Bakery flour dust exposure causes non-allergic inflammation and enhances allergic airway inflammation in mice.

BACKGROUND: Baker's asthma is one of the most commonly reported occupational lung diseases in countries where fresh bread is baked daily in large quantities, and is characterized by rhinitis, bronchial hyperresponsiveness, and reversible airflow obstruction. Epidemiological studies have identified pre-existing atopy as an important risk factor for developing baker's asthma, yet the aetiology and pathogenesis of baker's asthma remain poorly understood. OBJECTIVE: We sought to develop a mouse model of baker's asthma that could be used to characterize the development and progression of baker's asthma. METHODS: We were unable to sensitize mice to bakery flour dust or flour dust extract. We assessed total inflammatory cells, cellular differential, total serum IgE and the pro-inflammatory cytokine response to oropharyngeally instilled bakery flour dust or flour dust extract by itself or in the context of ovalbumin (OVA) sensitization and challenge. RESULTS: Both bakery flour dust and flour dust extract consistently elicited a neutrophilic inflammation in a Toll-like receptor 4-independent manner; suggesting that endotoxin is not playing a role in the inflammatory response to flour dust. Moreover, bakery flour dust and dust extract significantly enhance the inflammatory response in OVA-sensitized and challenged mice. CONCLUSIONS: Bakery flour dust and flour dust extract are strongly pro-inflammatory and can cause non-allergic airway inflammation and can enhance allergen-mediated airway inflammation.

Successful treatment of Ochroconis gallopavum infection in an immunocompetent host.

Ochroconis gallopavum, a dematiaceous fungus, is a rare cause disease in immunocompromised patients and epidemic encephalitis in poultry. We report the first case of active O. gallopavum pulmonary infection in an immunocompetent host with rapid and complete response to oral antifungal therapy.

MR imaging of cavernous sinus invasion by mucormycosis: a case study.

Cavernous sinus thrombosis is a serious condition, which, if not recognized early, can lead to a fulminant course. Knowledge of risk factors along with early recognition of signs and symptoms may alter the course of this condition. We present a case of a patient with cavernous sinus thrombosis with characteristic findings on MRI. Biopsy of the sinuses revealed mucromycosis as the offending agent.

Cytofluorographic analysis of pokeweed mitogen-stimulated human peripheral blood cells in culture: age-related characteristics.

By use of monoclonal antibodies and flow cytometry techniques, peripheral blood mononuclear cells from young (20-30 years) and elderly (70+ years) subjects were analyzed before and after culture with pokeweed mitogen to gain insight into the cellular interactions responsible for the decreased B cell response observed in culture samples from the elderly. Data analysis of surface immunoglobulin-positive cells demonstrated no difference in the percentage of B cells in the elderly, while both plaque-forming cell and intracytoplasmic immunoglobulin assays showed significantly reduced B cell maturation (P = less than 0.01) compared with young controls. The B cell defect was shown to be functional and not a result of failure to proliferate and survive during incubation. Surface marker analysis of T cell subpopulations demonstrated a definite shift (P = less than 0.01) in the helper/suppressor T cell ratio in cultured samples from the elderly group (3.9) compared with young subjects (1.2). In addition to the absolute increase in the helper T cell population, forward-angle light scatter analysis demonstrated that, compared with young controls, a greater portion of the helper T cell population in the elderly subjects had characteristics of activated, blast-sized cells. The data reported in this study suggest that in the elderly group there is a functional immunoregulatory imbalance in the helper T cell subset.

B lymphocyte maturation in cultures from blood of elderly men: a comparison of plaque-forming cells, cells containing intracytoplasmic immunoglobulin and cell proliferation.

We have found, in 7-day pokeweed mitogen stimulated cultures of peripheral blood mononuclear cells, a marked deficiency in aged men (over 75 years) in maturation of B cells to antibody-producing cells. This finding was equally true whether maturation was measured by B cells with the specific function of producing anti-sheep erythrocyte plaques or by the histochemical technique of staining with fluorescent anti-globulin serum for plasmacytoid changes. The defect was functional, in that total cells at the end of 7 days of culture were numerically the same in young and old subjects. These differences were striking and almost uniform in aged subjects. Mixed leukocyte cocultures of young--old pairs revealed no suppression to account for defective B lymphocyte differentiation. Similarly, increased concentrations of pokeweed mitogen failed to stimulate the cells of the very elderly. Currently, we have no ready immunological explanation of these findings, and report the observation as a possible inherent cellular defect associated with extreme old age.

Variability in generation of anti-sheep erythrocyte plaque-forming cells from cultures of human peripheral blood. Influence of monocytes.

We have encountered two types of variability in the numbers of cells making antibodies in vitro to sheep erythrocytes (PFC) in pokeweed-stimulated human peripheral blood mononuclear lymphocytes (PBM). One is a variation in number of PFC generated by the PBM of one individual compared -o that of another, which is probably an in vitro counterpart to the well known individual variation in in vivo antibody responsiveness and presumed to be T cell controlled. The other variability is in numbers of PFC found in replicate tubes from a given individual. This variation is not T cell controlled, but rather is releated to the relative number of monocytes in the system. Enhancement by monocytes of the numbers of PFC generated is also demonstrated.

Adjuvant arthritis in T lymphocyte depleted rats.

Markedly T lymphocyte depleted rats were prepared by thymectomy, irradiation, and repopulation by bone marrow hematopoietic and lymphoid cells. Such rats had persistent T lymphopenia of about 20% of normal. When T depleted and normal rats were injected with adjuvant, all animals developed arthritis but with slightly less severity in the T depleted animals. Such experiments, and other observations, suggest a complex immunological mechanism in the pathogenesis of adjuvant arthritis in the rat.

Smoking and disease: effect on serum antitrypsin in hospitalized patients.

The mean serum antitrypsin (AT) activity for 1,829 patients hospitalized with medical problems exceeded the mean for a group of blood bank donors by 51%. Analysis of data from individual patients in terms of the general category (there were 16) of their disease and smoking status (smoker, nonsmoker, former smoker) indicated significant differences due to disease status and smoking status. The highest mean AT levels were associated with infectious, respiratory, and neoplastic diseases. Smokers had significantly higher mean levels than nonsmokers, and lung cancer patients had significantly higher mean levels than those with other malignant neoplasms. Among smokers (as a group) mean AT levels. through elevated relative to nonsmokers were not significantly related to duration or intensity of smoking; but former smokers showed a decline (with time following cessation of smoking) in their mean AT level to the mean level for nonsmokers. These findings provide further evidence of the sensitivity of serum antitrypsin activity to environmental influences.

Dichloroacetate-induced changes in liver of normal and diabetic rats.

Dichloroacetate (DCA) was administered orally to normal (nondiabetic) and streptozotocin-diabetic rats in a dose of 1000 mg/day/kg rat wt. One group of diabetic animals received DCA both orally and intraperitoneally. DCA therapy lowered the blood glucose values of diabetic animals but did not alter values in nondiabetic rats. The hepatic activity of glucokinase and pyruvate kinase were significantly lower in both DCA-treated nondiabetic and DCA-treated diabetic animals than values observed for untreated animals. However, DCA therapy was accompanied by remarkable increases in the activities of glucose-6-phosphate dehydrogenase and malic enzyme in both nondiabetic and diabetic animals. Glucose-6-phosphate dehydrogenase was 3-fold higher in DCA-treated nondiabetic animals whereas malic enzyme activity was 10-fold higher in the treated animals than observed in the untreated animals. Similar changes, although smaller in magnitude, were observed for these enzymes in the DCA-treated diabetic animals. Although DCA therapy was accompanied by a significant increase in the wet weights of the liver for both nondiabetic and diabetic animals, no morphological changes were seen by light or electron microscopy. Our observations coupled with those of previous investigators suggest that DCA therapy may have an important role in pyruvate metabolism and may lower the blood glucose concentration by inhibiting hepatic gluconeogenesis.