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[Evaluation of the immunological reactivity and hormonal profile in patients with breast cancer].

Excretion of 17-HOCS and estrogens as well as the levels of E-RFC and time-delayed DNCB and tuberculin (PPD) contact sensitization reaction were studied in 136 breast cancer patients. A decrease in immunological response in reproductive and menopausal patients was matched by the development of relative hyperestrogenism and elevation of 17-HOCS excretion in the former group and a rise in 17-HOCS excretion only in the latter.

17-Hydroxycorticosteroids↗

[Reaction of inhibition of macrophage electrophoretic mobility in differential diagnosis of carcinomas].

The reactivity of the lymphocytes from 40 carcinoma patients and 19 patients without detectable malignancies was tested by means of the macrophage-electrophoresis-mobility (MEM) test exposing lymphocytes from one individual to a large spectrum of antigenic preparations. Besides the encephalitogenic protein (EP) and the carcino-embryonic antigen (CEA) hypertonic KCl-extracts from human cancer and normal tissues were used as antigens to be tested. When performed in such a complex manner, the MEM-test resulted in characteristic reaction patterns allowing one not only to discriminate between cancer and noncancer, but also to draw a conclusion in which organ a carcinoma has arisen. The characteristic "immunological tumor profiles", thus obtained, are obviously due to the existance of common antigens in carcinomas of the same tissue origin. The CEA seems to be another antigen of high diagnostic value in that system, since the lymphocyte response to CEA was restricted to patients with tumors of the colon, rectum and stomach. The results show for the first time that lymphocytes of the tumor patients mentioned are able to react to CEA. The human lymphocyte response to CEA seems to be far more cancer- and (or embryo-specific than the reactions obtained with xenogenic hyperimmune sera) which areused for the detection of CEA in human sera or plasma samples. The "immunological tumor profile" opens a new step of quality among the attempts to develop immunological tumor tests.

Adenocarcinoma↗

Anti-beta2-glycoprotein I and anti-prothrombin antibodies in patients with the 'antiphospholipid' syndrome: immunological specificity and clotting profiles.

Lupus anticoagulant (LA) antibodies have been shown to be directed to protein-phospholipid complexes. In this study, we report on LA antibodies from patients with the 'antiphospholipid' syndrome (APS), that are directed to prothrombin and beta2-glycoprotein I, but not to the complexes of these plasma proteins to anionic phospholipids. The anti-prothrombin antibodies studied had different reactivities in two clotting assays: the dilute Russell's viper venom time (dRVVT) and the dilute kaolin clotting time (dKCT). Anti-prothrombin and anti-beta2-glycoprotein I (anti-beta2GPI) antibodies, affinity-purified from one patient with APS were not cross-reactive and had different effects in the dRVVT and dKCT clotting tests. Polyclonal anti-prothrombin antibodies, affinity-purified on a prothrombin column, from two patients with prothrombin reactivity in their plasma, have affinity constants to prothrombin of 104 and 192 nM. The patient with affinity-purified antibodies to prothrombin and beta2GPI, had affinity constants to prothrombin and beta2GPI, respectively, of 192 nM and 3030 nM, respectively. LA antibodies are a heterogeneous population of antibodies that have different immunological specificities and clotting test reactivities in different patients.

Adult↗

Heterogeneity, immunological comparison and concentration profiles of alpha-fetoproteins derived from late-gestational and early postnatal mouse tissue.

Four distinct alpha-fetoprotein (AFP) species were separated by ion-exchange chromatography of the approximately 70 000 dalton fraction of an extract of late-gestation fetal mice. Although chromatographicaly heterogeneous, antigenic differences among the AFP species resolved were not detected using classical double-diffusion methods. Analysis of the AFP contribution to total body saline-extractable protein of fetal and neonatal mice revealed an abrupt decrease in the fetal AFP contribution to total body saline-extractable protein commencing after the 18th day of gestation.

Absorption↗

Cytokine-dependent K+ channel profile of microglia at immunologically defined functional states.

Microglia were enriched in brain cell cultures from newborn mice as a result of supplementation with the growth factors macrophage colony-stimulating factor or granulocyte/macrophage colony-stimulating factor. When separately administered these two cytokines promote the outgrowth of loosely adherent cells with similar morphology which stained positive for CD11b and nonspecific esterase. Microglial cells isolated from both types of culture were electrophysiologically characterized using the whole cell configuration of the patch-clamp technique. Different resting membrane potentials were measured. In response to hyperpolarizing and depolarizing voltage commands 68 of 91 macrophage colony-stimulating factor-cultured microglial cells exhibited only an inward rectifying potassium current. By contrast, an outward potassium current was observed on 71 of 95 granulocyte/macrophage colony-stimulating factor-grown cells. Parallel testing of their capability for antigen presentation proved the activated functional state of these microglial cells. They induce antigen-specific T cell response without prior stimulus. In comparison, cells developed with macrophage colony-stimulating factor failed to present antigen. In such resting microglia a short-term treatment with granulocyte/macrophage colony-stimulating factor or interferon-gamma provoked a strong appearance of outward potassium currents, however, only the interferon-gamma-trigger resulted in efficient antigen presentation. The differential induction of both functional parameters suggests the detection of outward potassium currents to provide an electrophysiological activation marker of microglia which is subjected to cytokine regulation but not compellingly linked to antigen presentation.

Animals↗

Serial monitoring of immunological parameters following human hand transplant.

BACKGROUND: Although early successes have been achieved in human hand transplant, the changes of immunological parameters in the recipients and their relations to clinical events were not yet known. METHODS: In two patients undergoing hand transplantation, we prospectively determined lymphocyte subsets using flow cytometry as well as the serum levels of interleukin (IL)-2, IL-10, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma using enzyme linked immunosorbent assays during the first 6 months after transplantation. RESULTS: The decreases in CD, CD, CD T cell, the activated T cell (CD/CD, CD/HLA-DR(+)) as well as IL-2, IFN-gamma and corresponding significant peak in IL-10 in human hand transplant during the first post-transplant week were observed. Then these parameters recovered to the pre-transplant level except for an even higher level of CD T cell. The low CD/CD ratio was been maintained constantly. After 7 wk, IL-2, IFN-gamma, and IL-10 decreased to be maintained at a low or undetectable level except for slight increase in IL-10 at post-transplant month 5. There are no significant variation in TNF-alpha early after transplant. After 3 months, IL-10 was not detected again. CONCLUSIONS: The immunosuppressive agents had significantly effects on the immunological status in human hand transplant recipients. These profiles of immunological parameters would be useful data for the future immunomonitoring in human hand transplant recipients.

Adult↗

Do fish thrombocytes play an immunological role? Their cytoenzymatic profiles and function during an accidental piscine candidiasis in aquarium.

Fish (F) thrombocytes (THRs) from healthy trouts were studied in terms of cytoenzyme expression. FTHRs were positive to acid periodic of shiff (PAS) and acid phosphatase (ac. phos.) without tartaric acid (-TA) stainings, as well to alkaline phosphatase. However, when compared with autologous macrophages (M psi's), they were negative to naphthol cloroacetate esterase (AS-D), alpha-naphthyl acetate esterase (Anae), peroxidase (perox) and control ac. phos. with tartaric acid (+TA) stainings, thus indicating a lack of typical lysosomial enzymes. This evidence supports the notion that FTHRs are not true digesting cells. Quite interestingly, trouts and human M psi's were positive for PAS, AS-D, Anae, and perox stainings, thus confirming that cellular cytochemistries are maintained across evolution as their phagocytic functions. Additionally, blood films from trouts, accidentally infected with Candida albicans in aquarium, were morphologically analyzed. Actually, FTHRs interact with erythrocytes, potentiating the formation of rosettes around a central Mpsi. Polymorph nuclear cells and lymphocytes are present in these cellular aggregates, thus suggesting that FTHRs may represent a link between innate and adaptive immunity.

Alkaline Phosphatase↗

Elevated cytokine and chemokine levels and prolonged pulmonary airflow resistance in a murine Mycoplasma pneumoniae pneumonia model: a microbiologic, histologic, immunologic, and respiratory plethysmographic profile.

Because Mycoplasma pneumoniae is hypothesized to play an important role in reactive airway disease/asthma, a comprehensive murine model of M. pneumoniae lower respiratory infection was established. BALB/c mice were intranasally inoculated once with M. pneumoniae and sacrificed at 0 to 42 days postinoculation. All mice became infected and developed histologic evidence of acute pulmonary inflammation, which cleared by 28 days postinoculation. By contrast, M. pneumoniae persisted in the respiratory tract for the entire 42 days studied. Tumor necrosis factor alpha, gamma interferon, interleukin-6 (IL-6), KC (functional IL-8), MIP-1alpha, and MCP-1/JE concentrations were significantly elevated in bronchoalveolar lavage samples, whereas IL-4 and IL-10 concentrations were not significantly elevated. Pulmonary airflow resistance, as measured by plethysmography, was detected 1 day postinoculation and persisted even after pulmonary inflammation had resolved at day 28. Serum anti-M. pneumoniae immunoglobulin G titers were positive in all mice by 35 days. This mouse model provides a means to investigate the immunopathogenesis of M. pneumoniae infection and its possible role in reactive airway disease/asthma.

Airway Resistance↗

Immunology of pulmonary disease--profile of the granuloma.

Granuloma formation in the lung is initiated by a diversity of antigens and other agents including infection, chemicals, organic dusts and metabolic disturbances, all of which lead to chronic parenchymal inflammation and a varying expression of cellular infiltration, necrosis, vasculitis and fibrosis.

Granuloma↗

Immunologic characterization and molecular profile of carcinoembryonic antigen detected by monoclonal antibodies.

Four distinct monoclonal antibodies, which reacted with CEA preparations but not with nonspecific cross-reacting antigen or with nonspecific cross-reacting antigen 2, were established. Except for monoclonal antibody AS001 , all of these monoclonal antibodies immunoprecipitated molecular forms of 200K and 180K daltons that are not bridged by disulfide bonds. Immunodepletion experiments and sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis revealed that these monoclonal antibodies recognized the same antigenic structure when 125I-CEA preparation was used. Monoclonal antibody AS001 is of particular interest, because this antibody reacted only with a 200K dalton molecule which is a part of the molecules recognized by the other three monoclonal antibodies. The rosette inhibition assay and the immunoprecipitation experiments suggest that each monoclonal antibody recognizes a different antigenic determinant. The antigenic determinants recognized by monoclonal antibodies YK013 and AS001 may be peptides in nature, whereas the determinants recognized by antibodies YK024 or AS005 might be carbohydrate. The radioimmunoassay with monoclonal antibody AS001 was established, and the results clearly indicate that the incidence of positivity for the sera from digestive tract cancer patients and from lung cancer patients obtained by monoclonal antibody AS001 was higher than that obtained by the polyclonal antibody. Monoclonal antibody AS001 was able to detect the corresponding antigen in the sera, which the polyclonal antibody failed to detect. This study therefore suggests that monoclonal antibodies may enhance and improve the diagnostic value in cancer patients with undetectable or lower CEA levels detected by conventional anti-CEA antibodies.

Animals↗

Bovine colostrums: a review of clinical uses.

Bovine colostrums are the "early" milk produced by cows during the first several days post-parturition. This "early" milk has a nutrient profile and immunological composition that differs substantially from "mature" milk. Included in the nutrient profile are higher amounts of immunoglobulins, growth factors, cytokines, and nucleosides than are found in milk. Bovine colostrums are also rich in oligosaccharides, antimicrobials, and immune-regulating factors. Available evidence suggests a beneficial effect of supplementation of bovine colostrums in improving body composition, aspects of athletic performance, diarrhea in persons with immune-deficiency syndromes, NSAID-induced gastrointestinal disturbances, and aspects of the acute phase response that occurs secondary to surgery. Specific hyperimmune bovine colostrums, produced to have high neutralizing titer activity against Cryptosporidia, H. pylori, measles, rotavirus, and Shigella sp., appear to have clinical utility in conditions associated with these infectious organisms.

Animals↗

Clinical diagnosis in Karwinskia humboldtiana polyneuropathy.

Intoxication by Karwinskia humboldtiana presents a neurological picture similar to that for Guillain-Barré syndrome or other polyradiculoneuropathies. Clinical diagnosis in poisoned humans may be difficult if no evidence of previous fruit ingestion is available. We present our experience in the clinical diagnosis of Karwinskia humboldtiana polyneuropathy, as confirmed by toxin detection in blood. We designed an open trial at the Pediatric Neurology service and included all cases with acute ascending paralysis that were admitted to our hospital in the last two years. In all cases, we performed hematological, immunological and biochemical profiles, CSF analysis including immunological studies, oligoclonal bands and myelin basic protein determinations. Electrodiagnostic studies were performed, including motor conduction velocities, distal latencies, F-wave latency and compound muscle action potential (CAMP) amplitude. The presence of Karwinskia humboldtiana toxins in blood were determined by thin layer chromatography. In six cases, T-514 Karwinskia humboldtiana toxin was detected. These cases had a symmetric motor polyneuropathy with the absence of tendon reflexes and no sensory signs or cranial nerve involvement. Only one patient required assisted ventilation due to bulbar paralysis. In two of these cases, a sural nerve biopsy revealed a segmental demyelination with swelling and phagocytic chambers in Schwann cells and without lymphocytic infiltration. All six cases survived, with complete recovery in five. We conclude that this intoxication is common in Mexico. The availability of toxin detection in blood samples allows the clinician to establish an accurate diagnosis and should be included in the study of children with polyradiculoneuropathy, especially in countries where this poisonous plant grows.

Child↗

Mast cell typing: demonstration of a distinct hematopoietic cell type and evidence for immunophenotypic relationship to mononuclear phagocytes.

The immunologic surface marker profile of human mast cells (MCs) was established using a combined toluidine/immunofluorescence staining procedure [49 monoclonal antibodies (MoAbs) tested]. Ascites (n = 9) MCs as well as enzymatically dispersed MCs from all organs tested (lung n = 11, skin n = 7, intestinum n = 10) exhibited an identical marker profile. MCs were recognized by MoAbs clustered as CD9 (anti-gp24), CD33 (anti-gp67), and CD45 (anti-gp220) as well as by MoAbs directed against membrane-bound IgE. MoAB YB5B8 (anti-gp145) selectively recognized MCs. Most significantly, however, MCs were stained by MoAbs MAX1 (anti-gp65), MAX3 (anti-gp68), MAX11 (anti-gp65), and MAX24 (anti-gp65). These antibodies bind to surface membrane antigens associated with a late stage of monocyte/macrophage differentiation. Thus, our results provide definite evidence that MCs share surface membrane markers with mononuclear phagocytes. In contrast, MCs are stained neither by lymphatic markers (CD1-8, 10, 19-24) nor by myelomonocytic markers (CD11-17). MCs also lack the interleukin-2 (IL-2) receptor (CD25), the T10 antigen (CD38), and most of the myelocytic markers expressed on peripheral blood (PB) basophils. Thus, MCs displayed a unique phenotype within the hematopoietic system. This new approach enabled us to enrich human lung MCs to a purity greater than 95% by means of negative selection with complement-mediated cell lysis. Purified MCs were subsequently stained with MoAbs and analyzed by flow cytometry, which confirmed the results obtained from the double-staining experiments. We next examined cultured metachromatic cells derived from bone marrow (BM) and peripheral blood colony-forming units (CFU). These metachromatic cells previously could not be classified by morphologic criteria alone and have therefore been termed basophil-like/MC-like cells. In this study, toluidine blue-positive cells obtained from either pooled multipotential colonies (day 14-CFU-GEM) or pooled myelocytic colonies (day 16/17-CFU-GM/G/M) were recognized by MoAbs MY7 (CD13), VIM12 (CD11b), and VIM2, as well as by an anti-IgE MoAb, after preincubation with IgE. In contrast, CFU-derived metachromatic cells were not stained by MoAb YB5B8. This marker profile corresponds to the immunologic phenotype of blood basophils and excluded a detectable formation of mature MCs in colonies derived from cultured hematopoietic stem cells.

Antigens, Surface↗

Can worms defend our hearts? Chronic helminthic infections may attenuate the development of cardiovascular diseases.

The established risk factors for atherosclerosis fail to fully explain the extent and severity of coronary artery diseases in 50% of the patients. Thus, the causative agents and processes, which may be involved in the pathogenesis of atherosclerosis, are being sought. Notoriously, atherosclerosis and cardiovascular event rates are much lower in developing countries. Clinically, severe infections by intracellular pathogens are widespread mostly in developing countries with poor sanitation, nutrition and massive worm infections. A link between atherosclerosis and helminth infections has never been examined. Based on the present knowledge of immune and infectious mechanisms related to atherosclerosis, it is proposed that chronic helminthic infections can have a significant bearing on the epidemiology of cardiovascular diseases. How can helminthic infections affect the cardiovascular risk? (1) Helminths evade or suppress host immune responses, by producing anti-inflammatory and other immunomodulatory molecules. (2) Helminths induce chronic Th2 activation, which can modify cytokine profiles and immunological responses to heat shock proteins, Chlamydia pneumoniae and cytomegalovirus. (3) The chronic Th2 profile may modulate monocyte activation and chemotaxis to inflammatory sites (atherosclerotic plaques). (4) Chronic Th2 activation may lead to a cytokine profile that could be beneficial for attenuation of atherosclerosis development (upregulation of IL-4, IL-10 and IL-13 and downregulation of proinflammatory cytokines). (5) Helminthic infections may reduce plasma LDL level not only by affecting the host nutrition, but also via modulation of naturally occurring antibodies to cholesterol. Studies are needed to clarify these suggestions. If the hypothesis that helminthic infections impact atherosclerosis is correct, it should be taken into consideration in atherosclerosis immunomodulation therapy and especially in the design of vaccines and vaccine trials.

Animals↗