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Biomedical subjects

J L Williams

Publications and source records attributed to J L Williams.

At least 91 records · Page 5Linked to original sources
PubMed2000

Response to bio-terrorism directed against animals.

The Animal and Plant Health Inspection Service (APHIS) has a long history of rapid direction, control, and eradication of devastating diseases. Our immediate response mechanisms to diseases such as avian influenza, Venezuelan equine encephalomyelitis, and Newcastle disease, have long been recognized by the global emergency response community as models of control and eradication. APHIS and the U.S. livestock industries, in partnership with the Animal Agriculture Coalition, re-evaluated the Nation's animal health emergency preparedness and response systems. The group identified areas that negatively impact, biologically and/or economically, the Nation's animal and food production industries. To counter the increased risks including bioterrorism, APHIS plans to establish a world-class "Center of Excellence for Animal Health Emergency Management." APHIS, Intelligence agencies, other Federal departments, State governments, and industries are working together to provide accurate information on the foreign and domestic threats posed to the U.S. agricultural sector by biological weapons. Additionally, the same agencies and organizations are evaluating, updating, and improving the coordination and training mechanisms necessary to respond in the even of a widespread pest or disease outbreak.

Animal Diseases↗
PubMed1999

Transgenic milk as a method for the production of recombinant antibodies.

Recombinant antibodies and their derivatives are increasingly being used as therapeutic agents. Clinical applications of antibodies often require large amounts of highly purified molecules, sometimes for multiple treatments. The development of very efficient expression systems is essential to the full exploitation of the antibody technology. Production of recombinant protein in the milk of transgenic dairy animals is currently being tested as an alternative to plasma fractionation for the manufacture of a number of blood factors (human antithrombin, human alpha-1-antitrypsin, human serum albumin, factor IX). The ability to routinely yield mg/ml levels of antibodies and the scale-up flexibility make transgenic production an attractive alternative to mammalian cell culture as a source of large quantities of biotherapeutics. The following review examines the potential of transgenic expression for the production of recombinant therapeutic antibodies.

Animals↗
PubMed1999

Neurogenesis in the median domain of the embryonic brain of the grasshopper Schistocerca gregaria.

Embryonic development in the median domain of the brain of the grasshopper Schistocerca gregaria was investigated with immunohistochemical, histological, and intracellular dye injection techniques. The early head midline is divisible into a dorsal median domain and a ventral median domain based on the orientation of cell somata in each region. At 25% of embryogenesis, a single large midline precursor differentiates in the dorsal median domain and produces a lineage of six neuronal progeny before degenerating. No further precursors arise. In addition, the primary commissure pioneers and a pair of lateral neurons differentiate directly from the ectoderm in this region. Lucifer yellow dye injected into the midline precursor stains only this cell and its progeny. Similarly, there is no dye coupling from the primary commissure pioneers to the midline lineage or to neuroblasts of the brain hemispheres. Neurogenesis in the dorsal median domain therefore proceeds separately within each subset of cells, and is not related to development in the brain hemispheres. Beginning at 42% of embryogenesis, the primary commissure pioneers undergo a morphological transformation and concomittantly express the Term-1 antigen. Expression continues throughout embryogenesis and into the adult, where the midline primary commissure pioneer cells are the only ones labeled by Term-1 in the entire brain. The cellular organization of the dorsal median domain therefore remains remarkably conserved throughout embryogenesis, even as the brain undergoes extensive morphological transformation.

Animals↗
PubMed1999

Filippi syndrome: report of three additional cases.

Filippi syndrome is an autosomal recessive condition characterized by variable soft tissue syndactyly of the fingers and toes, microcephaly, pre- and postnatal growth retardation, mildly abnormal craniofacial appearance, and mental retardation. We report on three unrelated individuals with Filippi syndrome. All have microcephaly, minor facial anomalies, variable syndactyly of digits, growth impairment, and developmental delay. One patient also has polydactyly, which has not been reported previously in the Filippi syndrome.

Abnormalities, Multiple↗
PubMed1999

Shear strength of the physis varies with anatomic location and is a function of modulus, inclination, and thickness.

Slipped capital femoral epiphysis involves the gradual displacement of the femoral head relative to the neck. Many theories have arisen to explain this slip. Frequently cited etiological factors include increases in physeal thickness and inclination. Slipped epiphysis has been postulated to result from shear overload that causes separation through the hypertrophic cellular zone. We sought to answer the following questions: (a) Do significant regional differences in strength and stiffness exist within a given physis? (b) Are regional differences in resistance to shear related to thickness and inclination of the physis? (c) Does physeal compression cause mammillary interdigitation to begin sooner and increase the resistance to shear before, during, and after failure? (d) Does shear failure occur at displacements detectable by radiography? and (e) Does cleavage occur throughout the entire columnar zone, and do the chondrocyte columns remain intact on both sides of the cleavage plane? We prepared beam-shaped microstructural samples from different sites of the bovine proximal tibial physis. We determined thickness, inclination, ultimate stress and strain, modulus, and strain energy density at ultimate stress as a function of location. Using scanning electron microscopy, we also examined the entire failed surface of several samples. Forty-eight samples were tested by displacing the epiphysis end anteriorly, without axial (across the thickness) constraint; 41 were sheared while an average axial compressive stress of 0.3 MPa was applied to the physis. The posterior region had the greatest strength and stiffness, lowest physeal thickness, and steepest inclination. Compressing the plate did not increase the shear strength or tangent modulus. Ultimate strength varied inversely with thickness and increased when shearing up steeper inclinations; however, it was more strongly associated with the modulus, implying that additional factors control both strength and modulus. Scanning electron microscopy revealed that the plane of fracture differed widely between and within samples, involving all zones of the growth plate. On either side of the fracture, individual chondrocyte columns remained intact, although separated from neighboring columns.

Animals↗
PubMed1999

A 5x genome coverage bovine BAC library: production, characterization, and distribution.

A bovine large-insert DNA library has been constructed in a Bacterial Artificial Chromosome (BAC) vector. The source DNA was derived from lymphocytes of a Jersey male. High-molecular-weight DNA fragments were produced by treatment with EcoRI/EcoRI methylase and cloned into the EcoRI site of pBACe3.6. In total, 157,240 individual BACs have been picked into 384-well plates. Approximately 190 randomly chosen clones have been characterized by Pulsed Field Gel Electrophoresis (PFGE) and have an average insert size of 105 kb, suggesting library coverage representing 5-6 genome equivalents. The frequency of clones without inserts is 4%. The chromosomal location of 51 BACs was studied by FISH; 3 showed more than one signal, indicating a chimerism frequency of roughly 6%. Approximately 50% of the clones in the library contain Simple Repeat Sequences (microsatellites), and 4% of the clones contain centromeric repeats. Insert stability was assessed by restriction digestion of DNA prepared from 20 clones after serial culture for one and three nights. Only one clone showed any evidence of an altered restriction pattern. Clones from 360 x 384-well plates (138,240 colonies) were gridded onto high-density membranes, and PCR superpools were produced from the same set of clones. Both membranes and superpools are available from the RZPD, Berlin (http://www.rzpd.de). PCR 4-D superpools have been prepared from an additional 23,000 clones. The library has been screened for a total of 24 single-copy sequences; positive clones have been obtained in all cases.

Animals↗
PubMed1999

A comparative study in rats of the in vitro and in vivo pharmacology of the acetylcholinesterase inhibitors tacrine, donepezil and NXX-066.

The in vitro and in vivo effects of the novel acetylcholinesterase inhibitors donepezil and NXX-066 have been compared to tacrine. Using purified acetylcholinesterase from electric eel both tacrine and donepezil were shown to be reversible mixed type inhibitors, binding to a similar site on the enzyme. In contrast, NXX-066 was an irreversible non-competitive inhibitor. All three compounds were potent inhibitors of rat brain acetylcholinesterase (IC50 [nM]; tacrine: 125 +/- 23; NXX-066: 148 +/- 15; donepezil: 33 +/- 12). Tacrine was also a potent butyrylcholinesterase inhibitor. Donepezil and tacrine displaced [3H]pirenzepine binding in rat brain homogenates (IC50 values [microM]; tacrine: 0.7; donepezil: 0.5) but NXX-066 was around 80 times less potent at this M1-muscarinic site. Studies of carbachol stimulated increases in [Ca2+]i in neuroblastoma cells demonstrated that both donepezil and tacrine were M1 antagonists. Ligand binding suggested little activity of likely pharmacological significance with any of the drugs at other neurotransmitter sites. Intraperitoneal administration of the compounds to rats produced dose dependent increases in salivation and tremor (ED50 [micromol/kg]; tacrine: 15, NXX-066: 35, donepezil: 6) with NXX-066 having the most sustained effect on tremor. Following oral administration, NXX-066 had the slowest onset but the greatest duration of action. The relative potency also changed, tacrine having low potency (ED50 [micromol/kg]; tacrine: 200, NXX-066: 30, donepezil: 50). Salivation was severe only in tacrine treated animals. Using in vivo microdialysis in cerebral cortex, both NXX-066 and tacrine were found to produce a marked (at least 30-fold) increase in extracellular acetylcholine which remained elevated for more than 2 h after tacrine and 4 h after NXX-066.

Acetylcholinesterase↗
PubMed1999

Temporal patterns of colonic blood flow and tissue damage in an animal model of colitis.

This study tested the hypothesis that altered colonic blood flow may contribute to tissue damage during the development of colitis in the rabbit. This was achieved by using radioactive microspheres to measure colonic blood flow at various times after colitis induction with trinitrobenzene sulfonic acid. Significant colonic damage occurred 6 hours post colitis induction and persisted throughout the 5 day study. Blood flow to the muscularis propria and mucosa/muscularis mucosae compartments increased significantly from 5 minutes until one hour post induction. At 6 and 12 hours post induction colonic blood flow returned to control levels before increasing again from 24 to 96 hours. This second increase in flow was, however, predominantly in the mucosa/muscularis mucosae compartment. Blood flow in the stomach and non-gastrointestinal tissues did not change significantly at any time. These data demonstrate that increased colonic blood flow may be disrupted in the early stages of colitis and that this coincides with the onset of significant damage. It is concluded that maintenance of elevated colonic blood flow throughout the development of colitis may help to ameliorate subsequent tissue injury.

Animals↗
PubMed1999

Production of goats by somatic cell nuclear transfer.

In this study, we demonstrate the production of transgenic goats by nuclear transfer of fetal somatic cells. Donor karyoplasts were obtained from a primary fetal somatic cell line derived from a 40-day transgenic female fetus produced by artificial insemination of a nontransgenic adult female with semen from a transgenic male. Live offspring were produced with two nuclear transfer procedures. In one protocol, oocytes at the arrested metaphase II stage were enucleated, electrofused with donor somatic cells, and simultaneously activated. In the second protocol, activated in vivo oocytes were enucleated at the telophase II stage, electrofused with donor somatic cells, and simultaneously activated a second time to induce genome reactivation. Three healthy identical female offspring were born. Genotypic analyses confirmed that all cloned offspring were derived from the donor cell line. Analysis of the milk of one of the transgenic cloned animals showed high-level production of human antithrombin III, similar to the parental transgenic line.

Animals↗
PubMed1999

Discriminating among cattle breeds using genetic markers.

Genetic markers provide a potentially powerful means of identifying the breed of individual animals. In this study diallelic and microsatellite loci were compared for their efficiency in discriminating among cattle breeds. Data were simulated for seven European cattle breeds using allele frequencies estimated at 20 microsatellite and 30 diallelic markers. Animals were assigned to the breed for which their genotype had the highest probability, and the power of the method assessed by estimating the error rate or proportion of animals misclassified. The number of markers required for discriminating among pure, or both pure and crossbreed, animals was investigated using either randomly sampled markers or markers selected on individual error rate. The relationship between individual marker variability and discriminatory power was also investigated. Microsatellite markers were found to be more powerful than diallelic markers for distinguishing among the breeds. The most discriminatory markers were those with the highest average heterozygosity and observed number of alleles. The number of markers needed to achieve a particular error rate could be reduced by selecting markers with the lowest individual error rates. Discrimination among both crossbreeds and pure breeds required approximately three times as many markers as discrimination among pure breeds alone.

Animals↗
PubMed1999

Failed instrumental delivery: how safe is the use of a second instrument?

An audit of failed instrumental deliveries was undertaken to assess the incidence of complications and the adequacy of documentation. When one instrument has failed to effect delivery, the use of a second instrument could in most cases be used to complete the delivery without harm to the mother or baby. However in a small but significant number of cases there are severe maternal or perinatal complications, and these could be the subject of litigation. This could be avoided by adequate pre-application assessment, standard conduct of instrumental delivery and full documentation. Inadequate documentation could be overcome by the use of a pro forma. Selective use of plastic and metal cups could reduce the incidence of failed attempts.

Journal Article↗
PubMed1999

A high proportion of bovine blastocysts produced in vitro are mixoploid.

Fluorescence in situ hybridization with chromosome 6- and chromosome 7-specific probes was used to assess the extent of chromosome abnormalities in developing bovine blastocysts at 7-8 days after insemination in vivo or in vitro. Interphase nuclei (N = 10 946) were analyzed from 151 blastocysts produced in vitro and from 28 blastocysts recovered from superovulated animals. This revealed that 72% (109 of 151) of the in vitro-produced blastocysts were mixoploid, i.e., were a mixture of normal, diploid, and polyploid cells. However, only a small fraction of the total number of cells were chromosomally abnormal. Of the mixoploid blastocysts, 83% (91 of 109) contained less than 10% polyploid cells, 13% (14 of 109) contained 11-25% polyploid cells, and only 4% (4 of 109) of the blastocysts had more than 25% polyploid cells per blastocyst. In contrast, a significantly lower proportion (25%) of mixoploidy was found in 28 bovine blastocysts developed in vivo (p < 0.0001). All of the mixoploid blastocysts that had developed in vivo contained less than 10% polyploid cells. No entirely aneuploid blastocysts, i. e., blastocysts in which all cells had the same type of chromosome abnormality, were found in either of the groups. Taken together, the most common chromosome abnormalities observed were diploid-triploid mixoploidies and diploid-tetraploid mixoploidies. Thus, our results confirm earlier reports that morphologically normal bovine blastocysts developed in vivo are often mixoploids. We further show that in vitro-produced bovine blastocysts have a high rate of mixoploidy. Although the difference in mixoploidy rate detected in this study may not be general, it is an interesting phenomenon for further studies.

Animals↗
PubMed1999

Experimental colitis increases blood-brain barrier permeability in rabbits.

Extraintestinal manifestations of inflammatory bowel disease are numerous. This study examined the effects of two models of acute colitis on cerebral blood flow (CBF) and permeability of the blood-brain barrier in rabbits. CBF (measured with radiolabeled microspheres), or the extraction ratio or permeability-surface area (PS) product of the blood-brain barrier to fluorescein and FITC-dextran, was measured 48 h after colitis induction with acetic acid (HAc) or trinitrobenzene sulfonic acid (TNBS). PS product for fluorescein increased (P < 0.05) in TNBS colitis (1.33 x 10(-5) +/- 0.52 x 10(-5) ml/s and 0.48 x 10(-5) +/- 0.13 x 10(-5) ml/s (mean +/- SE) for treated (n = 14) and untreated (n = 10) animals, respectively. PS product for the larger FITC-dextran was not different in TNBS colitis (0.24 x 10(-5) +/- 0.09 x 10(-5) ml/s, n = 7) compared with untreated controls (0.19 x 10(-5) +/- 0.04 x 10(-5) ml/s, n = 8). PS product for fluorescein increased (P < 0.01) in HAc colitis compared with vehicle (2.66 x 10(-5) +/- 1.46 x 10(-5) ml/s and 0.33 x 10(-5) +/- 0.05 x 10(-5) ml/s, respectively; n = 6 in each group). The extraction of fluorescein from the blood to the brain increased by 75% during TNBS colitis when compared with vehicle (P < 0.05). CBF and cerebrovascular resistance did not change from the untreated control after TNBS colitis. Our data suggest that, irrespective of induction method, acute colitis increases the permeability of the blood-brain barrier to small molecules without changing CBF.

Acetic Acid↗
PubMed1999

Stimulation of Plasmodium falciparum gametocytogenesis by conditioned medium from parasite cultures.

Plasmodium falciparum gametocyte development was examined in erythrocyte monolayer cultures prepared with Cell-Tak, a cell and tissue adhesive. The monolayers, which were stable for up to 10 days in culture, supported multiple cycles of asexual growth and the development of clusters of stage IV gametocytes. Small numbers of chicken erythrocytes incorporated into the monolayers served as internal reference standards for parasite counts. This permitted quantitative assessment of gametocyte formation under different culture conditions. Gametocyte formation was limited in monolayers grown in standard culture medium but it increased slightly in monolayers cocultured with suspensions of parasitized erythrocytes. The number of gametocytes increased significantly in monolayers grown in parasite-conditioned medium. In both cases the changes resulted from increased numbers of stage II and III gametocytes in the monolayers. These results suggest that parasite conditioned medium contains a factor(s) that stimulates sexual development.

Animals↗