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121.
Innovations in human genetics education. Genetic applications for health professionals: an outreach continuing-education model program 总被引:2,自引:2,他引:0
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A system for extending continuing education in genetics to nurses and other practicing health professionals was developed in an eight-state area. Coordinators from state agencies received special training at the University of Colorado to administer the course in local communities. A combination of classroom instruction, independent study, computer-assisted instruction, and case-study methods for course delivery was included. More than 300 health professionals have completed the course, and 14 coordinators from seven states have been prepared to administer future courses. The model has demonstrated high potential for replication in other regions. 相似文献
122.
Resolution of a missense mutant in human genomic DNA by denaturing gradient gel electrophoresis and direct sequencing using in vitro DNA amplification: HPRT Munich. 总被引:11,自引:0,他引:11
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N F Cariello J K Scott A G Kat W G Thilly P Keohavong 《American journal of human genetics》1988,42(5):726-734
The combination of denaturing gradient gel electrophoresis (DGGE) and in vitro DNA amplification has allowed us to (1) localize a DNA mutation to a given 100-bp region of the human genome and (2) rapidly sequence the DNA without cloning. DGGE showed that a mutation had occurred, but the technique revealed little about the nature or position of that mutation. The region of the genome containing the mutation was amplified by the polymerase chain-reaction technique, providing DNA of sufficient quality and quantity for direct sequencing. Amplification was performed with a 32P end-labeled primer that allowed direct Maxam-Gilbert sequencing of the amplified product without cloning. HPRTMunich was found to contain a single-base-pair substitution, a C-to-A transversion at base-pair position 397. We report the generation of a 169-bp, wild-type DNA probe that encompasses most of exon 3 of the human hypoxanthine guanine phosphoribosyltransferase (HPRT) gene and contains a low-temperature melting domain of approximately 100 bp. HPRTMunich, an HPRT mutant isolated from a patient with gout, has a single amino acid substitution; the corresponding DNA sequence alteration must lie within the low-temperature melting domain of exon 3. We report the separation of HPRTMunich from the wild-type sequence using DGGE. In addition to base-pair substitutions, DGGE is also sensitive to the methylation state of the molecule. The cDNA for HPRT was cloned into a vector and propagated in Escherichia coli dam+ and dam- strains; thus, methylated and unmethylated HPRT cDNA was obtained.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
123.
A patient with moderate to severe hemophilia B has been found to have a large insertion within his factor IX gene. The site of insertion is located in a DNA segment of approximately 0.8 kb between exon IV and an EcoRI site within intron D. The size of the DNA insertion is approximately 6 kb, and it contains at least two TaqI sites, two EcoRI sites, and one HindIII site. The insert probably originates from outside the FIX gene and does not represent an internal duplication. We propose that this abnormal FIX gene be called FIX El Salvador in recognition of the birthplace of the patient. 相似文献
124.
125.
P M Jordan M J Warren H J Williams N J Stolowich C A Roessner S K Grant A I Scott 《FEBS letters》1988,235(1-2):189-193
The dipyrromethane cofactor of Escherichia coli porphobilinogen deaminase was specifically labelled with 13C by growth of the bacteria in the presence of 5-amino[5-13C]levulinic acid. Using 13C-NMR spectroscopy, the structure of the cofactor was confirmed as a dipyrromethane made up of two linked pyrrole rings each derived from porphobilinogen. The chemical shift data indicate that one of the pyrrole rings of the cofactor is covalently linked to the deaminase enzyme through a cysteine residue. Evidence from protein chemistry studies suggest that cysteine-242 is the covalent binding site for the cofactor. 相似文献
126.
The Differential Contribution by Individual Enzymes of Glycolysis and Protein Catabolism to the Relationship between Heterozygosity and Growth Rate in the Coot Clam, Mulinia Lateralis 总被引:1,自引:1,他引:0
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The locus-specific effects of heterozygosity upon individual growth rate were determined for 15 polymorphic enzymes among 1906 individuals from a single cohort sample of the marine bivalve Mulinia lateralis. Two measures of individual growth rate (total wet weight and shell length) were made at collection and after a period of growth in the laboratory. The correlation between heterozygosity and growth rate was independently determined for each locus using multiple linear regression, thereby providing a rank of individual locus effects; these differed significantly. The four estimated rankings of relative locus effects (initial length, initial weight, length added in the laboratory, and added weight) were not statistically different. That is, a locus with a large effect of heterozygosity on growth rate in nature had a similarly large effect on laboratory growth rate. The effect of a locus was not related to heterozygosity per se; some highly heterozygous loci had no detectable correlation with growth rate. The data contained two pairs of relatively tightly linked loci; in both cases one locus of a pair had significant effects on growth rate, while the other had no effect. Loci with large and significant correlations with growth rate synthesize enzymes which function in protein catabolism or glycolysis; heterozygosity in enzymes of the pentose shunt, redox balance, or other miscellaneous metabolic roles was not correlated with growth rate. Since the metabolic basis for the correlation is known to derive from individual differences in net energy status, particularly energetic costs of whole-body protein turnover, these data indicate that phenotypic effects (e.g., variation in growth rate) are determined by heterozygosity at the studied genes, not other linked loci. 相似文献
127.
The data presented in the accompanying paper (J. P. Cogswell, R. P. Phipps, and D. W. Scott, Cell. Immunol. 114, 55-70, 1988) indicate that certain macrophage-like and lymphoid dendritic-like (P388AD.2) tumor lines which express major histocompatibility encoded class II (Ia) antigens and produce interleukin 1 (IL-1) are uniquely able to present hapten-modified self (HMS) in an immunogenic fashion in vivo. In the current study, the relationship between phenotype and function has been confirmed utilizing a completely in vitro system. This investigation revealed that B-cell priming required T cells restricted to P388AD.2's I-A antigens. In addition, exogenous IL-1 reconstituted the response of an IL-1-deficient tumor (P388AD.2-ILd), although it had no effect on the other nonimmunogenic Ia+ tumor lines. Unlike the in vivo system, effective B-cell tolerance was induced when P388AD.2 was modified with high concentrations (10 mM) of hapten or when highly haptenated tumor was added to 0.1 mM TNBS-modified P388AD.2. These results suggest that positive regulation of in vitro immune responses to HMS is dependent upon the phenotype of the accessory cell carrier (with lymphoid dendritic-like cells being unusually potent), while negative regulation is associated with high epitope density. This system now allows the dissection of the properties of different accessory cells and the signals required for B-cell priming or tolerance induction. 相似文献
128.
It was recently demonstrated that a lymphoid dendritic-like tumor, P388AD.2, presented hapten-modified self (HMS) in an immunogenic fashion even after injection via the normally "tolerogenic" intravenous (iv) route. To determine whether this property was unique to the P388AD.2 line, other hapten-modified tumors were administered iv and the result of their presentation was measured by changes in the number of splenic plaque-forming cells (PFC) following in vitro challenge with thymic-independent antigens. Of the six tumors tested, two (P388 and J774.5R) primed for augmented PFC responses, while four others (P388NA.10, P388D1, WEHI-231, and 70Z/3) did not. When these tumors were compared for Ia expression and production of interleukin-1 (IL-1), it was discovered that (1) all of the immunogenic tumors were Ia+ and IL-1 producing (IL-1+), although not all Ia+,IL-1+ tumors could elicit augmented PFC responses; (2) none of the tumors that were deficient in either Ia expression or IL-1 production could prime B-cell responses in vivo; and (3) the ability to augment PFC responses was proportional to the density of Ia on the immunogenic tumors. These results demonstrated that P388AD.2 was not the only tumor line capable of presenting HMS iv as an immunogen, and that the accessory cell phenotype is critical for the induction of an immunogenic response in vivo. 相似文献
129.
R B Scott S C Diamant G R Greenburg 《Canadian journal of physiology and pharmacology》1988,66(12):1499-1504
The plasma levels of the enteric hormones, motilin and pancreatic polypeptide, cycle in association with fasting intestinal motility and are altered by feeding. Intravenous administration of motilin causes gallbladder contraction and increased sphincter of Oddi phasic motor activity, whereas pancreatic polypeptide causes gallbladder relaxation. To determine if endogenous plasma levels of motilin and pancreatic polypeptide control sphincter of Oddi and gallbladder motility, and regulate duodenal bile acid delivery, we measured during fasting and after feeding the correlation between (a) changes in plasma motilin or pancreatic polypeptide, and (b) the duodenal delivery of a steady-state hepatic output of radiolabelled bile acid. Four dogs were prepared with duodenal cannulas. Duodenal motility was recorded manometrically. Plasma levels of pancreatic polypeptide and motilin were determined during a full cycle of the migrating myoelectric complex for 20 min before and 40 min after ingestion of a standard meal. To assess the effect of the sphincter of Oddi and the gallbladder together, or the gallbladder alone on duodenal bile acid delivery, the dogs received a continuous i.v. infusion of [14C]taurocholic acid (TCA); duodenal delivery of TCA was quantitated with the sphincter of Oddi intact using duodenal marker perfusion, or with the sphincter of Oddi cannulated and zero outflow resistance. In the interdigestive period with the sphincter of Oddi intact, only 0.1 (r2) of the variance of duodenal bile acid delivery can be predicted from the variance of motilin, and the correlation of plasma pancreatic polypeptide with duodenal TCA delivery is opposite that expected if pancreatic polypeptide caused gallbladder relaxation.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
130.
Filaggrin is a specific epidermal protein which is the precursor of the free amino acids, urocanic acid and pyrrolidone carboxylic acid which are largely responsible for the ability of the stratum corneum of the skin to remain hydrated at low environmental humidity. The distribution of filaggrin shown by immunofluorescence in the stratum corneum of the rat changed dramatically during the first hours of postnatal life. During late foetal development, filaggrin accumulated through the entire thickness of the stratum corneum, indicating that there was a block on the subsequent processing of the protein which normally would convert it to free amino acids. Immediately after birth this block was lifted and normal proteolysis of the filaggrin took place in the outer part of the stratum corneum, leaving the normal adult pattern of a thin zone of cells containing filaggrin at the bottom of the stratum corneum. This activation of filaggrin proteolysis was dependent on the drop in external water activity caused by the transition from an aqueous environment in utero to a dryer environment after birth and it could be blocked by maintaining a 100% humidity atmosphere around the newborn rat after birth. In isolated stratum corneum in vitro, filaggrin proteolysis took place only between 80 and 95% relative humidity, both higher and lower relative humidity blocked the proteolysis. Application of occlusive patches to adult rats prevented the normal proteolysis of filaggrin, indicating that this mechanism controls not only the massive filaggrin proteolysis occurring after birth but also the proteolysis occurring during normal stratum corneum maturation. The stratum corneum therefore has the ability to respond to changes in external humidity by altering the level of the stratum corneum where it converts its reserves of filaggrin into water binding amino acids, such that under humid conditions water binding components will be produced in only the most superficial stratum corneum, or even not produced at all. 相似文献