Immune alteration associated with exposure to toxic chemicals.

Immunological abnormalities including lymphocyte subset, lymphocyte immune functional assays, chemical antibodies, and different markers for autoimmune response were examined in individuals exposed to a variety of chemicals in computer manufacturing plants. A comparison of 289 individuals exposed to chemicals to 120 controls revealed that exposed individuals had a significantly higher percentage with either increased or decreased T helper/T suppressor ratios. In addition, the individuals with abnormal T4/T8 ratios demonstrated significant elevation in chemical-hapten antibodies. Therefore, 87 exposed subjects with abnormal T4/T8 ratios were selected for further evaluation by lymphocyte phenotypic expression and T cell, B cell, NK activity, and autoimmune markers, and were compared to 60 controls. The comparison of exposed individuals with controls indicated elevation of T cell (CD3), B cell (CD19), and activated T cell (CD10, CD15, CD26, CD38), suppressed T cell and B cell function decreased or increased NK cell cytotoxic activity. Autoimmunity due to chemical exposure was evidenced by elevation of TA1 phenotype frequencies and presence of rheumatoid factor, immune complexes, ANA, and anti myelin basic protein antibodies. We conclude that chemical exposure may induce immune abnormalities including immune suppression and autoimmunity.     

Long-term evaluation of five biomaterials for angioplastic enlargement of the pulmonary artery in a young dog model

In 45 young dogs an enlargement angioplasty of the left pulmonary artery was performed using patches made from one of three autologous materials (jugular vein, unmodified pericardium, and glycerolized pericardium) or from two heterologous materials (lyophilized human dura mater and modified bovine carotid artery). Catheterization and angiographic studies performed 5 to 6 months after the operation showed that all patched vessels had remained patent, except in three dogs which had received heterologous implants. The animals were killed 5-24 months after operation (mean weight increase: 84%), and the implants were studied by optical microscopy and morphometry, scanning and transmission electron microscopy, and indirect immunofluorescence with antidog Factor VIII rabbit antiserum. The two heterologous tissues exhibited limited biocompatibility, as estimated from 10 criteria obtained at histologic studies. Conversely, all three autologous biomaterials were characterized by infiltration of noninflammatory cells, near-complete endothelialization, and neosynthesis of structural proteins; infectious foci were very rare or absent. These results suggest that autologous tissues, although deendothelialized at the time of implantation, constitute the most suitable material for patch angioplasty, as far as endothelial triggering, cellularity and resistance to infection are concerned.     

Plant-produced idiotype vaccines for the treatment of non-Hodgkin's lymphoma: safety and immunogenicity in a phase I clinical study

Plant-made vaccines have been the subject of intense interest because they can be produced economically in large scale without the use of animal-derived components. Plant-made therapeutic vaccines against challenging chronic diseases, such as cancer, have received little research attention, and no previous human clinical trials have been conducted in this vaccine category. We document the feasibility of using a plant viral expression system to produce personalized (patient-specific) recombinant idiotype vaccines against follicular B cell lymphoma and the results of administering these vaccines to lymphoma patients in a phase I safety and immunogenicity clinical trial. The system allowed rapid production and recovery of idiotypic single-chain antibodies (scFv) derived from each patient's tumor and immunization of patients with their own individual therapeutic antigen. Both low and high doses of vaccines, administered alone or co-administered with the adjuvant GM-CSF, were well tolerated with no serious adverse events. A majority (>70%) of the patients developed cellular or humoral immune responses, and 47% of the patients developed antigen-specific responses. Because 15 of 16 vaccines were glycosylated in plants, this study also shows that variation in patterns of antigen glycosylation do not impair the immunogenicity or affect the safety of the vaccines. Collectively, these findings support the conclusion that plant-produced idiotype vaccines are feasible to produce, safe to administer, and a viable option for idiotype-specific immune therapy in follicular lymphoma patients.     

Chromate detoxification potential of Staphylococcus sp. isolates from an estuary

Chromium (Cr) pollution is an emerging environmental problem. The present study was carried out to isolate Cr-resistant bacteria and characterize their Cr detoxification and resistance ability. Bacteria screened by exposure to chromate (Cr⁶⁺) were isolated from Mandovi estuary Goa, India. Two isolates expressed high resistance to Cr⁶⁺ (MIC ≥ 300 µg mL⁻¹), Cr³⁺ (MIC ≥ 900 µg mL⁻¹), other toxic heavy metals and displayed a pattern of resistance to cephalosporins and ß-lactams. Biochemical and 16 S rRNA gene sequence analysis indicated that both isolates tested belonged to the Staphylococcus genus and were closely related to S. saprophyticus and S. arlettae. Designated as strains NIOER176 and NIOER324, batch experiments demonstrated that both removed 100% of 20 and 50 µg mL⁻¹ Cr⁶⁺ within 4 and 10 days, respectively. The rate of reduction in both peaked at 0.260 µg mL⁻¹ h⁻¹. ATP-binding cassette (ABC) transporter gene involved in transport of a variety of substrates including efflux of toxicants was present in strain NIOER176. Through SDS-PAGE analysis, whole-cell proteins extracted from both strains indicated chromium-induced specific induction and up-regulation of 24 and 40 kDa proteins. Since bacterial ability to ameliorate Cr⁶⁺ is of practical significance, these findings demonstrate strong potential of some estuarine bacteria to detoxify Cr⁶⁺ even when its concentrations far exceed the concentrations reported from many hazardous effluents and chromium contaminated natural habitats. Such potential of salt tolerant bacteria would help in Cr⁶⁺ bioremediation efforts.

     

Immune response to dietary proteins, gliadin and cerebellar peptides in children with autism

The mechanisms behind autoimmune reaction to nervous system antigens in autism are not understood. We assessed the reactivity of sera from 50 autism patients and 50 healthy controls to specific peptides from gliadin and the cerebellum. A significant percentage of autism patients showed elevations in antibodies against gliadin and cerebellar peptides simultaneously. For examining cross-reaction between dietary proteins and cerebellar antigens, antibodies were prepared in rabbits, and binding of rabbit anti-gliadin, anti-cerebellar peptides, anti-MBP, anti-milk, anti-egg, anti-soy and anti-corn to either gliadin- or cerebellar-antigen-coated wells was measured. In comparison to anti-gliadin peptide binding to gliadin peptide at 100%, the reaction of anti-cerebellar peptide to gliadin peptide was 22%, whereas the binding of anti-myelin basic protein (MBP), anti-milk, anti-egg and anti-soy to gliadin was less than 10%. Further examination of rabbit anti-gliadin (EQVPLVQQ) and anti-cerebellar (EDVPLLED) 8 amino acid (AA) peptides with human serum albumin (HSA) and an unrelated peptide showed no binding, but the reaction of these antibodies with both the cerebellar and gliadin peptides was greater than 60%. This cross-reaction was further confirmed by DOT-immunoblot and inhibition studies. We conclude that a subgroup of patients with autism produce antibodies against Purkinje cells and gliadin peptides, which may be responsible for some of the neurological symptoms in autism.     

Detection of trichothecene mycotoxins in sera from individuals exposed to Stachybotrys chartarum in indoor environments

To date, no study has effectively demonstrated a direct human exposure to mycotoxins in mold-contaminated buildings. Therefore, the authors investigated the presence of trichothecene mycotoxins in sera from individuals exposed to indoor molds (specifically Stachybotrys chartarum). Sera from occupants of contaminated (test samples, n=44) and uncontaminated (control samples, n=26) buildings were analyzed using a competitive enzyme-linked immunosorbent assay (ELISA) highly specific for macrocyclic trichothecenes. Twenty-three samples were significantly different (p < 0.05) from normal human serum tested in the same manner, whereas only 1 of the control samples tested positive. Mass spectrometry analysis could not confirm the presence of intact S. chartarum macrocyclic trichothecenes. The authors hypothesize that this result was caused by uncharacterized ELISA-reactive metabolic breakdown products. Data from this study suggest that trichothecene mycotoxins can be demonstrated in the tissues of certain individuals exposed to S. chartarum in contaminated buildings.     

Evaluation of a commercial web-based weight loss and weight loss maintenance program in overweight and obese adults: a randomized controlled trial

Background  

Obesity rates in adults continue to rise and effective treatment programs with a broad reach are urgently required. This paper describes the study protocol for a web-based randomized controlled trial (RCT) of a commercially available program for overweight and obese adult males and females. The aim of this RCT was to determine and compare the efficacy of two web-based interventions for weight loss and maintenance of lost weight.