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Biomedical subjects

C A Morris

Publications and source records attributed to C A Morris.

At least 19 recordsLinked to original sources
PubMed2003

Bovine parotid secretory protein: structure, expression and relatedness to other BPI (bactericidal/permeability-increasing protein)-like proteins.

Members of the family of BPI (bactericidal/permeability-increasing protein)-like proteins are as yet incompletely characterized, particularly in cattle, where full-length sequence information is available for only three of the 13 family members known from other species. Structural bioinformatic analyses incorporating bovine homologues of several members of the BPI-like protein family, including two forms of bovine parotid secretory protein (PSP), showed that this family is also present in cattle. Expression analyses of several members of the BPI-like protein family in cattle, including PSP (Bsp30), von Ebner's minor salivary gland protein (VEMSGP) and lung-specific X protein (LUNX), showed a restricted pattern of expression, consistent with earlier hypotheses that these proteins function in the innate immune response to bacteria. The possible role of bovine PSP in susceptibility to pasture bloat in cattle is discussed.

Animals↗
PubMed2002

Evaluation of single-nucleotide polymorphisms in CAPN1 for association with meat tenderness in cattle.

Micromolar calcium activated neutral protease (CAPN1) was evaluated as a candidate gene for a quantitative trait locus (QTL) on BTA29 affecting meat tenderness by characterization of nucleotide sequence variation in the gene. Single-nucleotide polymorphisms (SNP) were identified by sequencing all 22 exons and 19 of the 21 introns in two sires (Piedmontese x Angus located at the U.S. Meat Animal Research Center in Clay Center, NE; Jersey x Limousin located at AgResearch in New Zealand) of independent resource populations previously shown to be segregating meat tenderness QTL on BTA29. The majority of the 38 SNP were found in introns or were synonymous substitutions in the coding regions, with two exceptions. Exons 14 and 9 contained SNP that were predicted to alter the protein sequence by the substitution of isoleucine for valine in Domain III of the protein, and alanine for glycine in Domain II of the protein. The resource populations were genotyped for these two SNP in addition to six intronic polymorphisms and two silent substitutions. Analysis of genotypes and shear force values in both populations revealed a difference between paternal CAPN1 alleles in which the allele encoding isoleucine at position 530 and glycine at position 316 associated with decreased meat tenderness (increased shear force values) relative to the allele encoding valine at position 530 and alanine at position 316 (P < 0.05). The association of maternal alleles with meat tenderness phenotypes is consistent with the hypothesis of CAPN1 as the gene underlying the QTL effect in two independent resource populations and presents the possibility of using these markers for selective breeding to reduce the numbers of animals with unfavorable meat tenderness traits.

Alleles↗
PubMed2001

Modulation of contractile activation in skeletal muscle by a calcium-insensitive troponin C mutant.

Calcium controls the level of muscle activation via interactions with the troponin complex. Replacement of the native, skeletal calcium-binding subunit of troponin, troponin C, with mixtures of functional cardiac and mutant cardiac troponin C insensitive to calcium and permanently inactive provides a novel method to alter the number of myosin cross-bridges capable of binding to the actin filament. Extraction of skeletal troponin C and replacement with functional and mutant cardiac troponin C were used to evaluate the relationship between the extent of thin filament activation (fractional calcium binding), isometric force, and the rate of force generation in muscle fibers independent of the calcium concentration. The experiments showed a direct, linear relationship between force and the number of cross-bridges attaching to the thin filament. Further, above 35% maximal isometric activation, following partial replacement with mixtures of cardiac and mutant troponin C, the rate of force generation was independent of the number of actin sites available for cross-bridge interaction at saturating calcium concentrations. This contrasts with the marked decrease in the rate of force generation when force was reduced by decreasing the calcium concentration. The results are consistent with hypotheses proposing that calcium controls the transition between weakly and strongly bound cross-bridge states.

Animals↗
PubMed2001

Comprehensive linkage map of bovine chromosome 27.

The results of genotypic data contributed to the International Society for Animal Genetics (ISAG) Bovine Chromosome 27 Workshop are presented. Eight laboratories contributed 23 261 informative meioses from 44 loci. Eighteen loci were typed by at least two laboratories and were used to construct a consensus linkage map. Twenty-one loci were subsequently incorporated into a comprehensive map. The sex-averaged consensus map covered 66.9 cM. The sex-averaged comprehensive map was 75.5 cM, while the female and male maps were 73.1 and 63.7 cM, respectively. Five loci were excluded from the analysis because of ambiguous position in the linkage group and a low LOD score (less than 2.0). Average distance between loci in the comprehensive map was 1.98 cM.

Animals↗
PubMed2001

Comprehensive linkage map of bovine chromosome 11.

The results of genotypic data contributed to the International Society of Animal Genetics (ISAG) Bovine Chromosome 11 (BTA11) Workshop are presented. Six laboratories contributed a total of 26 199 informative meioses from 80 loci. Thirty-six loci were typed by at least two independent laboratories and were used to construct a consensus linkage map of the chromosome. The remaining loci were subsequently incorporated into a comprehensive map. The sex-averaged consensus map covered 128.9 cM. The female consensus map was 101.2 cM, while the male consensus map was 129.8 cM. The comprehensive sex-averaged map was 134.2 cM and the average genetic distance between loci was 1.72 cM.

Animals↗
PubMed2001

Complement activation by apoptotic endothelial cells following hypoxia/reoxygenation.

Reperfusion of ischaemic tissue initiates an inflammatory reaction that increases tissue injury. Complement activation at the endothelium contributes to this inflammation. This study investigated the mechanism of complement activation following reoxygenation of hypoxic human umbilical vein endothelial cells (HUVEC) as a model for complement activation observed on endothelium in reperfused ischaemic tissue. HUVEC cultured in 1% oxygen followed by reoxygenation activated the classical complement pathway resulting in C3 deposition. There was an increase in apoptotic cells in these cultures that was demonstrated by binding of fluorescein isothiocyanate-Annexin V and staining for hypodiploid nuclei. To determine if apoptotic HUVEC activate complement, uniformly apoptotic cells were produced by serum and growth factor deprivation. These cells, but not the control HUVEC, activated the classical complement pathway in the absence of antibody or other serum factors. To determine if apoptotic cells in the reoxygenated cultures were activating complement, fluorescent analysis was done. Annexin V binding and C3d deposition on cells from reoxygenated cultures showed complete concordance on the subpopulation of apoptotic cells. In addition, complement activation following reoxygenation of HUVEC was eliminated by treatment of the cultures with a caspase inhibitor during reoxygenation. These results suggest that oxidative damage to endothelial cells during reoxygenation initiates apoptosis with exposure of phosphatidylserine. Apoptotic cells directly activate the classical pathway of complement by binding C1. Activation of complement at the endothelium may contribute to the inflammatory response as well as clearance and repair.

Amino Acid Chloromethyl Ketones↗
PubMed2001

The subtle facial signs of prenatal exposure to alcohol: an anthropometric approach.

OBJECTIVES: The purpose was to demonstrate that an objective, multivariate case definition of fetal alcohol syndrome (FAS) and partial fetal alcohol syndrome (PFAS) can be derived by means of craniofacial anthropometry. STUDY DESIGN: Craniofacial measurements (n = 21) were taken of 100 individuals who had been exposed to alcohol before birth (41 FAS, 59 PFAS) and 31 members of a control group. Multivariate discriminant analysis was used to identify craniofacial measurements that best differentiated the 3 groups (FAS, PFAS, and control). RESULTS: Both the FAS and PFAS groups had a unique craniofacial phenotype that could be accurately discriminated from that of the control group. Stepwise discriminant analysis identified 6 craniofacial measurements that could differentiate individuals with and without prenatal alcohol exposure with 96% accuracy, 98% sensitivity, and 90% specificity. CONCLUSIONS: Individuals with FAS and PFAS have a distinctive facial phenotype that can be characterized anthropometrically. The phenotypic case definition could be used as a screening tool to identify individuals prenatally exposed to alcohol who do not exhibit a "classic" FAS phenotype but exhibit a more subtle craniofacial dysmorphia.

Adolescent↗
PubMed2001

Bacterial populations on 30-night extended wear silicone hydrogel lenses.

PURPOSE: Ocular infection and inflammation during hydrogel lens extended wear is often associated with colonization of the lenses with bacteria. This study compares colonization of a high Dk silicone hydrogel contact lens (lotrafilcon A) worn on a 30-night extended wear basis to a low Dk HEMA-based lens (etafilcon A) worn on a 6-night extended wear schedule. METHODS: The group wearing the low Dk/t soft contact lens (n = 63) replaced their lenses weekly and the group wearing high Dk/t soft contact lenses replaced their lenses monthly (n = 64). Lens allocation was assigned randomly at enrollment. Worn lenses, from one eye only, were collected aseptically and placed in sterile vials. Microbial growth on various media was enumerated and the number of colony forming units (cfu) per lens was calculated in categories of normal ocular microbiota (such as coagulase-negative staphylococci and Propionibacterium spp.) and known ocular pathogens (such as Staphylococcus aureus and gram-negative bacteria). The proportion of samples colonized with these bacteria and the extent of colonization were compared between the two groups. The proportion of sterile lenses was calculated, and the types of bacteria on each lens group were compared. RESULTS: No differences between the low and high Dk/t Soft contact lens groups were observed in the proportion of lenses colonized by Propionibacterium spp. (48% vs 43%, P = 0.4) or coagulase-negative staphylococci (47% vs 54%, P = 0.2). Similarly, no differences were found for lenses colonized by S. aureus (0% vs 2%, P = 0.1) or gram-negative bacteria (3% vs 2%, P = 0.8). The types of bacteria isolated from the high and low Dk/t lenses were similar. There were no differences in the number of sterile samples (28% vs 27%, P = 0.8) from each group. CONCLUSIONS: These findings suggest that high Dk/t silicone hydrogel materials are colonized by similar numbers and types of microorganisms during extended wear compared to HEMA-based material. Most lenses were colonized by commensal bacteria during 30-night extended wear with high Dk/t lenses and during 6-night extended wear with low Dk/t lenses. The incidence of sterile samples was the same between the high and low Dk/t soft contact lens groups.

Adult↗
PubMed2000

The Williams syndrome cognitive profile.

Williams syndrome is a rare neurodevelopmental disorder caused by a hemizygous deletion of approximately 1.5 megabases on chromosome 7q11.23. In this article, we outline a Williams Syndrome Cognitive Profile (WSCP) that operationalizes the cognitive characteristics of the syndrome using measures of absolute and relative performance on subtests of the Differential Abilities Scales (Elliot, 1990a). Testing confirmed excellent sensitivity and specificity scores for the WSCP. Seventy-four of 84 individuals with Williams syndrome fit the WSCP while only 4 participants in a contrast group met all of the WSCP criteria. It was also found that the WSCP does not vary greatly with chronological age or overall level of cognitive ability for individuals with Williams syndrome. Possible applications for the WSCP include psychoeducational evaluation and empirical research such as the search for genotype/phenotype relations in this genetically based syndrome.

Adolescent↗
PubMed2000

Williams syndrome and related disorders.

Three clinical conditions displaying phenotypic overlap have been linked to mutation or deletion of the elastin gene at 7q11.23. Supravalvar aortic stenosis, an autosomal dominant disorder characterized by elastin arteriopathy, is caused by mutation or intragenic deletions of ELN resulting in loss of function. Autosomal dominant cutis laxa, a primarily cutaneous condition, is the result of frameshift mutations at ELN that cause a dominant-negative effect on elastic fiber structure. Williams syndrome, a neurodevelopmental disorder is due to a 1.5 Mb deletion that includes ELN and at least 15 contiguous genes. The disorder is characterized by dysmorphic facies, mental retardation or learning difficulties, elastin arteriopathy, a unique cognitive profile of relative strength in auditory rote memory and language and extreme weakness in visuospatial constructive cognition, and a typical personality that includes overfriendliness, anxiety, and attention problems. The understanding of these disorders has progressed from phenotypic description to identification of causative mutations and insight into pathogenetic mechanisms for some aspects of the phenotype.

Aortic Stenosis, Supravalvular↗
PubMed2000

Sporidesmin-induced mortality and histological lesions in mouse lines divergently selected for response to toxins in endophyte-infected fescue.

For eight generations, mouse lines were selected for smaller or larger reduction in postweaning gain from endophyte-infected fescue seed in the diet. After five generations in which there was no further selection for divergence in response to fescue toxicosis, the current experiment was conducted to determine whether resistant (R) and susceptible (S) lines differed in response to the mycotoxin sporidesmin (SPD). At approximately 8 wk of age, R and S mice that had never consumed endophyte-infected fescue seed were randomly assigned (five to seven per line x sex x SPD dose subclass) to receive dimethyl sulfoxide (DMSO) carrier or 10, 20, 30, or 40 mg/kg SPD by oral gavage. At death or euthanasia 14 d after treatment, livers and kidneys were collected for histological examination. Mice receiving 40 mg/kg SPD died sooner than mice receiving 30 mg/kg (63 vs 134 h; P = .02), but there was no line or line x dose interaction effect for time to death. Within those mice, neither line, dose, nor their interaction influenced liver weight or liver weight as a proportion of body weight. The R mice were more resistant to SPD than S mice; LD50 values were 23.6 and 31.8 mg/kg for the S and R lines, respectively (P < .05). Sporidesmin caused dose-related liver and kidney lesions in both lines. Selection lines did not differ significantly in the incidence of infarcts of hepatic lobules. However, at 30 and 40 mg/kg SPD doses, severity of this lesion was higher in affected S than in affected R mice. At the higher SPD doses, there also was a greater incidence of hepatic subacute cholangitis in S mice than in R mice. Foci of acute tubular necrosis were found in kidneys of mice receiving 20, 30, or 40 mg/kg SPD, with no protection against these lesions in the R line. Foci of tubular basophilia (indicative of tubular regeneration) were present in all line x dose subgroups, but incidence was not SPD dose-dependent in either line. In summary, divergent selection for weight gain response to ingestion of endophyte-infected fescue seed resulted in a favorable correlated response in survival following exposure to a chemically distinct toxin. It may be possible therefore, to select livestock populations for simultaneous resistance to a variety of toxins.

Acremonium↗
PubMed1999

Identification and characterization of a recombinant metallothionein protein from a marine alga, Fucus vesiculosus.

A cDNA library was constructed from macroalgae adapted to prolonged elevated environmental copper levels. To investigate the possible existence of a metallothionein (MT) gene, the library was screened with degenerate probes designed using plant MT cysteine-rich motifs. A gene was identified (1229 bp) with a putative open reading frame (204 bp) encoding a 67-amino-acid protein exhibiting several characteristic features of MT proteins, including 16 cysteine residues (24%) and only one aromatic residue. Although the protein sequence showed high identity with plant and invertebrate MTs, it contained a unique 'linker' region (14 amino acid residues) between the two putative metal-binding domains which contained no cysteine residues. This extended linker is larger than the tripeptide found in archetypal vertebrate MTs, but does not conform either with the 40-amino-acid linkers commonly found in plant MT sequences. An S-peptide Fucus MT fusion protein expressed in Escherichia coli exhibited a relative molecular mass of approximately 14 kDa. The recombinant fusion bound seven Cd ions, of which 50% were dissociated at pH 4.1. Under anaerobic conditions, the Cd ions were displaced by Cu(I), which associated with the protein at a ratio of 13:1. Laboratory exposure of F. vesiculosus to elevated copper resulted in induction of the MT gene. Thus this paper describes, for the first time, an MT gene identified from macroalgae which is induced by copper exposure and whose encoded protein product binds cadmium and copper.

Amino Acid Sequence↗
PubMed1999

Familial antiphospholipid antibody syndrome: criteria for disease and evidence for autosomal dominant inheritance.

OBJECTIVE: To develop diagnostic criteria for a familial form of antiphospholipid antibody syndrome (APS), identify families with >1 affected member, examine possible modes of inheritance, and determine linkage to potential candidate genes. METHODS: Family members of probands with primary APS were analyzed for clinical and laboratory abnormalities associated with APS. Families with > or =2 affected members were analyzed by segregation analysis and typed for candidate genetic markers. RESULTS: Seven families were identified. Thirty of 101 family members met diagnostic criteria for APS. Segregation studies rejected both environmental and autosomal recessive models, and the data were best fit by either a dominant or codominant model. Linkage analysis showed independent segregation of APS and several candidate genes. CONCLUSION: Clinical and laboratory criteria are essential to identify the spectrum of disease associated with APS. We believe a set of criteria was developed that can precisely define affected family members with APS. Modeling studies utilizing these criteria strongly support a genetic basis for disease in families with APS and suggest that a susceptibility gene is inherited in an autosomal dominant pattern. However, in these families, APS was not linked with HLA, Fas, or other candidate genes, including beta2-glycoprotein 1, HLA, T cell receptor beta chain, Ig heavy chain, antithrombin III, Fas ligand, factor V, complement factor H, IgK, and Fas.

Adolescent↗
PubMed1999

Catalase gene is associated with facial eczema disease resistance in sheep.

Facial eczema (FE) is a hepatogenous photosensitization disease of ruminant animals, particularly in sheep which vary widely in their susceptibility to the disease. The liver damage is caused by the mycotoxin, sporidesmin. There is evidence that the toxicity of sporidesmin is due to its ability to generate 'active oxygen' species. We evaluated the catalase gene, which encodes an enzyme with antioxidant functions, as a candidate for determining the susceptibility of sheep to the disease. Two microsatellite markers, OarSHP3 and OarSHP4, which flank the sheep catalase gene, were isolated from a Yeast Artificial Chromosome (YAC) clone. These markers mapped the catalase locus by linkage to ovine chromosome 15. Eleven informative markers spaced throughout chromosome 15, inclusive of the catalase marker OarSHP4, gave no significant linkage with the disease traits when analysed in four outcross resource pedigrees. However, OarSHP3 and OarSHP4 allele frequencies showed significant differences between FE resistant and susceptible selection-lines. Comparison of sequences of catalase cDNAs from sheep of resistant and susceptible lines showed only two silent mutations. A single nucleotide polymorphisms (KP1) in exon 6 of the catalase gene also showed significant differences in allele frequencies between the selection lines. The lack of evidence for linkage in outcross pedigrees, but the significant association in the genetic lines, implies that catalase is involved in determining the susceptibility of sheep to facial eczema, and that the candidate gene's effect is probably recessive or minor.

Alleles↗
PubMed1998

A novel human gene, WSTF, is deleted in Williams syndrome.

Williams syndrome (WS) is a developmental disorder caused by deletion of multiple genes at chromosome 7q11.23. Here, we report the identification and characterization of a novel gene, WSTF, that maps to the common WS deletion region. WSTF encodes a novel protein of 1425 amino acids with unknown function. It contains one PHD-type zinc finger motif followed by a bromodomain. Both motifs are found in many transcription regulators, suggesting that WSTF may function as a transcription factor. WSTF is ubiquitously expressed in both adult and fetal tissues. The WSTF gene consists of 20 exons spanning about 80 kb. Fluorescence in situ hybridization analysis shows that WSTF is deleted in 50/50 WS individuals. Hemizygous deletion of WSTF may contribute to WS.

Amino Acid Sequence↗
PubMed1998

A novel human gene FKBP6 is deleted in Williams syndrome.

Williams syndrome (WS) is a developmental disorder caused by haploinsufficiency of genes at 7q11.23. We have shown that hemizygosity of elastin is responsible for one feature of WS, supravalvular aortic stenosis. We have also implicated LIM-kinase 1 hemizygosity as a contributing factor to impaired visual-spatial constructive cognition in WS. Here we identify and characterize a novel gene, FKBP6, within the common WS deletion region. FKBP6 shows homology to the FK-506 binding protein (FKBP) class of immunophilins. FKBP6 has a putative N-terminal FK-506 binding and peptidylproyl isomerase (rotamase) domain and, like known high-molecular-weight FKBPs, an imperfect C-terminal tetratricopeptide repeat domain. FKBP6 is expressed in testis, heart, skeletal muscle, liver, and kidney. FKBP6 consists of nine exons and is completely contained within a 35-kb cosmid clone. Fluorescence in situ hybridization experiments show that FKBP6 gene is deleted in 40/40 WS individuals. Hemizygous deletion of FKBP6 may contribute to certain defects such as hypercalcemia and growth delay in WS.

Amino Acid Sequence↗
PubMed1998

Current methods for stallion semen cryopreservation: a survey.

Various factors affect the success of AI with frozen-thawed semen in horses. Stallion variability is thought to be one of the major factors, but semen processing and evaluation techniques, thawing protocols, packaging systems and timing of insemination are far from standardized among laboratories. Our objective was to survey current methods for stallion semen cryopreservation used commercially around the world. From the answers to the questions in the survey, we attempted to provide an overview of procedures that are standard as well as those that are used by only few laboratories and to review critically the efficacy of these procedures. Twenty-five questionnaires were sent to individuals or laboratories in 14 countries that were i.v. involved in freezing stallion semen for commercial purposes. Questionnaires were returned from 10/14 countries with 21/25 (84%) of the addresses responding. From the responses, it became evident that most of prefreezing, freezing and thawing and post-thawing processing procedures were far from standardized. The great variety of procedures makes it difficult to accept any of them as reliable. In order to increase the credibility of AI technology in the horse, laboratories need to standardize processing methods as well as the record-keeping systems. In addition, it is evident that no group of research mares is large enough to provide meaningful fertility data. It is therefore imperative to have multicentered collaborative studies to record and disseminate information about methods and the corresponding fertility rate. to gain valuable information and be able to compare different protocols.

Animals↗