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Biomedical subjects

C A Morris

Publications and source records attributed to C A Morris.

At least 37 records · Page 2Linked to original sources
PubMed2000

Evaluation of a liquid formulation of monensin to control bloat in pasture-fed milking cows.

AIM: To evaluate the effectiveness of a liquid formulation of monensin in reducing bloat score in milking cows grazing pasture. METHODS: A Friesian x Jersey crossbred herd which had been genetically selected for high bloat susceptibility since 1973 was used in this study. Two trials were conducted, each involving two groups of 15 cows, randomly allocated to Treated or Control groups. Trial 1 involved twice-daily administration of a novel liquid formulation of monensin given to Treated cows at morning and afternoon milkings. Trial 2 involved once-daily administration of the same product to Treated cows at the morning milking only. Control cows received no preventative treatment. The total daily dose of monensin in each trial was 300 mg per cow, given in a total volume of 100 ml of liquid. Animals were scored for bloat twice-daily whilst grazing on white-clover/ryegrass or red-clover pastures. The scoring system used a scale of 0, 1, 1.5, 2, 2.5, or 3, representing scores of increasing bloat severity as assessed by palpation of abdominal pressure on the left and right sides of the cow. RESULTS: In Trial 1, severe bloat was recorded at 9 out of 23 scoring sessions. Twelve Control cows required therapeutic treatment for bloat on at least one day, compared to 3 cows in the Treated group (p=0.003). In Trial 2, severe bloat in 3 of 9 scoring sessions led to 8/15 Control animals requiring therapeutic treatment compared to 1/14 cows in the Treated group (p=0.02). CONCLUSIONS: Oral drenching with the liquid formulation of monensin tested was effective in reducing bloat score in milking cows grazed on pasture.

Journal Article↗
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↗
PubMed1998

Development of mini-gel technology in two-dimensional electrophoresis for mass-screening of samples: application to tears.

Despite the extensive literature available on tear proteins and lipids, very little has been reported on the tear fluid as a whole and it's changes in contact lens wear or ocular diseased patients. Initially a human reflex tear two-dimensional map was created by Molloy et al. (Electrophoresis 1997, 18, 2811-2815), using this information a process for mass-screening was established. The large format two-dimensional technique was evaluated, using a basal tear reference map, and modified to describe a fast, efficient and cost effective method of protein separation. The use of one pH 3-10 18 cm nonlinear immobilised pH gradient (IPG) strip and two mini-gels for the second-dimensional sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) results in an effective separation of tear proteins which will be applied in diagnostic studies of tear samples.

Acrylic Resins↗
PubMed1998

Complete physical map of the common deletion region in Williams syndrome and identification and characterization of three novel genes.

Williams syndrome (WS) is a contiguous gene deletion 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 (SVAS). We have also implicated LIM-kinase 1 hemizygosity as a contributing factor to impaired visual-spatial constructive cognition in WS. However, the common WS deletion region has not been completely characterized, and genes for additional features of WS, including mental retardation, infantile hypercalcemia, and unique personality profile, are yet to be discovered. Here, we present a physical map encompassing 1.5 Mb DNA that is commonly deleted in individuals with WS. Fluorescence in situ hybridization analysis of 200 WS individuals shows that WS individuals have the consistent deletion interval. In addition, we identify three novel genes from the common deletion region: WS-betaTRP, WS-bHLH, and BCL7B. WS-betaTRP has four putative beta-transducin (WD40) repeats, and WS-bHLH is a novel basic helix-loop-helix leucine zipper (bHLHZip) gene. BCL7B belongs to a novel family of highly conserved genes. We describe the expression profile and genomic structure for each of these genes. Hemizygous deletion of one or more of these genes may contribute to developmental defects in WS.

Amino Acid Sequence↗
PubMed1998

Tear changes in contact lens wearers following overnight eye closure.

PURPOSE: Tear protein composition alters during eye closure, by becoming rich in secretory IgA (sIgA) and certain complement proteins. This may reflect altered ocular defense mechanisms during eye closure. Since overnight wear of contact lenses (CLs) is associated with an increased risk of corneal infection and inflammation, this study aimed to quantify tear protein changes with overnight soft CL wear. METHODS: Non-stimulated tears were collected from 9 CL wearers prior to CL wear (baseline), after daily CL wear, and after 8 h sleep. Lenses were removed following wear and were extracted in 80% urea at 95 degrees C. Secretory IgA, complement C3 and C4, were measured using ELISA and total protein using the Pierce BCA assay. Assays were performed on tear samples and CL extracts. RESULTS: Baseline tear protein concentrations were: 0 total tear protein (9.37 +/- 2.97 mg/mL), C3 (4.4 +/- 2.1 micrograms/mL), C4 (0.1 +/- 0.1 micrograms/mL), and sIgA (0.84 +/- 0.34 mg/mL). There were no differences in any protein levels between daily CL wear and no CL wear (p > 0.05). Following sleep, protein concentrations were: total tear protein (43.64 +/- 24.30 mg/mL), C3 (72.5 +/- 49.9 micrograms/mL), C4 (6.7 +/- 5.2 micrograms/mL), and sIgA (5.53 +/- 5.15 mg/mL). Total protein extracted from CLs after daily wear was 90 +/- 27 micrograms/CL and, after overnight wear, 152 +/- 24 micrograms/CL. Negligible levels of C3, C4 and sIgA were recovered from CL extracts. CONCLUSIONS: Uncomplicated daily use of soft CLs does not appear to alter certain tear proteins compared with baseline levels. Uptake of these proteins by the CL does not appear to deplete the tear protein levels. Overnight levels of all tear proteins were increased, compared to daily CL wear.

Adult↗
PubMed1998

Genetic aspects of supravalvular aortic stenosis.

Supravalvular aortic stenosis (SVAS) occurs as an autosomal dominant trait or as part of the phenotype of the usually sporadic condition Williams syndrome. SVAS is the result of mutation or deletion of the elastin gene (ELN), located at chromosome 7q11.23. Thus, SVAS may be more appropriately termed an elastin arteriopathy. Studies have demonstrated various point mutations and intragenic deletions of ELN resulting in nonsyndromic SVAS. Individuals with Williams syndrome are hemizygous for the elastin gene, owing to a 1 to 2 megabase deletion of a portion of the long arm of chromosome 7 that encompasses ELN. This submicroscopic deletion is readily detected by fluorescent in-situ hybridization, useful in the diagnosis of Williams syndrome. The severity of SVAS is quite variable, both in series of Williams syndrome patients and within SVAS kindreds, suggesting that other genetic factors are involved in expression of the phenotype. Experiments with elastin knockout mice will likely yield clues regarding the role of elastin in arterial morphogenesis and the pathogenesis of obstructive vascular disease.

Animals↗
PubMed1997

Establishment of the human reflex tear two-dimensional polyacrylamide gel electrophoresis reference map: new proteins of potential diagnostic value.

To understand the changes in protein expression associated with various physiological states as well as the development of pathological eye disease, we have begun to map the protein components of normal human reflex tears. An analytical reference map of normal human reflex tears was created using two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) with pH 3.5-10 immobilized pH gradients (IPGs). Micropreparatively loaded gels were transferred to polyvinylidene difluoride (PVDF) and analysed by a combination of N-terminal sequence tagging and amino acid compositional analysis. Thirty spots were sequence tagged, resulting in identification of six different proteins (lipocalin, lysozyme, lactotransferrin, zinc-alpha-2 glycoprotein, cystatin S, cystatin SN) that matched to entries in the SWISS-PROT database. A group of N-terminally blocked proteins was clearly identified from SWISS-PROT by amino acid analysis, isoelectric point (pI) and molecular weight (Mr). A number of highly expressed protein components remain unidentified despite being subjected to amino acid analysis and Edman sequencing. A majority of the abundant proteins showed varying degrees of charge heterogeneity attributed to post-translational processing such as glycosylation and N-terminal truncation. We have identified a previously undescribed protein that we have named lacryglobin. This protein displays strong homology with mammaglobin, a protein overexpressed in breast cancer. The discovery of this homologue in tears offers the potential for disease diagnosis by screening tear fluid proteins.

Databases, Factual↗