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81.
The Neu1 locus, in the S region of the murine histocompatibility-2complex, regulates the sialic acid content of several liverlysosomal enzymes. Three alleles, Neu1a, Neu1b, and Neu1c, havebeen described on the basis of differential sialylation of theenzyme liver acid phosphatase. The Neu1a allele occurs in asmall number of mouse strains, e.g., SM/J and is associatedwith sialidase deficiency. We recently described G9, a sialidasegene in the human major histocompatibility complex (Milner etal. (1997) J. Biol. Chem., 272, 4549–4558), and we nowreport the characterization of the equivalent gene in mouse.The protein product of the murine G9 gene is 409 amino acidsin length and is 83% identical to its human orthologue. Expressionof the murine G9 protein in insect cells has confirmed thatit is a sialidase, with optimal activity at pH 5. To elucidatethe basis of sialidase deficiency in mouse strains carryingthe Neu1a allele, we have sequenced the G9 coding regions frommice carrying the three Neu1 alleles and hence defined the aminoacid sequence characteristic of each allotype. Of particularinterest is a Leu-209 to Ile mutation that is unique to theNeu1a allotype and is associated with reductions in sialidaseactivity of 68% and 88% compared to the Neu1b and Neu1c allotypes,respectively, when these three protein variants are expressedin insect cells. Additional factors, such as differential expression,may also influence the activities of the Nen1 allotypes in vivo.We have observed that the level of G9 mRNA is substantiallyreduced in mice carrying the Neu1a allele compared to the Neu1b(85–95% reduction) and Neu1c (70% reduction) alleles. H2 complex MHC Neu1 sialidase  相似文献   
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Proteolytic activity of proteasome on myofibrillar structures   总被引:5,自引:0,他引:5  
The physiologic function of proteasome remains unclear. Evidence suggests a role in degradation of ubiquitin-protein conjugates, MHC antigen presentation, and some specificity of substrate within certain cell types. To explore further the properties of proteasome we have examined its effect on a well defined structure, the myofibril. We find that despite its large size (20S) proteasome is able to degrade myofibrils and intact, permeabilized muscle fibrils. The proteins degraded showed some specificity because actin, myosin and desmin were degraded faster than -actinin, troponin T and tropomyosin. Changes in ultrastructure were slow and included a general loss of structure with Z and I bands effected before the M band and costameres.  相似文献   
84.
Spondyloepiphyseal dysplasia tarda (SEDL) is an X-linked recessive disorder characterized in affected males by short stature resulting from a growth defect of the vertebral bodies. We have extended our earlier studies by analyzing 15 families with newly identified microsatellite DNA markers; analysis of recombination events with these markers indicates that the gene responsible for SEDL is located in Xp22 between DXS 16 and DXS 987 on an interval spanning approximately 2 Mb.  相似文献   
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Calmodulin antagonists inhibited hormone-stimulated cyclic AMP accumulation in both cultured cells and cell lysates of mouse B16 melanoma. Particulate preparations of B16 melanoma contained 34-45% of total cell calmodulin, which could not be dissociated by extensive washing irrespective of the presence of EGTA in the buffer. The adenylate cyclase activity in such preparations was unaffected by the addition of exogenous calmodulin. However, the rare-earth-metal ion La3+, which can mimic or replace Ca2+ in many systems, produced an immediate inhibition of agonist-stimulated adenylate cyclase activity and preincubation of particulate preparations was La3+ followed by washing with La3+-free buffer dissociated calmodulin (96% loss) from particulate preparations. The loss of calmodulin from particulate preparations was associated with a decrease in agonist responsiveness (74%) and a marked change in the Ca2+-sensitivity of the enzyme, low concentrations of calcium (approx. 10 nM) now failing to stimulate enzyme activity, high concentrations of calcium (greater than or equal to 100 nM) producing greater-than-normal inhibition of enzyme activity. Direct activation of adenylate cyclase by the addition of pure calmodulin was now demonstrable in such calmodulin-depleted particulate preparations. Half-maximal stimulation of agonist-responsive adenylate cyclase occurred at 80 nM-calmodulin in the presence of 10 microM free Ca2+. Maximal stimulation by calmodulin (at 300-600 nM) restored enzyme activity to 89 +/- 5% (mean +/- S.E.M., n = 7) of the activity in untreated, calmodulin-intact, preparations.  相似文献   
87.
Septal deviation is often associated with hypertrophy of the contralateral inferior turbinate. Failure to reduce the size of the turbinate at the time of septal reconstruction may result in persistent nasal obstruction. The authors present their experience with 408 patients who underwent one of four turbinate procedures over a 6-year period. Most patients underwent unilateral turbinate surgery, although bilateral procedures were undertaken in 7 percent of patients. A graduated surgical approach was taken that varied according to the amount of turbinate enlargement and the degree to which mucosa and bone were involved. Full-thickness excision of the anterior third to half of the inferior turbinate (turbinectomy) became a favored procedure. Relief of nasal obstruction was obtained in greater than 90 percent of patients. Healing was satisfactory regardless of the method, and complications, including hemorrhage and infection, were few. Long-term follow-up revealed no untoward sequelae, and no patient developed atrophic rhinitis. The authors conclude that turbinate surgery, particularly when unilateral, in the carefully selected patient with nasal obstruction is a useful adjunct to septal surgery.  相似文献   
88.
Summary Activities of the microvillar enzymes -glutamyl-transpeptidase (GGTP), aminopeptidase M (APM), phosphodiesterase and maltase have been examined in second-trimester amniotic fluid as possible aids to the early prenatal diagnosis of cystic fibrosis (CF). The two peptidases, GGTP and APM, gave best results. If the fifth percentile of the normal range is used as an action line, the sensitivity of a positive test (low GGTP value) is 78% and the predictability 84%. At the tenth percentile the sensitivity is 100% and the predictability 77%. These approximate figures apply only to pregnancies where there has been a previous affected child. Until the primary protein defect in CF is discovered, this may prove an acceptable form of prenatal diagnosis to the high-risk mother.  相似文献   
89.
Abstract— The tetrahydrofolate-dependent serine hydroxymethyl transferase ( l -serine: tetrahydrofolate 10-hydroxymethyl transferase, EC 2.1.2.1) reaction in rat or human brain homogenates incubated aerobically is dependent on added reducing agents for full activity in order to protect the readily oxidized substrate, tetrahydrofolate. In this role, 0.1 m m -NADH is as affective as 10m m -2-mercaptoethanol and it can be shown that the NADH prevents destruction of tetrahydrofolate incubated with brain homogenates. If the dihydropteridine reductase (NADPH:6,7-dihydropteridine oxidoreductase, EC 1.6.99.7) activity of the brain homogenate is inhibited by a specific antiserum, NADH, but not 2-mercaptoeth-anol, is no longer effective. Furthermore, an homogenate of a brain biopsy from a human lacking dihydropteridine reductase requires added dihydropteridine reductase for maximal stimulation by NADH of the serine hydroxymethyl transferase reaction. We conclude that dihydropteridine reductase mediates the NADH stimulation and can play a role in preserving tetrahydrofolate from oxidation. The rinding of greatly reduced folate levels in the brain biopsy from the human lacking dihydropteridine reductase supports this postulated role of dihydropteridine reductase in folate metabolism.  相似文献   
90.
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