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Biomedical subjects

J L Williams

Publications and source records attributed to J L Williams.

At least 73 records · Page 4Linked to original sources
PubMed2001

Transgenic production from in vivo-derived embryos: effect on calf birth weight and sex ratio.

We examined transgenic-cattle production by DNA microinjection into 1-, 2-, and 4-cell embryos, analyzing the impact on calf size and subsequent viability. Embryos were either collected at an abattoir by flushing oviducts from superovulated and artificially inseminated cows (in vivo-derived) or obtained by in vitro maturation and in vitro fertilization of oocytes aspirated from excised ovaries (in vitro-derived). A human serum albumin (hSA) milk-expression DNA construct was microinjected, either in one of the visible pronuclei of in vitro- and in vivo-derived 1-cell embryos or in the nuclei of two blastomeres of 2- and 4-cell in vivo-derived embryos. Microinjection-induced mortality (lysis and developmental block) was equivalent ( approximately 40%) for all microinjected embryos. Embryos were co-cultured with BRL cells in B-2 medium containing 10% fetal calf serum (FSC). Overall, embryo development to morulae/blastocysts was significantly greater for in vivo-derived ova (15.5%) than for in vitro-derived oocytes (9.3%). All morulae and blastocysts were transferred to synchronized recipient females on Days 6-8 post-fertilization. A total of 189 calves were delivered. Birth weights were significantly greater for calves generated from in vitro-derived oocytes compared with those generated from in vivo-derived oocytes. One transgenic bull calf was obtained from the microinjection of a 2-cell embryo. Fluorescence in situ hybridization (FISH) analysis of lymphocytes detected one transgenic integration site in all cells. Transmission frequency of the hSA transgene in embryos obtained through IVM/IVF/IVC utilizing the semen of the transgenic calf confirmed that it was not mosaic.

Animals↗
PubMed2001

Genomic organization, comparative analysis, and genetic polymorphisms of the bovine and ovine prion Doppel genes (PRND).

The doppel protein (Dpl) is a prion-like protein encoded by the gene PRND, which has been found downstream of the prion gene, PRNP, in human and mouse. This paper describes the isolation and structural organization of the bovine and ovine PRND genes, which are composed of two exons compared with the three of human and mouse. Intergenic distances between PRNP and PRND were covered by means of long-range PCR and found to be 16.8 and 20 kb, in cattle and sheep respectively. The 5' and 3' untranslated regions (UTR) were analyzed to identify transcription regulatory sequences and compared with those from the PRND and PRNP sequences published for other species. Three polymorphisms (R50H, N110H, and R132Q) were revealed in the cattle coding region; two synonymous substitutions (I12I, A26A) were found in sheep. None of the polymorphisms was significantly associated with either Bovine Spongiform Encephalopathy (BSE) in cattle or scrapie in sheep.

Animals↗
PubMed2001

Tensile properties of the physis vary with anatomic location, thickness, strain rate and age.

The variable outcome of physeal distraction has raised questions as to the mechanism by which bone lengthening is achieved. Is it by stretching of the matrix or does it stimulate growth? In order to explore the contribution of matrix stretching, we sought to answer the following questions in an animal model: (a) Are the tensile properties of the lateral side of the proximal tibial physis different from the medial? (b) Are the tensile properties strain-rate dependent? (c) Does the growth plate fracture through any preferred zone in tension? (d) Are the tensile properties of the bovine growth plate a function of age? (e) Are thicker growth plates weaker in tension? (f) Are the tensile properties of the bovine growth plate comparable to those of a child's? We compared bone-cartilage-bone specimens (0.5 x 2.5 mm2 in cross-section) from the lateral, central and medial regions of the proximal tibial growth plates of 12- to 18-month heifers. 70 specimens were tested to failure in tension at 0.0004, 0.004 and 0.04 mm/s. Tensile strength and tangent modulus were 33% and 25% greater, respectively, on the lateral side compared with the medial, and both were increased at the higher strain rates. We found no difference in the ultimate strains by region or strain rate. Thicker growth plates were weaker. Scanning electron microscopy revealed a three-dimensional fracture pattern extending from the upper columnar into the reserve zone. Bundles of intact chondrons remained intact, but only on the metaphyseal side, having been torn from an interterritorial matrix which remained mostly on the epiphyseal side of the fracture. We compared 21 specimens of 12- to 18-month and 19 specimens of 5-month calves from similar regions of the proximal tibia. These were tested to failure in tension at 0.004 mm/s. The older bovine growth plate was 25% thinner, 34% stronger and failed at 65% greater strain. For comparison, we tested eight samples from the femoral capital growth plate of two cerebral palsy patients. These were twice as thick as our bovine samples and about half as strong, but with similar ultimate strain values.

Age Factors↗
PubMed2001

Anisotropic elasticity of cortical and cancellous bone in the posterior mandible increases peri-implant stress and strain under oblique loading.

The aim of this study was to compare implant-bone interface stresses and peri-implant principal strains in anisotropic versus isotropic three-dimensional finite element models of an osseointegrated implant in the posterior mandible. We obtained anisotropic (transversely isotropic) elastic constants for mandibular bone and derived equivalent isotropic constants by averaging over all possible spatial orientations. A finite element model was constructed using ten-node tetrahedral p-elements, providing curved edges where necessary and increasing the accuracy of the results in regions of high stress gradients. Perfect bonding was assumed at the implant-bone interface. An oblique load was applied at the coronal aspect of the crown with 100 N vertical and 20 N bucco-to-lingual components. Implant-bone interface stresses exceeded reported bond strengths and principal strains reached yield strain levels in the cortical crest. Anisotropy increased what were already high levels of stress and strain in the isotropic case by 20 to 30% in the cortical crest. In cancellous bone, anisotropy increased what were relatively low levels of interface stress in the isotropic case by three- to four-fold to exceed bond strength levels. Anisotropy has subtle, yet significant effects on interface stresses and peri-implant strains and careful consideration should be given to its use in finite element studies of dental implants.

Alveolar Process↗
PubMed2001

cDNA microarray analysis of adapting bowel after intestinal resection.

BACKGROUND/PURPOSE: Studies of the genetic regulation of various physiologic processes have been hampered by methodologies that are limited to the analysis of individual genes. The advent of cDNA microarray technology has permitted the simultaneous screening of numerous genes for alterations in expression. In this study, cDNA microarrays were used to evaluate gene expression changes during the intestinal adaptive response to massive small bowel resection (SBR). METHODS: Male ICR mice (n = 20) underwent either a 50% SBR or sham operation and then were given either orogastric epidermal growth factor (EGF, 50 microg/kg/d) or saline. After 3 days, cDNA microarray analysis was performed on mRNA extracted from the remnant ileum. RESULTS: From over 8,700 different genes, the array identified 27 genes that were altered 2-fold or greater after SBR. Small proline-rich protein 2 (sprr2), the gene with the greatest expression change (4.9-fold), was further upregulated by EGF. This gene has never been characterized in the intestine or described in intestinal adaptation. CONCLUSIONS: cDNA microarray analysis showed enhanced expression of sprr2, a gene not previously known to be involved in the physiology of adaptation after SBR. This technology provides a more rapid and efficient means of dissecting the complex genetic regulation of gut adaptation.

Adaptation, Biological↗
PubMed2001

Routine evaluation of the cervical spine in head-injured patients with dynamic fluoroscopy: a reappraisal.

BACKGROUND: The mechanism for clearing the cervical spine in patients with altered mental status remains controversial. Recommendations have ranged from removal of the cervical collar after 24 hours in patients with normal radiographs, to indefinite immobilization in a cervical collar, and recently cervical flexion-extension examinations using dynamic fluoroscopy. The purpose of this study was to evaluate the efficacy and safety of dynamic fluoroscopy flexion-extension examinations in identifying ligamentous cervical spine injury and clearing the cervical spine in patients with altered mental status after trauma. METHODS: Patients with a Glasgow Coma Scale score < 13 for greater than 48 hours after admission and normal cervical spine radiographs were candidates for fluoroscopic evaluation. The protocol required visualization of the entire cervical spine, through T1, through full extension and flexion under the direct supervision of a radiologist. Oblique fluoroscopic views were obtained, as necessary, to visualize the cervicothoracic junction. Demographic data, fluoroscopy time, total time per study, true and false positives and negatives, and complications were recorded. RESULTS: From July 1992 through December 1999, fluoroscopic examinations were performed on 301 patients. There were 297 true-negative examinations, 2 true-positive examinations (stable injuries), 1 false-negative examination, and 1 false-positive examination. The incidence of ligamentous injury identified by fluoroscopy in this study was 2 of 301 (0.7%). Unstable cervical spine ligamentous injuries were identified in only 0.02% of all trauma patients. One patient developed quadriplegia when fluoroscopic evaluation was performed after two protocol violations. CONCLUSION: Unstable cervical spine ligamentous injury without fracture is a rare occurrence. The cervical spine may be cleared after a normal cervical spine series (plain radiograph and computed tomographic scan) as recommended in the 1998 Eastern Association for the Surgery of Trauma guidelines. If dynamic fluoroscopy is to be used, adherence to the protocol, including review of the cervical spine radiographs before fluoroscopy and visualization of the entire cervical spine, C1-T1, is mandatory to ensure patient safety.

Adult↗
PubMed2001

Dietary soy exerts an antihypertensive effect in spontaneously hypertensive female rats.

This study tested the hypothesis that dietary soy would attenuate the development of hypertension in female spontaneously hypertensive rats (SHR). Female SHR and control Wistar-Kyoto rats were obtained at 4 wk of age, randomly assigned to either an ovariectomized (OVX) group or a sham-operated group, and placed on a soy diet or control casein diet. After a minimum of 8 wk on their respective diets, mean arterial pressure (MAP) and heart rate (HR) were recorded before and after inhibition of nitric oxide synthase, air-jet stress, or ganglionic blockade. The major finding of this study is that MAP was reduced in the OVX SHR consuming soy diet compared with the casein-fed controls (150 +/- 4 vs. 164 +/- 3 mmHg). Plasma genistein concentrations were increased in the soy-fed OVX SHR (1.23 +/- 0.31 microM) compared with the casein-fed OVX SHR (nondetectable). However, there was no difference in plasma genistein concentrations between sham-operated and OVX SHR (1.37 +/- 0.42 vs. 1.23 +/- 0.31 microM). Inhibition of nitric oxide synthase increased MAP and decreased HR in all groups; diet did not affect this response. Air-jet stress increased MAP and HR in all groups. However, these responses were exaggerated in the soy-fed SHR. Finally, ganglionic blockade abolished the antihypertensive effect of soy diet in the OVX SHR. These findings indicate that dietary soy exerts an antihypertensive effect in OVX SHR. This effect does not involve the nitric oxide system but may be related to an as yet undefined interaction with the autonomic nervous system.

Animals↗
PubMed2001

The concerns of patients under palliative care and a heart failure clinic are not being met.

Patients with a terminal illness, identified by palliative care teams working in Manchester, and patients attending a heart failure clinic, were asked to participate in a prospective survey to determine their main concerns. Data were collected from 213 palliative care (PC) patients (mostly with cancer) and 66 patients with heart failure (HF). The median ages of the two patient groups were similar, but the HF patients were more likely to be male and living with a partner; 13% of PC and 7% of HF patients reported that they had no carer. The PC patients had more district nurse, hospice, social work and physiotherapy input. The most frequently reported troublesome problems for PC patients were pain (49%), loss of independence (30%) and difficulty walking (27%). HF patients reported dyspnoea (55%), angina (32%) and tiredness (27%) as the most troublesome problems. From a checklist of symptoms, the frequency of tiredness (PC = 77%, HF = 82%) and difficulty getting about (PC = 71%, HF = 65%) were high in each group. Psychological problems were reported by 61% of PC and 41% of HF patients. Cardiac patients reported more breathlessness and cough than PC patients (83% vs 49% and 44% vs 26%, respectively). Reduced libido was more common in cardiac patients (42% vs 21%). Patient disclosure of troublesome problems to professional carers was high (>87% in both PC and HF patients). Documented action was greater for physical than social or psychological problems. For PC patients, documented action was recorded for 83% physical, 43% social/functional and 52% psychological problems. For HF patients documented action was recorded for 74% cardiac, 60% physical - non-cardiac, 30% social/functional and 28% psychological problems. Clearly many patients' troublesome problems were not being addressed. As a result of this study, specific action by health care professionals was taken in 50% of PC patients and 71% of HF patients. We plan to target specific educational events on the treatment of physical problems, psychological assessment and social service provision.

Activities of Daily Living↗
PubMed2000

Commitment to the production of male and female gametocytes in the human malaria parasite Plasmodium falciparum.

Commitment to the production of female and male gametocytes was studied in the NF54 line of the human malaria parasite Plasmodium falciparum. The development of sibling parasites derived from individual schizonts was followed, and 2 antisera against the female gametocyte-specific protein Pfg377 and the male gametocyte-specific protein alpha-tubulin II were used to determine the sex of sibling gametocytes. The experiment showed that individual cohorts of sibling gametocytes were stained in a mutually exclusive fashion by only one or the other antiserum, indicating that individual schizonts committed to yield sexual parasite progeny produce gametocytes of the same sex. This work suggests that in P. falciparum commitment to sexual differentiation occurs prior to schizont maturation, at the same moment when the sex of the resulting gametocytes is determined.

Animals↗
PubMed2000

Effects of free radicals and leukocytes on increases in blood-brain barrier permeability during colitis.

This study examined the role of leukocytes and free radicals on increases in permeability of the blood-brain barrier (BBB) in rabbits with acute colitis. Trinitrobenzene sulfonic acid (TNBS) was used to induce colitis in male New Zealand White rabbits. The extraction ratio of fluorescein was used as an index of the permeability of the BBB. The extraction ratio for fluorescein was 1.0 x 10(-3) +/- 2 x 10(-4) ml/g and 1.1 x 10(-3) +/- 3 x 10(-4)ml/g (mean +/- SE) for saline (N = 7) and ascorbic acid-treated (N = 8) rabbits with sham colitis. Conversely, TNBS-induced acute colitis increased the extraction ratio over 70% in saline (N = 8) and ascorbic acid-treated (N = 8) animals. Vinblastine significantly reduced the number of circulating leukocytes, whereas the permeability of the BBB was augmented by 54% in rabbits with TNBS-induced acute colitis (N = 8). Vinblastine had no effect on the permeability of the BBB in rabbits with sham colitis (N = 8). These data suggest that free radicals are not responsible for BBB disruption, and leukocytes may protect the BBB during acute colitis.

Acute Disease↗
PubMed2000

Anisotropic elastic properties of cancellous bone from a human edentulous mandible.

The elastic moduli have not been reported for cancellous bone from the edentulous mandible. Accurate values are needed for finite element modeling of the mandible. The aim of this study was to determine elastic modulus values in three orthogonal directions for cancellous bone taken from an edentulous jaw and to relate these values to apparent density and volume fraction. Seven samples were obtained from the edentulous mandible of a 74-year-old female. Young's modulus was determined by compression testing of cubes cut with the faces aligned with the anatomic axes. Bone volume fraction averaged 0.33 (SD 0.14) and apparent density averaged 0.55 g/cc (SD 0.29). Young's modulus was greatest in the mesio-distal direction (mean 907 MPa, SD 849 MPa), followed by the bucco-lingual (mean 511 MPa, SD 565 MPa) and infero-superior direction (mean 114 MPa, SD 78 MPa). The infero-superior direction was less than the bucco-lingual (P = 0.03) and mesio-distal (P = 0.002). The mesio-distal and bucco-lingual directions could not be shown to be different (P = 0.32). This suggests a model of transverse isotropy for cancellous bone in the jaw, where the symmetry axis is along the infero-superior (weakest) direction.

Aged↗
PubMed2000

Genetic variation in the bovine myostatin gene in UK beef cattle: allele frequencies and haplotype analysis in the South Devon.

Work on Belgian Blue cattle revealed that an 11 base pair (bp) deletion within the bovine myostatin gene (GDF8) is associated with the double-muscled phenotype seen in this breed. Investigations focusing on other European breeds known to show double-muscling identified several mutations within the coding region of the gene associated with the double-muscled phenotype in different breeds. The number of mutations found suggest that myostatin is highly variable within beef cattle. Variations that alter the structure of the gene product such that the protein is inactivated are associated with the most pronounced form of double-muscling as seen in the Belgian Blue. However, other mutations may have a less extreme affect on muscle development. While overt double-muscling gives rise to a high incidence of dystocia (calving difficulty), it is possible that some variants may give enhanced muscling, but with limited calving problems. We describe sequence analysis of the myostatin gene in ten beef breeds commonly used in the UK and show that the 11-bp deletion responsible for double-muscling in the Belgian Blue is also present in the South Devon cattle population. Allele frequencies and haplotypes in the South Devon and a polymerase chain reaction (PCR) based test for the deletion are described. PCR amplification across the deleted region provides a quick and effective test with clear identification of heterozygous individuals. We discuss our results with regard to the effect of genotype on phenotype and differences observed between the Belgian Blue and the South Devon.

Animals↗
PubMed2000

Testing for the presence of previously identified QTL for milk production traits in new populations.

Five chromosomal regions previously associated with milk production traits were tested in 16 families of Black and White cattle from the UK. The traits were also linearly transformed into genetically and phenotypically independent variables normalized by phenotypic variances ('canonical traits'). Significant associations with the untransformed and canonical traits were found for bovine chromosome 6. There was also evidence that chromosome 9 influenced these traits. The linear transformation clarified the effects of chromosomal regions; regions with effects on all three untransformed traits (milk, fat and protein yields) were generally condensed into an effect on a single canonical trait. Comparison of our results with those reported previously for American Holstein cattle suggested that the QTL may not be the same.

Animals↗
PubMed2000

Determination of red cell volume in infants needing blood transfusion.

The total circulating red cell volume (RCV) is a better guide to the oxygen-carrying capacity of the blood in the whole circulation than is the haemoglobin concentration (Hb) or haematocrit in a blood sample. Pre- and post-transfusion RCV (and blood volume (BV)) may be determined by flow cytometry by exploiting antigen differences between transfused donor red cells and the recipient's red cells. This paper describes the use of red cell antigen differences of Duffy, Kidd, MN and RhD between donor and recipient. In 20 infants, transfused on 21 occasions, pretransfusion RCV ranged from 12 to 39 mL kg(-1) body weight. Only at one transfusion could no usable donor-recipient antigen differences be exploited. Measurement of RCV, used routinely, may determine the transfusion requirements of sick infants more accurately, with the aim of normalizing RCV and BV--securing euvolaemia--at the end of the transfusion. This may allow a complete correction of the RCV deficiency at the first occasion of transfusion. This approach may reduce donor exposures and also optimize oxygen transport and organ perfusion of the infant undergoing intensive management, perhaps leading ultimately to improved survival rates and fewer long-term complications of neonatal intensive care.

Autoantigens↗
PubMed2000

Effect of genistein on cardiovascular responses to angiotensin II in conscious unrestrained rats.

Soybeans contain genistein, a phytoestrogen that may have beneficial effects in coronary artery disease, osteoporosis, and breast cancer. In vitro studies demonstrated that genistein reduced vascular smooth muscle contractions to angiotensin II. We tested the hypothesis that genistein attenuates the overall cardiovascular responses to angiotensin II via nongenomic mechanisms in conscious rats. Mean arterial blood pressure (MAP) was recorded from conscious unrestrained Sprague-Dawley rats (n = 26) approximately 48 hours after surgery. Cumulative dose response curves to angiotensin II (10-200 ng/kg/min) were constructed before and after i.v. treatment with genistein given as a single bolus dose of 160 microg/kg or 1500 microg/kg, or as a loading dose of 160 microg/kg followed by an infusion at a rate of 20 microg/kg. Angiotensin II infusions were associated with graded increases in arterial pressure ranging between 0+/-1 and 35+/-4 mm Hg. These pressor responses were accompanied by significant dose-dependent decreases in heart rate. None of the genistein treatment regimens significantly affected the pressor responses to angiotensin II. Accordingly, we conclude that short-term i.v. treatment with genistein does not depress pressor responsiveness to angiotensin II.

Angiotensin II↗