Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Elevated activities of cysteine proteinases such as cathepsins B and L and cancer procoagulant have been linked to tumor malignancy. In the present study we examined the hypothesis that these elevated activities could be due to impaired regulation by the endogenous low molecular mass cysteine proteinase inhibitors (cystatins). Inhibitors from human sarcoma were compared to those from human liver, a normal tissue in which the inhibitors had been characterized previously. An extract of cystatins from sarcoma was less effective against papain and cathepsin B (liver or tumor) than was an extract from liver. This reduced inhibitory capacity in sarcoma was not due to a reduction in either the concentrations or specific activities of the cystatins or an absence of any family or isoform of cystatins. We purified two members of the cystatin superfamily (stefin A and stefin B) to homogeneity and determined their individual inhibitory properties. Stefins B from liver and sarcoma exhibited comparable inhibition of papain and cathepsin B. In contrast, stefin A from sarcoma exhibited a reduced ability to inhibit papain, human liver cathepsins B, H and L and human and murine tumor cathepsin B. The Ki for inhibition of liver cathepsin B by sarcoma stefin A was 10-fold higher than that for inhibition of liver cathepsin B by liver stefin A, reflecting a reduction in the rate constant for association and an increase in the rate constant for dissociation. Cancer is now the third pathologic condition reported to be associated with alterations in cystatins, the other two being amyloidosis and muscular dystrophy.
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PMID:Inhibitory properties of low molecular mass cysteine proteinase inhibitors from human sarcoma. 280 24

Various kinds of lesions exist which should be discriminate from malignant or premalignant or borderline lesions. If there were a morphologic technical procedure on detection of malignant transformation of the cells at the initiation stage, before the lesion would develop a definitely identical with malignant lesion, such method must be most highly applicable for pathologists. DNA diagnosis has realized a warning of diagnosis of certain diseases or genetical maldevelopment prior to develop their clinical manifestation. Gene analysis has introduced in ++phragmatical screening test for certain diseases such as diabetes mellitus, thalassemia, T-cell leukemia or lymphoma, neuroblastoma, muscular dystrophy of Duchenne or Becker type, Ph' chromosome and so on. Immunohistochemical technology has provided an intracellular oncogene detection in some neoplastic malignancies such as n-myc in neuroblastoma. Amplification of c-erb B2 (also referred as neu and HER-2/neu) has indicated a higher malignant mammary carcinoma with poor-prognosis, even their size small and early stage. Oncogene analysis is expected to be available sperimposing on pathological morphology.
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PMID:[Detection of early stage cancer: pathological aspect with special reference to differential diagnosis]. 317 85

A high performance liquid chromatographic method is described for monitoring forphenicinol, a possible therapeutic drug for cancer and muscular dystrophy, in human plasma and erythrocytes. Forphenicinol in the deproteinized samples was separated from interfering biogenic substances on an aminopropyl-bonded silica (Unicil NH2) column within 10 minutes with isocratic elution, and determined with fluorescence detection. The detection limits for forphenicinol in plasma and erythrocytes are 65 pmol (12.8 ng)/ml and 160 pmol (31.5 ng)/ml, respectively, corresponding to 2 pmol each in a 100 microliters injection volume. The method is very simple, and sensitive enough to permit the quantification of forphenicinol in the blood samples from man dosed with forphenicinol.
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PMID:Simple determination of forphenicinol in human plasma and erythrocytes by HPLC with native fluorescence detection. 350 26

The polyamines, putrescine, spermidine, and spermine have been established as biochemical markers of normal and pathological growth. In malignancy, the urinary concentrations of spermidine reflect the tumor cell loss and the urinary level of putrescine is related both to the number of tumor cells in cell cycle and to the tumor cell loss factor. A greater than twofold increase in urinary spermidine within 72 hr of chemotherapy predicts a complete or a partial response with a high degree of accuracy. Urinary putrescine may be valuable, not only in assessing the early response to therapy but also in determining whether the chemotherapy promotes a later burst of cell proliferation. Erythrocyte spermidine concentrations also appear to track alterations in tumor kinetics. Alterations in intracellular and extracellular polyamines in other pathologies such as psoriasis, muscular dystrophy, and cystic fibrosis also accurately reflect the disease activity and, in those cases studied, response to therapy. Therefore, the determination of polyamine concentrations in extracellular fluids and in erythrocytes allows for (1) the early assessment of response to multimodality therapy, (2) disease or tumor staging, and (3) assessment of disease activity including long-term monitoring of polyamine concentrations to pinpoint remission and relapse in adjuvant patients. Information obtained by the monitoring of polyamines could result in prolongation of survival time of patients as well as assist in the design of the most effective therapy regimen for the pathology. Since other such specific kinetic markers are not available, polyamines should be clinically utilized to track tumor evolution and tumor response to therapy in those patients at high risk, in which such measurements could be translated into therapeutic efficacy.
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PMID:Clinical relevance of polyamines. 633 65

We have been searching for enzyme inhibitors in culture filtrates of microbes and have found leupeptin, antipain, chymostatin, elastatinal, pepstatin, hydroxypepstatin, pepstanone and phosphoramidon as specific inhibitors of serine, thiol, carboxyl and metallo proteases. We found significant activities of aminopeptidases, phosphatase and esterase on surface membranes of various mammalian cells. We discovered bestatin, amastatin, forphenicine, esterastin and ebelactones A and B as specific inhibitors against these enzymes. These inhibitors were proved to bind to cells and modify immune responses. The usefulness of bestatin in cancer treatment has been suggested by clinical studies. It has been shown by several investigators that some endopeptidases such as Ca2+-activated neutral proteases and some other serine proteases may play important roles in muscular dystrophy. In addition to these endopeptidases, we found an abnormal increase in various enzyme activities in dystrophic mice and chickens. Especially, aminopeptidase activities are markedly increased. Moreover, its inhibitor bestatin became interesting on the aspects of its binding to cell surfaces. Bestatin and leupeptin which inhibit Ca2+-dependent protease showed some therapeutic effects against mouse dystrophy. Investigating enzyme activities in synovial fluid of patients with rheumatoid arthritis and osteoarthritis, we found increased activities of aminopeptidases, chymotrypsin-like enzyme, and phosphatase in rheumatoid arthritis but not in osteoarthritis. In chronic hemodialysis patients, RNase activity in serum is markedly elevated. Thus, enzyme inhibitors are increasing their potential usefulness in treatment of various diseases.
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PMID:The relationships between enzyme inhibitors and function of mammalian cells. 704 7

A broad spectrum of immunologic parameters was investigated in 13 cases of myotonic muscular dystrophy (MyD), including those for cellular immunity which has attracted little attention in the past. One was a 46-year-old woman having both MyD and a thymoma. This association between MyD and thymoma is probably coincidental without biologic significance. There was no evidence of malignancy in the remaining 12 patients. The delayed cutaneous hypersensitivity reaction to dinitrochlorobenzene was anergic in 3 patients and showed impaired positive reactivity in 3 patients, as compared with no failure of response in normal adults or children with Duchenne muscular dystrophy. A high proportion of patients with MyD displayed positive tuberculin reactions, as did controls. Our case of MyD with a thymoma showed marked lymphocytopenia in peripheral blood, but the number of lymphocytes in peripheral blood in the remaining 12 patients was normal. Uptake of tritiated thymidine by lymphocytes in the presence of phytohemagglutinin was normal. Serum gammaglobulin was reduced in 4 patients with MyD. The mean value of serum immunoglobulin level was decreased only in the class of IgG. A wider derangement of immunologic function may occur in MyD than was previously recognized.
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PMID:Immunologic derangement in myotonic dystrophy--abnormal contact sensitization to dinitrochlorobenzene. 741 Nov 70

This article reviews the available data on the role of the peroxisome in the growth, differentiation and degeneration of mammalian tissues. Developmental progressions of peroxisomes are described, along with the influence of inhibitors of peroxisomal enzymes, peroxisome proliferators and morphogenetic agents on the ontogeny of experimental animals. The role of the peroxisome in protecting tissues from damage by oxygen free radicals is also described, as is the changing role of the peroxisome in the ageing animal. Amongst the degenerative diseases which have been associated with free radical damage are cancer, atherosclerosis, muscular dystrophy, rheumatoid arthritis and the senile degeneration of brain function. In all these conditions, the major characteristics of molecular damage have been considered, along with the particular role of the peroxisome in alleviating these effects. Proposals for further research into peroxisomal function during ontogeny and the degenerative changes associated with ageing are developed, and the possibility of palliative treatments discussed.
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PMID:On the role of the peroxisome in ontogeny, ageing and degenerative disease. 756 65

Reactive oxygen species and free radicals that are produced during normal metabolism can potentially damage cellular macromolecules. Defenses against such damage include a number of antioxidant enzymes that specifically target the removal or dismutation of the reactive agent. We report here the isolation and regional mapping of a human gene, TDPX1, that encodes an enzyme homologous to a yeast thioredoxin-dependent peroxide reductase (thioredoxin peroxidase, TPX). The human TDPX1 coding sequence was determined from the product of a polymerase chain reaction (PCR) amplification of human cDNA. Based on PCR analysis of DNA from a human/rodent somatic cell hybrid panel, the TDPX1 locus was assigned to chromosome 13. Further localization of the locus to 13q12 was accomplished by fluorescence in situ hybridization analysis, using as a probe DNA from a yeast artificial chromosome (YAC) that contains the TDPX1 gene. It was also determined by PCR analysis of various YACs that the TDPX1 locus is in the region of the dinucleotide repeat markers D13S289 and D13S290. This regional mapping localizes the TDPX1 gene to a genomic region recently shown to contain the breast cancer susceptibility gene BRCA2 and a gene associated with a form of muscular dystrophy. Oxygen radical metabolism has been hypothesized to be important for cancer, muscular dystrophy, and other disorders, so TDPX1 should be considered a candidate gene for these diseases.
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PMID:Localization of TDPX1, a human homologue of the yeast thioredoxin-dependent peroxide reductase gene (TPX), to chromosome 13q12. 760 88

Until recently, good animal models of human disease have been available only in limited numbers, largely because of technical difficulties associated with transgenesis. As a consequence of recent rapid advances principally, but not exclusively, focused around the use of embryonic stem cells, it is now theoretically possible to model the genetic lesion underlying any human disease in the mouse. This has led not only to a better understanding of complex disease processes, such as those associated with malignancy, but, as in the cases of cystic fibrosis and duchenne muscular dystrophy, is now allowing the development of novel therapy regimes.
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PMID:Murine genetic models of human disease. 791 24

There is no published research on coping with muscular dystrophy among adults. In the present study, two questionnaires, the Reaction to the Diagnosis of Cancer Questionnaire (RDCQ) and the Mental Adjustment to Cancer scale (MAC), were modified in order to measure coping with muscular dystrophy (MD). A total of 60 people (16-64 years) with diagnosed MD answered the questionnaires in two interviews including semi-structured questions. The replies to these questions were analysed by two independent judges on the basis of the RDCQ and MAC categories for coping. The purpose was twofold: to investigate if cancer-coping categories could be used for the classification of interview answers concerning coping with MD, and to gain knowledge about specific coping with MD. Analysis indicated that 82% of replies to semi-structured questions concerned with emotion/appraisal-focused coping with MD can be described by means of RDCQ and MAC categories. Eight new categories were developed to classify the remaining 18%: Anticipation, Creation of new life values, Minimization, Establishment of control over everyday life, Secretiveness, Fear, Social comparison and Coping with heredity. In addition, 997 replies were classified to represent problem-focused coping. The judges reached good agreement with respect to the proportions of replies in the respective coping categories. However, kappa (kappa) values were within the range of fair to good agreement.
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PMID:Assessment of coping with muscular dystrophy: a methodological evaluation. 793 Jan 50


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