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Antibodies raised in animals against the Streptococcus agalactiae proteins c alpha and R4 and normal human serum antibodies target distinct epitopes.

https://arctichealth.org/en/permalink/ahliterature9738
Source
J Med Microbiol. 2003 May;52(Pt 5):379-83
Publication Type
Article
Date
May-2003
Author
Sylvester R Moyo
Johan A Maeland
Author Affiliation
Department of Medical Microbiology, Faculty of Medicine, University of Zimbabwe Medical School, PO Box A178, Avondale, Harare, Zimbabwe.
Source
J Med Microbiol. 2003 May;52(Pt 5):379-83
Date
May-2003
Language
English
Publication Type
Article
Keywords
Animals
Antibodies, Bacterial - biosynthesis - blood - immunology
Antibodies, Monoclonal - immunology
Antibody Specificity
Antigens, Bacterial - immunology
Bacterial Proteins - immunology
Blotting, Western
Enzyme-Linked Immunosorbent Assay
Epitopes - immunology
Female
Heat
Humans
Immune Sera - immunology
Mice
Mice, Inbred BALB C
Norway
Pregnancy
Pregnancy Complications, Infectious - immunology
Protein Denaturation
Rabbits
Research Support, Non-U.S. Gov't
Sodium Dodecyl Sulfate - chemistry
Streptococcal Infections - immunology
Streptococcus agalactiae - immunology
Zimbabwe
Abstract
The targets for normal human serum antibodies that react with proteins c(alpha) and R4 isolated from group B streptococci (GBS; Streptococcus agalactiae) have been studied and compared with the targets for murine monoclonal and rabbit polyclonal antibodies raised against these proteins. The proteins were extracted by trypsin digestion and purified by precipitations and gel filtration and testing was based on enzyme immunoassays. The immune antibodies showed specificity for the corresponding protein, targeted that protein in Western blotting and recognized their targets after heat treatment (100 degrees C) of the proteins. Human antibodies in a commercial gammaglobulin preparation targeted a site(s) common to c(alpha) and R4. This target failed to bind the antibodies in Western blotting and was destroyed by heating. c(alpha)- and R4-reactive antibodies in sera from healthy pregnant women recognized the common, heat-labile determinant(s), but contained little or no antibodies against the heat-stable c(alpha)- or R4-specific determinants. These results are consistent with the notions that (i) the normal human antibodies and the immunization-induced animal antibodies targeted different sites on the c(alpha) and R4 proteins and that (ii) the natural human antibodies targeted conformational epitopes and the immune antibodies targeted linear epitopes. These findings are important for further clarification of GBS immunology and immunoprotection in humans.
PubMed ID
12721312 View in PubMed
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Cold adaptation of enzymes: structural, kinetic and microcalorimetric characterizations of an aminopeptidase from the Arctic psychrophile Colwellia psychrerythraea and of human leukotriene A(4) hydrolase.

https://arctichealth.org/en/permalink/ahliterature156329
Source
Biochim Biophys Acta. 2008 Nov;1784(11):1865-72
Publication Type
Article
Date
Nov-2008
Author
Adrienne L Huston
Jesper Z Haeggström
Georges Feller
Author Affiliation
Laboratory of Biochemistry, University of Liège, B-4000 Liège-Sart Tilman, Belgium.
Source
Biochim Biophys Acta. 2008 Nov;1784(11):1865-72
Date
Nov-2008
Language
English
Publication Type
Article
Keywords
Adaptation, Physiological
Alteromonadaceae - enzymology
Amino Acid Sequence
Aminopeptidases - chemistry - isolation & purification - metabolism - physiology
Arctic Regions
Calorimetry, Differential Scanning
Cold Temperature
Epoxide Hydrolases - chemistry - isolation & purification - metabolism - physiology
Fluorescence
Humans
Kinetics
Protein Conformation
Protein Denaturation
Protein Folding
Structure-Activity Relationship
Thermodynamics
Abstract
The relationships between structure, activity, stability and flexibility of a cold-adapted aminopeptidase produced by a psychrophilic marine bacterium have been investigated in comparison with a mesophilic structural and functional human homolog. Differential scanning calorimetry, fluorescence monitoring of thermal- and guanidine hydrochloride-induced unfolding and fluorescence quenching were used to show that the cold-adapted enzyme is characterized by a high activity at low temperatures, a low structural stability versus thermal and chemical denaturants and a greater structural permeability to a quenching agent relative to the mesophilic homolog. These findings support the hypothesis that cold-adapted enzymes maintain their activity at low temperatures as a result of increased global or local structural flexibility, which results in low stability. Analysis of the thermodynamic parameters of irreversible thermal unfolding suggests that entropy-driven factors are responsible for the fast unfolding rate of the cold-adapted aminopeptidase. A reduced number of proline residues, a lower degree of hydrophobic residue burial and a decreased surface accessibility of charged residues may be responsible for this effect. On the other hand, the reduction in enthalpy-driven interactions is the primary determinant of the weak conformational stability.
PubMed ID
18599387 View in PubMed
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Comparative Evaluation on the Quality and Shelf life of Atlantic Salmon (Salmo salar L.) Filets Using Microwave and Conventional Pasteurization in Combination with Novel Packaging Methods.

https://arctichealth.org/en/permalink/ahliterature297844
Source
J Food Sci. 2018 Dec; 83(12):3099-3109
Publication Type
Journal Article
Date
Dec-2018
Author
Jørgen Lerfall
Anita Nordeng Jakobsen
Dagbjørn Skipnes
Lene Waldenstrøm
Sunniva Hoel
Bjørn Tore Rotabakk
Author Affiliation
Dept. of Biotechnology and Food Science, Norwegian Univ. of Science and Technology (NTNU), NO-7491, Trondheim, Norway.
Source
J Food Sci. 2018 Dec; 83(12):3099-3109
Date
Dec-2018
Language
English
Publication Type
Journal Article
Keywords
Adult
Animals
Carbon Dioxide - metabolism
Color
Consumer Behavior
Female
Food contamination - analysis
Food Handling
Food Microbiology
Food Packaging
Food Quality
Food Storage
Hot Temperature
Humans
Male
Microwaves
Norway
Pasteurization
Protein Denaturation
Salmo salar - microbiology
Seafood - analysis - microbiology
Surveys and Questionnaires
Taste
Vacuum
Young Adult
Abstract
A comparative evaluation on the effect of carbon dioxide (CO2 ) on quality and shelf life of Atlantic salmon loins pasteurized with microwave and conventional technology was conducted. The experimental design allowed CO2 to enter the salmon muscle before (soluble gas stabilization [SGS] + vacuum) or after pasteurization (CO2 emitter + vacuum), whereas the control samples (vacuum only) were not presented for CO2 . This setup resulted in six different groups; three heated with microwaves and three with conventional pasteurization. The core temperature of microwave samples was 58.8 ± 2.2 °C, whereas the surface temperature was equal to the oven temperature (62 °C) during conventional pasteurization and close to the core temperature during microwave pasteurization (57.6 ± 1.4 °C). Microwave-heated samples showed higher microbial growth; decreased shelf life; and darker (lower L* -value), more reddish (higher a* -value), and yellowish (higher b* -value) colors compared to conventional-heated salmon. Lowest liquid loss (LL) was observed in salmon packaged with the CO2 emitter, whereas a SGS step prior to pasteurization did not affect the LL negatively as compared to samples packaged in vacuum only. Treatment with CO2 , independent of the prestep using SGS or an emitter, resulted in increased shelf life. Protein denaturation, microbial growth, product color, product shelf life, and sensory properties of the salmon loin were significantly affected by the applied pasteurization method (microwave- or conventional pasteurization). However, the heat load was probably too high to detect differences resulting from the pretreatment using SGS or packaging with CO2 emitter. PRACTICAL APPLICATION: Recent developments with increased time pressure from both work and past time activities have led to a tremendous increase in the demand for convenient, tasty ready-to-use food options. Furthermore, contemporary trends for consumption of fresh or lightly processed seafood stress the need to develop processing methods that allow a fulfillment of these demands, while still offering a reasonable shelf life. Carbon dioxide in combination with either microwave or conventional pasteurization is innovative processing technology that can meet consumer's demand of such products.
PubMed ID
30440091 View in PubMed
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[Denaturation stabilization of alpha-amylase from Aspergillus oryzae]

https://arctichealth.org/en/permalink/ahliterature13264
Source
Ukr Biokhim Zh. 1975 Jul-Aug;47(4):453-7
Publication Type
Article
Author
O S Tsyperovych
I P Halych
L O Kloesnyk
H H Artyukh
Source
Ukr Biokhim Zh. 1975 Jul-Aug;47(4):453-7
Language
Ukrainian
Publication Type
Article
Keywords
Amylases - isolation & purification - metabolism
Aspergillus - enzymology
Aspergillus oryzae - enzymology
Binding Sites
Calcium - pharmacology
Drug Stability
English Abstract
Heat
Kinetics
Protein Binding
Protein Denaturation
Urea - pharmacology
Abstract
Denaturation of alpha-amylase from Aspergillus oryzae was studied under the effect of heating urea and some other denaturating agents. Inhibition in the enzyme denaturation, deviation from the first order equation and, consequently, establishment of the false equilibrium in the system are shown. The values are calculated for the reaction rate constants of alpha-amylase denaturation under the effect to heat (40 degrees C) and urea. A method is developed for isolating native amylase stabilized by heating at 40 degrees C during the period of inactivation slowing down and preservation to the 50-70% activity in the system. It is shown that in the presence of calcium ions the stability of the isolated native enzyme is 13.0 +/- 2.5% hihger on the average to heating up to 40 degrees C, 28.4 %/- 7.2% higher - to the effect of 5.5 M urea and 18.4 +/- 3.6% higher - to 18% alcohol.
PubMed ID
1209773 View in PubMed
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Destabilization of Ca2+-free gelsolin may not be responsible for proteolysis in Familial Amyloidosis of Finnish Type.

https://arctichealth.org/en/permalink/ahliterature195582
Source
Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2334-9
Publication Type
Article
Date
Feb-27-2001
Author
G. Ratnaswamy
M E Huff
A I Su
S. Rion
J W Kelly
Author Affiliation
Department of Chemistry and the Skaggs Institute of Chemical Biology, Scripps Research Institute, 10550 North Torrey Pines Road (MB12), La Jolla, CA 92037, USA.
Source
Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2334-9
Date
Feb-27-2001
Language
English
Publication Type
Article
Keywords
Amyloidosis - ethnology - genetics - metabolism
Calcium - metabolism
Circular Dichroism
Finland
Gelsolin - chemistry - genetics - metabolism
Genetic Predisposition to Disease
Humans
Hydrolysis
Models, Molecular
Mutation
Protein Conformation
Protein Denaturation
Spectrometry, Fluorescence
Thermodynamics
Urea - chemistry
Abstract
Mutations at position 187 in secreted gelsolin enable aberrant proteolysis at the 172-173 and 243-244 amide bonds, affording the 71-residue amyloidogenic peptide deposited in Familial Amyloidosis of Finnish Type (FAF). Thermodynamic comparisons of two different domain 2 constructs were carried out to study possible effects of the mutations on proteolytic susceptibility. In the construct we consider to be most representative of domain 2 in the context of the full-length protein (134-266), the D187N FAF variant is slightly destabilized relative to wild type (WT) under the conditions of urea denaturation, but exhibits a T(m) identical to WT. The D187Y variant is less stable to intermediate urea concentrations and exhibits a T(m) that is estimated to be approximately 5 degrees C lower than WT (pH 7.4, Ca(2+)-free). Although the thermodynamic data indicate that the FAF mutations may slightly destabilize domain 2, these changes are probably not sufficient to shift the native to denatured state equilibrium enough to enable the proteolysis leading to FAF. Biophysical data indicate that these two FAF variants may have different native state structures and possibly different pathways of amyloidosis.
Notes
Cites: Hum Mol Genet. 1996 Sep;5(9):1237-438872462
Cites: Cell. 1996 Sep 6;86(5):699-7028797816
Cites: Nature. 1997 Feb 27;385(6619):787-939039909
Cites: Chem Biol. 1997 Feb;4(2):119-259190286
Cites: Cell. 1997 Aug 22;90(4):661-709288746
Cites: Biochemistry. 1997 Dec 16;36(50):15848-559398317
Cites: Amyloid. 1998 Mar;5(1):55-669547007
Cites: Proc Natl Acad Sci U S A. 1998 May 26;95(11):6448-539600986
Cites: Prog Biophys Mol Biol. 1999;71(2):155-24110097615
Cites: Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3590-410097081
Cites: Chem Biol. 1999 May;6(5):293-30410322122
Cites: Biochemistry. 1999 Jul 13;38(28):8972-8010413470
Cites: Nat Struct Biol. 1999 Sep;6(9):876-8310467101
Cites: Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11247-5210500162
Cites: Science. 1999 Dec 3;286(5446):1939-4210583954
Cites: Biochemistry. 2000 May 9;39(18):5322-3110820002
Cites: Biochemistry. 2000 Sep 26;39(38):11677-8310995235
Cites: Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):10706-1110995458
Cites: Biochemistry. 1970 Dec 8;9(25):5015-234991411
Cites: Science. 1997 Jan 31;275(5300):630-19019820
Cites: Nature. 1986 Oct 2-8;323(6087):455-83020431
Cites: Methods Enzymol. 1986;131:266-803773761
Cites: Bioessays. 1987 Oct;7(4):176-92825660
Cites: J Mol Biol. 1988 Oct 20;203(4):1127-332850369
Cites: Biochemistry. 1988 Oct 18;27(21):8069-743233196
Cites: FEBS Lett. 1990 Jan 15;260(1):85-72153578
Cites: EMBO J. 1990 Dec;9(12):4103-92174356
Cites: FEBS Lett. 1990 Dec 10;276(1-2):75-72176164
Cites: Biochemistry. 1991 Sep 10;30(36):8753-81653607
Cites: Adv Hum Genet. 1991;20:69-123, 309-111839349
Cites: J Biol Chem. 1992 Jul 25;267(21):14616-211321812
Cites: Biochemistry. 1992 Aug 4;31(30):6865-701637821
Cites: Biochemistry. 1992 Sep 15;31(36):8654-601390650
Cites: Biophys J. 1993 Aug;65(2):799-8058218904
Cites: Lab Invest. 1994 Apr;70(4):558-648176895
Cites: Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5446-508202506
Cites: Biophys J. 1994 Sep;67(3):1216-287811936
Cites: Crit Rev Clin Lab Sci. 1994;31(4):325-547888076
Cites: Adv Protein Chem. 1995;46:217-477771319
Cites: Protein Sci. 1995 Oct;4(10):2138-488535251
Cites: Curr Opin Struct Biol. 1996 Feb;6(1):11-78696966
Cites: Biochemistry. 1996 Jul 30;35(30):9700-98703941
Comment In: Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2117-811226199
PubMed ID
11226240 View in PubMed
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Dietary caloric restriction may delay the development of cataract by attenuating the oxidative stress in the lenses of Brown Norway rats.

https://arctichealth.org/en/permalink/ahliterature50661
Source
Exp Eye Res. 2004 Jan;78(1):151-8
Publication Type
Article
Date
Jan-2004
Author
Keyang Wang
Dayu Li
Fang Sun
Author Affiliation
Department of Ophthalmology, College of Physicians and Surgeons of Columbia University, New York, NY 10032-3702, USA. kw32@columbia.edu
Source
Exp Eye Res. 2004 Jan;78(1):151-8
Date
Jan-2004
Language
English
Publication Type
Article
Keywords
Aging - metabolism
Animals
Ascorbic Acid - metabolism
Caloric Restriction
Cataract - metabolism - prevention & control
Chromatography, High Pressure Liquid
Crystallins - chemistry - metabolism
Glutathione - metabolism
Lens, Crystalline - metabolism
Male
Oxidative Stress - physiology
Protein Denaturation
Rats
Rats, Inbred BN
Research Support, Non-U.S. Gov't
Solubility
Sulfhydryl Compounds - metabolism
Abstract
Dietary caloric restriction (CR) is the only experimental intervention that can reliably retard the development of cataract in a normal animal model. Here we have studied the possible mechanisms by which CR retards the age-related degeneration of the lens of Brown Norway rats. We have found that CR slowed protein insolubilization and blunted declines of the total soluble thiols, protein thiols, reduced glutathione and ascorbic acid levels in the lenses of old BN rats. From the lens protein point of view, the development of cataract in rat lenses has 3 stages: (1) the precipitation of gamma-crystallin, (2) the insolubilization of beta-crystallin, and (3) the final precipitation of alpha-crystallin which was saturated with other denatured lens proteins. A similar sequence is also observed when the lens proteins are subjected to oxidative stress in vitro. These data are the first to suggest that CR may retard the age-related degeneration of the lens by attenuating the oxidative stress in the lens. Since oxidative stress is likely a main cause of human cataract, CR intervention may be relevant to humans as well.
PubMed ID
14667836 View in PubMed
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Effect of lipid matrix and cytoskeleton proteins on Ca2+-activated K+ channels in erythrocytes of alcoholic and II type diabetes mellitus patients.

https://arctichealth.org/en/permalink/ahliterature47442
Source
Bull Exp Biol Med. 2002 Oct;134(4):345-8
Publication Type
Article
Date
Oct-2002
Author
V D Prokop'eva
I V Petrova
A V Sitozhevskii
S V Kremeno
V I Koryukin
M B Baskakov
N A Bokhan
V V Novitskii
Author Affiliation
Siberian State Medical University, Tomsk, Russia.
Source
Bull Exp Biol Med. 2002 Oct;134(4):345-8
Date
Oct-2002
Language
English
Publication Type
Article
Keywords
Alcoholism - blood
Calcium - blood
Cell Membrane Permeability
Comparative Study
Cytoskeletal Proteins - metabolism
Diabetes Mellitus, Type 2 - blood - metabolism
Erythrocyte Membrane - metabolism
Erythrocyte Volume
Erythrocytes - metabolism
Humans
Hydrogen-Ion Concentration
Lipids - blood
Osmolar Concentration
Potassium Channels - metabolism
Protein Denaturation
Abstract
We studied the effect of changes in erythrocyte volume and irreversible thermal denaturation of cytoskeleton proteins and lipid matrix on activity of Ca(2+)-activated K+ channels in erythrocytes of alcoholic and patients with II type diabetes mellitus. Changes in Ca(2+)-dependent potassium permeability of erythrocyte membrane in alcoholic patients and patients with II type diabetes mellitus are related to modification of cytoskeleton, rather than to changes in lipid matrix.
PubMed ID
12533755 View in PubMed
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Functional expression of human mutant phosphofructokinase in yeast: genetic defects in French Canadian and Swiss patients with phosphofructokinase deficiency.

https://arctichealth.org/en/permalink/ahliterature216343
Source
Am J Hum Genet. 1995 Jan;56(1):131-41
Publication Type
Article
Date
Jan-1995
Author
N. Raben
R. Exelbert
R. Spiegel
J B Sherman
H. Nakajima
P. Plotz
J. Heinisch
Author Affiliation
Arthritis and Rheumatism Branch, National Institute of Arthritis, Musculoskeletal, and Skin Diseases, National Institutes of Health, Bethesda, MD 20892.
Source
Am J Hum Genet. 1995 Jan;56(1):131-41
Date
Jan-1995
Language
English
Publication Type
Article
Keywords
Adult
Alleles
Base Sequence
Canada
Catalysis
Enzyme Induction
Female
France - ethnology
Glycogen Storage Disease Type VII - genetics
Hot Temperature
Humans
Male
Molecular Sequence Data
Phosphofructokinase-1 - biosynthesis - chemistry - deficiency - genetics
Point Mutation
Protein Denaturation
Recombinant Fusion Proteins - biosynthesis - chemistry
Saccharomyces cerevisiae - genetics
Switzerland
Abstract
Human phosphofructokinase (PFK) is a tetrameric enzyme, encoded by muscle, liver, and platelet genes. Deficiency of muscle PFK (PFK-M), glycogenosis type VII (Tarui disease), is an autosomal recessive disorder characterized by an exertional myopathy and hemolytic syndrome. Several disease-causing mutations have been identified in the PFK-M gene in Japanese, Ashkenazi Jewish, and Italian patients. We describe the genetic defects in French Canadian and Swiss patients with the disease, and we use a genetically well-defined yeast system devoid of endogenous PFK for structure-function studies of the mutant PFKs. A G-to-A transition at codon 209-in exon 8 of the PFK-M gene, changing an encoded Gly to Asp, is responsible for the disease in a homozygous French Canadian patient. Gly-209-mutated protein is completely inactive in the yeast system. The Swiss patient is a genetic compound, carrying a G-to-A transition at codon 100 in exon 6 (Arg to Gln) and a G-to-A transition at codon 696 in exon 22 (Arg to His). The mutants expressed in yeast generate functional enzyme with modest changes in thermal stability. The advantages and limitations of the yeast system for expression of human mutant PFKs are discussed.
Notes
Cites: FEBS Lett. 1991 Sep 2;289(1):77-821832648
Cites: Biotechniques. 1994 Sep;17(3):412, 4147818886
Cites: J Biol Chem. 1993 Mar 5;268(7):4963-78444874
Cites: Hum Genet. 1993 Apr;91(3):241-48478007
Cites: Hum Mutat. 1992;1(6):445-661301956
Cites: Anal Biochem. 1993 May 1;210(2):235-447685563
Cites: J Biol Chem. 1994 Mar 25;269(12):8911-88132627
Cites: Am J Hum Genet. 1994 May;54(5):812-97513946
Cites: Arch Neurol. 1967 Nov;17(5):512-234228297
Cites: J Biol Chem. 1972 Dec 10;247(23):7502-94264130
Cites: Biochemistry. 1973 Oct 23;12(22):4303-94270764
Cites: Blood. 1979 Aug;54(2):389-400156568
Cites: Blood. 1981 Apr;57(4):724-326451249
Cites: Neurology. 1981 Sep;31(9):1077-866943439
Cites: Philos Trans R Soc Lond B Biol Sci. 1981 Jun 26;293(1063):53-626115424
Cites: Somatic Cell Genet. 1982 Jan;8(1):95-1046213050
Cites: Hum Genet. 1983;63(4):374-96222962
Cites: Mol Cell Biochem. 1983;52(1):75-916306441
Cites: Mol Cell Biochem. 1983;57(2):147-546228716
Cites: Nature. 1984 May 31-Jun 6;309(5967):467-96233492
Cites: Nucleic Acids Res. 1985 May 10;13(9):3131-454000972
Cites: Hum Genet. 1986 Sep;74(1):34-402944814
Cites: Biochem J. 1987 Mar 15;242(3):667-712954542
Cites: Anal Biochem. 1987 Apr;162(1):156-92440339
Cites: FEBS Lett. 1987 Oct 19;223(1):113-62822475
Cites: J Clin Invest. 1987 Nov;80(5):1479-852960695
Cites: Methods Enzymol. 1987;155:501-273431470
Cites: Neurology. 1988 Jun;38(6):956-602966901
Cites: Yeast. 1986 Sep;2(3):163-73333305
Cites: Gene. 1989 Mar 15;76(1):167-92526044
Cites: Gene. 1989 Apr 15;77(1):177-832526045
Cites: Biochem Biophys Res Commun. 1990 Jan 30;166(2):637-412137340
Cites: Nature. 1990 May 31;345(6274):444-62342576
Cites: J Biol Chem. 1990 Jun 5;265(16):9006-102140567
Cites: J Biol Chem. 1990 Jun 5;265(16):9392-52140573
Cites: Biochem Biophys Res Commun. 1990 Dec 31;173(3):1317-212148476
Cites: Gene. 1991 Aug 15;104(2):277-821833270
Cites: Neurology. 1994 Jun;44(6):1097-1008208408
Cites: Am J Hum Genet. 1994 Aug;55(2):305-138037209
Cites: Mol Microbiol. 1993 Nov;10(4):867-767934848
Cites: Biochemistry. 1991 Feb 12;30(6):1478-841825177
PubMed ID
7825568 View in PubMed
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Hereditary nonpolyposis colorectal cancer families not complying with the Amsterdam criteria show extremely low frequency of mismatch-repair-gene mutations.

https://arctichealth.org/en/permalink/ahliterature21978
Source
Am J Hum Genet. 1997 Aug;61(2):329-35
Publication Type
Article
Date
Aug-1997
Author
J. Wijnen
P M Khan
H. Vasen
H. van der Klift
A. Mulder
I. van Leeuwen-Cornelisse
B. Bakker
M. Losekoot
P. Møller
R. Fodde
Author Affiliation
MGC-Department of Human Genetics, Medical Genetics Center, Leiden University, The Netherlands.
Source
Am J Hum Genet. 1997 Aug;61(2):329-35
Date
Aug-1997
Language
English
Publication Type
Article
Keywords
Carrier Proteins
Case-Control Studies
Colorectal Neoplasms, Hereditary Nonpolyposis - enzymology - ethnology - genetics
Czech Republic
DNA Repair - genetics
DNA-Binding Proteins
Denmark
Electrophoresis, Polyacrylamide Gel - methods
Germ-Line Mutation
Humans
Italy
Microsatellite Repeats
MutS Homolog 2 Protein
Neoplasm Proteins - genetics
Netherlands
Nuclear Proteins
Nucleic Acid Heteroduplexes
Protein Denaturation
Proto-Oncogene Proteins - genetics
Reference Standards
Research Support, Non-U.S. Gov't
Abstract
Hereditary nonpolyposis colorectal cancer (HNPCC) is a common autosomal dominant cancer-susceptibility condition characterized by early onset colorectal cancer. Germ-line mutations in one of four DNA mismatch repair (MMR) genes, hMSH2, hMLH1, hPMS1, or hPMS2, are known to cause HNPCC. Although many mutations in these genes have been found in HNPCC kindreds complying with the so-called Amsterdam criteria, little is known about the involvement of these genes in families not satisfying these criteria but showing clear-cut familial clustering of colorectal cancer and other cancers. Here, we applied denaturing gradient-gel electrophoresis to screen for hMSH2 and hMLH1 mutations in two sets of HNPCC families, one set comprising families strictly complying with the Amsterdam criteria and another set in which at least one of the criteria was not satisfied. Interestingly, hMSH2 and hMLH1 mutations were found in 49% of the kindreds fully complying with the Amsterdam criteria, whereas a disease-causing mutation could be identified in only 8% of the families in which the criteria were not satisfied fully. In correspondence with these findings, 4 of 6 colorectal tumors from patients belonging to kindreds meeting the criteria showed microsatellite instability, whereas only 3 of 11 tumors from the other set of families demonstrated this instability. Although the number of tumors included in the study admittedly is small, the frequencies of mutations in the MMR genes show obvious differences between the two clinical sets of families. These results also emphasize the practical importance of the Amsterdam criteria, which provide a valid clinical subdivision between families, on the basis of their chance of carrying an hMSH2 or an hMLH1 mutation, and which bear important consequences for genetic testing and counseling and for the management of colorectal cancer families.
PubMed ID
9311737 View in PubMed
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14 records – page 1 of 2.