A newly developed problem-based medical genetics course that was integrated into the fourth-year medical school curriculum of the University of Texas Health Science Center at San Antonio is described. To provide a basic genetic background for the clinical rotations, a supplemental computer tutorial is required during the second year. These two formats prepare the medical students to recognize genetic diseases, to provide basic genetic counseling in their daily practice, and to appropriately refer patients to genetic specialists.

Linkage relationships between the cystic fibrosis (CF) locus and three polymorphic DNA markers were examined in 14 families, five of which were of Hispanic origin. Tight linkage was found between the CF locus and MET (maximum lod score = 7.16 at theta = .001), and between CF and pJ3.11 (maximum lod score = 3.87 at theta = .001). We observed two recombinations between CF and collagen, yielding a maximum lod score of 0.359 at theta = .125, and one recombination in the cluster CF-MET-pJ3.11. Analysis by the seriation method indicates the order COL-pJ3.11-CF-MET.

Human haptoglobin (Hp) is a protein that binds free hemoglobin and circulates in plasma of vertebrates as a tetrachain (alpha beta)2 structure. This study maps HPA and HPB, the genes encoding the Hp alpha and beta chains to human chromosome band 16q22 by in situ hybridization.

DNA sequencing shows that the intragenic duplication within the human haptoglobin Hp2 allele was formed by a non-homologous, probably random, crossing-over within different introns of two Hp1 genes, probably in an Hp1F / Hp1S heterozygote.

Haptoglobin is a transport glycoprotein which removes free hemoglobin from the circulation of vertebrates. In human populations haptoglobin is polymorphic due to three alleles, Hp alpha 1F, Hp alpha 1S and Hp alpha 2. The Hp alpha 2 allele is roughly twice the length of the Hp alpha 1 alleles and is the product of a partial gene duplication possibly resulting from an unequal crossover event in a heterozygous genotype Hp alpha 1F/Hp alpha 1S. In the study described here we compare the cDNA encoding Hp alpha 1S to that encoding Hp alpha 2FS . Both have a leader sequence followed by the genotypic alpha chain sequence, a beta sequence and an untranslated sequence in the 3' end. The cDNA encoding Hp alpha 2FS is composed of alpha 1F and alpha 1S domains differing by four nucleotide replacements. Hp alpha 1S cDNA contains the same replacement site mutations found in the alpha 1S domain of Hp alpha 2FS , indicating that this coding region has sustained few, if any, mutations since its incorporation into the Hp alpha 2FS gene.

Research Articles| November 06 2008 Studies of Human Urinary Protein Fragments from Extracellular Matrix Proteins: A Progress Report Subject Area: Cardiovascular System , Nephrology L.W. Schneider; L.W. Schneider University of Texas Health Science Center, San Antonio, Tex., USA; University of Texas Medical Branch, Galveston, Tex., USA Search for other works by this author on: This Site PubMed Google Scholar D.R. Barnett; D.R. Barnett University of Texas Health Science Center, San Antonio, Tex., USA; University of Texas Medical Branch, Galveston, Tex., USA Search for other works by this author on: This Site PubMed Google Scholar S.D. Carson; S.D. Carson University of Texas Health Science Center, San Antonio, Tex., USA; University of Texas Medical Branch, Galveston, Tex., USA Search for other works by this author on: This Site PubMed Google Scholar R.M. Goldblum; R.M. Goldblum University of Texas Health Science Center, San Antonio, Tex., USA; University of Texas Medical Branch, Galveston, Tex., USA Search for other works by this author on: This Site PubMed Google Scholar P.H. van Bragt; P.H. van Bragt University of Texas Health Science Center, San Antonio, Tex., USA; University of Texas Medical Branch, Galveston, Tex., USA Search for other works by this author on: This Site PubMed Google Scholar H.J.A. Brejwo; H.J.A. Brejwo University of Texas Health Science Center, San Antonio, Tex., USA; University of Texas Medical Branch, Galveston, Tex., USA Search for other works by this author on: This Site PubMed Google Scholar J.D. Bell; J.D. Bell University of Texas Health Science Center, San Antonio, Tex., USA; University of Texas Medical Branch, Galveston, Tex., USA Search for other works by this author on: This Site PubMed Google Scholar L.C. Travis; L.C. Travis University of Texas Health Science Center, San Antonio, Tex., USA; University of Texas Medical Branch, Galveston, Tex., USA Search for other works by this author on: This Site PubMed Google Scholar B.H. Bowman B.H. Bowman University of Texas Health Science Center, San Antonio, Tex., USA; University of Texas Medical Branch, Galveston, Tex., USA Search for other works by this author on: This Site PubMed Google Scholar Renal Physiology (1983) 6 (4): 157–162. https://doi.org/10.1159/000172896 Article history Accepted: December 13 1982 Published Online: November 06 2008 Content Tools Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation L.W. Schneider, D.R. Barnett, S.D. Carson, R.M. Goldblum, P.H. van Bragt, H.J.A. Brejwo, J.D. Bell, L.C. Travis, B.H. Bowman; Studies of Human Urinary Protein Fragments from Extracellular Matrix Proteins: A Progress Report. Renal Physiology 1 April 1983; 6 (4): 157–162. https://doi.org/10.1159/000172896 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsRenal Physiology Search Advanced Search Article PDF first page preview Close Modal This content is only available via PDF. 1983Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements. You do not currently have access to this content.

Recombinant plasmids containing human cDNA encoding haptoglobin, a plasma protein that binds free hemoglobin, have been isolated by screening an adult human liver library with a mixed oligonucleotide probe. Four cDNA clones containing inserts have been obtained that span 1,218 nucleotides of the haptoglobin coding sequence, including the 3' end of the haptoglobin cDNA. The cDNA sequence included a leader sequence followed by alpha 2-chain and beta-chain sequences. A heretofore unseen arginine residue was deduced between the human alpha- and beta-chain sequences. This is a probable site of limited proteolysis leading to the formation of the alpha and beta polypeptides in mature haptoglobin. A comparison of the haptoglobin alpha-beta-junction region and the heavy-light-chain junction of tissue-type plasminogen activator strengthens the evolutionary homology found in haptoglobin and the serine proteases. The Hp alpha 2 gene, which was shown earlier to be a partial duplication produced by unequal crossing-over between Hp alpha 1 genes, has been impossible to align by protein characterization. The cDNA sequence establishes the alignment of Hp alpha 2FS in the Hp alpha 2 gene studied here.

In the current study, the cystic fibrosis cationic mucociliary inhibitor has been purified from urine by ion exchange chromatography, gel filtration, lectin affinity chromatography, isoelectric focusing, and high performance liquid chromatography. The molecular size of the cationic mucociliary inhibitor was estimated to be in the range of 4,000 to 13,500 MW, by its elution on Sephadex G-50, and between 7,500 and 12,750 MW, by urea-sodium dodecyl sulfate polyacrylamide gel electrophoresis. In addition to the cationic mucociliary inhibitor, an anionic mucociliary inhibitor was also detected in the urinary fraction isoelectrically focused between pH 4.5 and 4.9. The identity of the mucociliary inhibitor as a glycoprotein was established in the current study by affinity chromatography on Phaseolus lunatus lectin, by radiolabeling the carbohydrate with galactose oxidase and tritiated sodium boro-hydride, and by determining the presence of a large concentration of glucosamine and small amounts of galactosamine by amino acid analysis. The amino acio analysis of the purified major component of the cationic mucociliary inhibitor reveals that the glucosamine concentration represents a high percentage of the composition of the glycoprotein. Speculation: The purification of a cationic mucociliary inhibitor from cystic fibrosis urine will facilitate the construction of antibody reagents which can be utilized for feasibility studies of prenatal diagnosis and heterozygote detection.

Excessive protein loss through the gastrointestinal tract is difficult to diagnose and quantitate because of the nonavailability of radiolabelled proteins and the disadvantages of their administration to children. Alpha-l-antitrypsin (α1AT) is an endogenous protein which is resistant to proteolytic digestion in the intestine, not found in the diet and as suggested by others should reflect plasma protein loss into the GI tract. We investigated its usefulness by measuring the fecal α1AT concentration in 24 patients with no malabsorption, 12 patients with cystic fibrosis (high fecal nitrogen), 10 patients with fat malabsorption only and 3 patients with protein-losing enteropathies. Stool aliquots were taken from 48-72 hour homogenized stool collections which had been evaluated for fecal fat. Five lambda samples were directly applied to and quantitated by radial immunodiffusion plates specific for anti-human αlAT (Boehringer-Mannheim). "Normal" daily αlAT loss expressed in mg/kg body wt/day was 1.70 ± 1.32 with similar values for cystic fibrosis (0.99 ± 0.68, p>0.05) and isolated fat malabsorption (1.51 ± 1.03, p>0.05). The α1AT loss for the 3 patients with protein-losing enteropathies (two with lymphangectasia, one undiagnosed) varied from 4.4-48 mg/kg per day and correlated with clinical criteria for protein loss. Conclusion: Fecal α1AT quantitation may be specific for measuring protein loss into the gastrointestinal tract.

Five fragments of collagen have been purified from human urine. The fragments cross-reacted with basement membrane collagen from pig kidney cortices when tested against antiserum to basement membrane collagen, type IV, from murine tumor. The concentrations of these fragments were sufficient for amino acid analysis, immunological analysis, and in one case, preliminary analytical amino acid sequencing. Compositional analysis of the fragments indicated concentrations of hydroxylysine, hydroxyproline, and glycine that are typical of collagen. High values of hexosamines and neutral sugars were also found. An NH2-terminal sequence of 18 residues was obtained for one fragment of Mr approximately 6,500. This sequence was unique among proteins reported to date, but was obviously collagen-like. A urinary source of basement membrane collagen fragments will permit molecular characterization of basement membrane in inherited or acquired diseases affecting this structure.

The complete amino acid sequences and the disulfide arrangements of the two chains of human haptoglobin 1-1 were established. The alpha 1 and beta chains of haptoglobin contain 83 and 245 residues, respectively. Comparison of the primary structure of haptoglobin with that of the chymotrypsinogen family of serine proteases revealed a significant degree of chemical similarity. The probability was less than 10(-5) that the chemical similarity of the beta chain of haptoglobin to the proteases was due to chance. The amino acid sequence of the beta chain of haptoglobin is 29--33% identical to bovine trypsin, bovine chymotrypsin, porcine elastase, human thrombin, or human plasmin. Comparison of haptoglobin alpha 1 chain to activation peptide regions of the zymogens revealed an identity of 25% to the fifth "kringle" region of the activation peptide of plasminogen. The probability was less than 0.014 that this similarity was due to chance. These results strongly indicate haptoglobin to be a homolog of the chymotrypsinogen family of serine proteases. Alignment of the beta-chain sequence of haptoglobin to the serine proteases is remarkably consistent except for an insertion of 16 residues in the region corresponding to the methionyl loop of the serine proteases. The active-site residues typical of the serine proteases, histidine-57 and serine-195, are replaced in haptoglobin by lysine and alanine, respectively; however, aspartic acid-102 and the trypsin specificity, residue, aspartic acid-189, do occur in haptoglobin. Haptoglobin and the serine proteases represent a striking example of homologous proteins with different biological functions.

Crassostrea virginica, the oyster native to the gulf coast, has served as a source of ciliated epithelium for studies on the inhibitory factor in cystic fibrosis. In these studies, protein molecules with biological activity, obtained from serum, urine, saliva, and cells from cystic fibrosis homozygotes and heterozygotes, were detected, purified, and characterized. Properties of these factors are similar to those detected by other ciliated systems in mussel gills and rabbit trachea. Although none of the ciliated assays in their present stage of development offer a reliable means for heterozygote screening or for prenatal diagnosis, they represent powerful tools for characterizing biologically active molecules related to cystic fibrosis. The importance of purifying and characterizing the various cystic fibrosis factors described by several laboratories is based on evidence that their biological activities observed in vitro mimic some of the expressions of the disease observed in vivo and that the concentration of the mucociliary inhibitor in serum and fibroblast medium preparations from cystic fibrosis heterozygotes is approximately one-half of that in serum and fibroblast medium preparations from homozygotes.