Heterogeneous proteolytic specificity and activity of the house dust mite proteinase allergen Der p I

Background Exposure of the skin or respiratory tract to proteinases is frequently associated with allergic sensitization. This is of particular significance in the domestic indoor environment where the proteolytic activity of Der p I, the group I allergen of the house dust mite Dermatophagoides pteronyssinus, may influence the allergenicity of mites. Using class-specific proteinase inhibitors and active-site affinity chromatography, we have previously shown that Der p I exhibits a mixed cysteine-serine proteinase activity. Measurement of the amount of cleavage, however, did not determine whether the inhibitors used were targeting exactly the same proteolytic mechanism. Objective To resolve this issue, we have examined whether the cleavage specificity of the cysteine and serine proteinase activities of Der p I was the same. Methods HPLC and mass spectrometry were used to analyse and identify the products of a Der p I-digested peptide substrate and thus identify the peptide bonds cleaved. Results Der p I cleaves different peptide bonds, depending upon the class of proteolytic mechanism used. In the model peptide substrate insulin B chain, the cysteine and serine proteinase activities of Der p I showed preference for glutamic acid and arginine respectively in the P1 position. Conclusion These data suggest the existence of more than one mechanistic form of the allergen immunologically identified as Der p I. If proteolytic activity is indeed a function of allergenicity, this information may have important implications for the pathogenicity of Der p I and the ability of innate antiproteinase defences in the respiratory tract to prevent immune sensitization.     

Identification of 12 novel mutations in the CFTR gene

Over 200 mutations, besides the deletion     

Successful treatment of concomitant pulmonary Nocardiosis and aspergillosis in an immunocompromised renal patient

A case is reported of rapid onset concomitant pulmonary infection withNocardia andAspergillus fumigatus in a patient six weeks after the institution of immunosuppressive therapy for renal vasculitis. Pulmonary lesions completely resolved on treatment with a combination of imipenem, cotrimoxazole and a prolonged course of itraconazole.     

Structural and geometrical isomers of carotenoids in human plasma

We have quantitatively analyzed human plasma for the following carotenoids: all-trans-lutein, all-trans-zeaxanthin, alpha-cryptoxanthin, beta-cryptoxanthin, the sum of all-trans-lycopene and its cis isomers, alpha-carotene and beta-carotene. In addition, we have tentatively identified and quantified 13-cis-lutein and 13-cis-zeaxanthin in human plasma. The latter two cis isomers are also apparent in samples of two common food items, spinach and corn meal. We have analyzed the ratios of all of the members of the beta, beta family of carotenoids (zeaxanthin, beta-cryptoxanthin and beta-carotene) to their corresponding beta, epsilon structural isomers (lutein, alpha-cryptoxanthin and alpha-carotene) in human plasma. There are marked differences in these ratios, with beta-carotene and beta-cryptoxanthin predominating in the carotene and monohydroxy-xanthophyll classes and lutein predominating in the dihydroxy-xanthophyll class. These differences could be attributable to dietary intake or to specific mechanisms in the way humans absorb and utilize these compounds.     

Stimulation of energy intake and growth by saccharin in rats

Rats fed wet diets containing saccharin consumed 12-14% more energy and gained 24-55% more weight than rats fed the same diets without saccharin. Saccharin-induced stimulation of intake was usually not so pronounced during the first week as during subsequent weeks of each experiment. Similar results were obtained using diets high in starch and fat. However, these effects could be obliterated by simply exposing the rats to unsweetened (plain) diet or to saccharin in water for several days before the sweetened diets were introduced. Furthermore, although stimulation of intake by saccharin was observed with diets containing 80% water, no such effect was observed with a diet containing 60% water. Rats given low-energy sweetened water in addition to their 80% water diet consumed substantially more fluid but not more or less energy than rats given unsweetened water. Preference tests suggest that saccharin increases diet palatability only very slightly; this finding is one of several observations suggesting that stimulation of intake by saccharin cannot be interpreted in terms of increased diet palatability. These results suggest that dietary hyperphagia results from the interaction between innate and learned responses to the taste of foods. Osmotic factors did not seem to exert a major influence in these experiments.     

Altered motility and bacterial flora after functional end-to-end anastomosis

The functional end-to-end technique with a gastrointestinal stapler is commonly used for small-bowel anastomosis, but the effects of this anatomically side-to-side anastomosis on motility are unknown. Fasting small-bowel myoelectric activity and culture results were compared in six animals undergoing handsewn end-to-end and functional end-to-end anastomoses. Serosal electrodes were placed at 10 cm intervals, and the small bowel was divided 25 and 55 cm from the ligament of Treitz. The functional end-to-end and end-to-end techniques were performed in each animal in random order. Fasting myoelectric recordings were obtained at weekly intervals for up to 20 weeks after operation. New electrodes were placed, and additional recordings were obtained from 29 to 39 weeks, 51 to 63 weeks, and 108 to 112 weeks after operation. The recordings were visually inspected for passage of phase 3 of the migrating myoelectric complex (MMC). By 12 to 20 weeks after operation, 91% of MMCs crossed the end-to-end anastomoses versus 22% across the functional end-to-end anastomosis (p less than 0.001). Even 2 years after surgery only 56% of MMCs crossed the functional end-to-end anastomosis. Quantitative bacterial cultures suggested a trend toward bacterial overgrowth in the functional end-to-end anastomosis. These results demonstrate that the functional end-to-end anastomosis alters small-bowel motility to a greater degree than an end-to-end anastomosis and may predispose to bacterial overgrowth.     

Indications for relaparotomy

From 1980 to 1987, 10,446 patients were operated on. In 152 patients, the necessity of a repeated operative intervention arose. In 106 patients the emergency, in 42--delayed, and in 4--elective relaparotomies were performed. There were the following indications for relaparotomy: diffuse and circumscribed peritonitis (78 patients), ileus (46), eventration (11), hemorrhage (12), others (5). Diagnosis of postoperative complications requiring relaparotomy is difficult. The postoperative lethality was 26%.