Walter L. Trudeau

Activating SRC mutation in a subset of advanced human colon cancers.

The discovery of Rous sarcoma virus (RSV) led to the identification of cellular Src (c–Src), a non-receptor tyrosine kinase, which has since been implicated in the development of numerous human cancers. c-Src has been found to be highly activated in colon cancers, particularly in those metastatic to the liver. Studies of the mechanism of c-Src regulation have suggested that c-Src kinase activity is downregulated by phosphorylation of a critical carboxy-terminal tyrosine (Tyr 530 in human c-Src, equivalent to Tyr 527 in chicken Src) and have implied the existence of activating mutations in this C-terminal regulatory region. We report here the identification of a truncating mutation in SRC at codon 531 in 12% of cases of advanced human colon cancer tested and demonstrate that the mutation is activating, transforming, tumorigenic and promotes metastasis. These results provide, for the first time, genetic evidence that activating SRC mutations may have a role in the malignant progression of human colon cancer.

Serum IgE and human immunodeficiency virus (HIV) infection

Human immunodeficiency virus infection is characterized by a progressive depletion of helper T-lymphocytes and, like allergic diseases, is associated with altered T cell regulation. Total serum IgE was measured in 67 infected male subjects, 27 uninfected heterosexual male subjects, and 18 uninfected homosexual male subjects. The mean IgE level (132 IU/ml) of infected subjects with a helper T-lymphocyte number less than or equal to 200/mm3 was significantly greater than mean IgE levels of the uninfected heterosexual (38 IU/ml) and homosexual (35 IU/ml) groups. IgE levels were inversely related to both helper T cell and suppressor/cytotoxic T cell numbers but not to IgG or IgA levels. The increase in IgE was not a reflection of an increased prevalence of atopic disease (allergic asthma, allergic rhinitis, or atopic dermatitis) in the infected subjects. The elevation of IgE may be related to a difference among the groups in T cell production of IgE regulatory lymphokines.

Elevated serum levels of IL‐8 in patients with HIV infection

Scrum levels of IL‐8 were determined in HIV‐infected individuals and the results were compared with those for HIV controls. The IL‐8 levels were measured by an ELISA with a MoAb and a polyclonal antibody to recombinant IL‐8. The means and 95% confidence intervals of IL‐8 in sera of 36 HIV‐infected individuals and 32 matched controls were 275 and 216 349 pg/ml, and 8 and 4 14 pg/ml, respectively, showing a 34‐fold increase in IL‐8 in the circulation of HIV‐infected individuals. This increase does not appear to be related to the disease state, infection or systemic medical agents. This finding suggests the possible involvement of IL‐8 in the pathogenesis of HIV‐induced disease.

House dust mite allergy in Florida. Mite survey in households of mite-sensitive individuals in Tampa, Florida.

This study evaluated the prevalence of positive house dust mite skin tests in a population of atopic individuals and identified the mite species present in mattress and house dust samples in homes of the Tampa Bay area. Four hundred consecutive individuals were evaluated for respiratory complaints and skin tested with standardized extracts of Dermatophagoides pteronyssinus (Dp) and Dermatophagoides farinae (Df). Two hundred forty individuals (60%) had a positive skin test to the mite extracts. Dust samples were collected in 40 homes of mite-allergic individuals and analyzed by light microscopy. Mite species were found in 53 of the 60 dust samples (20 mattresses and 40 carpets). Mite numbers ranged from 110-6200 mites/g of mattress dust and from 120-5500 mites/g of carpet dust. Eleven different mite species were identified and Blomia tropicalis (Bt), not previously identified in the United States, was found in 30% of the samples. Dp and Df wee the predominant species. These observations suggest that house dust mite allergy is common in the Tampa Bay area and that the house dust mite fauna comprises several mite species besides Dp and Df. Prospective studies in progress are designed to confirm the role of different mite species in house dust mite allergy.

Sensitization to Blomia tropicalis: Skin test and cross-reactivity studies ☆ ☆☆ ★

This study evaluated the prevalence of positive percutaneous skin test results to Blomia tropicalis, Dermatophagoides pteronyssinus, and D. farinae in 167 consecutive persons (61 males, 106 females; mean age, 38.7 years; range, 14 to 75 years) with asthma or rhinitis, or both, in Tampa, Fla. Forty-nine had asthma with or without rhinitis, and 118 had rhinitis alone. RAST and RAST inhibition analysis of all three mite species were performed by using pooled patient sera. Prepared extracts of B. tropicalis and standardized D. pteronyssinus and D. farinae (1:50 wt/vol) were used for percutaneous skin tests. One hundred twelve subjects (67%) had a positive result to at least one mite species; 38%, 62%, and 60% reacted to B. tropicalis, D. pteronyssinus, and D. farinae, respectively. Positive skin test results to both D. pteronyssinus and D. farinae occurred in 96 subjects (57%); 56 of these subjects (58%) were also positive to B. tropicalis. Positive skin test results to B. tropicalis, D. pteronyssinus, or D. farinae alone occurred in four (2%), five (3%), and four (2%), respectively. RAST and RAST inhibition data indicate that B. tropicalis contains unique allergens. The high rate of skin test reactivity to B. tropicalis extracts, and its unique allergenic composition, warrants its use in the diagnosis and treatment of allergic disorders in Tampa.

Source of the aeroallergen of soybean dust: A low molecular mass glycopeptide from the soybean tela

Airborne soybean allergens in the dust generated during the unloading of soybeans in the harbor caused asthma epidemics in Barcelona, Spain. The major allergen causing the epidemics was a glycopeptide less than 14 kd molecular mass abundant in soybean dust. This allergen occurs in all parts of the soybean plant at all stages of growth, but the telae (hulls) and pods are by far the richest source. Small amounts of a similar cross-reacting allergen are found in some other grain dusts. The botanical function and significance of this soybean plant component is not known nor is the potential for airborne dispersion of this allergen at other grain-handling sites.

House dust mite, cat, and cockroach allergen concentrations in daycare centers in Tampa, Florida

BACKGROUND Allergen exposure in early childhood is a risk factor for sensitization and the development of asthma. Studies performed in Europe, New Zealand, and Singapore indicated the presence of indoor allergens in childcare centers and schools. However, the importance of indoor allergens in daycare centers in humid and warm regions of the world is not known. OBJECTIVE To measure total mite counts, Der p 1, Der f 1, Fel d 1, and Per a 1 allergens in dust samples and mite allergen airborne concentrations in daycare centers in Tampa, Florida, United States. METHODS Twenty daycare centers were surveyed for mite, cat, and cockroach allergens in Tampa, FL. One dust and two air samples (one during the day and one during the night) were collected in each center. Dust samples were extracted and analyzed for mite (Der p 1 and Der f 1), cat (Fel d 1), and cockroach (Per a 1) allergens. Mite airborne allergen concentrations were analyzed by RAST inhibition and expressed in standardized mite allergen units per m3 of air (AU/m3). RESULTS Mites were identified in 15 samples, and concentrations ranged from 10 to 1,200 mites/g (298 +/- 355.2). The most prevalent mite species was Dermatophagoides pteronyssinus ( Der p 1). Der p 1 and/or Der f 1 were detected in 10 daycare centers. Der p 1 was detected in eight centers and ranged from I to 21.8 microg/g of dust (5.4 +/- 6.9); Der f 1 was detected in 3 centers and ranged from 0.2 to 2.1 microg/g of dust (1.3 +/- 0.9). Per a 1 and Fel d 1 were detected in all centers in small quantities; Per a 1 ranged from 8 to 1,806 ng/g (263.1 +/- 449.7) and Fel d 1 from 0.2 to 120 U/g of dust (16.6 +/- 31.7), respectively. Airborne mite allergen was detected in 18 centers and ranged from 0.01 to 2.7 AU/m3 during the day (0.2 +/- 0.6) and from 0.01 to 0.12 AU/m3 during the night (0.06 +/- 0.03), P = 0.001. CONCLUSIONS Mite, cat, and cockroach allergens are present in daycare centers in Tampa, FL. Mite allergen concentrations exceeded levels that have been associated with sensitization and symptoms in allergic subjects in 40% of these centers.

Prevalence of specific IgE to the storage mite, Aleuroglyphus ovatus

Aleuroglyphus ovatus (Ao) is a storage mite that has a worldwide distribution and has been found in stored bran, wheat, chicken meal, and dried fish products. Ao was isolated from a chicken meal sample, cultured on whole wheat flour at 75% relative humidity, and 1 gm of pure Ao bodies were extracted, 1:20 wt/vol, in 0.2 mol/L of ammonium bicarbonate. Der p I, major allergen of Dermatophagoides, pteronyssinus (Dp), or Der f I major allergen to Dermatophagoides farinae (Df), was not detected in extracts of Ao. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed 25 bands (6 to 110 kd), and thin-layer isoelectric focusing revealed 19 bands (isoelectric point, 3.5 to 9.3). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis immunoblots with six different sera identified nine IgE binding bands (16 to 100 kd). Thin-layer isoelectric focusing immunoblots identified 16 IgE binding bands (isoelectric point, 4.5 to 9.3). An aliquot of the Ao extract was diluted in bicarbonate buffer (pH 9.2) and adsorbed to plastic microtiter plates. RAST to Ao and Dp were performed with sera of 163 atopic individuals (88 with allergic rhinitis and 75 with allergic asthma with or without allergic rhinitis). All individuals had appropriately positive skin tests that correlated with a history of exacerbation secondary to allergen exposure. RAST results to Dp and Ao were analyzed by regression analysis (r = 0.64; p = 0.0001). Fifty-five individuals were RAST positive to Dp alone, 32 to Ao and Dp, and three to Ao alone; 73 individuals were negative to Ao and Dp. RAST inhibition demonstrated moderate cross-reactivity between Ao and Dp.

Positive nasal challenge responses to Blomia tropicalis

BACKGROUND Blomia tropicalis, a dust mite commonly found in subtropical and tropical environments, is the fourth most common mite in the United States. Thirty-eight percent of 167 consecutive subjects evaluated for allergic respiratory symptoms in the Tampa Bay area had positive skin test responses to B. tropicalis. METHODS Nasal challenges were performed in 19 subjects with allergic rhinitis; 12 had positive skin test responses to B. tropicalis (group I), and seven had negative skin test responses to B. tropicalis but positive skin test responses to Dermatophagoides pteronyssinus and D. farinae (group II). Subjects were challenged with a normal saline control solution and increasing concentrations of a 1 mg/ml in-house extract of B. tropicalis (1:125,000 vol/vol, 1:25,000 vol/vol, 1:5000 vol/vol, 1:1000 vol/vol, and 1:200 vol/vol). Inspiratory nasal airway resistance (was measured every 5 minutes for 15 minutes by posterior rhinomanometry at 50 Pa after each nasal challenge. RESULTS Nasal challenge response was considered positive and stopped when the mean inspiratory nasal airway resistance was greater than twice the mean inspiratory nasal airway resistance after the normal saline challenge. Ten of 12 (83%) subjects in group I and none of seven (0%) subjects in group II had positive nasal challenge responses to B. tropicalis (p = 0.0024). CONCLUSION B. tropicalis is allergenic and should be considered as a cause of allergic rhinitis when evaluating a patient who lives in an area where it is endemic.

Insulin treatment acutely increases the concentration of phosphatidylserine in rat adipose tissue

Abstract Insulin treatment in vivo or in vitro for 60 min elicited 40 and 35% increases, respectively, in phosphati-dylserine concentration in rat adipose tissue. This effect, along with previously observed insulin-induced increases in phosphatidic acid and inositides, may contribute to known effects of insulin on pyruvate dehydrogenase, low K m phosphodiesterase and, perhaps, other enzymes.