A Quantitative Study of Specific Immunoglobulins to Mosquito Salivary Gland Antigen in Hypersensitive and Common Types of Mosquito Bite Reaction

This study was designed with two purposes: first, to elucidate immunologic mechanisms in different cutaneous reactions, particularly in hypersensitivity to mosquito bites, and, second, to develop a more reliable and safer method of identifying the causative species of mosquito in severe cases. The amounts of IgG, IgG₄ and IgE specific to the mosquito salivary gland extract of Aedes albopictus were determined in the sera of 116 volunteers with normal reactions, either immediate or delayed, and 4 patients with severe systemic symptoms caused by mosquito bites. Titers of IgG and IgE in the severe cases were considerably higher than in volunteers with normal reactions, but there were no differences in IgG, titers between the two groups. These results indicate that high titers of IgG and IgE may be involved in development of systemic symptoms in severe cases and verify the possibility of in vitro tests to identify causative species of the mosquito.     

Phenotype of endomyocardial biopsy-derived T-lymphocyte cultures and chronic rejection after heart transplantation

Chronic rejection (CR) is a major problem in long-term survival in heart transplantation. We analysed whether the occurrence of CR correlates with the incidence of acute rejections (AR) or with characteristics of endomyocardial biopsy-derived cell cultures. CR was diagnosed by annual angiography and defined as all coronary vascular changes. One year after transplantation 24 of the 63 patients had CR (38%). The incidence of AR in CR + and CR — patients was comparable. The patients in both groups had similar individual median percentages of EMB-yielding cell cultures. During the first year the CR — patients had more cultures in which at least 60% of the cells were CD4 + T cells (50% vs 37%, P = 0.05), due to a stronger CD4 predominance in the first 6 months. In the second year the CD4 predominance in the patients diagnosed as CR + after 1 year tended to be higher (P = 0.08). The patients had comparable percentages of cultures predominated by CD8 + T cells, γδ T cells or NK cells, irrespective of the time interval. These results might indicate that CD4 + T lymphocytes play a dual role in the aetiology of CR.     

Conventional 4-field box radiotherapy technique for cancer cervix: potential for geographic miss without CECT scan-based planning

BACKGROUND: The advantage of 4-field radiation to the pelvis is that the use of lateral portals spares a portion of the small bowel anteriorly and rectum posteriorly. The standard lateral portals defined in textbooks are not always adequate especially in advanced cancer cervix. METHODS: An analysis was done to determine adequacy of margins of standard lateral pelvic portals with CECT defined tumor volumes. The study included 40 patients of FIGO stage IIB and IIIB treated definitively for cancer cervix between 1998 and 2000. An inadequate margin was defined if the cervical growth and uterus were not encompassed by the 95% isodose. RESULTS: An inadequate posterior margin was common with bulky disease (P = 0.06) and with retroverted uterus (P = 0.08). Menopausal status, FIGO stage, associated myoma, and age were of no apparent prognostic significance. Bulk retained significant on multivariate analysis. An inadequate anterior margin was common in premenopausal (P = 0.01); anteverted uterus (P = 0.02); associated myoma (P = 0.01); and younger patients (P = 0.03). It was not influenced by bulk or stage. Menopausal status and associated myoma retained significant on multivariate analysis. CONCLUSION: Without the knowledge of precise tumor volume, the 4-field technique with standard portals is potentially risky as it may under dose the tumor through lateral portals and the standard AP/ PA portals are a safer option.     

Cardiovascular effects of Leu-enkephalin in the nucleus tractus solitarius of the rat

Microinjections of Leu-enkephalin into the dorsal vagal complex induced hypotension and bradycardia. Both naloxone, given at a dose conferring selectivity for μ receptors, and the S antagonist ICI 154,129 prevented the cardiovascular effects of Leu-enkephalin. Naloxone was also found to decrease the gain of the baroreflex. These results suggest that Leu-enkephalin is involved in cardiovascular regulation through activation of δ-, and possibly μ-, opioid receptors in the dorsal vagal complex.     

Activation of guinea pig eosinophil respiratory burst by leukotriene B4: role of protein kinase C

Leukotriene B4 (LTB4) and the protein kinase C activator, 4-beta-phorbol dibutyrate (PDBu), both induced a pronounced and concentration-dependent stimulation of hydrogen peroxide (H2O2) generation by purified guinea pig peritoneal eosinophils in the concentration range 1 nM-1 microM. The LTB4 response was inhibited competitively by the specific LTB4 receptor antagonist, U-75302, with a KB of 25 nM, while the concentration-response curves for both stimuli were shifted rightwards (3.8-fold and 2.8-fold for LTB4 and PDBu, respectively) by the competitive protein kinase C inhibitor, 1-O-hexadecyl-2-O-methylglycerol at a concentration of 300 microM. LTB4 appears, therefore, to induce respiratory burst in eosinophils via a receptor-mediated mechanism involving protein kinase C.     

Analysis of gene expression in MOG-induced experimental autoimmune encephalomyelitis after treatment with a novel brain-penetrating antioxidant

Accumulating data from experimental studies indicate that oxidative stress has a major role in the pathogenesis of multiple sclerosis (MS). It has been suggested that local production of reactive oxygen species, probably by macrophages, mediates axonal damage in both MS patients and the mouse model experimental autoimmune encephalomyelitis (EAE). We have shown previously that our novel brain-penetrating antioxidant, N-acetylcysteine amide (AD4), reduces the clinical and pathological symptoms, including inflammation and axonal damage in myelin oligodendrocyte glycoprotein (MOG)-induced chronic EAE in mice. The aim of this study was to examine the molecular mechanism by which AD4 exerts protection in MOG-induced EAE mice. Therefore, we analyzed gene-expression profile in the spinal cords of MOG-induced chronic EAE mice and compared them with MOG-induced mice treated with AD4, using a cDNA microarray. We found that MOG treatment up-regulated genes encoding growth factors, cytokines, death receptors, proteases, and myelin structure proteins, whereas MOG- and AD4-treated mice demonstrated gene expression profiles similar to that seen in na?ve healthy mice. In conclusion, our study shows that chronic AD4 administration suppresses the induction of various pathological pathways that play a role in EAE and probably in MS.     

Human T cells that have been conditioned by the proteolytic activity of the major dust mite allergen Der p 1 trigger enhanced immunoglobulin E synthesis by B cells

BACKGROUND: We have previously demonstrated that the proteolytic activity of Der p 1 selectively cleaves human CD25, the 55 kDa alpha subunit of the IL-2 receptor. As a result of cleavage of surface CD25, peripheral blood T cells produce less IFN-gamma and more IL-4, thereby leading to progressive polarization of the T cells towards a Th2 cytokine profile. Therefore, these observations underline the potential role of the proteolytic activity of Der p 1 in creating a microenvironment conducive for IgE synthesis. OBJECTIVE: To study the effect of T cells that have been conditioned by the proteolytic activity of Der p 1 on IgE synthesis by B cells. METHODS: We have examined this concept in experiments whereby T cells that have been exposed to either proteolytically active or inactive Der p 1 were cocultured with autologous B cells and IgE antibody synthesis was monitored. RESULTS: Here we demonstrate for the first time that coculturing T cells that have been in contact with proteolytically active Der p 1 with autologous B cells leads to augmentation of IgE antibody responses. CONCLUSIONS: The proteolytic activity of Der p 1 conditions human T cells, which then become empowered to trigger enhanced IgE synthesis by B cells.     

The Effect of Acute and Chronic Exercise on Thyroid Hormones in Obesity

Abstract Thyroid hormones were measured before, during and after acute exercise (60 min) or physical training (3 months) in obese women. Thyroid stimulating hormone concentration increased during acute work and decreased immediately after. No changes were seen during the two following days. An increase was seen after ten days as well as after three months of physical training. Thyroxine concentrations showed no changes. 3,5,3′-Triiodothyronine decreased slightly immediately after acute exercise, and after three months of physical training, 3,3′,5′-triiodothyronine (reverse triiodothyronine) increased slowly during and after acute exercise. A negative correlation was found between changes in fasting insulin and thyroxine and a positive correlation between changes in blood pressure and triiodothyronine after training. Lack of agreement in previous reports is probably due to methodological differences such as methods more or less susceptible to fatty acid interference, and thyroid hormones changing differently during acute work and before and after physical training. The duration of the study may also be of importance, even 3 months possibly being too short for attaining equilibrium in thyroid homeostasis.     

Use of a sensitive enzyme immunoassay for human thyrotropin in the diagnosis of hyperthyroidism

A sensitive, simultaneous sandwich enzyme immunoassay for TSH was evaluated especially for its ability to distinguish hyperthyroid patients from the euthyroid population. A total of 140 patient samples was analzyed by this assay as well as with a two-step sandwich radioimmunoassay. The diagnostic sensitivity of the thyrotropin assay was 92.5% and the specificity was 88%. False negatives by thyrotropin assay included two patients with Graves' disease who were being treated with propranolol at the time of testing and one patient who was considered hyperthyroid while receiving synthroid. Twelve patients with elevated free thyroxine index levels were considered euthyroid and 50% of these had thyrotropin values that were undetectable; most were elderly patients with nonthyroidal illnesses. Although the thyrotropin enzyme immunoassay had good sensitivity and precision for the detection of hyperthyroidism, our data suggest the limitation of a single thyrotropin determination in establishing the euthyroid state, especially in elderly patients with associated nonthyroidal illnesses and hyperthyroxinemia.     

Relationship of sperm superoxide dismutase-like activity with other sperm-specific enzymes and experimentally induced lipid peroxidation in infertile men

Summary. Superoxide dismutase-like activity (SOD-like), isoenzyme lactate dehydrogenase-C4 (LDH-C4) and NADH-diaphorase activities in spermatozoa have been investigated from 58 normozoospermic and 27 oligozoospermic men. Significantly higher SOD-like, LDH-C4 and diaphorase activities ( P <0.01, P <0.005 and P <0.0001, respectively) were detected in spermatozoa from oligozoospermic men, compared to the activities found in normozoospermic samples. SOD-like activity (mean±SE) in oligozoospermic samples amounted to 8.3±1.6 U 10⁻⁸ spermatozoa, while in spermatozoa in normozoospermic men with a sperm concentration above 20 million of spermatozoa per ml amounted to 4.2±0.5 U 10⁻⁸. There was a close correlation between the SOD-like activity and biochemical indicators of the presence of residual cytoplasm i.e. isoenzyme LDH-C4 and NADH-diaphorase (r = 0.53 and r = 0.66 in normozoospermic and r = 0.63 and r = 0.54 in oligozoospermic men, respectively). A positive relationship between SOD-like activity and experimentally-induced lipid peroxidation was detected in 54 infertile men (r = 0.30; P <0.05). These findings suggest that a higher level of superoxide dismutase-like activity may reflect a defect in the development or maturation of spermatozoa and, thereby, a decreased fertility potential. Hence, determination of SOD-like activity may give information on the state of maturity of human spermatozoa, while its role in the antioxidative protection remains to be determined.