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Articles 44491 - 44520 of 45108

Full-Text Articles in Medicine and Health Sciences

The Creation Of Transgenic Animal “Models” For Human Genetic Disease, Bernard Rollin Jan 1992

The Creation Of Transgenic Animal “Models” For Human Genetic Disease, Bernard Rollin

Biomedicine and Animal Models in Research Collection

Transgenic animals will be created to study human genetic disease as soon as the technological capability exists to do so. Extant laws permit such animals to be created. The mindset of the research community makes it inevitable. It is also clear that such diseases can cause enormous amounts of pain and suffering. Responsible researchers need to explore all possible avenues for controlling such pain and suffering. Thus far the research community has not engaged this issue vis a vis animals. The development of methodologies for controlling pain and suffering is likely to be exportable to numerous areas of animal research, …

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Family Physicians, Chiropractors, And Back Pain, Peter Curtis, Geoffrey M. Bove Jan 1992

Family Physicians, Chiropractors, And Back Pain, Peter Curtis, Geoffrey M. Bove

Biomedical Sciences Faculty Publications

In this article, major aspects of back care provided to patients by family physicians and chiropractors are reviewed, and the recent guidelines on spinal manipulation therapy are discussed. These guidelines should be useful for family physicians wishing to refer patients to chiropractors.

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Phosphorylation Of The Rex Protein Of Human T-Cell Leukemia Virus Type 1, Yoshifumi Adachi, Terry D. Copeland, Chiaki Takahashi, Tetsuya Nosaka, Aftab Ahmed, Stephen Oroszlan, Masakazu Hatanaka Jan 1992

Phosphorylation Of The Rex Protein Of Human T-Cell Leukemia Virus Type 1, Yoshifumi Adachi, Terry D. Copeland, Chiaki Takahashi, Tetsuya Nosaka, Aftab Ahmed, Stephen Oroszlan, Masakazu Hatanaka

Pharmacy Faculty Articles and Research

Rex protein, the posttranscriptional regulator of human T-cell leukemia virus type I (HTLV-I), is required for the control of viral structural protein expression and virus replication. Rex is a phosphoprotein found predominantly in the cell nucleolus, whose function is thought to be regulated by its nucleolar localization and phosphorylation. Therefore, we investigated the in vivo phosphorylation of Rex protein in more detail. Phosphorylation of Rex occurred in all HTLV-I-infected cell lines examined in vivo, primarily at serine residues and to a very small extent at threonine residues. Treatment of cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) led to significant but transient enhancement of …

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[Project Proposal] Microscopic Analysis Of Intracranial Aneurysm Wall And Its Parent Arteries, George Austin, Steve Fisher Jan 1992

[Project Proposal] Microscopic Analysis Of Intracranial Aneurysm Wall And Its Parent Arteries, George Austin, Steve Fisher

The Dr. George M. Austin Neurology Research Collection

Microscopic Analysis of Intracranial Aneurysm Wall and its Parent Arteries. George Austin, M.D., Steve Fisher, M.D., N.d. [1992 or later] Project proposal. 7 pg.

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Bibliography, George M. Austin (1992), George M. Austin Jan 1992

Bibliography, George M. Austin (1992), George M. Austin

The Dr. George M. Austin Neurology Research Collection

Bibliography, 169 entries 14 pg., last entry is for 1992

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Priming Of Peripheral Lymph Node B Cells With Tnp-Ficoll: Role Of Lymphokines In B Cell Differentiation, S. Niranjan Goud, Alan M. Kaplan, Subbarao Bondada Jan 1992

Priming Of Peripheral Lymph Node B Cells With Tnp-Ficoll: Role Of Lymphokines In B Cell Differentiation, S. Niranjan Goud, Alan M. Kaplan, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

We have previously shown that peripheral lymph node (PLN) B lymphocytes of adult DBA/ 25 mice failed to make an antibody responseto type 2 antigen TNP-Ficoll, but exhibited a good antibody response to type 1 antigen TNP-BruceNa abortus. In the present study we wanted to find out whether the unresponsivenessof PLN B cells to TNP-Ficoll is due to defectsin the early activation and proliferation stage or in the final differentiation stageof B cells. Therefore, we have used a two-step protocol of in vivo immunization of mice with TNP-Ficoll and the subsequent in vitro challenge with TNP-Brucella abortus and studied the …

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Purification Of Core-Binding Factor, A Protein That Binds The Conserved Core Site In Murine Leukemia Virus Enhancers., Shuwen W. Wang, Nancy A. Speck Jan 1992

Purification Of Core-Binding Factor, A Protein That Binds The Conserved Core Site In Murine Leukemia Virus Enhancers., Shuwen W. Wang, Nancy A. Speck

Dartmouth Scholarship

The Moloney murine leukemia virus causes thymic leukemias when injected into newborn mice. A major genetic determinant of the thymic disease specificity of the Moloney virus genetically maps to two protein binding sites in the Moloney virus enhancer, the leukemia virus factor b site and the adjacent core site. Point mutations introduced into either of these sites significantly shifts the disease specificity of the Moloney virus from thymic leukemia to erythroleukemia (N. A. Speck, B. Renjifo, E. Golemis, T. Frederickson, J. Hartley, and N. Hopkins, Genes Dev. 4:233-242, 1990). We have purified several polypeptides that bind to the core site …

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Altered Expression Of Adenovirus 12 Dna-Binding Protein But Not Dna Polymerase During Abortive Infection Of Hamster Cells, Lynne A. Lucher, Benjawan Khuntirat, Jiansheng Zhao, Peter C. Angeletti Jan 1992

Altered Expression Of Adenovirus 12 Dna-Binding Protein But Not Dna Polymerase During Abortive Infection Of Hamster Cells, Lynne A. Lucher, Benjawan Khuntirat, Jiansheng Zhao, Peter C. Angeletti

Nebraska Center for Virology: Faculty Publications

Replication of human adenovirus type 12 DNA is blocked in abortively infected baby hamster kidney cells. The activity and accumulation of adenovirus 12 DNA polymerase is equivalent in infected hamster and human cell extracts. However, the accumulation of adenovirus type 12 DNA-binding protein is approximately 120-fold lower in extracts from infected hamster cells when compared to infected permissive human cells. This difference in accumulation is not because of replication of viral DNA during productive infection, since this difference is observed in the presence of hydroxyurea. The DNA-binding protein from infected hamster cells retains the ability to bind denatured DNA-cellulose. An …

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Faculty Publications 1991, Lsu Health Sciences Center New Orleans Jan 1992

Faculty Publications 1991, Lsu Health Sciences Center New Orleans

Historical Faculty Publications

This Faculty bibliography contains 580 publications.

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Multiple Alleles And Estimation Of Genetic Parameters: Computational Equations Showing Involvement Of All Alleles, R Chakraborty Jan 1992

Multiple Alleles And Estimation Of Genetic Parameters: Computational Equations Showing Involvement Of All Alleles, R Chakraborty

Faculty, Staff and Student Publications

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year‐on‐year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non‐vesicular extracellular particles, characterisation and functional …

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The Ability Of Simian Virus 40 Large T Antigen To Immortalize Primary Mouse Embryo Fibroblasts Cosegregates With Its Ability To Bind To P53., Jiyue Y. Zhu, Marina Abate, Philip W. Rice, Charles N. Cole Dec 1991

The Ability Of Simian Virus 40 Large T Antigen To Immortalize Primary Mouse Embryo Fibroblasts Cosegregates With Its Ability To Bind To P53., Jiyue Y. Zhu, Marina Abate, Philip W. Rice, Charles N. Cole

Dartmouth Scholarship

The large T antigen encoded by simian virus 40 (SV40) plays essential roles in the infection of permissive cells, leading to production of progeny virions, and in the infection of nonpermissive cells, leading to malignant transformation. Primary mouse embryo fibroblasts (MEFs) are nonpermissive for SV40, and infection by wild-type SV40 leads to immortalization and transformation of a small percentage of infected cells. We examined the ability of an extensive set of mutants whose lesions affect SV40 large T antigen to immortalize MEFs. We found that immortalization activity was retained by all mutants whose lesions are located upstream of codon 346. …

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Validity Of Intelligence Test Scores In The Definition Of Learning Disability: A Critical Analysis, D. J. Francis, K. A. Espy, B. P. Rourke, J. M. Fletcher Nov 1991

Validity Of Intelligence Test Scores In The Definition Of Learning Disability: A Critical Analysis, D. J. Francis, K. A. Espy, B. P. Rourke, J. M. Fletcher

Developmental Cognitive Neuroscience Laboratory: Faculty Publications

The relationship of intelligence test performance to learning deficiency is a longstanding issue affecting treatment and research on learning disabled children. Despite many questions concerning the use of intelligence tests for classifying disabled learners, these tests have become entrenched in every form of work with these children (Kaufman, 1979; Sattler, 1988).

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Fc Receptors For Igg (Fc Gamma Rs) On Human Monocytes And Macrophages Are Not Infectivity Receptors For Human Immunodeficiency Virus Type 1 (Hiv-1): Studies Using Bispecific Antibodies To Target Hiv-1 To Various Myeloid Cell Surface Molecules, Including The Fc Gamma R., R I. Connor, N B. Dinces, A L. Howell, J L. Romet-Lemonne, J L. Pasquali, M W. Fanger Nov 1991

Fc Receptors For Igg (Fc Gamma Rs) On Human Monocytes And Macrophages Are Not Infectivity Receptors For Human Immunodeficiency Virus Type 1 (Hiv-1): Studies Using Bispecific Antibodies To Target Hiv-1 To Various Myeloid Cell Surface Molecules, Including The Fc Gamma R., R I. Connor, N B. Dinces, A L. Howell, J L. Romet-Lemonne, J L. Pasquali, M W. Fanger

Dartmouth Scholarship

Fc gamma Rs (Fc gamma RI, Fc gamma RII, and Fc gamma RIII) are highly expressed on human mononuclear phagocytes and function in the clearance of immune complexes and opsonized pathogens. We have examined the role of Fc gamma R in mediating antibody-dependent clearance of HIV-1 by human monocytes and monocyte-derived macrophages by using bispecific antibodies (BsAbs) to independently target the virus to Fc gamma RI, Fc gamma RII, or Fc gamma RIII. Virus production was markedly reduced in monocytes cultured with strain HIV-1IIIB opsonized with BsAbs that target the virus to either Fc gamma RI or Fc gamma RII …

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Statistical Interpretation Of Dna Typing Data, R Chakraborty Oct 1991

Statistical Interpretation Of Dna Typing Data, R Chakraborty

Faculty, Staff and Student Publications

No abstract provided.

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Lac+ Saccharomyces Cerevisiae, Robert C. Dickson, Kotikanyadanam K. Sreekrishna Sep 1991

Lac+ Saccharomyces Cerevisiae, Robert C. Dickson, Kotikanyadanam K. Sreekrishna

Molecular and Cellular Biochemistry Faculty Patents

The invention relates to novel, transformed strains of Lac+ Saccharomyces cerevisiae, capable of utilizing lactose as a sole carbon source, produced by inserting into the Saccharomyces cerevisiae a plasmid containing a lactose permease and a beta-galactosidase gene derived from Kluyveromyces lactis yeast.

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Translocation Of The Glucose Transporter Glut4 In Cardiac Myocytes Of The Rat., Jan W. Slot, Hans J. Geuze, Sander Gigengack, David E. James, Gustav E. Lienhard Sep 1991

Translocation Of The Glucose Transporter Glut4 In Cardiac Myocytes Of The Rat., Jan W. Slot, Hans J. Geuze, Sander Gigengack, David E. James, Gustav E. Lienhard

Dartmouth Scholarship

The insulin-regulated glucose transporter GLUT4 was immunolocalized in rat cardiac muscle under conditions of basal and stimulated glucose uptake, achieved by fasting and a combined exercise/insulin stimulus, respectively. In basal myocytes there was very little (less than 1%) GLUT4 in the different domains of the plasma membrane (sarcolemma, intercalated disk, and transverse tubular system). GLUT4 was localized in small tubulo-vesicular elements that occur predominantly near the sarcolemma and the transverse tubular system and in the trans-Golgi region. Upon stimulation approximately 42% of GLUT4 was found in the plasma membrane. Each domain of the plasma membrane contributed equally to this effect. …

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Phenylbutyl Nitrone Compositions And Methods For Prevention Of Gastric Ulceration, Robert A. Floyd, John M. Carney Jul 1991

Phenylbutyl Nitrone Compositions And Methods For Prevention Of Gastric Ulceration, Robert A. Floyd, John M. Carney

Pharmacology and Nutritional Sciences Faculty Patents

Compositions containing PBN, or active derivatives thereof, in a suitable pharmaceutical carrier for administration to a patient, are disclosed for treating or preventing gastric ulceration caused by ingestion of non-steroidal anti-inflammatories. Based on animal studies, the dosage is in the range of 3 to 300 mg/kg and is administered prior to, simultaneously, or shortly after ingestion of the NSAID compound(s). In the preferred embodiment, the range is between 10 and 30 mg/kg, depending on the dosage unit required to protect the mucosa. The preferred method of administration is orally, alone or in combination with the non-steroidal anti-inflammatory. It is believed …

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Inclusion Of Data On Relatives For Estimation Of Allele Frequencies, R Chakraborty Jul 1991

Inclusion Of Data On Relatives For Estimation Of Allele Frequencies, R Chakraborty

Faculty, Staff and Student Publications

No abstract provided.

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Phenyl Butyl Nitrone Compositions And Methods For Treatment Of Oxidative Tissue Damage, John M. Carney, Robert A. Floyd Jun 1991

Phenyl Butyl Nitrone Compositions And Methods For Treatment Of Oxidative Tissue Damage, John M. Carney, Robert A. Floyd

Pharmacology and Nutritional Sciences Faculty Patents

Compositions for treating tissue damage from ischemia contain PBN, or active derivatives thereof, which are active during ischemia in preventing ATP depletion of the cells which predisposes them to subsequent injury during reperfusion, and which are active during reperfusion as oxygen radical scavengers, in a suitable pharmaceutical carrier for systemic or local administration, especially to the CNS, spinal column and eyes. Based on animal studies, the dosage for treating damage due to stroke is in the range of 10 to 300 mg/kg. Similar dosages are useful in treating damage resulting from free radical generation during inflammation, either as a product …

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Risk Assessment For Developmental Toxicity: Airborne Occupational Exposure To Ethanol And Iodine, Donald R. Mattison Jun 1991

Risk Assessment For Developmental Toxicity: Airborne Occupational Exposure To Ethanol And Iodine, Donald R. Mattison

RISK: Health, Safety & Environment (1990-2002)

Dean Mattison explains hazard identification, hazard characterization and exposure characterization as furnishing a foundation for Risk assessment generally. He then illustrates their application in assessing the fetal Risk posed by two common substances. Ultimately, he argues that only after Risks have been so examined can women of child bearing age (or anyone) decide what if any measures are appropriate to avoid them.

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Book Reviews, Thomas G. Field Jr. Jun 1991

Book Reviews, Thomas G. Field Jr.

RISK: Health, Safety & Environment (1990-2002)

Reviews of the following two books: VALUING HEALTH Risks. COSTS, AND BENEFITS FOR ENVIRONMENTAL DECISION MAKING (P. Brett Hammond and Rob Coppock, eds.) THE LIABILITY MAZE: THE IMPACT OF LIABILITY LAW ON SAFETY AND INNOVATION (Peter W. Huber And Robert E. Litan, eds.)

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Fertile Women May Now Apply: Fetal Protection Policies After Johnson Controls, Barbara Ruhe Grumet Jun 1991

Fertile Women May Now Apply: Fetal Protection Policies After Johnson Controls, Barbara Ruhe Grumet

RISK: Health, Safety & Environment (1990-2002)

In its recent interpretation of Title VII of the Civil Rights Act, the U.S. Supreme Court leaves little room for permissible occupational sex discrimination. However, its decision has wider implications. Here, Professor Grumet takes a look at some of them from both a legal and a social perspective, including matters such as employees' reproductive freedom and employers' potential liability for a variety of possible injuries to employees' offspring.

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The Effect Of Total-Body Irradiation On Corneal Neovascularization In The Fischer 344 Rat After Chemical Cauterization, M. W. Scroggs, A. D. Proia, C. F. Smith, E. C. Halperin, G. K. Klintworth Jun 1991

The Effect Of Total-Body Irradiation On Corneal Neovascularization In The Fischer 344 Rat After Chemical Cauterization, M. W. Scroggs, A. D. Proia, C. F. Smith, E. C. Halperin, G. K. Klintworth

Osteopathic Medicine, Jerry M. Wallace School of

No abstract provided.

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Effect Of Delays In Processing On The Survival Of Mycobacterium Avium-M. Intracellulare In The Isolator Blood Culture System., C. Fordham Von Reyn, Stephen Hennigan, Sandra Niemczyk, Nicholas J. Jacobs Jun 1991

Effect Of Delays In Processing On The Survival Of Mycobacterium Avium-M. Intracellulare In The Isolator Blood Culture System., C. Fordham Von Reyn, Stephen Hennigan, Sandra Niemczyk, Nicholas J. Jacobs

Dartmouth Scholarship

Concentrations of Mycobacterium avium-M. intracellulare ranging from 10(-1) to 10(3) CFU/ml were added to blood, placed in Isolator tubes, and held at room temperature for intervals ranging from 4 h to 56 days before being processed (centrifugation and culture on Middlebrook 7H10 agar). At all concentrations tested, M. avium-M. intracellulare was recovered after hold times ranging from 4 h to 7 days; the number of final CFU actually increased progressively for hold times of 8 h or more. Hold times of up to 7 days did not increase the time from processing to the first appearance of visible colonies. At …

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Cytolytic And Ion Channel Forming Properties Of The N-Terminus Of Lymphocyte Perforin, David M. Ojcius, Pedro M. Persechini, Li-Mou Zheng, Paulo C. Notaroberto, Sandro C. Adeodato, John Ding-E. Young Jun 1991

Cytolytic And Ion Channel Forming Properties Of The N-Terminus Of Lymphocyte Perforin, David M. Ojcius, Pedro M. Persechini, Li-Mou Zheng, Paulo C. Notaroberto, Sandro C. Adeodato, John Ding-E. Young

All Dugoni School of Dentistry Faculty Articles

Perforin lyses cells by binding to the target cell membrane, where it polymerizes into large nonspecific pores. It is shown here that the first 34 amino acids of the N-terminal region of either human or murine perforin are soluble in aqueous medium and spontaneously insert into membranes. The N-terminal peptides lyse liposomes and nucleated cells, and they form ion channels in planar bilayers, some of which are comparable to those previously described for perforin. The lytic activity of the N-terminal domains does not require calcium, is independent of the lipid headgroup composition, and can be inhibited by heparin. Tumor cells …

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Mapping The Transcriptional Transactivation Function Of Simian Virus 40 Large T Antigen., Jiyue Y. Zhu, Philip W. Rice, Michele Chamberlain, Charles N. Cole Jun 1991

Mapping The Transcriptional Transactivation Function Of Simian Virus 40 Large T Antigen., Jiyue Y. Zhu, Philip W. Rice, Michele Chamberlain, Charles N. Cole

Dartmouth Scholarship

T antigen is able to transactivate gene expression from the simian virus 40 (SV40) late promoter and from several other viral and cellular promoters. Neither the mechanisms of transactivation by T antigen nor the regions of T antigen required for this activity have been determined. To address the latter point, we have measured the ability of a set of SV40 large T antigen mutants to stimulate gene expression in CV-1 monkey kidney cells from the SV40 late promoter and Rous sarcoma virus (RSV) long terminal repeat (LTR) promoter. Transactivation, although reduced, was retained by an N-terminal 138-amino-acid fragment of T …

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Interleukin-2-Triggered Raf-1 Expression, Phosphorylation, And Associated Kinase Activity Increase Through G1 And S In Cd3-Stimulated Primary Human T Cells., Antanina Zmuidzinas, Harvey J. Mamon, Thomas M. Roberts, Kendall A. Smith May 1991

Interleukin-2-Triggered Raf-1 Expression, Phosphorylation, And Associated Kinase Activity Increase Through G1 And S In Cd3-Stimulated Primary Human T Cells., Antanina Zmuidzinas, Harvey J. Mamon, Thomas M. Roberts, Kendall A. Smith

Dartmouth Scholarship

To gain further insight into the role of Raf-1 in normal cell growth, c-raf-1 mRNA expression, Raf-1 protein production, and Raf-1-associated kinase activity in normal human T cells were analyzed. In contrast to the constitutive expression of Raf-1 in continuously proliferating cell lines, c-raf-1 mRNA and Raf-1 protein levels were barely detectable in freshly isolated G0 T lymphocytes. Previous work with fibroblasts has suggested that Raf-1 plays a signaling role in the G0-G1 phase transition. In T cells, triggering via the T-cell antigen receptor (TCR)-CD3 complex (TCR/CD3) resulted in an approximately fourfold increase in c-raf-1 mRNA. In addition, the promotion …

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Reaction Of Chromium(Vi) With Glutathione Or With Hydrogen Peroxide: Identification Of Reactive Intermediates And Their Role In Chromium(Vi)-Induced Dna Damage, J Aiyar, H Berkovits, R Floyd, K Wetterhahn May 1991

Reaction Of Chromium(Vi) With Glutathione Or With Hydrogen Peroxide: Identification Of Reactive Intermediates And Their Role In Chromium(Vi)-Induced Dna Damage, J Aiyar, H Berkovits, R Floyd, K Wetterhahn

Dartmouth Scholarship

The types of reactive intermediates generated upon reduction of chromium(VI) by glutathione or hydrogen peroxide and the resulting DNA damage have been determined. In vitro, reaction of chromium(VI) with glutathione led to formation of two chromium(V) complexes and the glutathione thiyl radical. When chromium(VI) was reacted with DNA in the presence of glutathione, chromium-DNA adducts were obtained, with no DNA strand breakage. The level of chromium-DNA adduct formation correlated with chromium(V) formation. Reaction of chromium(VI) with hydrogen peroxide led to formation of hydroxyl radical. No chromium(V) was detectable at 24 degrees C (297 K); however, low levels of the tetraperoxochromium(V) …

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Strain-Specific Neutralizing Determinant In The Transmembrane Protein Of Simian Immunodeficiency Virus, Toshiaki Kodama, Dawn P. Wooley, Daniel P. Silva, Fulvia Dimarzo Veronese, Ronald C. Desrosiers Apr 1991

Strain-Specific Neutralizing Determinant In The Transmembrane Protein Of Simian Immunodeficiency Virus, Toshiaki Kodama, Dawn P. Wooley, Daniel P. Silva, Fulvia Dimarzo Veronese, Ronald C. Desrosiers

Neuroscience, Cell Biology & Physiology Faculty Publications

Monoclonal antibody SF8/5E11, which recognizes the transmembrane protein (TMP) of simian immunodeficiency virus of macaque monkeys (SIVmac), displayed strict strain specificity. It reacted with cloned and uncloned SIVmac251 but not with cloned SIVmac142 and SIVmac239 on immunoblots. This monoclonal antibody neutralized infection by cloned, cell-free SIVmac251 and inhibited formation of syncytia by cloned SIVmac251-infected cells; these activities were specific to cloned SIVmac251 and did not occur with the other viruses. Site-specific mutagenesis was used to show that TMP amino acids 106 to 110 (Asp-Trp-Asn-Asn-Asp) determined the strain specificity of the monoclonal antibody. This strain-specific neutralizing determinant is located within a …

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Selection Of Genetic Variants Of Simian Immunodeficiency Virus In Persistently Infected Rhesus Monkeys, Dawn P. Wooley, Ronald C. Desrosiers Apr 1991

Selection Of Genetic Variants Of Simian Immunodeficiency Virus In Persistently Infected Rhesus Monkeys, Dawn P. Wooley, Ronald C. Desrosiers

Neuroscience, Cell Biology & Physiology Faculty Publications

Genetic and antigenic variation may be one means by which lentiviruses that cause AIDS avoid elimination by host immune responses. Genetic variation in the envelope gene (env) was studied by comparing the nucleotide sequences of 27 clones obtained from two rhesus monkeys infected with molecularly cloned simian immunodeficiency virus. All 27 clones differed from each other and differed from the input clone in the gp120 (SU) portion of the envelope gene. Nucleotide substitutions were shown to accumulate with time at an average rate of 8.5 per 1,000 per year in SU. Surprisingly, the majority of nucleotide substitutions (81%) resulted in …

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