Our results suggested that both populations possess similar phagocytic and bactericidal activities. In assays measuring cytotoxicity, PIMs were more cytotoxic than PAMs against virally infected target cells; however, differences between these macrophage populations were not as marked when noninfected targets were used. LPS-stimulated PIMs produced more T-cell proliferative cytokines than PAMs, and both populations of nonstimulated macrophages produced similar amounts of the cytokines. In contrast, PAMs produced more TNF alpha and NO2- than PIMs when both populations were stimulated with LPS; however, nonstimulated PAMs and PIMs produced similar amounts of TNF alpha and NO2. These data suggest that bovine PIMs are immunologically active. Differences between the degrees of activity of PIMs and PAMs indicate that these macrophage populations may have different roles in lung surveillance.

  5. Mouse infection models for space flight immunology

    NASA Technical Reports Server (NTRS)

    Chapes, Stephen Keith; Ganta, Roman Reddy; Chapers, S. K. (Principal Investigator)

    2005-01-01

    Several immunological processes can be affected by space flight. However, there is little evidence to suggest that flight-induced immunological deficits lead to illness. Therefore, one of our goals has been to define models to examine host resistance during space flight. Our working hypothesis is that space flight crews will come from a heterogeneous population; the immune response gene make-up will be quite varied. It is unknown how much the immune response gene variation contributes to the potential threat from infectious organisms, allergic responses or other long term health problems (e.g. cancer). This article details recent efforts of the Kansas State University gravitational immunology group to assess how population heterogeneity impacts host health, either in laboratory experimental situations and/or using the skeletal unloading model of space-flight stress. This paper details our use of several mouse strains with several different genotypes. In particular, mice with varying MHCII allotypes and mice on the C57BL background with different genetic defects have been particularly useful tools with which to study infections by Staphylococcus aureus, Salmonella typhimurium, Pasteurella pneumotropica and Ehrlichia chaffeensis. We propose that some of these experimental challenge models will be useful to assess the effects of space flight on host resistance to infection.

  6. Laryngeal transplantation in minipigs: early immunological outcomes

    PubMed Central

    Birchall, M A; Ayling, S M; Harley, R; Murison, P J; Burt, R; Mitchard, L; Jones, A; Macchiarini, P; Stokes, C R; Bailey, M

    2012-01-01

    Despite recent tissue-engineering advances, there is no effective way of replacing all the functions of the larynx in those requiring laryngectomy. A recent clinical transplant was a success. Using quantitative immunofluorescence targeted at immunologically relevant molecules, we have studied the early (48 h and 1 week) immunological responses within larynxes transplantated between seven pairs of National Institutes of Health (NIH) minipigs fully homozygous at the major histocompatibility complex (MHC) locus. There were only small changes in expression of some molecules (relative to interindividual variation) and these were clearest in samples from the subglottic region, where the areas of co-expression of CD25+CD45RC-CD8- and of CD163+CD172+MHC-II- increased at 1 week after transplant. In one case, infiltration by recipient T cells was analysed by T cell receptor (TCR) Vβ spectratype analysis; this suggested that changes in the T cell repertoire occur in the donor subglottis mucosal tissues from day 0 to day 7, but that the donor and recipient mucosal Vβ repertoires remain distinct. The observed lack of strong immunological responses to the trauma of surgery and ischaemia provides encouraging evidence to support clinical trials of laryngeal transplantation, and a basis on which to interpret future studies involving mismatches. PMID:22288599

  7. Traveling Exhibitions: translating current science into effective science exhibitions

    NASA Astrophysics Data System (ADS)

    Dusenbery, P.; Morrow, C.; Harold, J.

    The Space Science Institute (SSI) of Boulder, Colorado has recently developed two museum exhibits called the Space Weather Center and MarsQuest. It is currently planning to develop two other exhibitions called Cosmic Origins and InterActive Earth. Museum exhibitions provide research scientists the opportunity to engage in a number of activities that are vital to the success of earth and space outreach programs. The Space Weather Center was developed in partnership with various research missions at NASA's Goddard Space Flight Center. The focus of the presentation will be on the Institute's MarsQuest exhibition. This project is a 5000 square-foot, 2.5M, traveling exhibition that is now touring the country. The exhibit's 3-year tour is enabling millions of Americans to share in the excitement of the scientific exploration of Mars and learn more about their own planet in the process. The associated planetarium show and education program will also be described, with particular emphasis on workshops to orient host museum staff (e.g. museum educators and docents). The workshops make innovative connections between the exhibitions interactive experiences and lesson plans aligned with the National Science Education Standards. SSI is also developing an interactive web site called MarsQuest On-line. The linkage between the web site, education program and exhibit will be discussed. MarsQuest and SSI's other exhibitions are good models for actively involving scientists and their discoveries to help improve informal science education in the museum community and for forging a stronger connection between formal and informal education.

  8. Exhibitions: Facing Outward, Pointing Inward

    ERIC Educational Resources Information Center

    McDonald, Joseph P.

    2007-01-01

    The Coalition of Essential Schools (CES) Exhibitions Project of the early 1990s produced a range of work that continues to inform the practice of using exhibitions as a "360 degree" method of transforming teaching and learning, community connections, school design, and assessment. Among that work was this paper coupling the origins of exhibitions…

  9. Immunological biomarkers predict HIV-1 viral rebound after treatment interruption

    PubMed Central

    Hurst, Jacob; Hoffmann, Matthias; Pace, Matthew; Williams, James P.; Thornhill, John; Hamlyn, Elizabeth; Meyerowitz, Jodi; Willberg, Chris; Koelsch, Kersten K.; Robinson, Nicola; Brown, Helen; Fisher, Martin; Kinloch, Sabine; Cooper, David A.; Schechter, Mauro; Tambussi, Giuseppe; Fidler, Sarah; Babiker, Abdel; Weber, Jonathan; Kelleher, Anthony D.; Phillips, Rodney E.; Frater, John

    2015-01-01

    Treatment of HIV-1 infection with antiretroviral therapy (ART) in the weeks following transmission may induce a state of ‘post-treatment control' (PTC) in some patients, in whom viraemia remains undetectable when ART is stopped. Explaining PTC could help our understanding of the processes that maintain viral persistence. Here we show that immunological biomarkers can predict time to viral rebound after stopping ART by analysing data from a randomized study of primary HIV-1 infection incorporating a treatment interruption (TI) after 48 weeks of ART (the SPARTAC trial). T-cell exhaustion markers PD-1, Tim-3 and Lag-3 measured prior to ART strongly predict time to the return of viraemia. These data indicate that T-cell exhaustion markers may identify those latently infected cells with a higher proclivity to viral transcription. Our results may open new avenues for understanding the mechanisms underlying PTC, and eventually HIV-1 eradication. PMID:26449164

  10. Immunological biomarkers predict HIV-1 viral rebound after treatment interruption.

    PubMed

    Hurst, Jacob; Hoffmann, Matthias; Pace, Matthew; Williams, James P; Thornhill, John; Hamlyn, Elizabeth; Meyerowitz, Jodi; Willberg, Chris; Koelsch, Kersten K; Robinson, Nicola; Brown, Helen; Fisher, Martin; Kinloch, Sabine; Cooper, David A; Schechter, Mauro; Tambussi, Giuseppe; Fidler, Sarah; Babiker, Abdel; Weber, Jonathan; Kelleher, Anthony D; Phillips, Rodney E; Frater, John

    2015-01-01

    Treatment of HIV-1 infection with antiretroviral therapy (ART) in the weeks following transmission may induce a state of 'post-treatment control' (PTC) in some patients, in whom viraemia remains undetectable when ART is stopped. Explaining PTC could help our understanding of the processes that maintain viral persistence. Here we show that immunological biomarkers can predict time to viral rebound after stopping ART by analysing data from a randomized study of primary HIV-1 infection incorporating a treatment interruption (TI) after 48 weeks of ART (the SPARTAC trial). T-cell exhaustion markers PD-1, Tim-3 and Lag-3 measured prior to ART strongly predict time to the return of viraemia. These data indicate that T-cell exhaustion markers may identify those latently infected cells with a higher proclivity to viral transcription. Our results may open new avenues for understanding the mechanisms underlying PTC, and eventually HIV-1 eradication. PMID:26449164

  11. Immunological Characterization of Asp f 2, a Major Allergen from Aspergillus fumigatus Associated with Allergic Bronchopulmonary Aspergillosis

    PubMed Central

    Banerjee, Banani; Greenberger, Paul A.; Fink, Jordan N.; Kurup, Viswanath P.

    1998-01-01

    The 37-kDa recombinant protein Asp f 2, encoding an allergen of Aspergillus fumigatus, was expressed in a prokaryotic expression system and immunologically evaluated for its functional and structural properties. The open reading frame for a 310-amino-acid-long protein was shown to encode a signal peptide of 31 amino acids. A native 37-kDa culture filtrate protein and a 55-kDa mycelial glycoprotein (gp55) exhibited complete N-terminal sequence homology to Asp f 2. A GenBank search for homologous proteins revealed 60 and 44% sequence homologies to the cytosolic protein ASPND1 from Aspergillus nidulans and fibrinogen binding protein from Candida albicans, respectively. The glycosylation sites and cysteine molecules are conserved in all the three proteins. The extracellular matrix protein laminin showed a dose-dependent interaction with Asp f 2. This protein, expressed as a major cell-associated protein within 24 h of in vitro fungal culture, comprises 20 to 40% of total fungal protein. Furthermore, both native and recombinant Asp f 2 exhibited specific immunoglobulin (IgE) binding with allergic bronchopulmonary aspergillosis (ABPA) and cystic fibrosis-ABPA patients, whereas A. fumigatus-sensitized allergic asthma and normal control subjects failed to show IgE binding with Asp f 2. These results indicate that Asp f 2 is a major allergen of A. fumigatus exhibiting IgE antibody binding with sera from patients with ABPA. The antigen should be explored further for its potential role in the differential diagnosis of A. fumigatus-associated allergic diseases. PMID:9784519

  12. Development of a novel protein biochip enabling validation of immunological assays and detection of serum IgG and IgM antibodies against Treponema pallidum pathogens in the patients with syphilis.

    PubMed

    Huang, Na-Li; Ye, Lei; Schneider, Marion E; Du, Yi-Xin; Xu, Yuan-Hong; Fan, Li-Bin; Du, Wei-Dong

    2016-01-15

    In this study, we developed a novel protein biochip methodology that was characterized by dithiobis (succinimidyl undecanoate) (DSU) and specialized for detection of serum IgG and IgM antibodies against Treponema pallidum pathogens in the patients with syphilis, respectively. The biochips were validated by a dimension of atomic force microscope (AFM). The visualized detection limit of IgG antibody on the biochip was 0.39μg/ml. Finally, 286 serum samples from the patients with syphilis were simultaneously tested on the rTpN15-17-47 coated biochips. The results were evaluated in comparison with the assays of T. pallidum particle agglutination (TPPA) and the toluidine red unheated serum test (TRUST). The result demonstrated that the relative positive rate in the 286 patients by biochip was 99.0%, similar to that by TPPA (97.9%, P>0.05) and higher than that by TRUST, (76.2%, P<0.01). The detection specificities were 100% for the biochip and the TPPA and 97.0% for the TRUST. Thus, the protein biochip would provide a useful platform not only for enabling concurrent detection of the infectious antibodies directed against T. pallidum on a larger scale, but also for monitoring therapy modality of the disease. PMID:26364122

  13. Immunological evaluation of allergic respiratory children with recurrent sinusitis.

    PubMed

    Costa Carvalho, Beatriz T; Nagao, Aparecida Tiemi; Arslanian, Cristina; Carneiro Sampaio, Magda M S; Naspitz, Charles K; Sorensen, Ricardo U; Leiva, Lily; Solé, Dirceu

    2005-09-01

    The objective of this study was to evaluate humoral immunity of allergic respiratory children with chronic/recurrent sinusitis. Twenty-seven allergic respiratory (persistent mild/moderate asthma and persistent allergic rhinitis) children (7-15-year old) with chronic or recurrent sinusitis were evaluated. Patients had symptoms and abnormal computer tomography scan even after two adequate treatments (long-lasting antibiotics, decongestants, and short-term oral corticosteroids). clinical examination, sweat test, total blood cell count, measurement of serum levels of: total and specific IgE, immunoglobulins (G, M, A), IgG subclasses, antibodies to Haemophilus influenza type b (IgG anti-Ps Hib) and pneumococcal serotypes (IgG anti-Ps 1, 3, 5, 6B, 9V, and 14) before and after active immunization (Act-Hib and Pneumo23, Aventis Pasteur SA, Lyon, France), Rubella neutralizing antibody titers and human immunodeficiency virus antibodies. Specific IgE to inhalant allergens higher than class III were observed in 24/27 patients. One patient had IgA plus IgG2 deficiency and other an IgG3 deficiency. Eight and 12 of 27 patients had IgG2 and IgG3 serum levels below 2.5th percentile, respectively. Immunological responses to protein and polysaccharide antigens were normal in all patients. Although our patients have been appropriately treated of their allergic diseases, they persisted with chronic/recurrent sinusitis and 60% of them had a documented osteomeatal complex blockade. In spite of the diagnosis of IgA plus IgG2 deficiency and an isolated IgG3 deficiency, in all patients an adequate response to Ps antigens was observed. Primary and/or secondary humoral immunodeficiency seems not to be the main cause of chronic/recurrent sinusitis in patients with respiratory allergic disease. PMID:16176402

  14. [A possible "immunologic" origin of idiopathic non-immunologic hydrops fetalis and initial results of preventive immunotherapy of subsequent pregnancies].

    PubMed

    Mallmann, P; Gembruch, U; Mallmann, R; Hansmann, M

    1989-01-01

    The cause of the nonimmune hydrops fetalis remains unsettled in spite of greatest efforts. Under an immunologic point of view of pregnancy as a successful course of an allograft it seems possible, that the idiopathic NIHF can be caused by an immunologic disorder in the meaning of a host-versus-graft-reaction. From 300 cases with prenatal diagnosed NIHF 37 (12.4%) could be classified after exclusion of all other causes as idiopathic and in 25 patients, as well as in 25 age- and parity-paired controls a differentiation of HLA-antigens and a determination of lymphocytotoxic antibodies using the NIH-, Prolonged incubation- and Cold-Complement Dependent-Cytotoxicity-Test (CoCoCy-Test) were performed. In cases with idiopathic NIHF the percentage of parents sharing 4 or 5 HLA-antigens was increased with 4/25 to 2/25 compared to the control group. In women with idiopathic NIHF the incidence of lymphocytotoxic antibodies was decreased, in dependence of the test-system used between 28 and 68% in the NIHF group and 24 and 80% in the control group. The percentage of women without lymphocytotoxic antibodies was increased in the NIHF group with 72% to 52%, in opposite to the control group in none of the patients a higher cytotoxicity with a lysing rate of more than 75% could be detected. In 4 cases with idiopathic NIHF, an increased paternal histocompatibility and a decreased incidence and percentage of lymphocytotoxic antibodies an immunotherapy was performed, in order to induce maternal blocking antibodies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2800657

  15. Immunology and immunity against infection: General rules

    NASA Astrophysics Data System (ADS)

    Zinkernagel, Rolf M.

    2005-12-01

    Simplified and generalizable rules of immune responses against infections or vaccines have been summarized into 20 statements previously (Scand. J. Immunol. 60 (2004) 9-13) and are restated in a slightly different form here. The key terms of immunology (e.g. specificity, tolerance and memory) are explained in terms of their co-evolutionary importance in the equilibrium between infectious agents and diseases with higher vertebrate hosts. Specificity is best defined by protective antibodies or protective activated T cells; e.g. serotype specific neutralizing antibodies against polio viruses represent the discriminatory power of an immune response very well indeed. Tolerance is reviewed in terms of reactivity rather than self-nonself discrimination. Immune respones are deleted against antigens expressed at sufficient levels within the lymphoheamopoetic system, but may well exist at both, the T and the B cell level against antigens strictly outside of secondary lymphatic organs. In this respect the immune system behaves identically against virus infections and against self antigens. Persistent virus infections delete responsive T cells, once eliminated immune T cell responses wane, if a virus keeps outside of secondary lymphatic tissues no immune response is induced. Immunological memory is usually defined as earlier and greater responses but this does not correlate with protective immunity stringently. It is summarized here that pre-existing titers of protective neutralizing antibodies or pre-existence of activated T cells are the correlates of protection acute cytopathic lethal infections and toxins or against intracellular parasites. It is concluded that many discrepancies and uncertainties in immunological research derive from model situations and experimental results that are correctly measured but cannot be related to co-evolutionary contexts, i.e. survival.

  16. Against the Odds Exhibition Opens

    MedlinePlus

    ... the National Institutes of Health in Bethesda, Md. Photo courtesy of Bill Branson NIH Director Dr. Elias ... addresses visitors to the opening of the exhibition. Photo courtesy of Bill Branson Brothers Niko and Theo ...

  17. Against the Odds Exhibition Opens

    MedlinePlus

    ... Bar Home Current Issue Past Issues Special Section Against the Odds Exhibition Opens Past Issues / Spring 2008 ... Research in Bethesda. Photo courtesy of Bill Branson "Against the Odds" is a remarkable story of achievement ...

  18. Some vexations that challenge viral immunology

    PubMed Central

    Rouse, Barry T.; Mueller, Scott N.

    2016-01-01

    The field of viral immunology seeks to understand mechanisms of virus-host interaction with a view of applying this knowledge to the design of effective vaccines and immunomodulators that control viral infections. This brief review discusses several areas of the field that hold substantial promise for translation, but where further work is critically required to find solutions. We emphasize that our fundamental understanding of virus-host relationships is moving in leaps and bounds, but we lag behind in applying this knowledge to the successful control of many viral infections. PMID:27303640

  19. Basic immunology of antibody targeted radiotherapy

    SciTech Connect

    Wong, Jeffrey Y.C. . E-mail: jwong@coh.org

    2006-10-01

    Antibody targeted radiotherapy brings an important new treatment modality to Radiation oncology clinic. Radiation dose to tumor and normal tissues are determined by a complex interplay of antibody, antigen, tumor, radionuclide, and host-related factors. A basic understanding of these immunologic and physiologic factors is important to optimally utilize this therapy in the clinic. Preclinical and clinical studies need to be continued to broaden our understanding and to develop new strategies to further improve the efficacy of this promising form of targeted therapy.

  20. Immunological characteristics of the elderly allograft recipient.

    PubMed

    Klinger, Marian; Banasik, Miroslaw

    2015-10-01

    The increasing number of elderly people with a demand for organ transplantation poses an important medical challenge. The effect of aging on the immune system concerns wide modifications with a considerable influence on transplant outcomes. Aging causes significant changes in immune cells repertoire. Thymic involution impairs the production of new naïve cells. Immune remodeling induces important alterations in the activity of immunological molecules. Therefore, clinical implications in elderly transplant recipients should consider appropriate organ allocation with adequate individualization of immunosuppression. PMID:26409504

  1. Immunologic abnormalities in melanoma-prone families.

    PubMed

    Dean, J H; Greene, M H; Reimer, R R; LeSane, F V; McKeen, E A; Mulvihill, J J; Blattner, W A; Herberman, R B; Fraumeni, J F

    1979-11-01

    Sixty members of 4 families prone to cutaneous malignant melanoma (CMM) and a genetically determined precursor nevus syndrome underwent extensive immunologic evaluation. The most consistent finding was a diminished in vitro response to pooled alloantigens in the one-way mixed leukocyte culture (MLC) and a tendency to low T-lymphocyte and B-lymphocyte levels. When compared to controls, low B-lymphocyte levels and reduced MLC responses were found not only in family members with CMM and/or precursor nevi but also in unaffected blood relatives and spouses. The genesis of the immune dysfunction and its possible relationship to melanoma pathogenesis remain to be clarified. PMID:159376

  2. The immunologic barriers to replacing damaged organs

    PubMed Central

    Cascalho, Marilia; Platt, Jeffrey L.

    2005-01-01

    The recent years have brought breathtaking advances in the biomedical sciences and biomedical engineering. These advances offer the promise that diseases responsible for most disability and early death may soon be addressed by replacing damaged organs with bio-engineered substitutes. Application of these technologies, however, is impeded by the immune response directed against foreign cells and tissues. Here we consider the potentiality and the limitations of these new technologies and how the technologies might be combined to generate novel approaches to organ replacement that overcome immunological barriers to success. PMID:12934939

  3. Immunological memory within the innate immune system

    PubMed Central

    Sun, Joseph C; Ugolini, Sophie; Vivier, Eric

    2014-01-01

    Immune memory has traditionally been the domain of the adaptive immune system, present only in antigen-specific T and B cells. The purpose of this review is to summarize the evidence for immunological memory in lower organisms (which are not thought to possess adaptive immunity) and within specific cell subsets of the innate immune system. A special focus will be given to recent findings in both mouse and humans for specificity and memory in natural killer (NK) cells, which have resided under the umbrella of innate immunity for decades. The surprising longevity and enhanced responses of previously primed NK cells will be discussed in the context of several immunization settings. PMID:24674969

  4. Tubulointerstitial nephritis and uveitis: an immunological disorder?

    PubMed

    Birnbacher, R; Balzar, E; Aufricht, C; Schmaldienst, S; Woloszczuk, W; Förster, E

    1995-04-01

    A 14-year-old boy with tubulointerstitial nephritis and uveitis (TINU syndrome) is described. Nephropathy improved without systemic cortisone treatment, whereas uveitis relapsed and was treated with topical steroids. Blood cell immunological analysis and serum analysis revealed signs of cytotoxic T-cell, macrophage and granulocyte activation, which declined as the clinical symptoms improved. This may be interpreted as an indication of their significance as markers in the pathogenesis of this syndrome or as part of a microbial-triggered immune response. PMID:7794717

  5. Guidelines for the use of allergen immunotherapy. Canadian Society of Allergy and Clinical Immunology.

    PubMed Central

    1995-01-01

    OBJECTIVES: To recommend guidelines for the use of allergen immunotherapy to treat allergies in patients for whom allergen avoidance and drug therapy have not been sufficiently effective. OPTIONS: High-dose or low-dose allergen immunotherapy for the treatment of IgE-mediated allergy to insect stings, allergic rhinoconjunctivitis and asthma. OUTCOMES: Clinical evaluation of symptoms, objective measurement of reactions to nasal or bronchial allergen challenge, immunologic changes as a result of allergen immunotherapy and, among patients with anaphylactic reactions to stinging insects, clinical outcome of intentional sting challenge. EVIDENCE: A search of MEDLINE was conducted to identify articles that presented results of allergen immunotherapy. Proceedings of symposia held by international subcommittees and of consensus meetings, as well as references obtained from these sources, were reviewed. The articles were grouped according to their main subject: immunologic effects, specific allergies, the results of randomized placebo-controlled clinical trials, types of allergen extract and protocols for allergen immunotherapy, adverse effects and deficiencies of allergen immunotherapy. VALUES: Each member of the working group assessed the importance of such issues as basic immunologic effects, clinical efficacy, adverse effects and inappropriate use; the working group then arrived at a consensus. BENEFITS, HARMS AND COSTS: Implementation of these guidelines would lead to the appropriate use of allergen immunotherapy and control inappropriate treatment, which could result in adverse effects and increased costs of services for patients with allergies. RECOMMENDATIONS: Allergen immunotherapy with specific, standardized allergenic materials, administered in high-dose schedules, is effective in patients with an allergy to insect stings or allergic rhinoconjunctivitis, and in some patients with asthma, who have been correctly diagnosed through a meticulous history corroborated

  6. America's first department of immunology: an informal history.

    PubMed

    Rose, Noel R

    2010-07-01

    America's first organized department devoted to the study of immunology was founded at Johns Hopkins University in 1916 by William Henry Welch. It has since generated multiple centers distributed throughout the university, which continue to promote education and conduct research in immunology to the present day. A review of its history may foretell future developments and directions of immunology in this and other institutions. PMID:20082151

  7. Greenhouse Earth: A Traveling Exhibition

    SciTech Connect

    Booth, W.H.; Caesar, S.

    1992-09-01

    The Franklin Institute Science Museum provided an exhibit entitled the Greenhouse Earth: A Traveling Exhibition. This 3500 square-foot exhibit on global climate change was developed in collaboration with the Association of Science-Technology Centers. The exhibit opened at The Franklin Institute on February 14, 1992, welcoming 291,000 visitors over its three-month stay. During its three-year tour, Greenhouse Earth will travel to ten US cities, reaching two million visitors. Greenhouse Earth aims to deepen public understanding of the scientific issues of global warming and the conservation measures that can be taken to slow its effects. The exhibit features hands-on exhibitry, interactive computer programs and videos, a theater production, a demonstration cart,'' guided tours, and lectures. supplemental educational programs at the Institute included a teachers preview, a symposium on climate change, and a satellite field trip.'' The development of Greenhouse Earth included front-end and formative evaluation procedures. Evaluation includes interviews with visitors, prototypes, and summative surveys for participating museums. During its stay in Philadelphia, Greenhouse Earth was covered by the local and national press, with reviews in print and broadcast media. Greenhouse Earth is the first large-scale museum exhibit to address global climate change.

  8. Design and function of a department of clinical immunology*

    PubMed Central

    Whittingham, Senga; Mackay, I. R.

    1971-01-01

    The recognition and successful treatment of diseases affecting the immunological system, together with organ grafting, has led in recent years to an upsurge in demand for laboratory services, research and teaching facilities concerned with clinical and experimental aspects of immunology. These developments have stimulated us to present a plan for floor space, staffing and services for a Department of Clinical Immunology in a major medical centre or university hospital serving, say, 800–1500 beds, and an outpatient department of corresponding dimensions. Such a Department would provide basic immunodiagnostic services and should have provision for research in Clinical Immunology. PMID:5091615

  9. 21 CFR 866.5240 - Complement components immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... tissues. Complement is a group of serum proteins which destroy infectious agents. Measurements of these proteins aids in the diagnosis of immunologic disorders, especially those associated with deficiencies...

  10. Immigrants in immunology: the benefits of lax borders.

    PubMed

    Stagaman, Keaton; Martinez, Emily S; Guillemin, Karen

    2015-05-01

    The field of immunology has a long history of illuminating fundamental biological processes of critical importance to human health. From an outsider's perspective, the questions are profoundly philosophical and the experimental approaches are elegantly precise. Yet immunology can also appear impenetrable. Here we recount the experience of two graduate students from the fields of ecology and computer science, who have immigrated into immunological terrain attracted by systems-level questions. We argue that such migrations enrich the field of immunology, and that cultural and institutional changes are needed to promote more interdisciplinary explorations. PMID:25866281

  11. Importance of exercise immunology in health promotion.

    PubMed

    Neto, J C Rosa; Lira, F S; de Mello, M T; Santos, Ronaldo Vagner T

    2011-11-01

    Chronic physical exercise with adequate intensity and volume associated with sufficient recovery promotes adaptations in several physiological systems. While intense and exhaustive exercise is considered an important immunosuppressor agent and increases the incidence of upper respiratory tract infections (URTI), moderate regular exercise has been associated with significant disease protection and is a complementary treatment of many chronic diseases. The effects of chronic exercise occur because physical training can induce several physiological, biochemical and psychological adaptations. More recently, the effect of acute exercise and training on the immunological system has been discussed, and many studies suggest the importance of the immune system in prevention and partial recovery in pathophysiological situations. Currently, there are two important hypotheses that may explain the effects of exercise and training on the immune system. These hypotheses including (1) the effect of exercise upon hormones and cytokines (2) because exercise can modulate glutamine concentration. In this review, we discuss the hypothesis that exercise may modulate immune functions and the importance of exercise immunology in respect to chronic illnesses, chronic heart failure, malnutrition and inflammation. PMID:20976509

  12. Immunological recognition of cuticular transplants in insects.

    PubMed

    Lackie, A M

    1983-01-01

    Transplantation of allogeneic and xenogeneic cuticle onto the American cockroach, Periplaneta americana, was carried out in order to compare the specificity of immune recognition of these 'skin grafts' with that of implanted tissues. In order to facilitate interpretation of results, the technique of transplanting cuticle from nymphal donors onto nymphal recipients was adopted - if donor subcuticular epidermis is not recognised as 'foreign', it will grow, fuse with the recipient's epidermal sheet and will be stimulated by the recipient's hormonal signals to produce new cuticle of donor type at the next moult. Neither allogeneic cuticle nor xenogeneic cuticle from Blatta orientalis were recognised as foreign by the immune system of P. americana - dark patches of Blatta-type cuticle were produced at the graft site post-moult. Conversely, xenogeneic cuticle of Blaberus craniifer was not visible post-moult. These results corroborate those from implantation studies, that allogeneic tissues from P. americana and xenogeneic tissues from B. orientalis are immunologically compatible with P. americana, whereas xenogeneic tissue from Blaberus craniifer is incompatible. Whether this incompatibility is immunological or 'positional' has not yet been determined; the observation that xenografts from Nauphoeta cinerea do not reappear on P. americana post-moult, whereas 50% of N. cinerea implants are not recognised as 'foreign', suggests that 'positional incompatibility' (i.e. the signals responsible for formation of cuticular pattern are incorrect for the donor epidermis) may also play an important part in the rejection of N. cinerea cuticular grafts. PMID:6341106

  13. Immunological aspects of liver cell transplantation

    PubMed Central

    Oldhafer, Felix; Bock, Michael; Falk, Christine S; Vondran, Florian W R

    2016-01-01

    Within the field of regenerative medicine, the liver is of major interest for adoption of regenerative strategies due to its well-known and unique regenerative capacity. Whereas therapeutic strategies such as liver resection and orthotopic liver transplantation (OLT) can be considered standards of care for the treatment of a variety of liver diseases, the concept of liver cell transplantation (LCTx) still awaits clinical breakthrough. Success of LCTx is hampered by insufficient engraftment/long-term acceptance of cellular allografts mainly due to rejection of transplanted cells. This is in contrast to the results achieved for OLT where long-term graft survival is observed on a regular basis and, hence, the liver has been deemed an immune-privileged organ. Immune responses induced by isolated hepatocytes apparently differ considerably from those observed following transplantation of solid organs and, thus, LCTx requires refined immunological strategies to improve its clinical outcome. In addition, clinical usage of LCTx but also related basic research efforts are hindered by the limited availability of high quality liver cells, strongly emphasizing the need for alternative cell sources. This review focuses on the various immunological aspects of LCTx summarizing data available not only for hepatocyte transplantation but also for transplantation of non-parenchymal liver cells and liver stem cells. PMID:27011904

  14. Xenotransplantation: Immunological hurdles and progress toward tolerance

    PubMed Central

    Griesemer, Adam; Yamada, Kazuhiko; Sykes, Megan

    2014-01-01

    The discrepancy between organ need and organ availability represents one of the major limitations in the field of transplantation. One possible solution to this problem is xenotransplantation. Research in this field has identified several obstacles that have so far prevented the successful development of clinical xenotransplantation protocols. The main immunologic barriers include strong T cell and B cell responses to solid organ and cellular xenografts. Additionally, components of the innate immune system can mediate xenograft rejection. Here, we review these immunologic and physiologic barriers and describe some of the strategies that we and others have developed to overcome them. We also describe the development of two strategies to induce tolerance across the xenogeneic barrier, namely thymus transplantation and mixed chimerism, from their inception in rodent models through their current progress in pre-clinical large animal models. We believe that the addition of further beneficial transgenes to Gal knockout swine, combined with new therapies such as Treg administration, will allow for successful clinical application of xenotransplantation. PMID:24517437

  15. Immunological aspects of liver cell transplantation.

    PubMed

    Oldhafer, Felix; Bock, Michael; Falk, Christine S; Vondran, Florian W R

    2016-03-24

    Within the field of regenerative medicine, the liver is of major interest for adoption of regenerative strategies due to its well-known and unique regenerative capacity. Whereas therapeutic strategies such as liver resection and orthotopic liver transplantation (OLT) can be considered standards of care for the treatment of a variety of liver diseases, the concept of liver cell transplantation (LCTx) still awaits clinical breakthrough. Success of LCTx is hampered by insufficient engraftment/long-term acceptance of cellular allografts mainly due to rejection of transplanted cells. This is in contrast to the results achieved for OLT where long-term graft survival is observed on a regular basis and, hence, the liver has been deemed an immune-privileged organ. Immune responses induced by isolated hepatocytes apparently differ considerably from those observed following transplantation of solid organs and, thus, LCTx requires refined immunological strategies to improve its clinical outcome. In addition, clinical usage of LCTx but also related basic research efforts are hindered by the limited availability of high quality liver cells, strongly emphasizing the need for alternative cell sources. This review focuses on the various immunological aspects of LCTx summarizing data available not only for hepatocyte transplantation but also for transplantation of non-parenchymal liver cells and liver stem cells. PMID:27011904

  16. Immunological and Toxinological Responses to Jellyfish Stings

    PubMed Central

    Tibballs, James; Yanagihara, Angel A.; Turner, Helen C.; Winkel, Ken

    2013-01-01

    Just over a century ago, animal responses to injections of jellyfish extracts unveiled the phenomenon of anaphylaxis. Yet, until very recently, understanding of jellyfish sting toxicity has remained limited. Upon contact, jellyfish stinging cells discharge complex venoms, through thousands of barbed tubules, into the skin resulting in painful and, potentially, lethal envenomations. This review examines the immunological and toxinological responses to stings by prominent species of jellyfish including Physalia sp. (Portuguese Man-o-War, Blue-bottle), Cubozoan jellyfish including Chironex fleckeri, several Carybdeids including Carybdea arborifera and Alatina moseri, Linuche unguiculta (Thimble jellyfish), a jellyfish responsible for Irukandji syndrome (Carukia barnesi) and Pelagia noctiluca. Jellyfish venoms are composed of potent proteinaceous porins (cellular membrane pore-forming toxins), neurotoxic peptides, bioactive lipids and other small molecules whilst the tubules contain ancient collagens and chitins. We postulate that immunologically, both tubular structural and functional biopolymers as well as venom components can initiate innate, adaptive, as well as immediate and delayed hypersensitivity reactions that may be amenable to topical anti-inflammatory-immunomodifier therapy. The current challenge for immunotoxinologists is to deconstruct the actions of venom components to target therapeutic modalities for sting treatment. PMID:21824077

  17. Clinical and Immunological Features of Common Variable Immunodeficiency in China

    PubMed Central

    Lin, Lian-Jun; Wang, Yu-Chuan; Liu, Xin-Min

    2015-01-01

    Background: Common variable immunodeficiency (CVID) is one of the most common symptomatic primary immunodeficiency syndromes. The purpose of this article was to broaden our knowledge about CVID for better diagnosis and treatment. Methods: Clinical and immunological features of 40 Chinese patients with CVID were analyzed retrospectively. Results: The median age at onset was 11-year-old (range 4–51 years). The median age at diagnosis was 14.5-year-old (range 5–66 years). The average time of delay in diagnosis was 5.3 years (range 1–41 years). The most common main complaint was fever due to infections (35 cases, 87.5%). Pneumonia (28 cases, 70%) was the most common type of infections. Bronchiectasis was present in 6 patients (15%). Autoimmune disease was detected in 6 cases of CVID, and malignancy in 2 cases. The median total serum levels of IgG, IgA, and IgM at diagnosis were 1.07 g/L, 0.07 g/L, and 0.28 g/L, respectively. The percentages of CD3−/CD10+ B-cells were 1%–3.14%. Conclusions: Infection is the most frequent presentation of CVID. Patients with unexplainable infections should receive further examination including serum immunoglobulin (Ig) and lymphocyte subset analysis. Regular and sufficient substitution with Ig is recommended. PMID:25635425

  18. Immunologic changes in TNF-alpha, sE-selectin, sP-selectin, sICAM-1, and IL-8 in pediatric patients treated for psoriasis with the Goeckerman regimen

    SciTech Connect

    Borska, L.; Fiala, Z.; Krejsek, J.; Andrys, C.; Vokurkova, D.; Hamakova, K.; Kremlacek, J.; Ettler, K.

    2007-11-15

    Psoriasis is a chronic inflammatory skin disease which is often manifested during childhood. The present study investigated changes in the serum levels of proinflammatory cytokines and soluble forms of adhesion molecules in children with psoriasis. The observed patient group of 26 children was treated with the Goeckerman regimen. This therapy combines dermal application of crude coal tar with ultraviolet radiation. The Psoriasis Area Severity Index decreased significantly after treatment by with the Goeckerman regimen (p < 0.001). Serum levels of the proinflammatory cytokine TNF-alpha and adhesion molecules sICAM-1, sP-selectin and sE-selectin decreased after the Goeckerman regimen. The TNF-alpha and sICAM-1 decreased significantly (p < 0.05). Our findings support the complex role of these immune parameters in the immunopathogenesis of psoriasis in children. The serum level of IL-8 increased after the Goeckerman regimen. This fact indicates that the chemokine pathway of IL-8 activity could be modulated by this treatment, most likely by polycyclic aromatic hydrocarbons.

  19. Considering High-Tech Exhibits?

    ERIC Educational Resources Information Center

    Routman, Emily

    1994-01-01

    Discusses a variety of high-tech exhibit media used in The Living World, an educational facility operated by The Saint Louis Zoo. Considers the strengths and weaknesses of holograms, video, animatronics, video-equipped microscopes, and computer interactives. Computer interactives are treated with special attention. (LZ)

  20. HER-2/neu protein-receptor-positive breast carcinoma: an immunologic perspective.

    PubMed

    Brown, R E; Bernath, A M; Lewis, G O

    2000-07-01

    Immunotherapy using a monoclonal antibody against the human epidermal growth factor receptor 2 protein, HER-2/neu, has proven to be clinically efficacious in about one-half of breast cancer patients who exhibit strong (3+) plasmalemmal immunoreactivity for this protein. The tumoricidal effect of this antibody relies in part upon antibody-dependent cell-mediated cytotoxicity. This report provides observations on certain factors or circumstances which could have an impact on this aspect of the therapeutic approach. These include: (1) concurrent medications; (2) the composition (immunophenotype) of peritumoral lymphocytes and the generally limited numbers of intratumoral T-lymphocytes/natural killer (NK) cells, monocytes, and neutrophilic granulocytes; (3) the presence of circulating HER-2/neu antigens which might bind the exogenous antibody and lead to immune complex formation; (4) the variable co-expression in the tumor of cytokines known to downregulate NK cell function (ie, transforming growth factor-beta1 [TGF-beta1] and platelet-derived growth factor [PDGF]-AB); and (5) the tumoral and/or stromal immunoreactivity for angiotensin-converting enzyme, which forms a part of one of the pathways for the activation of latent TGF-beta1 and for the biosynthesis of PDGF-AB. These observations provide an immunologic perspective for the use of monoclonal antibody therapy in HER-2/neu protein-receptor-positive breast carcinoma and suggest a role for the clinical laboratory in identifying potential avenues for additional manipulations of the immune system in individual cases in order to enhance the therapeutic response. PMID:10945564

  1. Veterinary Immunology Committee Toolkit Workshop 2010: Progress and plans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Third Veterinary Immunology Committee (VIC) Toolkit Workshop took place at the Ninth International Veterinary Immunology Symposium (IVIS) in Tokyo, Japan on August 18, 2020. The Workshop built on previous Toolkit Workshops and covered various aspects of reagent development, commercialisation an...

  2. 21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... system. 866.5500 Section 866.5500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... Systems § 866.5500 Hypersensitivity pneumonitis immunological test system. (a) Identification. A hypersensitivity pneumonitis immunological test system is a device that consists of the reagents used to measure...

  3. 21 CFR 866.5100 - Antinuclear antibody immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Antinuclear antibody immunological test system....5100 Antinuclear antibody immunological test system. (a) Identification. An antinuclear antibody... the autoimmune antibodies in serum, other body fluids, and tissues that react with cellular...

  4. 21 CFR 866.5460 - Haptoglobin immunological test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Haptoglobin immunological test system. (a) Identification. A haptoglobin immunological test system is a device... release hemoglobin) related to the formation of hemoglobin-haptoglobin complexes and certain kidney diseases. (b) Classification. Class II (special controls). The device is exempt from the...

  5. 21 CFR 866.5460 - Haptoglobin immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Haptoglobin immunological test system. (a) Identification. A haptoglobin immunological test system is a device... release hemoglobin) related to the formation of hemoglobin-haptoglobin complexes and certain kidney diseases. (b) Classification. Class II (special controls). The device is exempt from the...

  6. 42 CFR 493.837 - Standard; General immunology.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Standard; General immunology. 493.837 Section 493.837 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.837 Standard; General immunology. (a) Failure to attain a score of at least 80...

  7. 42 CFR 493.837 - Standard; General immunology.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 5 2012-10-01 2012-10-01 false Standard; General immunology. 493.837 Section 493.837 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.837 Standard; General immunology. (a) Failure to attain a score of at least 80...

  8. 42 CFR 493.837 - Standard; General immunology.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 5 2013-10-01 2013-10-01 false Standard; General immunology. 493.837 Section 493.837 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.837 Standard; General immunology. (a) Failure to attain a score of at least 80...

  9. 42 CFR 493.837 - Standard; General immunology.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Standard; General immunology. 493.837 Section 493.837 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.837 Standard; General immunology. (a) Failure to attain a score of at least 80...

  10. 42 CFR 493.837 - Standard; General immunology.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 5 2014-10-01 2014-10-01 false Standard; General immunology. 493.837 Section 493.837 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.837 Standard; General immunology. (a) Failure to attain a score of at least 80...

  11. Buffalo's Center for Immunology: A New Answer to an Old Dilemma

    ERIC Educational Resources Information Center

    Rose, Noel R.; Bogazzi, Pierluigi E.

    1972-01-01

    The Center for Immunology at the University of Buffalo provides a viable resource for educating medical students in immunology until a department of immunology can be developed within the medical school. (HS)

  12. Extraction, Characterization and Immunological Activity of Polysaccharides from Rhizoma gastrodiae.

    PubMed

    Chen, Juncheng; Tian, Shan; Shu, Xiaoying; Du, Hongtao; Li, Na; Wang, Junru

    2016-01-01

    A response surface and Box-Behnken design approach was applied to augment polysaccharide extraction from the residue of Rhizoma gastrodiae. Statistical analysis revealed that the linear and quadratic terms for three variables during extraction exhibited obvious effects on extraction yield. The optimum conditions were determined to be a liquid-to-solid ratio of 54 mL/g, an extraction temperature of 74 °C, an extraction time of 66 min, and three extractions. These conditions resulted in a maximum Rhizoma gastrodiae polysaccharide (RGP) extraction yield of 6.11% ± 0.13%. Two homogeneous polysaccharides (RGP-1a and RGP-1b) were obtained using DEAE cellulose-52 and Sephadex G-100 columns. The preliminary characterization of RGP-1a and RGP-1b was performed using HPLC-RID, HPGPC, and FTIR. Tests of the immunological activity in vitro showed that the two polysaccharides could significantly stimulate macrophages to release NO and enhance phagocytosis in a dose-dependent manner. In particular, RGP-1b (200 μg/mL) and LPS (2 μg/mL) had almost the same influence on the NO production and phagocytic activity of RAW 264.7 macrophages (p > 0.05). All the data obtained indicate that RGP-1a and RGP-1b have the potential to be developed as a health food. PMID:27347944

  13. Extraction, Characterization and Immunological Activity of Polysaccharides from Rhizoma gastrodiae

    PubMed Central

    Chen, Juncheng; Tian, Shan; Shu, Xiaoying; Du, Hongtao; Li, Na; Wang, Junru

    2016-01-01

    A response surface and Box-Behnken design approach was applied to augment polysaccharide extraction from the residue of Rhizoma gastrodiae. Statistical analysis revealed that the linear and quadratic terms for three variables during extraction exhibited obvious effects on extraction yield. The optimum conditions were determined to be a liquid-to-solid ratio of 54 mL/g, an extraction temperature of 74 °C, an extraction time of 66 min, and three extractions. These conditions resulted in a maximum Rhizoma gastrodiae polysaccharide (RGP) extraction yield of 6.11% ± 0.13%. Two homogeneous polysaccharides (RGP-1a and RGP-1b) were obtained using DEAE cellulose-52 and Sephadex G-100 columns. The preliminary characterization of RGP-1a and RGP-1b was performed using HPLC-RID, HPGPC, and FTIR. Tests of the immunological activity in vitro showed that the two polysaccharides could significantly stimulate macrophages to release NO and enhance phagocytosis in a dose-dependent manner. In particular, RGP-1b (200 μg/mL) and LPS (2 μg/mL) had almost the same influence on the NO production and phagocytic activity of RAW 264.7 macrophages (p > 0.05). All the data obtained indicate that RGP-1a and RGP-1b have the potential to be developed as a health food. PMID:27347944

  14. Unifying immunology with informatics and multiscale biology

    PubMed Central

    Kidd, Brian A; Peters, Lauren A; Schadt, Eric E; Dudley, Joel T

    2015-01-01

    The immune system is a highly complex and dynamic system. Historically, the most common scientific and clinical practice has been to evaluate its individual components. This kind of approach cannot always expose the interconnecting pathways that control immune-system responses and does not reveal how the immune system works across multiple biological systems and scales. High-throughput technologies can be used to measure thousands of parameters of the immune system at a genome-wide scale. These system-wide surveys yield massive amounts of quantitative data that provide a means to monitor and probe immune-system function. New integrative analyses can help synthesize and transform these data into valuable biological insight. Here we review some of the computational analysis tools for high-dimensional data and how they can be applied to immunology. PMID:24448569

  15. Reproductive immunology: biomarkers of compromised pregnancies

    SciTech Connect

    Faulk, W.P.; Coulam, C.B.; McIntyre, J.A.

    1987-10-01

    The objective of this paper is to consider several catagories of biomarkers of human pregnancy. The design of the report is to discuss useful and promising markers and techniques. Research gaps, needs, and priorities are also defined. Useful markers are mixed lymphocyte culture reactions, measures of lymphocytotoxic antibodies, histocompatibility (HLA) typing, and immunohematological evaluations. Promising markers are measures of major basic protein and early pregnancy factor, as well as determinations of trophoblast-lymphocyte cross-reactive (TLX) antigens. Promising techniques are flourescence-activated cell-sorter analysis of maternal blood for fetal and extraembryonic tissues and immunotherapy with TLX and other antigens to prevent spontaneous abortion. It is concluded that immunology has much to offer the development of biomarkers of human pregnancy.

  16. Overcoming immunological barriers in regenerative medicine

    PubMed Central

    Zakrzewski, Johannes L; van den Brink, Marcel R M; Hubbell, Jeffrey A

    2015-01-01

    Regenerative therapies that use allogeneic cells are likely to encounter immunological barriers similar to those that occur with transplantation of solid organs and allogeneic hematopoietic stem cells (HSCs). Decades of experience in clinical transplantation hold valuable lessons for regenerative medicine, offering approaches for developing tolerance-induction treatments relevant to cell therapies. Outside the field of solid-organ and allogeneic HSC transplantation, new strategies are emerging for controlling the immune response, such as methods based on biomaterials or mimicry of antigen-specific peripheral tolerance. Novel biomaterials can alter the behavior of cells in tissue-engineered constructs and can blunt host immune responses to cells and biomaterial scaffolds. Approaches to suppress autoreactive immune cells may also be useful in regenerative medicine. The most innovative solutions will be developed through closer collaboration among stem cell biologists, transplantation immunologists and materials scientists. PMID:25093888

  17. Overcoming immunological barriers in regenerative medicine.

    PubMed

    Zakrzewski, Johannes L; van den Brink, Marcel R M; Hubbell, Jeffrey A

    2014-08-01

    Regenerative therapies that use allogeneic cells are likely to encounter immunological barriers similar to those that occur with transplantation of solid organs and allogeneic hematopoietic stem cells (HSCs). Decades of experience in clinical transplantation hold valuable lessons for regenerative medicine, offering approaches for developing tolerance-induction treatments relevant to cell therapies. Outside the field of solid-organ and allogeneic HSC transplantation, new strategies are emerging for controlling the immune response, such as methods based on biomaterials or mimicry of antigen-specific peripheral tolerance. Novel biomaterials can alter the behavior of cells in tissue-engineered constructs and can blunt host immune responses to cells and biomaterial scaffolds. Approaches to suppress autoreactive immune cells may also be useful in regenerative medicine. The most innovative solutions will be developed through closer collaboration among stem cell biologists, transplantation immunologists and materials scientists. PMID:25093888

  18. Chymopapain. Chromatographic purification and immunological characterization.

    PubMed

    Buttle, D J; Barrett, A J

    1984-10-01

    Chymopapain (EC 3.4.22.6) was purified from commercially available spray-dried latex of papaya (Carica papaya) fruit by (NH4)2SO4 fractionation and fast protein chromatography on the Mono S cation-exchange column. Multiple forms of chymopapain separated chromatographically were shown to be immunologically identical. A major form was isolated and found to be homogeneous by several criteria, and fully active, and its N-terminal amino acid was identified as tyrosine. Latex from fresh unripe papaya fruit contained predominantly one form of chymopapain, and it is concluded that chymopapain is a single enzyme distinct from the other cysteine proteinases of C. papaya latex. PMID:6437389

  19. [Immunological analogies between ovarian cancer and pregnancy].

    PubMed

    Hanssen, S; Collinet, P; Leblanc, E; Salzet, M; Vinatier, D

    2013-05-01

    During pregnancy an environment allowing installation of tolerance toward the fetus is set up locally at the materno-fetal interface. Numerous effectors of immunity are involved in this tolerance (NK cell, T cell, Macrophages, dendritic cell). Specific mechanisms during pregnancy attract locally these immunological cells. In the decidua, they are educated toward tolerance. These mechanisms evolve during the pregnancy because at the end of the pregnancy, tolerance is broken to prepare and activate the labor. Ovarian tumors, after having surmounted the immunosurveillance, like trophoblast, chair the installation of a tolerance of their host facilitating the development of the disease. The blocking of these mechanisms of tolerance coupled with activation of mechanisms of defenses offer new perspectives in the treatment of the ovarian cancer. The authors suggest showing the analogies of the tolerance observed during ovarian cancer and pregnancy. The knowledge of the orchestration of the physiological mechanisms observed during pregnancy will offer new therapeutic targets. PMID:23182791

  20. Immunology of the maternal-fetal interface.

    PubMed

    Erlebacher, Adrian

    2013-01-01

    The immune cells that reside at the interface between the placenta and uterus are thought to play many important roles in pregnancy. Recent work has revealed that the composition and function of these cells are locally controlled by the specialized uterine stroma (the decidua) that surrounds the implanted conceptus. Here, I discuss how key immune cell types (natural killer cells, macrophages, dendritic cells, and T cells) are either enriched or excluded from the decidua, how their function is regulated within the decidua, and how they variously contribute to pregnancy success or failure. The discussion emphasizes the relationship between human and mouse studies. Deeper understanding of the immunology of the maternal-fetal interface promises to yield significant insight into the pathogenesis of many human pregnancy complications, including preeclampsia, intrauterine growth restriction, spontaneous abortion, preterm birth, and congenital infection. PMID:23298207