Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.4 (trypsin)
42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In previous studies of cell-cell and cell-substratum adhesion, we have identified differences in the behaviour between human skin fibroblasts cultured from normal individuals and patients with Duchenne muscular dystrophy (DMD). In these studies, monolayer cultures were dissociated by trypsinization and no detectable difference was noted in the efficiency of cell dissociation between normal and DMD fibroblast cultures. However, a detailed study by Kent has suggested that Duchenne fibroblasts exhibit increased sensitivity to trypsin. We have re-investigated this finding using an assay that directly measures the number of cells remaining attached to a substratum following trypsinization. In a series of experiments using cultures derived from five normal and five DMD individuals, we can detect no significant difference in the trypsin-induced detachment rates between normal and DMD skin fibroblasts. This observation applies to both growth-phase and stationary-phase cell cultures. This inconsistency with previously reported data on the trypsin-sensitivity of DMD cells is considered in terms of the different assays used and the effects of trypsin on cell-cell and cell-substratum adhesion. The relationship between abnormalities in the behaviour of DMD cells and the localization and primary structure of the DMD gene product are also discussed.
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PMID:The kinetics of cell-substratum detachment mediated by trypsin: a comparison of normal and Duchenne fibroblasts. 277 25

Faced to the success of the neonatal screening for phenylketonuria and congenital hypothyroidism, it was tempting to introduce screening of other metabolic diseases. "Ideal" diseases to be screened are treatable, are not easily recognized by clinical means during the neonatal period, need immediate therapy to prevent irreversible disabilities, have a reasonable frequency and can be detected by and easy test. There is some controversy concerning the list of diseases recommended for mass screening, among them four can be discussed: congenital adrenal hyperplasia, due to 21-hydroxylase deficiency, fulfils most of the criteria, but some changes in the general screening strategy should be made to provide a result as soon as possible, and at least before the 10th day of life; cystic fibrosis, immunoreactive trypsin is a good marker of the disease but its assay needs technical adaptation for mass screening; more information are also required about the efficacy of an early management of the disease; Duchenne muscular dystrophy has a good marker for neonatal screening (creatine kinase), but no treatment exists and the possibility of genetic counselling can only be provided; hypercholesterolaemia is a frequent disease; however, the good marker and the adequate treatment remain to be defined. Pilot programmes, on the behalf of the French Association for Neonatal Screening, are evaluation these problems. However, at the present time, a consensus has been reached that only phenylketonuria and hypothyroidism fulfils criteria for an efficient mass screening programme.
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PMID:[Screening for hereditary diseases. What other screening?]. 317 79

Polyclonal antibodies to dystrophin (the protein product of the human Duchenne muscular dystrophy gene) were used to identify and characterize dystrophin in isolated triads from rabbit skeletal muscle. Anti-dystrophin antibodies recognize an approximately 400,000-Da protein in isolated triads or heavy microsomes from skeletal muscle. Treatment of heavy microsomes with buffers containing high salt or EDTA to remove peripheral or extrinsic membrane proteins does not remove dystrophin; however, treatment of intact triads with trypsin shows that dystrophin is extremely sensitive to mild proteolytic digestion. Isolation of junctional complexes from skeletal muscle triads indicates that dystrophin is tightly associated with the triadic junction. Fractionation of the triadic junction into junctional transverse tubular membranes and junctional sarcoplasmic reticulum membranes has shown that dystrophin is enriched in junctional transverse tubular membranes. Thus, our results suggest that dystrophin is a component of the triad junction which is exposed to the cytoplasm and embedded in or attached to the transverse tubular membrane.
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PMID:Evidence for the association of dystrophin with the transverse tubular system in skeletal muscle. 328 50

Measurements of aggregation kinetics using couette viscometry show that freshly trypsinized skin fibroblasts from patients with Duchenne muscular dystrophy have values of intercellular adhesiveness approx. 40% those of normal cells. If cells are allowed to recover from the effects of trypsinization (by incubation for 2 h at 37 degrees C in serum-containing medium) the intercellular adhesiveness of both cell types increases, and normal and Duchenne cells aggregate to the same extent. Exposure to the ionophore monensin during the recovery phase leads to suppression of recovery in both cell types, and this effect of the drug is greater in Duchenne fibroblasts. These results are discussed in relation to other data on the reported differential effects of trypsin and monensin on normal and Duchenne fibroblasts.
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PMID:The effect of monensin on cell aggregation of normal and dystrophic human skin fibroblasts. 402 79

When skin fibroblasts from patients with Duchenne muscular dystrophy were treated with trypsin in the presence of divalent cations, they detached more rapidly from the substratum than did fibroblasts from normal individuals of similar age, sex, and passage number. This difference was observed when either the time of incubation or trypsin concentration was varied. The ease of detachment of both normal and dystrophic fibroblasts varied somewhat with culture age and plating density, although detachment was always greater for fibroblasts from dystrophic individuals. If the trypsin treatment was carried out in the absence of divalent cations, both types of fibroblasts detached rapidly from the substratum, suggesting that a divalent-cation dependent cell-substratum adhesion mechanism is altered in Duchenne muscular dystrophy fibroblasts.
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PMID:Increased rate of cell-substratum detachment of fibroblasts from patients with Duchenne muscular dystrophy. 657 72

A young female was diagnosed as having X-linked muscular dystrophy of the Duchenne type. Chromosome studies, including trypsin-Giemsa banding, Quinacrine fluorescence, and nucleolus organizer region (NOR) silver staining revealed an X-autosome reciprocal translocation t(X;21) (p21;p12). Utilizing both [3H] thymidine autoradiography and the BrdU-Hoechst 33258-Giemsa technique, lymphocytes and fibroblasts were found to show a preferential inactivation of the normal X suggesting the presence of a single mutant gene on the translocated X. This patient is one of seven reported cases of an X-linked muscular dystrophy associated with an X-autosome translocation. In all seven cases the exchange point in the X chromosome is in band p21 at or near the site of the Duchenne gene.
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PMID:Expression of an X-linked muscular dystrophy in a female due to translocation involving Xp21 and non-random inactivation of the normal X chromosome. 674 20

Increased [32P]-incorporation in tryptic peptides of the erythrocyte membrane protein spectrin Band 2 in Duchenne muscular dystrophy (DMD) was studied in a consecutive series of 10 matched DMD/control pairs. Spectrin was [32P]-phosphorylated by cyclic AMP-independent endogenous membrane protein kinase in the presence of [gamma-32P]ATP. [32P]-labeled spectrin was isolated, purified, and subjected to tryptic cleavage with excess trypsin. The resulting peptides were separated on a high-resolution 5%/15% stacking SDS--polyacrylamide gel electrophoresis system. Liquid scintillation counting was performed on sequential slices of unstained gels. A broad [32P]-labeled band containing a number of [32P]-polypeptides was found to be more highly [32P]-phosphorylated in DMD patients than in their matched controls. This band migrated with an apparent molecular mass of 4.8-5.2 kilodaltons and contained approximately 55% of total [32P] radioactivity covalently bound to spectrin peptides. These data demonstrated an increased [32P]-phosphorylation of an identifiable tryptic peptide fraction in DMD that is consistent with previous reports of increased spectrin Band 2 [32P]-phosphorylation in DMD.
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PMID:Increased [32P]-phosphorylation of tryptic peptides of erythrocyte spectrin in Duchenne muscular dystrophy. 731 88

The primary structure of erythrocyte spectrin bands I and II from controls and patients with Duchenne muscular dystrophy was compared by 2-dimensional peptide mapping. 125I-labelling was done either by the chloramine-T method or using the Bolton and Hunter reagent followed by treatment with trypsin or chymotrypsin, resulting in four different peptide maps from each band of spectrin. Although all the peptide maps of band I were considerably different to those of band II, there were no consistent differences in the maps of bands I and II from controls compared to the corresponding maps from patients with Duchenne muscular dystrophy.
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PMID:Erythrocyte spectrin in Duchenne muscular dystrophy. 731 86

Exercised mdx mice were used to evaluate the efficacy of two pharmacologic entities, cromolyn and compound 48/80. Beginning at 2 weeks of age, mdx mice were treated with either cromolyn (50 mg/kg/day), prednisone (2mg/kg/day), compound 48/80 (1mg/kg/day), or diluent vehicle. At 4 weeks of age, treated mice were subjected to twice weekly, forced treadmill running which has previously been shown to cause expressed weakness in mdx mice (Hudecki, Pollina et al., 1993). Strength was evaluated weekly through 6 weeks of age using a previously described "pull-test" procedure (Hudecki, Pollina et al., 1993). Serum creatine kinase (CK) and mast cell tryptase activities were evaluated from 6 week blood samples. There was a significant increase in strength in mdx mice treated with cromolyn (p < or = 0.05), while no significant increase in strength was found in mice treated with compound 48/80, or prednisone compared to vehicle controls. While no significant change in tryptase activity was found between treatments, CK activity was significantly increased in the cromolyn group compared to vehicle controls. However, when tryptase and CK were expressed as a combined factor (Tryp x CK), the cromolyn treated group was significantly different from all other groups. The results of this study suggest a possible use for cromolyn-like compounds in the treatment of Duchenne muscular dystrophy.
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PMID:Cromolyn increases strength in exercised mdx mice. 882 68

Duchenne muscular dystrophy is known to be caused by a defective gene of dystrophin, a 427-kDa cytoskeletal protein, but the effective therapeutic drug is presently unavailable. We previously reported that a trypsin-like protease designated as dystrypsin is markedly activated in the muscle microsomal fraction immediately before onset of the clinical signs in mdx mice, a dystrophin-deficient hereditary animal model for human Duchenne muscular dystrophy. In order to examine the possible participation of dystrypsin in the occurrence of the disease, we investigated the therapeutic effects of dystrypsin inhibitors on the occurrence and progress of muscular dystrophy. Here, we show that camostat mesilate, a low-molecular-weight inhibitor of trypsin-like proteases, including dystrypsin, is a candidate drug for Duchenne muscular dystrophy.
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PMID:Therapeutic effect of camostat mesilate on Duchenne muscular dystrophy in mdx mice. 1284 32


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