Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of derived and synthetic peptides has contributed greatly to our understanding of encephalitogenic determinants in the basic protein molecule. Peptides derived from BP by use of trypsin, pepsin, cathepsin D (brain and liver) and BNPS-skatole have proven most useful. Synthetic peptides have served to define the disease-inducing determinants with precision. A remarkable feature of these studies is that different antigenic determinants serve as encephalitogenic sites in different species. The encephalitogenic sites comprise short peptide domains of the BP polypeptide chain, only 8 residues (rat), 9 residues (guinea pig), and 10 residues (rabbit) in length. In view of the requirement for both haptenic and carrier specificity of an immunogenic molecule, it is impressive that these peptides themselves elicit the autoimmune disease, EAE. While less active than BP on a molar basis, they are nonetheless potent encephalitogens, producing clinical signs in rats and guinea pigs at less than 1 microgram dose. The data indicate that for most animal species (guinea pig, rat, monkey) there appears to be only one major encephalitogenic determinant, an unusual finding in view of the number of antigenic determinants for cell-mediated immunity existing in the BP molecule. Possibly a combination of genetic and anatomical factors may account for this phenomenon. A relationship may exist between multiple sclerosis and EAE as shown by peptide studies; lymphocytes are found in MS patients during exacerbation sensitized to the same region of BP active in the monkey. The major encephalitogenic sites are: Guinea Pig (9) Phe-Ser-Trp-Gly-Ala-Glu-Gly-Gln-Lys(Arg); Rabbit (10) Thr-Thr-His-Tyr-Gly-Ser-Leu-Pro-Gln-Lys; Rat (8) Ser-Gln-Arg-Ser-Gln-Asp-Glu-Asn; Monkey (14) Phe-Lys-Leu-Gly-Gly-Arg-Asp-Ser-Arg-Ser-Gly-Ser-Pro-Hser.
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PMID:Peptides and autoimmune disease. 8 85

Hypertonic saline (ie, 7.5% NaCl) was injected intravenously (4 ml/kg bolus) to determine its effects in feline and murine models of hemorrhagic shock. Hypertonic NaCl transiently improved mean arterial blood pressure (MABP), superior mesenteric artery blood flow (SMAF), and cardiac output (CO) during the oligemic period. These effects lasted from 15 to 75 min. However, after reinfusion of blood, shocked cats which received 7.5% NaCl during the oligemic period, maintained MABP, SMAF, and CO at significantly higher values compared to cats receiving 0.9% NaCl. The postreinfusion values of these hemodynamic variables in cats given hypertonic NaCl were not statistically different from those of sham-shock cats. Hypertonic NaCl did not attentuate the increase in plasma cathepsin D activity or plasma proteolysis in either cats or rats. Nevertheless, the plasma activity of a myocardial depressant factor (MDF) was significantly lower in shock cats and rats given hypertonic saline compared with the 0.9% NaCl groups (31 +/- 4 vs 54 +/- 7 U/ml, p less than 0.02, in cats; and 27 +/- 2 vs 51 +/- 7 U/ml, p less than 0.02, in rats). The beneficial effects of small-volume resuscitation with 7.5% NaCl during hemorrhagic shock in cats and rats are likely due to the transient hemodynamic improvement during the oligemic period rather than sustained improvement in splanchnic perfusion or in prevention of cellular injury during shock. Our results in two species (eg, cat and rat) suggest that small-volume resuscitation with 7.5% NaCl may be a useful initial treatment of hemorrhagic shock when supplemented by subsequent blood transfusion or perhaps some other appropriate pharmacologic intervention.
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PMID:Use of hypertonic saline in the treatment of hemorrhagic shock. 358 42

This experimental study was designed to evaluate the efficacy of associated naturally occuring antioxidants in the prevention of chemically induced breast cancer using DMBA in virgin female Wistar rats. Rats were randomly allocated to three groups: control group (CG; n = 20), induction group (IG; n = 100), and prevention group (PG; n = 70). A single dose (65 mg/kg) of DMBA was administered in the IG and PG animals at 50 days of age. PG animals also received a single dose of alpha-tocopherol (200 mg/rat) 1 hour after DMBA administration and an association of selenium (p-XSC, 40 ppm/day/rat) and ascorbic acid (540 mg/day/rat) in drinking water, daily, from carcinogenic induction until necropsy. Macroscopic study and pathology revealed a significantly lower development of neoplasms in the PG animals (p < 0.05); the number of rats with mammary tumors, breast cancer incidence, and the number of malignant breast tumors per rat as well as per tumor-bearing rat were significantly decreased in the PG animals. Other types of primary neoplasms existing in the IG animals totally disappeared in the PG animals. Immunostaining to hormone steroid receptors (ER and PR) and cathepsin D was similar in both groups. Overexpression of p53 and metallothioneine was significantly increased in the PG animals (p < 0.05) and immunostaining to bromodeoxiuridin and Ki-67 was also stronger in the remaining tumors in the PG animals. These data thus add to the accumulating evidence that those micronutrients in combination seem to be effective in reducing the incidence of malignant tumors. Nevertheless, remaining tumors seem to present more aggressive behavior and characteristics of drug resistance.
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PMID:Chemoprevention of DMBA-Induced Mammary Tumors in Rats by a Combined Regimen of Alpha-Tocopherol, Selenium, and Ascorbic Acid. 1134 29