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Biomedical subjects

G L Bennett

Publications and source records attributed to G L Bennett.

At least 91 records · Page 5Linked to original sources

Simulated influence of postweaning production system on performance of different biological types of cattle: III. Biological efficiency.

Methods were developed and incorporated into a previously published computer model to predict ME intake and calculate biological efficiencies in terms of grams of empty BW (EBW) and fat-free matter (FFM) gained/megacalorie of ME consumed from weaning to slaughter. Efficiencies were calculated for steers from F1 crosses of 16 sire breeds (Hereford, Angus, Jersey, South Devon, Limousin, Simmental, Charolais, Red Poll, Brown Swiss, Gelbvieh, Maine Anjou, Chianina, Brahman, Sahiwal, Pinzgauer, and Tarentaise) mated to Hereford and Angus dams, grown under nine backgrounding systems, finished at either a low (1.0 kg) or high (1.36 kg) ADG, and slaughtered at 300 kg carcass weight, small or greater degree of marbling, and 28% carcass fat. Backgrounding systems were high ADG (.9 kg) for 111, 167, or 222 d, medium ADG (.5 kg) for 200, 300, or 400 d, and low ADG (.25 kg) for 300 or 400 d, and 0 d backgrounding. The high ADG finishing system was more biologically efficient than the low ADG finishing system, and generally backgrounding systems were less biologically efficient than direct finishing after weaning (0 d backgrounding). Large-framed breeds were more efficient at the constant carcass weight and carcass fatness end point, and breeds that achieved the marbling end point at low levels of carcass fatness were more efficient at this end point. Some small-framed breeds gained EBW more efficiently but gained FFM less efficiently than some of the large-framed breeds. Variation in efficiency between genotypes was greatest with 0 d backgrounding and decreased in the other backgrounding systems.

Aging↗

Silage or limit-fed grain growing diets for steers: I. Growth and carcass quality.

The influence of energy source (silage- [S] or grain- [G] based) on organ growth, carcass quality, and meat acceptability independent of rate of gain was examined. Sixty-four Angus steers were allotted to one of the two treatments and given ad libitum access to silage or limit-fed grain for 145 d. All steers were then given ad libitum access to a grain diet for 45, 75, or 105 d. Eight steers from each treatment were slaughtered at the end of the growing phase and at each of the termination dates. The silage-based growing diet consisted (DM basis) of 55% sorghum silage (averaged 23.6% dry matter), 22% alfalfa hay, 10.8% ground shelled corn, and 10.8% soybean meal and contained 12.8% CP. Dry matter in the grain-based diet, composed of 76.5% ground shelled corn, 5% soybean meal, 13.6% cottonseed hulls, 3.5% molasses, and .4% salt and 1% limestone, contained 12.1% CP. It was limit-fed to produce rates of gain similar to the silage diet eaten ad libitum, using net energy for gain of each diet calculated from organic matter digestibility determined in digestion trials. The finishing diet was similar to the grain growing diet except that alfalfa hay replaced the cottonseed hulls. No implants or ionophores were used. High silage moisture decreased ADG the first 45 d, so steers fed grain gained faster, but thereafter gains were similar. At the end of the growing phase, steers fed grain had heavier shrunk and empty body weights and larger livers. However, liver size was not different when adjusted for growing ADG. By 45 d with ad libitum access to the finishing diet, 75% of the carcasses from steers fed both diets graded Choice. Steers fed silage had tougher (P < .05) steaks with less flavor intensity (P < .05) at the end of the growing phase; these differences diminished after 75 d on feed. These results suggest that choice beef can be produced in only 45 d in the feedlot, but tenderness and flavor among Choice carcasses remained inferior for steers fed silage for at least 75 d on a high-grain diet.

Animals↗

The use of magnetic resonance imaging in the diagnosis of stress fractures of the foot and ankle: four case reports.

Stress fractures result when bone is subjected to repeated loading which causes fatigue, cracking of the bone, and, eventually, a complete fracture. Stress fractures of the foot and ankle are common injuries affecting a broad range of the population, from the young to the elderly, the fitness enthusiast to the chronically debilitated. The diagnosis of stress fracture is not always obvious because radiographs are often negative, especially on initial presentation. In this report, we present four cases in which, after appropriate initial studies proved inconclusive, magnetic resonance imaging (MRI) was used to establish the diagnosis of stress fracture. We propose that MRI is a useful diagnostic modality in a select group of patients with suspected stress fractures of the foot and ankle.

Adolescent↗

Implications of genetic changes in body composition on beef production systems.

Changing the body composition of beef has implications for the entire beef production system. The dynamic nature of an animal's body composition and the production system itself make predictions of the implications of genetic change in body composition difficult. The cow-calf, stocker, and feeder segments of the production system will be affected differently. Leaner cattle tend to be slaughtered at heavier weights. Heavier weights effectively reduce composition differences of slaughter beef to less than the genetic differences. The effects of four pricing scenarios on slaughter weight and composition were evaluated for two leaner genotypes, one with no change in marbling and one with reduced marbling. A genetic difference of 1.0 yield grade at the same carcass weight resulted in slaughter beef that differed by .4 to 1.0 yield grade because of increased slaughter weights. Separate analyses suggested the stocker segment of beef production will be least affected by changes in body composition. Genotypes that are best fitted to slaughter requirements will have the most flexibility in types of stocker systems that can be used. The cow-calf segment of beef production has several options to adapt to leaner cattle. Management to reduce nutritional stress on leaner cows may be required by some producers. Increased selection for reproductive traits in cow genotypes may be needed. An alternative to selection for reproduction is terminal crossing to partially disassociate the slaughter animals' genotype from the cow's genotype.

Animal Husbandry↗

Characterization of two high affinity human interleukin-8 receptors.

Interleukin 8 (IL-8) and melanocyte growth-stimulatory activity/gro (MGSA) are structurally related proinflammatory cytokines that are chemoattractants and activators of neutrophils. Recently, cDNA clones encoding a high affinity IL-8 receptor (IL-8R-A) and a "low affinity" IL-8 receptor (IL-8R-B) have been isolated from human cDNA libraries. These two receptors have 77% amino acid identity and are members of the G protein-coupled superfamily of receptors with seven transmembrane domains. We have expressed these two receptors in mammalian cells and find that in this system both receptors bind IL-8 with high affinity (Kd approximately 2 nM). The receptor affinities differ for MGSA, however. IL-8R-A binds MGSA with low affinity (Kd approximately 450 nM); IL-8R-B binds MGSA with high affinity (Kd approximately 2 nM). The transfected cells respond to ligand binding with a transient increase in the intracellular Ca2+ concentration. A Ca2+ response is found for IL-8R-A following the binding of IL-8; no response is found for MGSA. A Ca2+ response for IL-8R-B follows the binding of both ligands. Blot hybridization with oligonucleotide probes specific for the two receptors shows that mRNA for both receptors is present in human neutrophils. Analysis of IL-8 and MGSA binding data on neutrophils as well as Ca2+ response and desensitization data shows that the presence of these two IL-8 receptors on the cell surface can account for the profile of these two ligands on neutrophils.

Amino Acid Sequence↗

Structure-function analysis of hepatocyte growth factor: identification of variants that lack mitogenic activity yet retain high affinity receptor binding.

Hepatocyte growth factor (HGF) is a potent mitogen for parenchymal liver, epithelial and endothelial cells. Structurally, it has similarities to kringle-containing serine proteases, although it does not possess proteolytic activity. A structure-activity relationship study of human HGF was performed by functional analysis of HGF substitution and deletion variants. Analysis of HGF variants was accomplished by defining their ability to induce DNA synthesis on hepatocytes in primary culture and to compete with wild-type HGF for binding to a soluble form of the HGF receptor. Three groups of variants were made: (i) substitutions at the cleavage site, (ii) substitutions within the protease-like domain and (iii) deletions of the beta-chain and/or kringle domains. Our results show that: (i) single-chain HGF is a zymogen-like promitogen in that cleavage into a two-chain form is required for biological activity, however, the single chain form of HGF still retains substantial receptor binding capacity; (ii) certain mutations in the protease-like domain result in variants that are completely defective for mitogenic activity, yet exhibit apparent receptor binding affinities similar to wild-type HGF (Kd approximately 50-70 pM); and (iii) a variant containing the N-terminal 272 residues of mature HGF showed only a 4-fold increase in Kd when compared with wild-type HGF indicating that a primary receptor binding determinant is located within this sequence.

Animals↗

Recovery of cholinergic phenotype in the injured rat neostriatum: roles for endogenous and exogenous nerve growth factor.

Polyclonal antibodies against recombinant human nerve growth factor (rhNGF) potently inhibited PC12 neurite outgrowth, blocked high-affinity 125I-rhNGF binding but not its receptor, and cross-reacted with rat, mouse, and human nerve growth factor (NGF) but not with brain-derived neurotrophic factor, neurotrophin-3, ciliary neurotrophic factor, insulin-like growth factor, epidermal growth factor, or activin A. Immunocytochemistry revealed many NGF-positive neurons in the rat neostriatum. The NGF-positive neurons disappeared by 3 days after mechanical injury to the neostriatum and were replaced by intensely NGF- and glial fibrillary acidic protein-positive astrocytes. Enzyme-linked immunosorbent assay measurements revealed that the NGF content of the injured striatum was elevated by eightfold 3 days postinjury and by twofold 2 weeks later. The high-affinity choline uptake (HACU) into cholinergic nerve terminals was decreased by 23% at 2 and 4 weeks postinjury, yet choline acetyltransferase (ChAT) activity in these neurons was unchanged at 2 weeks and decreased by 14% at 4 weeks. Daily infusion of 1 microgram of rhNGF into the injury area did not alter the loss of HACU. However, this treatment elevated ChAT activity by 23-29% above intact neostriatal levels and by 53-65% relative to HACU at both survival times. Thus, lesion-induced increases in NGF levels within astrocytes are associated with maintenance of striatal ChAT activity at normal levels following cholinergic injury, even with decreases in HACU. Pharmacologic doses of rhNGF can further augment ChAT activity in damaged cholinergic neurons, showing the usefulness of exogenous NGF even when endogenous NGF is elevated in response to injury.

Animals↗

Binding sites for vascular endothelial growth factor are localized on endothelial cells in adult rat tissues.

Vascular endothelial growth factor (VEGF) is a secreted heparin-binding mitogen; its growth-promoting activity is limited to vascular endothelial cells in vitro and VEGF also stimulates angiogenesis in vivo. To identify target cells for VEGF and investigate the potential physiological role of this factor, iodinated recombinant human VEGF (125I-rhVEGF) was used for in vitro ligand autoradiography on tissue sections from adult rats. 125I-rhVEGF exhibited saturable, displaceable binding to a single class of sites with high affinity and low capacity in all tissues and organs examined. Colocalization of 125I-rhVEGF binding with Factor VIII-like immunoreactivity demonstrated binding sites associated with vascular endothelial cells of both fenestrated and nonfenestrated microvessels and the endothelium of large vessels, while no displaceable binding was evident on nonendothelial cells. Specific binding was associated with quiescent as well as proliferating vessels. These findings support the hypothesis that VEGF plays a specific role in both the maintenance and in the induction of growth of vascular endothelial cells.

Animals↗

Thyroid follicular cells produce interleukin-8.

Interleukin-8 (IL-8) is a potent proinflammatory cytokine known to be produced by several cell types. To elucidate whether endocrine cells can also make IL-8, we have tested supernatants from eleven thyroid follicular cell primary cultures. IL-8 was readily detected under basal conditions (range 3.4-32.1 ng/ml from 1 x 10(5) cells in 3 days) and was increased 4-20 fold by stimulation with IL-1. TSH and tumor necrosis factor had an inconsistent effect, while gamma-interferon reduced basal and IL-1-stimulated IL-8 production. Since IL-8 can act as a chemoattractant for lymphocytes, these observations may explain in part the accumulation of lymphocytes within the gland in autoimmune thyroiditis.

Cells, Cultured↗

Predicting lean growth while accounting for correlated traits.

Lean tissue growth rate is usually estimated from indirect measurements including growth rate. A procedure to determine prediction equations for lean tissue growth rate is proposed. The procedure restricts the regression of fat growth rate on predicted lean growth rate to be equal to the regression of fat growth rate on actual lean growth rate. The restriction can be phenotypic or genetic if suitable parameter estimates are available. When applied phenotypically, selection on predicted lean tissue growth rate will result in selection differentials for both fat and lean tissue growth rates that are proportional to those obtained by direct selection for lean tissue growth rate. This restriction is desirable because expected correlated changes in fat are used to justify selection for lean tissue growth. Conventional prediction procedures have ignored correlated changes and obscured the original intent of using lean tissue growth rate as a biological selection criterion. When using conventional procedures to predict a biological selection criterion from indirect measurements, changes in important correlated traits may depend more on the choice of indirect measurements than on the choice of selection criterion.

Adipose Tissue↗

A computer model to predict the effects of level of nutrition on composition of empty body gain in beef cattle: I. Theory and development.

A computer model was developed to simulate differences in the composition of empty body gain of beef cattle resulting from differences in postweaning level of nutrition that are not associated with empty BW. Differences in rate of empty body gain of cattle of similar genotype reflect differences in the level of nutrition; hence, empty body gain was used to represent level of nutrition. The model was based on four assumptions: 1) as animals mature, the proportion of fat is greater in gain than in body weight, 2) effects on body composition caused by plane of nutrition that are not associated with empty BW are predictable from rate of empty BW gain, 3) effects resulting from changes in nutrition are not exerted immediately nor are they permanent, and 4) cattle approach an empty body composition equilibrium when empty body gain is zero. Six parameters were used to characterize mature fat-free matter, rate of change to body composition equilibrium, minimum and maximum fractional growth rate relative to fractional growth rate for empty BW, time lag of response to change in nutrition, and influence of stage of maturity and nutrition on rate of change for fat-free matter. Two parameters were specific for genotype and gender. Using results from the model, we were able to explain conflicting results obtained from compensatory gain experiments.

Adipose Tissue↗

A computer model to predict the effects of level of nutrition on composition of empty body gain in beef cattle: II. Evaluation of the model.

A computer model developed to predict composition of empty body gain of beef cattle fed at different levels of nutrition was evaluated with data from one unpublished and seven published experiments. These experiments used several breeds of beef cattle growing at rates that varied from negative to fast and various combinations of these growth rates. There was close agreement between observed and simulated absolute treatment means for fatness, except when animals were fed diets low in protein. In this case, experimental animals fed inadequate protein grew at slower rates and became fatter than contemporaries fed adequate protein, whereas the model predicted the opposite. Ability of the model to predict effects of nutrition not associated with changes in BW was evaluated using the proportion of residual variation in experimental fat percentage accounted for by the model, after fitting linear and quadratic terms for empty BW. The model accounted for 13.8 to 56.2% of the residual variation in observed fatness in four experiments in which significant differences in fatness were observed among nutritional treatments after accounting for differences in empty BW. Regression of observed fatness on model-simulated fatness resulted in regression coefficients that were positive and close to 1 in these four experiments. This suggests that the model can accurately predict some of the effects of nutrition on fatness that are not associated with changes in empty BW.

Adipose Tissue↗

Brain tumours and lymphomas in transgenic mice that carry HTLV-I LTR/c-myc and Ig/tax genes.

The human T-cell leukemia virus type 1 (HTLV-I) is associated with adult CD4+ T-cell leukemia (ATL) and tropical spastic paraparesis (TSP). In as much as only a small percentage of individuals infected with HTLV-I develop either disease, we set out to model a genetic partner for this virus in an effort to understand and possibly reproduce its pathophysiology. To this end we have developed a binary set of transgenic mice, one bearing the relatively inactive HTLV-I long terminal repeat (LTR) positioned to drive the c-myc oncogene and another bearing a fusion transgene consisting of the immunoglobulin promoter/enhancer driving the gene for the HTLV-I transcription activator, tax. Alone, the tax construct, though expressed in the thymus, spleen, lung and brain, has no deleterious effect. Alone, the HTLV-I LTR/c-myc construct is expressed at very low levels in lymphoid cells and occasionally induces lymphomas in older animals. When these two transgenic lines are mated, bigenic offspring harboring both transgenes exhibit dramatic tumor formation. As in the human, these animals develop CD4+ T-cell lymphomas, but they also develop central nervous system tumors by 25-90 days of age. The syndrome, which is 100% penetrant and lethal, provides an animal model for adult T-cell lymphoma and a source of cultured cells of neurogenic origin.

Animals↗

Extracellular domain-IgG fusion proteins for three human natriuretic peptide receptors. Hormone pharmacology and application to solid phase screening of synthetic peptide antisera.

The natriuretic peptide receptors (NPRs) are a family of three cell surface glycoproteins, each with a single transmembrane domain. Two of these receptors, designated NPR-A and NPR-B, are membrane guanylyl cyclases that synthesize cGMP in response to hormone stimulation. The third receptor, NPR-C, has been reported to function in the metabolic clearance of ligand and in guanylyl cyclase-independent signal transduction. We engineered three chimeric proteins consisting of the natriuretic peptide receptor extracellular domains fused to the Fc portion of human IgG-gamma 1. These molecules provide material for detailed studies of the human receptor's extracellular domain structure and interaction with the three human natriuretic peptides, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and type-C natriuretic peptide (CNP). The homodimeric fusion proteins, designated A-IgG, B-IgG, and C-IgG, were secreted from Chinese hamster ovary cells and purified by protein-A affinity chromatography. We present here the primary characterization of these fusion proteins as represented by the intrinsic hormone affinities measured by saturation binding and competition assays. The dissociation constant of 125I-ANP for A-IgG was 1.6 pM and for C-IgG, 1.2 pM. The dissociation constant of 125I-Y0-CNP (CNP with addition of tyrosine at the amino terminus) for B-IgG was 23 pM. The rank order of potency in competitive binding for A-IgG was ANP greater than BNP much greater than CNP, whereas for B-IgG the ranking was CNP much greater than ANP greater than BNP. For C-IgG, we observed ANP greater than CNP greater than or equal to BNP. These data demonstrate that the receptor-IgG fusion proteins discriminate among the natriuretic peptides in the same manner as the native receptors and provide a basis for future structural studies with these molecules. The purified fusion proteins have a variety of potential applications, one of which we illustrate by a solid phase screening assay in which rabbit sera from a series of synthetic-peptide immunizations were titered for receptor reactivity and selectivity.

Amino Acid Sequence↗

Increase in glia-derived nerve growth factor following destruction of hippocampal neurons.

It is currently believed that under normal conditions hippocampal neurons synthesize nerve growth factor (NGF) which may provide trophic support for cholinergic neurons projecting from the basal forebrain. The concept that glial cells are mobilized to increase the production of NGF following destruction of hippocampal neurons was examined. Excitotoxin-induced destruction of the dorsal hippocampal neurons resulted in a massive and prolonged increase in NGF-like immunoreactivity (LI). Immunostaining for NGF-LI and the glial marker, glial fibrillary acidic protein (GFAP), revealed that the source of increased NGF-LI production following the lesion were reactive astrocytes. Thus, glial cells assume the role of providing trophic support following loss of target neurons.

Animals↗

Increase in nerve growth factor-like immunoreactivity and decrease in choline acetyltransferase following contusive spinal cord injury.

We have previously described a graded spinal cord injury model in the rat. Mild contusive injury results in an initially severe functional deficit that is attenuated over time to reveal the mild chronic deficits that characterize this injury. In this study, we have shown that mild contusive injury also results in a significant decrease in choline acetyltransferase (ChAT) activity during the first week after injury. At 1 week ChAT activity is maximally reduced at the site of the contusion and is also significantly lowered throughout the spinal cord. ChAT activity then rebounds during the following 3 weeks, partially at the injury site where there is considerable loss of gray and white matter, and completely in rostral and caudal cord segments. The rebound in ChAT activity is temporally associated with the partial recovery of function. Further, the changes in ChAT activity after injury are mirrored by changes in nerve growth factor-like immunoreactivity (NGF-LI) as determined by a specific two-site ELISA. NGF-LI increases significantly after injury, reaching a maximum at 7 days after contusion and at the injury site. However, levels of NGF-LI are also significantly increased throughout the spinal cord. NGF-LI then decreases at 2 and 4 weeks as ChAT activity rebounds. Further experiments will be needed to examine the possibility of a role for NGF in promoting the recovery of function after spinal cord injury.

Animals↗