Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.1 (chymotrypsin)
 10,938 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Purified flagellar protein (p41) of Borrelia burgdorferi (strain B31) was subjected to chemical cleavage with hydroxylamine or proteolysis with V8 protease, endoproteinase Asp-N, or alpha-chymotrypsin. The resulting polypeptides were identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and their positions in the published DNA sequence of the p41 protein were determined by amino-terminal sequencing and amino acid analysis. Epitope specificities of antibody binding by a monoclonal antibody raised by immunization of mice with purified flagella and pooled sera from patients with multiple erythema migrans, late Lyme borreliosis, or secondary syphilis were analyzed by Western blots (immunoblots) of peptides transferred to Immobilon polyvinylidene difluoride filters. The major epitope binding one murine monoclonal antibody (158) was localized to a carboxy-terminal domain that includes residues 300 to 336. The dominant epitopes binding human polyclonal antibodies are in the central portion of the molecule (residues 182 to 218) that is not conserved compared with other bacterial flagellins. Additional reactive epitopes were identified in the amino-terminal domain of the protein. Sera from patients with syphilis bound strongly to the amino-terminal conserved domain, providing a structural basis for cross-reactivity seen in standard enzyme-linked immunosorbent assays, but not to the central part of the molecule. Specific and cross-reactive antigenic determinants need to be considered in the design of improved immunodiagnostics for spirochetal diseases.
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PMID:Mapping the major antigenic domains of the native flagellar antigen of Borrelia burgdorferi. 137 61

Digestive enzymes in faeces have been reported to possess skin irritation potential. The present study was designed to investigate the in vivo irritant potentials of faecal concentrations of proteolytic and lipolytic digestive enzymes in bile salt mixtures. In a 21-day cumulative irritation assay, clinical evaluation and noninvasive bioengineering techniques were used. 5 days occlusive exposure to phosphate buffer (pH = 8) caused no visual skin damage but reflectance spectroscopy demonstrated significant vasodilation (p < 0.01) and increases in transepidermal water loss (TEWL) and skin pH were also observed (p < 0.01). These increases were still present at days 12 and 19. Occlusive exposure to physiologic concentrations of faecal enzymes resulted in significant visual and objective scores at day 5, 12, and 19, with increased readings as a function of exposure time (p < 0.01). The enzyme mixture containing lipase caused delayed onset of skin erythema and epidermal barrier disruption compared to elastase and chymotrypsin containing solutions. Prolonged occlusive exposure to digestive enzymes in faecal concentrations caused severe skin erythema and epidermal barrier disruption in a human model, suggesting a possible etiologic role of digestive enzymes in perianal, circumstomal or diaper dermatitis.
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PMID:Faecal enzymes: in vivo human skin irritation. 818 14

A girl, 5.7 years old, gained tolerance to egg white ingestion in spite of high immunoglobulin E (IgE) antibody titers to egg white but retained contact urticaria against egg white. She developed atopic dermatitis on her face at 2 months of age and showed high IgE antibody titers to egg white and cow's milk. Accidental ingestion of egg products initiated immediate symptoms such as wheezing, urticaria, erythema and edema of the eyelids and conjunctiva three times. These symptoms were confirmed by challenge tests using boiled egg white at 3.9 years of age. She also reacted positively to a 20 min patch test on her volar arm with raw egg white. However, there were no reactions to the oral challenge test by boiled egg and freeze-dried egg white at 5.1 and 5.7 years of age, respectively. This non-responsiveness was confirmed by a double-blind, placebo-controlled food challenge using freeze-dried egg white. Nevertheless, she showed positive reactions to a 20 min patch test with freeze-dried egg white. Her IgE antibody titers to the egg white components including ovomucoid, ovalbumin, ovotransferrin and lysozyme as well as egg white were high from 2.9 to 5.7 years old. Her IgE antibody titers for the ovomucoid fragments digested by pepsin, chymotrypsin and trypsin were not lower than those of positive control subjects. The binding activity of IgE antibody to ovomucoid, however, decreased from 2.9 to 5.6 years as shown by radioallergosorbent test (RAST) inhibition assays. The IgE antibody showed weaker binding activity to pepsin- and chymotrypsin-digested ovomucoid that were filtered through cut-off 10,000 filter at the age of 2.1 and 5.7 years. We speculated that the maturation of secretion of digestive enzymes was involved in the mechanisms of the acquisition of tolerance to egg white ingestion in spite of the persistence of contact urticaria.
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PMID:A case retaining contact urticaria against egg white after gaining tolerance to ingestion. 912 58

Several species of Culicoides biting midges are important pests and vectors of pathogens affecting humans and other animals. Bluetongue is the most economically important arthropod-borne animal disease in the United States. Culicoides variipennis is the primary North American vector of the bluetongue viruses. A reddish halo surrounding a petechial hemorrhage was noticed at the site of C. variipennis blood feeding in previously unexposed sheep and rabbits. Salivary gland extracts of nonblood-fed C. variipennis injected intradermally into sheep and rabbits induced cutaneous vasodilation in the form of erythema. A local, dose-dependent erythema, without edema or pruritus, was noted 30 min after injection. Erythema was inapparent with salivary gland extracts obtained after blood feeding. This observation suggested that the vasodilatory activity was inoculated into the host skin at the feeding site. The vasodilatory activity was insoluble in ethanol and destroyed by trypsin or chymotrypsin, which indicated that vasodilation was due to a protein. The association of cutaneous vasodilation with a salivary protein was corroborated by reversed-phase, high-performance liquid chromatography (HPLC). Fractionation of salivary gland extracts by molecular sieving HPLC resulted in maximal vasodilatory activity that coeluted with a protein having a relative molecular weight (MWr) of 22.45 kD. The C. variipennis vasodilator appears to be biologically active at the nanogram level. This vasodilator likely assists C. variipennis during feeding by increasing blood flow from host superficial blood vessels surrounding the bite site. The identification of a salivary vasodilator in C. variipennis may have implications for the transmission of Culicoides-borne pathogens and in the development of dermatitis resulting from the sensitization of humans and animals to Culicoides salivary antigens.
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PMID:Identification of a salivary vasodilator in the primary North American vector of bluetongue viruses, Culicoides variipennis. 931 53

Lipase hypersecretion syndrome (LHS) is a paraneoplastic syndrome seen exclusively as a result of pancreatic acinar cell carcinoma (ACC). In LHS, acinar enzymes (lipase, trypsin and chymotrypsin) which are normally secreted to the duodenum for digestive purposes, are instead released to the blood by the carcinoma cells. In a way, it is "endocrine-ization" of an "exocrine" function. These circulating enzymes, especially lipase, exerts its digestive action on other tissues, especially on the subcutaneous tissues in the pressure poins of legs, creating a picture often mistaken as erythema nodosum or rheumatic nodules. The bone and joints may also be effected, which mostly appears to be secondary to the complications and super-infection of the skin lesions. Eosinophilia also often accompanies this syndrome. The accurate diagnosis of LHS requires the identification of the pancreatic primary as well as its correct classification as acinar because a variety of pancreatic tumors can be associated with skin lesions, ranging from rare metastasis of adenocarcinoma to the necrolytic migratory erythema caused by glucagon-producing neuroendocrine tumors. Towards this differential, the diagnostic characteristics of acinar cell carcinomas that have been better elucidated in the past decade often need to be employed in increasingly smaller specimens and the liver, especially since most LHS cases also have liver metastasis (presumably due to the by-pass of the "first-pass" liver metabolism phenomenon). ACC (and LHS) occur in patients in their 60's. The pancreatic mass is often large, round, demarcated and closely resemble neuroendocrine and solid-pseudopapillary neoplasms but are more atypical/proliferative, and commonly show single prominent nucleoli and a distinctive chromophilia. Immunostaining with trypsin/chymotrypsin, negativity of beta-catenin help in the differential; as a caveat, neuroendocrine differentiation is common in ACCs. In conclusion, LHS is a rare type of paraneoplastic syndrome specific to ACC. The accurate diagnosis requires attention to their subtle diagnostic characteristics.
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PMID:Lipase hypersecretion syndrome: A distinct form of paraneoplastic syndrome specific to pancreatic acinar carcinomas. 3130 Feb 57