ABSTRACT
The present study investigated the effects of a single 10-minute exposure to e-cigarette vapor on ventilation in adult male Long-Evans rats. Ventilation was recorded using awake, unrestrained whole-body plethysmography. Baseline recordings were taken the day before full-body exposure to either room air (n = 9; air control group) or e-cigarette vapor (n = 9; treatment group). Post-exposure recordings were taken immediately after the 10-minute room air or vapor exposure. As part of the ventilation protocol, in addition to recording the subject's ventilation in room air, the subjects were also exposed to 10% oxygen (balanced with nitrogen) to assess the effects of e-cigarette vapor on an increased drive to breathe. Ventilation data were analyzed using a 2x2x2 mixed-model ANOVA measuring treatment (vape vs. air) x time (baseline vs. post-treatment) x condition (normoxia vs. hypoxia) for breathing frequency, tidal volume, and minute ventilation. Breathing frequency increased in both treatment groups (air and vape) with exposure to normobaric hypoxia (p < 0.001), with no effect of time (baseline vs. post-treatment) for either group. Tidal volume increased in both treatment groups (air and vape) with exposure to normobaric hypoxia (p < 0.001), and an effect of time (baseline vs. post-treatment) was observed (p = 0.010) for the vape group. Minute ventilation increased in both treatment groups (air and vape) with exposure to normobaric hypoxia (p < 0.001), and an effect of time (baseline vs. post-treatment) was observed (p < 0.001) for the vape group. In conclusion, immediately following a single 10-minute e-cigarette vapor exposure, both tidal volume and minute ventilation were reduced during normoxia and normobaric hypoxia, indicating a decrease in ventilation after a single 10-minute e-cigarette vapor exposure. Furthermore, this exposure also blunted the physiological response to acute hypoxia exposure. Subjects in the vape group, while breathing more rapidly as expected, experienced shallower breathing than the air group during hypoxia. The findings in this study confirm that vaping could result in reduced lung function.
ABSTRACT
Theodor Fahr is well known as a pioneer in renal pathology and the eponym of "Fahr's disease". While his professional merits are undisputed, his relationship to National Socialism remains unclear. On the one hand, he signed the public "oath of allegiance" of German professors to Adolf Hitler, on the other hand, he appeared as a mentor to his Jewish colleague Paul Kimmelstiel. In 1945, Fahr committed suicide after being dismissed by the Allied military government for political reasons. However, he left behind memoirs in which he outlined himself as a determined opponent of National Socialism. It is precisely these ambiguities that form the starting point of this study. The aim is to reconstruct Fahr's personal and professional career and to outline his political stance in the Third Reich. In addition, it will be clarified how Fahr's life and work were received after 1945 and whether (or how) his relationship to National Socialism was addressed. This study is based on different types of sources: Various archival documents on Fahr and Kimmelstiel are compared and contrasted with Fahr's unpublished autobiography and the available secondary literature on Fahr and his work. The analysis shows that Fahr's relationship to National Socialism became more distanced over time. However, he did not emerge as a critic of Nazi ideology during the Third Reich - even though he claimed in his memoirs that he had consistently despised Hitler. While Fahr is not to be considered an ardent National Socialist, he held to the stereotype of the "unscrupulous" Jew. The study concludes that Fahr was a politically ambivalent character with a distinctly anti-Semitic disposition, which he tried to soften by emphasizing his relationships with individual Jewish colleagues such as Kimmelstiel.
Subject(s)
National Socialism/history , Pathologists/history , Germany , History, 20th Century , HumansABSTRACT
Fritz Meyer (1875-1953) is undoubtedly one of the most enigmatic pathologists and internists of his time: He emerged early as a major researcher in the field of infectious diseases. Later, he also focused on heart and lung diseases and became a celebrity doctor who treated ambassadors and prominent contemporaries of the United States. The course of his life was as unusual as his professional activities: At the beginning of the Third Reich, Meyer experienced far-reaching repression due to his Jewish ancestry, which led to forced emigration to the USA. Although he achieved professional success in his new homeland, he returned to Germany in 1948 - as one of very few Jewish emigrants from the Third Reich. This article takes these peculiarities as an opportunity to take a closer look at Fritz Meyer: It recapitulates the biography and scientific merits of the Jewish pathologist and pays special attention to the background of his emigration to the USA and his later remigration to Germany. The central basis of the study are contemporary newspaper articles and various archival sources evaluated for the first time. These sources are compared with the sparse secondary literature on Meyer and other persecuted pathologists. The results of the study can be summarized in five points: (1) Meyer's research on infectious diseases - especially diphtheria, tuberculosis and serum therapy - was considered leading-edge at the time. (2) Meyer suffered widespread repression after 1933, which led him to emigrate to the United States in 1935. (3) Thanks to influential contacts, he was able to continue his professional career in the U.S. almost seamlessly. (4) In the postwar period, he decided to return to Germany, mainly out of attachment to Europe. (5) His reintegration in Germany seemed to be successful - however, he died only a few years after his remigration. The analysis leads to the conclusion that Meyer's social reintegration in postwar Germany was significantly facilitated by his professional reputation and his largely apolitical demeanor in public; nevertheless, it can be shown that he secretly lamented the lack of consciousness of guilt of the German postwar population. Several indications cast doubt on his intention to remain permanently in Germany. This includes the fact that he held on to his U.S. citizenship until the end of his life and that his wife remained in the United States.
Subject(s)
Pathologists/history , Pathology, Clinical/history , Emigrants and Immigrants/history , Emigration and Immigration , History, 19th Century , History, 20th Century , Humans , Jews/historyABSTRACT
BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) act as cofactors worsening the allergic reactions induced by food allergens. AIM: The aim of this study was to evaluate the effect of both lysine acetylsalicylate (L-ASA) (non-selective cyclooxygenase (COX) inhibitor) and valdecoxib (selective COX-2 inhibitor) in basophils activated by peach lipid transfer protein (Pru p 3) in patients with food-dependent NSAID-induced anaphylaxis (FDNIA). METHODS: Twenty Pru p 3-allergic patients with FDNIA group, eleven peach anaphylaxis not exacerbated by NSAIDs (no-NSAID group) and 5 healthy volunteers were recruited. Basophil activation (BA) was measured as expression of CD63 (Flow(2) CAST(™) ; Bühlmann(®) ), after stimulation with Pru p 3, both alone and in combination with L-ASA (1.13, 3.38 and 6.78 mm) or valdecoxib (0.87, 7.8 and 31.25 µm). RESULTS: Basophils from no-NSAID group were significantly more reactive and sensitive to Pru p 3 than those from the FDNIA group. In both groups, an increase in BA was observed when basophils were exposed to Pru p 3 and L-ASA. In the FDNIA group, valdecoxib partially terminates the BA induced by Pru p 3, whereas in the no-NSAID group, a dual effect was observed depending on the concentration tested. CONCLUSIONS: This study indicates that subjects with food-induced anaphylaxis differ from FDNIA subjects in the higher reactivity and sensitivity of their basophils to allergen challenge. We have shown a direct effect of NSAIDs on basophils using a human model of FDNIA. Our results also suggest that selective COX2 inhibitors might be a safe alternative. BA test may be a useful tool in the study of the pathogenic mechanism of the cofactor phenomenon.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Basophils/drug effects , Basophils/immunology , Food Hypersensitivity/immunology , Immunoglobulin E/immunology , Adult , Allergens/immunology , Anaphylaxis/diagnosis , Anaphylaxis/immunology , Biomarkers , Disease Progression , Female , Food/adverse effects , Food Hypersensitivity/diagnosis , Humans , Immunoglobulin E/blood , Immunophenotyping , Male , Middle Aged , Severity of Illness Index , Young AdultABSTRACT
BACKGROUND: Dermatophagoides pteronyssinus specific IgE (sIgE) measurement is a major diagnostic test for the detection of sensitization to that allergen. METHODS: To investigate the effect of climate on the seasonal variations of D.pteronyssinus sIgE, we studied the tests performed in an insular population during a 10-year period. The association with meteorological factors was evaluated with multiple regression analyses. RESULTS: Of 24,879 tests performed for D. pteronyssinus sIgE, 16,719 (67.2%) were D. pteronyssinus sIgE positive; 24.5% were tested for asthma and 46.07% for rhinitis. D. pteronyssinus sIgE levels showed a seasonal pattern with an annual peak in November. In the multivariate analyses solar radiation (r = -0.94) and relative humidity (r = 0.86) were independent factors associated with D. pteronyssinus sIgE levels. The resulting model could explain 93% (p < 0.001) of D. pteronyssinus sIgE variability. CONCLUSIONS: Our population showed a seasonal pattern of D. pteronyssinus sIgE explained by relative humidity and solar radiation.
Subject(s)
Antigens, Dermatophagoides/immunology , Dermatophagoides pteronyssinus/immunology , Immunoglobulin E/blood , Meteorological Concepts , Animals , Asthma/immunology , Humans , Rhinitis, Allergic , Rhinitis, Allergic, Perennial/immunology , Seasons , Skin TestsABSTRACT
PURPOSE: To estimate the risk of hemorrhagic complications associated with 25-gauge pars plana vitrectomy (PPV) when warfarin (Coumadin; Bristol-Myers Squibb, New York, NY) or clopidogrel (Plavix; Bristol-Myers Squibb) are continued throughout the surgical period, as compared with a control group. DESIGN: A single-center, retrospective, cohort study of 289 consecutive patients receiving either warfarin therapy or clopidogrel therapy or neither of those therapies who underwent 25-gauge PPV. PARTICIPANTS: Included were 61 patients (64 eyes; 64 PPV procedures) in the warfarin group and 118 (125 eyes; 136 PPV procedures) in the clopidogrel group. Warfarin patients were subdivided into 4 groups by international normalized ratio (INR). A control group included 110 patients (110 eyes; 110 PPV procedures) who were not receiving warfarin or clopidogrel. METHODS: Retrospective chart review for which the criteria included: 25-gauge PPV, minimum age of 19 years, warfarin or clopidogrel use, and, if taking warfarin, an INR obtained within 5 days of surgery. MAIN OUTCOME MEASURES: Incidence of intraoperative and postoperative hemorrhagic complications. RESULTS: The most common indications for anticoagulation therapy included: atrial fibrillation (38%), valvular heart disease (17%), and thromboembolic disease (16%). The most common indications for antiplatelet therapy included: cardiac stent (49%), coronary artery bypass grafting (24%), and history of transient ischemic attack (16%). No patient experienced anesthesia-related hemorrhagic complications resulting from peribulbar or retrobulbar block. Transient vitreous hemorrhage occurred in 1 (1.6%) of 64 PPV procedures in the warfarin group (P = 0.6531), 5 (3.7%) of 136 PPV procedures in the clopidogrel group (P = 1.0), and 4 (3.6%) of 110 PPV procedures in the control group. No choroidal or retrobulbar hemorrhages occurred in any patient. CONCLUSIONS: The rate of 25-gauge PPV hemorrhagic complications in patients who underwent systemic anticoagulation or who were receiving platelet inhibitor therapy is extremely low. Given the risks associated with stopping these therapies, the authors recommend that patients continue their current therapeutic regimen without cessation.
Subject(s)
Anticoagulants/administration & dosage , Platelet Aggregation Inhibitors/administration & dosage , Ticlopidine/analogs & derivatives , Vitrectomy/adverse effects , Vitreous Hemorrhage/etiology , Warfarin/administration & dosage , Aged , Cardiovascular Diseases/drug therapy , Choroid Hemorrhage/diagnosis , Choroid Hemorrhage/etiology , Clopidogrel , Humans , Incidence , Intraocular Pressure/physiology , Intraoperative Complications , Microsurgery , Middle Aged , Postoperative Complications , Retinal Diseases/surgery , Retrobulbar Hemorrhage/diagnosis , Retrobulbar Hemorrhage/etiology , Retrospective Studies , Risk Factors , Ticlopidine/administration & dosage , Visual Acuity/physiology , Vitreous Hemorrhage/diagnosisABSTRACT
The objective of this work was to study the role of mannose-binding lectin (MBL) and C-reactive protein (CRP) in pneumococcal pneumonia, to determine whether MBL acts as an acute-phase reactant and whether the severity of the disease correlates with MBL levels. The study comprised 100 patients with pneumococcal pneumonia. The pneumonia severity score was calculated and graded into a risk class of mortality (Fine scale). The MBL genotypes and the levels of MBL and CRP at the acute and recovery phases were determined. Fifty patients with the wild-type MBL genotype showed higher MBL levels in each phase (P < 0.001) and an increased risk to developing bacteraemia, odds ratio (OR) 2.74, 95% confidence interval (CI) 1.01-7.52) (P = 0.02), but this did not correlate with the pneumonia severity class. CRP levels in the acute phase, 79.53 mg/l [standard deviation (s.d.) 106.93], were higher in the subjects with positive blood cultures (P = 0.003), and remained higher [20.12 mg/l (s.d. 31.90)] in the group of patients with an underlying disease (P = 0.01). No correlation was observed between the levels of MBL and CRP in each phase, or with the pneumonia severity score. We cannot conclude that MBL acts uniformly as an acute-phase reactant in pneumococcal pneumonia. MBL levels do not correlate well with the severity of the pneumonia. The risk of developing bacteraemia could be enhanced in individuals with the wild-type MBL genotype.
Subject(s)
Acute-Phase Reaction , Community-Acquired Infections/metabolism , Mannose-Binding Lectin/metabolism , Pneumonia, Pneumococcal/metabolism , Streptococcus pneumoniae , Adult , Aged , Aged, 80 and over , Bacteremia/genetics , Bacteremia/metabolism , Bacteremia/mortality , Community-Acquired Infections/genetics , Community-Acquired Infections/mortality , Female , Genetic Predisposition to Disease , Humans , Male , Mannose-Binding Lectin/genetics , Middle Aged , Pneumonia, Pneumococcal/genetics , Pneumonia, Pneumococcal/mortality , Risk Assessment , Statistics, NonparametricABSTRACT
The aetiology of Behçet's disease (BD) is still unknown, but genetic and environmental factors are involved. HLA-B*51 is considered a susceptibility marker and some MICA alleles have also been associated. Cytotoxic T lymphocytes have been suggested as responsible for BD lesions by engaging MICA through NKG2D surface molecules. In the present study, HLA-B and MICA alleles were typed by polymerase chain reaction using sequence-specific primers, in 165 healthy Spanish controls and 42 BD patients. In the healthy group, MICA*008 (28.48%), MICA*004 (17.58%), MICA*002 (14.24%) and MICA*009 (9.39%) were the predominant alleles and the most common haplotype was MICA*004-B*44 (12.12%). MICA*001 (5.15%), MICA*004, MICA*011 (4.54%) and MICA*018 (5.15%) were more frequent, and MICA*010 (1.81%) and MICA*008 were less prevalent than in other Caucasoid populations. Similar results have been reported in North African individuals and this could support the hypothesis of a common ancestral origin of both populations. The frequencies of MICA*009 and MICA*019 were significantly increased in our BD patients in comparison with controls: 22.62% versus 9.39% and 10.71% versus 1.81% respectively. The increase of MICA*019 had not been described in other BD cohorts, and it corroborates the genetic heterogeneity at MICA locus in BD patients. High-affinity MICA alleles for NKG2D were more frequent in controls than in patients. Moreover, high-affinity alleles were not found in homozygous BD patients. These results argue against the hypothesis of an autoaggressive response in BD patients through MICA-NKG2D interactions.
Subject(s)
Behcet Syndrome/genetics , Behcet Syndrome/immunology , Histocompatibility Antigens Class I/genetics , Histocompatibility Antigens Class I/immunology , Polymorphism, Genetic , Case-Control Studies , Gene Frequency , HLA-B Antigens/genetics , Haplotypes , Humans , NK Cell Lectin-Like Receptor Subfamily K , Receptors, Immunologic/immunology , Receptors, Natural Killer Cell , Spain , White PeopleABSTRACT
UNLABELLED: Humoral mechanisms of rejection after kidney transplantation (TX) can be identified through the detection of diffuse complement C4d deposits in peritubular capillaries (PTC) in graft biopsies or donor-specific antibodies (DSA) in serum samples. It has been hypothesized that ischemic injury in the graft may facilitate humoral responses. Kidney grafts from non-heart-beating donors (NHBD) present more often severe ischemia lesions than grafts from heart-beating or living donors. METHODS: We reviewed kidney TX biopsies performed from May 2002 to November 2004 with special interest paid to recipients from NHBD. We checked corresponding frozen tissue for the detection of C4d in PTC using immunofluorescence with a monoclonal antibody against C4d. We also collected post-TX contemporaneous DSA data, either flow crossmatches or cytotoxic PRA. RESULTS: During this period, we performed 22 kidney TXs from NHBD of a total of 326 kidney TX (either single or combined with other grafts). Nine patients of this group underwent 12 biopsies for delayed graft function over 15 days or deteriorating scans. All biopsies showed acute tubular necrosis, but one also presented IA Banff acute rejection and another one had neutrophils in PTC. Frozen tissue from these 12 biopsies did not have diffuse C4d deposits in PTC. Serum samples of seven of nine patients were available: four had negative DSA flow crossmatches and three had 0% PRA within the same period. We diagnosed acute humoral rejection (AHR) in 13 patients-with acute renal dysfunction, C4d in biopsies and DSA after kidney TX-of 38 with high clinical suspicion for AHR. We detected C4d in seven biopsies of 30 patients performed more than 6 months after TX. CONCLUSIONS: Severe ischemic injury does not necessarily determine the activation of humoral mechanisms of rejection mediated through DSA. Therefore, C4d is extremely interesting for the identification of humoral rejection in any clinical setting after kidney TX.
Subject(s)
Complement C4b/analysis , Heart Arrest , Kidney Transplantation/physiology , Peptide Fragments/analysis , Tissue Donors , Antibody Formation , Biopsy , Graft Rejection/diagnosis , Humans , Kidney Transplantation/immunology , Kidney Transplantation/pathology , Retrospective Studies , Transplantation, HomologousABSTRACT
Eleven AJCC stage IV melanoma patients with progressive disease after treatment with biochemotherapy were treated with autologous dendritic cells pulsed with heterologous tumor cell lysates. The vaccine used mature DCs (CD1a+++, CD40++, CD80++, CD83+, and CD86+++) generated from peripheral blood monocytes in the presence of GM-CSF and IL-4. After 7 days, DCs were matured with a defined cocktail of cytokines (IL-1+IL-6+TNF-alpha+PGE2) and simultaneously pulsed with lysates of heterologous melanoma cell lines, for 2 days. A total of 4 x 10(6) DCs was injected monthly under ultrasound control in an inguinal lymph node of normal appearance. The study was closed when all patients died as a consequence of tumor progression. No sign of toxicity was observed during the study. One patient experienced a partial response lasting 5 months, and two patients showed a mixed response which lasted 3 months. The median survival of the whole group was 7.3 months (range 3-14 months). This vaccination program had specific antitumoral activity in highly pretreated and large tumor burden stage IV melanoma patients and was well tolerated. The clinical responses and the median survival of the group of patients, together with the low toxicity of our DC vaccine, suggest that this approach could be applied to earlier AJCC stage IV melanoma patients.
Subject(s)
Cancer Vaccines/therapeutic use , Dendritic Cells/immunology , Immunotherapy , Melanoma/therapy , Skin Neoplasms/therapy , Adult , Antineoplastic Agents/therapeutic use , Female , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Humans , Interferon-gamma/blood , Interleukin-4/metabolism , Male , Melanoma/immunology , Melanoma/mortality , Melanoma/pathology , Middle Aged , Neoplasm Staging , Pilot Projects , Skin Neoplasms/immunology , Skin Neoplasms/mortality , Skin Neoplasms/pathology , Survival Rate , T-Lymphocytes, Cytotoxic/immunology , Tumor Cells, CulturedABSTRACT
BACKGROUND: Acute humoral rejection, or rejection associated with de novo production of anti-HLA donor-specific antibodies (DSA) after kidney transplantation (KTx), is a clinicopathologic entity that is not completely understood. Recent studies have proposed criteria for its diagnosis, including: (1) steroid-resistant acute dysfunction; (2) positive post-Tx donor-specific crossmatch (XM); and (3) widespread C4d deposits in peritubular capillaries (PTC) upon renal biopsy. METHODS: During 2002, prospective screening for AHR was established at our unit, seeking DSA post-KTx in selected cases of steroid-resistant acute rejection or acute dysfunction in high-risk sensitized or re-Tx patients. Frozen donor lymphocytes were used for post-Tx flow cytometry (FC) XM and high-definition flow PRA for patients with no frozen donor cells. We treated patients diagnosed with DSA using plasma exchange and polyclonal immunoglobulin. RESULTS: Post-Tx DSA studies were performed in 9 of 94 patients transplanted during 2002. We detected DSA post-Tx in 3 of 9 recipients: 2 by FCXM and 1 using high-definition flow PRA. Two were highly sensitized pre-Tx, but the third patient was a 70-year-old woman receiving a first Tx (PRA=0%). All 3 recipients presented with severe steroid-resistant acute renal dysfunction during the first 2 weeks post-Tx. Biopsies showed some features of AHR (neutrophils in PTC); 1 case showed no signs of concomitant cellular rejection. All rejection episodes were treated successfully (XM became negative and renal function recovered) by combining plasma exchange and polyclonal immunoglobulin. CONCLUSIONS: The use of specific tools, like the crossmatch, in cases of acute, steroid-resistant renal graft dysfunction is important to identify and treat otherwise undetected humoral mechanisms of rejection.
Subject(s)
Graft Rejection/immunology , Kidney Transplantation/immunology , Acute Disease , Aged , Antibody Formation , Female , Flow Cytometry , Histocompatibility Testing , Humans , Isoantibodies/blood , Lymphocytes/immunology , Plasma Exchange , Reoperation , Tissue DonorsABSTRACT
BACKGROUND: In simultaneous liver-kidney transplantation (SLKT), the liver has been described to protect the kidney from rejection, and acceptable results are possible despite a pretransplant positive crossmatch. At our center, 21 SLKT have been performed since 1993, 2 of them against a positive crossmatch. OBJECTIVES: In this study we retrospectively analyzed two cases of SLKT after positive pretransplant crossmatch. METHODS: Two highly sensitized women (30 and 52 years) with hepatic cirrhosis VHC on hemodialysis after a first KT failure were assessed. Pretransplant panel reactive antibodies (PRA) by complement dependent cytotoxicity NIH (CDC) were 81% and 99% respectively. Both patients received a SLKT. CM was performed at pretransplant and 24 and 48 hours posttransplant by CDC and by flow cytometry with double labeling with CD3-PE and antihuman IgG-FITC. Patients received ATG, cyclosporine, and prednisone therapy. RESULTS: CM was positive pretransplant by CDC and flow cytometry. At 48 hours, CDC became almost negative (10%-20% mortality) and flow cytometry became negative. One of the patients experienced an episode of acute rejection at 10 days posttransplant that resolved with steroid pulses. Both patients presently have working grafts 26 and 24 months posttransplant (Cr, 1.1 and 1.5 mg/dL; GOT, 34 and 14 IU/L; GTP, 29 and 12 IU/L; GGT, 9 and 66 IU/L). CONCLUSIONS: Our experience suggests that a positive crossmatch is not an absolute contraindication for SLKT. Good graft and patient survival rates are possible even among highly sensitized patients.
Subject(s)
Histocompatibility Testing/methods , Kidney Transplantation/immunology , Liver Transplantation/immunology , Adult , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Female , Flow Cytometry , Humans , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/physiology , Liver Transplantation/physiology , Middle Aged , Retrospective Studies , Treatment OutcomeABSTRACT
'Chueta' was the name given to the Catholic descendants of Jewish victims of the last Spanish Inquisition process in Majorca Island in the western Mediterranean. We have studied the allele distribution of HLA-A, -B, -Cw, -DRB1 and -DQB1 loci of 103 random, healthy, unrelated individuals belonging to the ancient Majorcan Jewish community, known locally as Chuetas, and 589 individuals from the Balearic population selected because of their typical Balearic - Majorca, Minorca or Ibiza - lineages and according to their ancestor's place of birth. Our aim was to establish the genetic relationship between Majorcan Chuetas, and Balearic and other Jewish and Mediterranean populations. Our results have shown that, to a remarkable extent, they have retained their biological identity, with a unique pattern, in terms of gene and haplotype frequencies, separate from the other populations of Majorca. The Chuetas were found to be more related to Moroccan and Libyan Jews than other Majorcans. Characteristic Jewish haplotypes, A26-B38-DRB1*13, A24-B38-DRB1*11, A1-B52-DRB1*15/16, were found in our study. Some peculiarities were observed in the distribution of common haplotypes among the three main Balearic Islands. The Ibizan population was genetically different from the other Balearic populations, with a high frequency of some haplotypes, for example, A29-Cw*16-B44-DRB1*07-DQB1*03; A1-Cw*07-B8-DRB1*03-DQB1*02. We also found a new haplotype, A25-Cw*12-B39-DRB1*11-DQB1*03(3.5%), in Ibizans and a more limited variability in the HLA alleles that were expressed, perhaps because of genetic isolation. The genetic diversity of the populations from Majorca and Minorca were similar and more related to the mainland Spanish population.
Subject(s)
HLA Antigens/genetics , Jews/genetics , Polymorphism, Genetic , Alleles , Gene Frequency , Genes, MHC Class I , Genes, MHC Class II , HLA-DQ Antigens/genetics , HLA-DQ beta-Chains , HLA-DR Antigens/genetics , HLA-DRB1 Chains , Haplotypes , Humans , Mediterranean Islands , PhylogenyABSTRACT
The aim of the study was to determine possible factors related to the risk of developing recurrent bacterial respiratory tract infections in HIV-1-infected patients, regardless of the degree of immune cellular impairment. Thirty-three HIV-1 seropositive patients with previous repetitive bacterial respiratory tract infections (case group), 33 HIV-1 seropositive controls (matched by CD4-cell counts) without these antecedents and 27 healthy controls were studied before and after administration of pneumococcal and Haemophilus influenzae type b vaccines. Clinical or toxicological variables, cutaneous tests, complement factors, beta2-microglobulin, serum IgM, IgA, IgG and subclasses, specific antibodies (IgG, IgG2, IgA) against pneumococcal vaccine and polyribosylribitol phosphate (PRP), their avidity, opsonophagocytosis and IgG(2)m and Fc(gamma)RIIa allotypes were determined. A history of drug abuse (P = 0.001), less likelihood of receiving high activity antiretroviral treatment high activity antiretroviral treatment (HAART) (P = 0.01), higher levels of HIV-1 viral load (P < 0.05), serum IgG (P < 0.01) and beta2-microglobulin (P < 0.01) were observed in the case group. Also, a lower increase in specific antibodies to pneumococcal vaccine and PRP was demonstrated in the cases in comparison with the two control groups. No differences were observed in the avidity of antibodies, opsonophagocytic capacity or IgG(2)m and Fc(gamma)RIIa allotypes between the three groups. These data indicate that vaccination strategies against encapsulated bacteria can be unsuccessful in the HIV-1-infected patients presenting repetitive bacterial respiratory tract infections if behavioural aspects or measures to improve adherence to HAART therapies are not considered.
Subject(s)
AIDS-Related Opportunistic Infections/etiology , Antibodies, Bacterial/blood , HIV Infections/complications , HIV-1 , Respiratory Tract Infections/etiology , AIDS-Related Opportunistic Infections/diagnosis , AIDS-Related Opportunistic Infections/immunology , AIDS-Related Opportunistic Infections/prevention & control , Adult , Antibodies, Bacterial/classification , Antibodies, Bacterial/immunology , Antigens, CD/genetics , Antiretroviral Therapy, Highly Active , Case-Control Studies , Demography , Female , HIV Infections/drug therapy , HIV Infections/immunology , Haemophilus Vaccines/immunology , Humans , Immunoglobulin Allotypes , Male , Middle Aged , Opsonin Proteins/metabolism , Phagocytosis , Pneumococcal Vaccines/immunology , Polymorphism, Genetic , Receptors, IgG/genetics , Recurrence , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/immunology , Respiratory Tract Infections/prevention & control , Risk FactorsABSTRACT
Dado que las Inmunodeficiencias Primarias (IDP) son enfermedades poco frecuentes, resulta de utilidad epidemiológica desarrollar registros nacionales específicos. El Registro Español de Inmunodeficiencias Primarias (REDIP) fue creado en 1993. Se admitieron los pacientes diagnosticados a partir de enero de 1980 hasta la actualidad. Los casos registrados hasta octubre de 2001 han sido 2.242. Las inmunodeficiencias remitidas han sido diagnosticadas de acuerdo con los criterios de la OMS (1997) (1). Los síndromes más registrados son, en orden de frecuencia, en primer lugar la deficiencia selectiva de IgA (832 registros), seguida por la inmunodeficiencia variable común (430), las inmunodeficiencias combinadas severas y deficiencias de células T (282), las deficiencias de complemento (256), la agammaglobulinemia ligada al sexo (91), la deficiencia de subclases de IgG (90), y la enfermedad granulomatosa crónica (66). El tratamiento sustitutivo con gammaglobulina endovenosa consta registrado en 696 pacientes, de éstos 553 pertenecen al grupo de deficiencias predominantes de anticuerpos. El trasplante de médula ósea se ha realizado en 63 pacientes. El registro mantiene un aumento constante y regular, presentando variaciones importantes en la contribución al mismo entre las distintas comunidades autónoma (AU)
Due to the low frequency of primary immunodeficiency disorders (PIDs), national registries are useful to characterize the incidence and prevalence of the diff e rent disorders . The Spanish Register for Primary Immunodeficiencies (REDIP) began in 1993. Two thousand two hundred and forty two cases (n=2242) of primary immunodeficiencies were re g i s t e red till October 2001. PIDs nomenclature and diagnostic criteria were made according to the report of the Wo r l d Health Organization Scientific Group (1997). The most frequent disorders were IgA deficiency (832 registers) and common variable immunodeficiency (CVI) (430), followed by s e v e re combined immunodeficiency and predominantly T cell defects (282), complement deficiencies (256), X-linked agammaglobulinemia (91), IgG subclass deficiency (90) and chronic granulomatous disease (66). The cases of complement deficiencies were higher than the European Register due to the recent special collaboration of groups working with these diseases. Gammaglobulin replacement was the therapy in 696 patients, 553 of them belonging to antibody deficient grow up. Sixty-three bone marrow transplants were done. Important differences in the number of cases submitted from different areas in our country were found (AU)
Subject(s)
Humans , Immunologic Deficiency Syndromes/epidemiology , gamma-Globulins/therapeutic use , Diseases Registries/statistics & numerical data , IgG Deficiency/epidemiologyABSTRACT
BACKGROUND: allergic disease caused by Parietaria judaica (Pj) has been widely documented in Mediterranean area. Profilins have been identified as widely distributed allergenic proteins. The role of Pj profilin in specific immune response in Pj-sensitized patients is unknown. METHODS: skin prick test and determination of specific and total IgE levels in serum were performed in all patients (n = 28) and non-allergic controls (n = 18). Peripheral blood mononuclear cells (PBMC) were isolated from both groups and stimulated with crude extract or highly purified Pj profilin. The production of type I and type II cytokines was determined by specific and polyclonal stimuli in patients and controls. T-cell lines specific to Pj profilin were established and cross-reactivity with another highly purified profilin from Phleum pratense (Phl p) was evaluated. RESULTS: Pj profilin-sensitized patients showed a small but significantly increased in T-cell proliferative response to this profilin compared with non-atopic controls. The production of interleukin (IL)-4 and interferon (IFN)-γ in response to the specific stimulus was undetectable. However, the production of IL-4 in response to a polyclonal stimulus [phytohemagglutinin (PHA)] was significantly higher in atopic patients than in controls. The T-cell response did not correlate with the magnitude of response to skin prick tests with Pj profilin or with Pj-specific serum IgE levels. In addition, the production of IL-4 in response to a polyclonal stimulus (PHA) did not correlate with the individual skin prick tests to Pj profilin or with Pj-specific IgE levels in serum. The T-cell lines tested showed no cross-reactivity with Phl p profilin. CONCLUSIONS: our results suggest that Pj profilin is partly responsible for the T-cell-mediated response in patients allergic to Pj. The high skin reactivity to Pj profilin is these patients was accompanied by a small increase in the T-cell response to this profilin. The response was highly specific since Pj profilin specific T-cell lines showed no cross-reactivity with a highly homologous profilin from Phl p. The lack of correlation between the proliferative T-cell response and polyclonal IL-4 production with allergen-specific serum IgE and skin reactivity probably indicates that some of the responding T-cells may be involved in immune reactions other than those supporting IgE production.
Subject(s)
Allergens/immunology , Antigens, Plant/immunology , Cell Proliferation , Hypersensitivity/immunology , Immunoglobulin E/immunology , Plant Extracts/immunology , Profilins/immunology , T-Lymphocytes/immunology , Adult , Female , Humans , Male , Middle Aged , Parietaria/immunology , Plant Proteins/immunology , Skin Tests , Young AdultABSTRACT
Background: allergic disease caused by Parietaria judaica (Pj) has been widely documented in Mediterranean area. Profilins have been identified as widely distributed allergenic proteins. The role of Pj profilin in specific immune response in Pj-sensitized patients is unknown. Methods: skin prick test and determination of specific and total IgE levels in serum were performed in all patients (n = 28) and non-allergic controls (n = 18). Peripheral blood mononuclear cells (PBMC) were isolated from both groups and stimulated with crude extract or highly purified Pj profilin. The production of type I and type II cytokines was determined by specific and polyclonal stimuli in patients and controls. T-cell lines specific to Pj profilin were established and cross-reactivity with another highly purified profilin from Phleum pratense (Phl p) was evaluated. Results: Pj profilin-sensitized patients showed a small but significantly increased in T-cell proliferative response to this profilin compared with non-atopic controls. The production of interleukin (IL)-4 and interferon (IFN)-γ in response to the specific stimulus was undetectable. However, the production of IL-4 in response to a polyclonal stimulus [phytohemagglutinin (PHA)] was significantly higher in atopic patients than in controls. The T-cell response did not correlate with the magnitude of response to skin prick tests with Pj profilin or with Pj-specific serum IgE levels. In addition, the production of IL-4 in response to a polyclonal stimulus (PHA) did not correlate with the individual skin prick tests to Pj profilin or with Pj-specific IgE levels in serum. The T-cell lines tested showed no cross-reactivity with Phl p profilin. Conclusions: our results suggest that Pj profilin is partly responsible for the T-cell-mediated response in patients allergic to Pj. The high skin reactivity to Pj profilin is these patients was accompanied by a small increase in the T-cell response to this profilin. The response was highly specific since Pj profilin specific T-cell lines showed no cross-reactivity with a highly homologous profilin from Phl p. The lack of correlation between the proliferative T-cell response and polyclonal IL-4 production with allergen-specific serum IgE and skin reactivity probably indicates that some of the responding T-cells may be involved in immune reactions other than those supporting IgE production (AU)
Antecedentes: La enfermedad alérgica originada por Parietaria judaica (Pj) ha sido ampliamente documentada en la zona Mediterránea. Las profilinas han sido identificadas como proteínas alergénicas de amplia distribución. El papel de la profilina de Pj en la respuesta inmunológica específica en pacientes sensibilizados a la Pj es desconocida. Métodos: Se determinaron en todos los pacientes (n = 28) y controles normales no atópicos (n = 18) el test de reactividad cutánea y los niveles tanto de IgE específicas como totales en suero. Se aislaron células mononucleares de sangre periféica (PBMC) en ambos grupos y fueron estimuladas con el extracto crudo o con la profilina altamente purificada de Pj. Se determinaron también la producción de citocinas de tipo I y de tipo II, con estimulaciones específicas o policlonales en pacientes y controles. Establecimos líneas de células T específicas por la profilina de Pj y evaluamos la reactividad cruzada con otra profilina altamente purificada de Phleum pratense (Phl p). Resultados: Los pacientes sensibilizados a la profilina de Pj muestran un ligero pero significativo incremento en la respuesta proliferativa T frente la profilina respecto con el grupo de controles no alérgicos. La producción de IL-4 y IFN-γ en respuesta a estímulos específicos fue indetectable. Sin embargo, la producción de IL-4 en respuesta a un estímulo policlonal (PHA), fue significativamente mayor en pacientes atópicos que en los controles no alérgicos. La respuesta celular T no se corresponde ni con la magnitud de la repuesta en la reactividad cutánea a la profilina de Pj ni con los niveles de IgE en suero específicos para la Pj. La producción de IL-4 frente a un estímulo policlonals (PHA), no se correlaciona con la reactividade cutánea a la profilina ni con los niveles de IgE en suero. Las líneas específicas T testadas no mostraron ninguna reactividad cruzada con la profilina de (Phl p). Conclusiones: Nuestros resultados sugieren que la profilina de Pj es responsable en parte de la respuesta mediada por células T en pacientes alérgicos a la Pj. La elevada reactividad cutánea de estos pacientes, se acompaña de un pequeño incremento en la respuesta de células T a esta profilina. La respuesta es muy específica porque las líneas de células T no presentaron respuesta cruzada con la profilina altamente homóloga de Phl p. La falta de correlación entre la respuesta proliferativa de las células T y la producción policlonal de IL-4 con los niveles de IgE específicos en suero y la reactividad cutánea probablemente indica que algunas de las células T respondedoras estarían involucradas en una reacción inmunitaria diferente a la que promueve la producción de IgE (AU)
Subject(s)
Humans , Parietaria/adverse effects , Food Hypersensitivity/immunology , Immunoglobulin E/analysis , Hypersensitivity, Immediate/immunology , Antigens, Plant/adverse effects , Profilins/immunology , Skin Irritancy Tests , Dietary Proteins/adverse effects , Case-Control StudiesABSTRACT
In this paper we describe the clinical and molecular features of a new case (GOR) of homozygous human TAP2 deficiency, analysing the phenotype and function of NK cells. The patient presented from infancy with recurrent sinopulmonary infections; a selective IgG2 deficiency, negative antibody response to polysaccharide vaccination and low level of cell surface expression of HLA class I antigens were found. The sequence of TAP2 gene identified a single mutation, a C to T substitution changing the CGA arg codon at amino acid 220 into TGA stop codon in exon 3. By using MoAbs for KIRs, CD94, CD94/NKG2A and ILT2 we observed, in agreement with others, that the latter two receptors were overexpressed on TAP2-deficient NK cells. The inhibitory CD94/NKG2A and triggering CD94/NKG2C NK receptors, specific for HLA-E, appeared to be functional in a limited number of NK clones that could be expanded in vitro. Expression of HLA-E was virtually undetectable in GOR B-LCL and very faint in PBMC, further supporting that interactions of class I leader sequence nonamers with HLA-E in the ER depend on a functional TAP complex.
Subject(s)
ATP-Binding Cassette Transporters/genetics , Cysteine Endopeptidases , Killer Cells, Natural/immunology , Multienzyme Complexes , Severe Combined Immunodeficiency/immunology , ATP Binding Cassette Transporter, Subfamily B, Member 2 , ATP Binding Cassette Transporter, Subfamily B, Member 3 , ATP-Binding Cassette Transporters/metabolism , Amino Acid Sequence , Cells, Cultured , Cytotoxicity Tests, Immunologic , Histocompatibility Antigens Class I/metabolism , Homozygote , Humans , Immunophenotyping , K562 Cells , Molecular Sequence Data , Mutation , Proteasome Endopeptidase Complex , Proteins/metabolism , Severe Combined Immunodeficiency/genetics , T-Lymphocyte Subsets/classificationABSTRACT
BACKGROUND: Phleum pratense (Phl p) pollen is a known cause of allergic disease worldwide. Profilins have been identified as functional plant pan-allergens. The role of Phl p profilin in the specific immune response in sensitized Phl p patients is unknown. METHODS: Skin prick test and specific serum IgE levels were performed in 26 patients allergic to Phl p and in 18 nonallergic control donors. Peripheral blood mononuclear cells were isolated from both groups and stimulated with crude extract or highly purified Phl p profilin, and the production of type I and type II cytokines was determined in patients and controls stimulated with specific and polyclonal stimulus. T-cell lines specific to Phl p profilin were established from PBMCs and cross-reactivity with another highly purified profilin from Parietaria judaica (Pj) was evaluated. RESULTS: Patients allergic to Phl p profilin showed increased T-cell-proliferative responses to this profilin compared with control subjects. The production of IL-4 and IFN-gamma in response to the specific stimulus was undetectable. However, the production of IL-4 and IFN-gamma in response to a polyclonal stimulus (PHA) was measurable and different for atopic patients and control subjects: IL-4 was higher (p < 0.001) in allergic patients and IFN-gamma lower (although not significant) in controls. Neither the T-cell responses nor the production of IL-4 in response to a polyclonal stimulus (PHA) correlated with the individual degree of cutaneous response to Phl p profilin or to the levels of specific Phl p IgE. The T-cell lines tested did not show any cross-reactivity with Pj profilin. CONCLUSIONS: Phl p profilin is in part responsible for the T-cell mediated immunological response in patients allergic to Phl p. The response is very specific since Phl p profilin specific T-cell lines did not show cross-reactivity with a highly homologous profilin from Parietaria judaica (Pj). The lack of correlation between the proliferative T-cell response and polyclonal IL-4 production with allergen-specific serum IgE and SPT probably indicates that some of the responding T-cells may be involved in immune reactions other than the support of IgE production.
Subject(s)
Allergens/immunology , Contractile Proteins , Hypersensitivity, Immediate/immunology , Immunoglobulin E/immunology , Microfilament Proteins/immunology , Plant Proteins/immunology , Pollen/immunology , Rhinitis, Allergic, Seasonal/immunology , T-Lymphocyte Subsets/immunology , Adult , Cell Line , Cross Reactions , Humans , Hypersensitivity, Immediate/etiology , Interferon-gamma/biosynthesis , Interleukin-4/biosynthesis , Lymphocyte Activation , Profilins , Rhinitis, Allergic, Seasonal/etiology , Skin Tests , T-Lymphocyte Subsets/metabolismABSTRACT
Background: Phleum pratense (Phl p) pollen is a known cause of allergic disease worldwide. Profilins have been identified as functional plant pan-allergens. The role of Phl p profilin in the specific immune response in sensitized Phl p patients is unknown. Methods: skin prick test and specific serum IgE levels were performed in 26 patients allergic to Phl p and in 18 nonallergic control donors. Peripheral blood mononuclear cells were isolated from both groups and stimulated with crude extract or highly purified Phl p profilin, and the production of type I and type ll cytokines was determined in patients and controls stimulated with specific and polyclonal stimulus. T-cell lines specific to Phl p profilin were established from PBMCs and cross-reactivity with another highly purified profilin from Parietaria judaica (Pj) was evaluated. Results: patients allergic to Phl p profilin showed increased T-cell-proliferative responses to this profilin compared with control subjects. The production of IL-4 and IFN-g in response to the specific stimulus was undetectable. However, the production of IL-4 and IFN-g in response to a polyclonal stimulus (PHA) was measurable and different for atopic patients and control subjects: IL-4 was higher (p < 0.001) in allergic patients and IFN-g lower (although not significant) in controls. Neither the T-cell responses nor the production of IL-4 in response to a polyclonal stimulus (PHA) correlated with the individual degree of cutaneous response to Phl p profilin or to the levels of specific Phl p IgE. The T-cell lines tested did not show any cross-reactivity with Pj profilin. Conclusions: Phl p profilin is in part responsible for the T-cell mediated immunological response in patients allergic to Phl p. The response is very specific since Phl p profilin specific T-cell lines did not show cross-reactivity with a highly homologous profilin from Parietaria judaica (Pj). The lack of correlation between the proliferative T-cell response and polyclonal IL-4 production with allergen-specific serum IgE and SPT probably indicates that some of the responding T-cells may be involved in immune reactions other than the support of IgE (AU)
Antecedentes: el polen de Phleum pratense (Phl p) es una de las causas más frecuentes de alergia respiratoria en el mundo occidental. Las profilinas han sido identificadas como proteínas pan-alergénicas con una amplia distribución en el reino vegetal. El papel de la profilina de Phl p en la respuesta inmunológica específica en pacientes sensibilizados al Phl p es desconocida. Métodos: se practicaron a 26 pacientes alérgicos a Phl p y a 18 controles no atópicos pruebas cutáneas cuantificadas a profilina de Phl p, así como determinación de IgE específica a polen de Phl p. Se aislaron células mononucleares de sangre periférica (PBMC) en ambos grupos y tras estímulo con el extracto crudo o con la profilina altamente purificada de Phl p, se determinó la producción de citocinas de tipo I y de tipo II, por medio de estimulaciones específicas o policlonales tanto en pacientes como en controles. Se establecieron líneas de células T específicas por la profilina de Phl p y se evaluó la posible reactividad cruzada con otra profilina altamente purificada de Parietaria judaica (Pj). Resultados: los pacientes sensibilizados a la profilina de Phl p mostraron un incremento en la respuesta proliferativa T frente la profilina respecto al grupo de controles no alérgicos. La producción de IL-4 e IFN-g en respuesta al estímulo específico fue indetectable. Sin embargo, la producción de IL-4 en respuesta a un estímulo policlonal (PHA) fue significativamente mayor en pacientes alérgicos que en los controles y la producción de IFN-Υ fue menor en el grupo de alérgicos que en los controles. Ni la respuesta celular T ni la producción de IL-4 frente a un estímulo policlonal se corresponden con la magnitud de la respuesta en la reactividad cutánea a la profilina de Phl p, o con los niveles de IgE específica a Phl p en suero. Las líneas específicas T testadas no mostraron ninguna reactividad cruzada con la profilina de Pj.Conclusiones: nuestros resultados sugieren que la profilina de Phl p es responsable en parte de la respuesta mediada por células T en pacientes alérgicos a Phl p. La respuesta es muy específica porque las líneas de células T no presentaron respuesta cruzada con la profilina altamente homóloga de Pj. La falta de correlación entre la respuesta proliferativa de las células T y la producción policlonal de IL-4 con los niveles de IgE específicos en suero y la reactividad cutánea probablemente indica que algunas de las células T respondedoras podrían estar involucradas en reacciones inmunitarias distintas de las que promueven la producción de IgE (AU)