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Biomedical subjects

G L Bennett

Publications and source records attributed to G L Bennett.

At least 109 records · Page 6Linked to original sources

Selective activation of the B natriuretic peptide receptor by C-type natriuretic peptide (CNP).

The natriuretic peptides are hormones that can stimulate natriuretic, diuretic, and vasorelaxant activity in vivo, presumably through the activation of two known cell surface receptor guanylyl cyclases (ANPR-A and ANPR-B). Although atrial natriuretic peptide (ANP) and, to a lesser extent, brain natriuretic peptide (BNP) are efficient activators of the ANPR-A guanylyl cyclase, neither hormone can significantly stimulate ANPR-B. A member of this hormone family, C-type natriuretic peptide (CNP), potently and selectively activated the human ANPR-B guanylyl cyclase. CNP does not increase guanosine 3',5'-monophosphate accumulation in cells expressing human ANPR-A. The affinity of CNP for ANPR-B is 50- or 500-fold higher than ANP or BNP, respectively. This ligand-receptor pair may be involved in the regulation of fluid homeostasis by the central nervous system.

Animals↗

Cloning and expression of cDNAs for two distinct murine tumor necrosis factor receptors demonstrate one receptor is species specific.

Complementary DNA clones encoding two distinct tumor necrosis factor receptors were isolated from a mouse macrophage cDNA library. The cDNA for murine tumor necrosis factor receptor type 1 (mTNF-R1) predicts a mature polypeptide of 425 amino acids that is 64% identical to its human counterpart, whereas the cDNA of murine tumor necrosis factor receptor type 2 (mTNF-R2) predicts a mature protein of 452 amino acids that is 62% identical to human tumor necrosis factor receptor type 2. The two murine tumor necrosis factor receptors have limited sequence homology (approximately 20% identity) in their extracellular regions but no apparent similarity in their cytoplasmic portions. Northern (RNA) analysis indicates a single 2.6-kilobase (kb) transcript for mTNF-R1; a 3.6-kb and a more predominant 4.5-kb transcript are observed for mTNF-R2. A human cell line transfected with either mTNF-R1 or mTNF-R2 expression vectors specifically bound 125I-labeled recombinant murine tumor necrosis factor alpha (TNF-alpha). Although mTNF-R1 had a similar affinity for both recombinant murine TNF-alpha and human TNF-alpha, mTNF-R2 showed strong specificity for recombinant murine TNF-alpha. This result suggests that the various activities of human tumor necrosis factor alpha reported in mice or in murine cell lines are probably mediated by mTNF-R1.

Amino Acid Sequence↗

Recombinant human nerve growth factor is biologically active and labels novel high-affinity binding sites in rat brain.

Iodinated recombinant human nerve growth factor (125I-rhNGF) stimulated neurite formation in PC12 cell cultures with a half-maximal potency of 35-49 pg/ml, compared with 39-52 pg/ml for rhNGF. In quantitative ligand autoradiography, the in vitro equilibrium binding of 125I-rhNGF to brain sections showed a 10-fold regional variation in density and was saturable, reversible, and specifically displaced by up to 74% with rhNGF or murine NGF (muNGF). At equilibrium, 125I-rhNGF bound to these sites with high affinity (Kd 52-85 pM) and low capacity (Bmax less than or equal to 13.2 fmol/mg of protein). Calculation of 125I-rhNGF binding affinity by kinetic methods gave average Kd values of 24 and 31 pM. Computer-generated maps revealed binding in brain regions not identified previously with 125I-muNGF, including hippocampus; dentate gyrus; amygdala; paraventricular thalamus; frontal, parietal, occipital, and cingulate cortices; nucleus accumbens; olfactory tubercle; subiculum; pineal gland; and medial geniculate nucleus. NGF binding sites were distributed in a 2-fold increasing medial-lateral gradient in the caudate-putamen and a 2-fold lateral-medial gradient in the nucleus accumbens. 125I-rhNGF binding sites were also found in most areas labeled by 125I-muNGF, including the interpedunucular nucleus, cerebellum, forebrain cholinergic nuclei, caudoventral caudate-putamen, and trigeminal nerve nucleus. 125I-rhNGF binding sites were absent from areas replete with low-affinity NGF binding sites, including circumventricular organs, myelinated fiber bundles, and choroid plexus. The present analysis provides an anatomical differentiation of high-affinity 125I-rhNGF binding sites and greatly expands the number of brain structures that may respond to endogenous NGF or exogenously administered rhNGF.

Animals↗

Triple arthrodesis in adults.

Twenty-two adult patients who underwent a triple arthrodesis because of hindfoot pain and/or deformity were reviewed retrospectively with a minimum 3-year follow-up. All procedures were performed by the same surgeon using a two-incision technique and internal fixation. Objective results were good in eight (36%) patients, fair in 13 (59%), and poor in one (5%). There were two asymptomatic nonunions of the talonavicular joint, no infections, and no neuromas. Eleven patients had radiographic evidence of tibiotalar arthritis, and eleven patients had midfoot arthritic changes that had progressed after the operation. Patient satisfaction with the procedure was high, and 21 of 22 (95%) patients felt that they were improved overall and would have the surgery again if indicated. Although the procedure is technically demanding, patient satisfaction is high and complications can be kept to a minimum if proper surgical technique is utilized.

Adult↗

Genetic and environmental effects on carcass characteristics of Southdown x Romney lambs: I. Growth rate, sex, and rearing effects.

Carcass data from more than 4,400 Southdown x Romney ewe and wether lambs collected over a 16-yr period were analyzed for the effects of sex, rearing status, and growth rate. Ewe lambs grew more slowly than wethers and had .78 kg less carcass weight at the same age. The carcass weight advantage for wethers was nearly all caused by heavier fat-free weight. Based on fat depths, the fat on ewe lambs was distributed in more anterior and ventral parts of the carcass relative to wether lambs. Lambs reared as twins had 1.73 kg less carcass weight and correspondingly reduced carcass measurements compared with lambs reared as singles. Sex and rearing status interacted for some traits. However, in no case was a significant sex difference reversed in single- and twin-related lambs. Growth rate effects were determined by regressing average change in carcass measurements on average carcass weight gain over a 5-wk period. When carcass weight remained constant over a 5-wk period, fat weight increased by .12 kg, fat-free weight and muscle measurements decreased, and bone lengths increased. For each kilogram of increase in 5-wk carcass weight gain, the marginal increase in fat weight was .41 kg and that of fat-free weight was .59 kg. At the average 5-wk carcass weight gain of 1.4 kg, fat and fat-free gains were As carcass weight gain increased above 1.4 kg, fat-free gain exceeded fat gain.

Adipose Tissue↗

Genetic and environmental effects on carcass characteristics of Southdown x Romney lambs: II. Genetic and phenotypic variation.

Approximately 4,400 crossbred lambs from Southdown sires and Romney ewes were slaughtered at approximately 18, 23, and 28 wk of age over a 16-yr period. Live weights, carcass measurements, and chemical percentages were analyzed to estimate genetic and phenotypic parameters. Heritabilities of postweaning weights and gains were about .20. Heritabilities of fat and water percentages were about .35 adjusted for age. Heritability of kidney fat percentage was .53. Heritabilities of fat depth and muscle measurements ranged from .21 to .37. Crutch depth (h2 = .73) and cannon bone length (h2 = .74) were the most highly heritable carcass measurements. The genetic correlation between carcass fat and fat-free weight was .47 when lambs were slaughtered at a constant age. Fat-free weight was nearly uncorrelated with percentages of fat, water, and protein when lambs were slaughtered at the same age. Carcass measurements increased accuracy of selection for fat-free weight at a constant age very little compared with using only carcass weight. However, this does not mean that additional measurements are useless. The addition of carcass measurements to the selection criteria would result in correlated responses in chemical composition that more closely resembled direct selection for fat-free weight. Carcass weight would be of little value when used by itself to reduce fat weight adjusted for carcass weight. Direct measurement of carcass composition resulted in 1.6 to 2.6 times more predicted response for reduced fat weight than any combination of carcass weight and one fat depth measurement.

Adipose Tissue↗

Endothelial and leukocyte forms of IL-8. Conversion by thrombin and interactions with neutrophils.

We have recently shown that endothelial cell-derived IL-8 inhibits neutrophil adhesion to IL1-beta-activated human umbilical vein endothelial cell monolayers. IL-8 secreted by T lymphocytes or monocytes has been characterized as a promoter of neutrophil degranulation and chemotaxis. The IL-8 isolated from each of these cell types is a mixture of two IL-8 polypeptides, one consisting of 72 amino acids (herein called [ser-IL-8]72) and the other 77 amino acids (an N-terminal extended form herein called [ala-IL-8]77). IL-8 derived from T lymphocytes and monocytes is predominantly [ser-IL-8]72, whereas endothelial-derived IL-8 is highly enriched (greater than 80%) in [ala-IL-8]77. We address the relationship and activities of these two forms of IL-8 using recombinant proteins expressed by both mammalian cells and Escherichia coli. Thrombin was found to efficiently convert [ala-IL-8]77 to [ser-IL-8]72. In contrast, urokinase and tissue-type plasminogen activator were unable to cleave [ala-IL-8]77, and trypsin generated multiple IL-8 cleavage fragments. In competitive binding assays using 125I[ala-IL-8]77 neutrophils exhibited a twofold preference for [ser-IL-8]72 over [ala-IL-8]77. Both forms of IL-8 inhibited neutrophil adhesion to IL-1-beta-activated HUVEC monolayers by up to 90%. However, [ser-IL-8]72 was approximately 10-fold more potent than [ala-IL-8]77 in these assays (ED50 approximately 0.3 nM for [ser-IL-8]72 vs approximately 3 nM for [ala-IL-8]77. Both forms of IL-8 promoted degranulation of cytochalasin B-treated neutrophils [[ser-IL-8]72 (ED50 greater than 10 nM) was two- to three-fold more potent than [ala-IL-8]77], although in this regard they were less active than FMLP. Our data suggest that [ala-IL-8]77 and [ser-IL-8]72 have qualitatively similar and potentially complex biological activities, and that full activation of IL-8 requires cleavage to the [ser-IL-8]72 form. In the case of inflamed endothelial cells this activation could be mediated by thrombin generated in the procoagulant environment associated with these cells.

Cell Adhesion↗

A sensitive radioimmunoprecipitation assay for the detection and quantitation of antibodies to the envelope glycoprotein gp120 of the human immunodeficiency virus (HIV-1).

A radioimmunoprecipitation (RIP) assay was developed to detect antibodies to the envelope glycoprotein gp120 of the human immunodeficiency virus (HIV-1). The assay, which utilized recombinant gp120 (rgp120), was quantitative, reproducible, and specific for antibodies to rgp120 or antibodies to native gp120 resulting from natural infection with HIV. Polyethylene glycol-8000 (PEG), used in the assay at a final concentration of 10% to precipitate immune complexes, was demonstrated to be effective in titering sera from different animal species. Provided samples were diluted at least 1:100, antibody titers could be determined either by the classical dilution method or by interpolation from a calibration curve prepared with a positive serum. The humoral response of animals immunized with rgp120 was monitored and a positive correlation was found between titers determined in the RIP assay and the ability of the sera to neutralize. In addition, RIP titers of HIV-positive human sera correlated very well with reactivity obtained in a commercial HIV immunoblot assay. The assay has the advantage of quantitation, fast turnaround time, and versatility.

Animals↗

Genetic implications of a simulation model of litter size in swine based on ovulation rate, potential embryonic viability and uterine capacity: I. Genetic theory.

A simulation model of litter size in swine based on ovulation rate, uterine capacity and potential embryo viability was compared to three genetic models to clarify its genetic characteristics. The simulation model is equivalent to independent culling based on fixed levels of potentially viable embryos and uterine capacity. Litter size also can be described by a combination of additive, additive x additive, mean environment x additive, random environment and additive x random environment effects. A third genetic model that can describe the simulation model is the associative effects model, in which litter size is the result of grouping two genotypes. The fixed independent culling levels model predicts that genetic parameters will change as the component means change. This genetic model also predicts that selection on an index of ovulation rate and uterine capacity would improve selection response for litter size. This genetic model predicts asymmetry of correlated responses in ovulation rate and uterine capacity when selecting for high and low litter size. The nonadditive genetic model predicts covariances among relatives that are different from their additive relationships; however, simulated results did not detect any differences. The nonadditive genetic model also predicts that heterosis for litter size will differ among crosses based on the mean environment and on additive x additive genetic interaction. The associative effects model predicts that selection for litter size will always lead to a positive response in litter size.

Animals↗

Genetic implications of a simulation model of litter size in swine based on ovulation rate, potential embryonic viability and uterine capacity: II. Simulated selection.

Direct selection for ovulation rate, uterine capacity, litter size and embryo survival and selection for indexes of ovulation rate with each of the remaining traits were simulated for a swine population. The relationships among these traits were determined from a simulation model that assumed that litter size was always less than or equal to both ovulation rate and uterine capacity. Heritabilities of ovulation rate and uterine capacity were assumed to be .25 and .20, respectively, and uncorrelated genetically and phenotypically. No additional genetic variation was assumed. Responses to weak selection pressure were simulated by recurrent updating of phenotypic variances and covariances combined with the heritabilities of ovulation rate and uterine capacity. Two indexes of ovulation rate and uterine capacity each resulted in 37% greater increase in litter size than direct selection for litter size. Indexes of ovulation rate and either litter size or embryo survival increased litter size by 21% more than direct selection for litter size. Selection for ovulation rate, uterine capacity or embryo survival was 6, 35 and 79%, respectively, less effective than direct selection for litter size. Responses to intense selection pressure were determined by direct simulation of genotypes and phenotypes of individuals. The two indexes of ovulation rate and uterine capacity exceeded direct selection for litter size by 39 and 27%. The indexes of ovulation rate and either litter size or embryo survival exceeded direct selection for litter size by 19 and 13%, respectively. Intense selection for ovulation rate or uterine capacity decreased selection response by 26 and 67%, respectively, relative to direct selection for litter size. Intense selection for embryo survival decreased litter size slightly.

Animals↗

Overexpression of transforming growth factor alpha in psoriatic epidermis.

Transforming growth factor alpha (TGF-alpha) is produced by and required for the growth of epithelial cells and is angiogenic in vivo. Since epidermal hyperplasia and angiogenesis are hallmarks of psoriasis, TGF-alpha gene expression was analyzed in epidermal biopsies of normal and psoriatic skin. TGF-alpha messenger RNA and protein are much more abundant in lesional psoriatic epidermis than in normal-appearing skin of psoriatic patients or in normal epidermis. In contrast, messenger RNA levels of transforming growth factor beta 1 (TGF-beta 1), which inhibits epithelial cell growth, are not significantly different in normal, uninvolved, and lesional psoriatic epidermis. Thus, psoriatic epidermal hyperplasia may involve increased expression of a keratinocyte mitogen (TGF-alpha) rather than deficient expression of a growth inhibitor (TGF-beta 1).

Blotting, Northern↗

Laser use in foot surgery.

Laser is an acronym for Light Amplification by the Stimulated Emission of Radiation. Laser surgery is rapidly gaining the interest of both the medical practitioner and the general public. Since the first reported use of laser surgery in podiatry in 1980, a large number of laser surgery centers for treatment of foot and ankle disorders have appeared throughout the country. A relative paucity of literature exists about applications of lasers in foot and ankle surgery, and orthopaedic surgery as a whole. This is further compounded by the fact that very few of the existing studies are scientifically significant, either due to inadequate numbers, questionable study design, or a combination of these factors. At the present time, it appears that the only worthwhile application of lasers in foot and ankle surgery is for the treatment of plantar warts that are resistant to more conventional methods of treatment. As more well-controlled studies on the applications of lasers become available, the future of lasers in foot and ankle surgery will become more apparent. The purpose of this study is to present a summary of the use of lasers in orthopaedic foot and ankle surgery. The current clinical applications will be presented, followed by an overview of basic laser physics, laser characteristics and effects on tissue, and laser safety. Because of the growing interest in laser surgery by the medical profession, and the increasing public awareness of this relatively new and exciting technology, it is important that orthopaedic surgeons have a good understanding of laser surgery.

Foot Diseases↗

Integration of ovulation rate, potential embryonic viability and uterine capacity into a model of litter size in swine.

A mathematical model of litter size in swine was developed from ovulation rate, potential embryonic viability and uterine capacity. The model assumed that ovulation rate was reduced to potentially viable embryos by factors innate to the ovum and embryo. Potentially viable embryos then could be further reduced to uterine capacity, the maximum number of fetuses that a female can carry to term. Consequently, litter size can be no greater than either ovulation rate or uterine capacity. Means and variances of ovulation rate and potential embryonic viability used in the model were based on experimental results. The mean and variance of uterine capacity were varied until the simulated mean and variance of litter size were equal to experimental results. Simulated results of relationships among ovulation rate, embryo survival and litter size were similar to observed experimental relationships. Heritabilities of simulated litter size and embryo survival were similar to literature values when the heritability of ovulation rate was set at .25 and the heritability of uterine capacity was set at either .15 or .20. Litter size was simulated for 25 combinations of average ovulation rate and uterine capacity to develop equations relating mean ovulation rate and uterine capacity to litter size, embryo survival and correlations among them. Results suggest that changing either ovulation rate or uterine capacity independently will not result in large changes in litter size. Consequently, the model suggests that a single gene, hormonal manipulation or nutritional change will not result in large increases in litter size and that combinations of factors will be needed to increase litter size.

Algorithms↗

Intramedullary fixation of unstable distal radius fractures. A method of fixation allowing early motion.

During a four-year period, we have treated unstable fractures of the distal radius with closed anatomic reduction and insertion of a Rush intramedullary rod through a small dorsoradial wrist incision, followed by early controlled range of motion. In an attempt to reduce the stiffness commonly seen in the fingers, wrist, and elbow, a simple method of more stable fixation and early motion was instituted. Patient assessment using common anatomic and functional classification systems revealed good to excellent results in 35 of 36 patients (98%). Only three patients had complications, and these were all minor in nature. Three rods were removed, all because of prominence and irritation of the tip of the rod over the radial styloid. The procedure is technically reproducible, and has a very high rate of patient acceptance and satisfaction.

Adult↗

Extensive hemosiderin deposition in the medial meniscus of a knee. Its possible relationship to degenerative joint disease.

Hemosiderin deposition in the tissues of the musculoskeletal system is unusual, and deposition of these pigments in the menisci of the knee is extremely rare. Conditions that may predispose to these changes include rheumatoid arthritis, hemochromatosis, pigmented villonodular synovitis, hemophilia, and tuberculous arthritis. A 79-year-old woman developed extensive hemosiderin deposition in the medial meniscus of a knee. Hemosiderin within meniscal chondrocytes was associated with degenerative joint disease and suggested a cause and effect relationship.

Aged↗

Periodic rotational crosses. I. Breed and heterosis utilization.

Periodic rotational crosses differ from conventional rotations by using sire breeds an unequal number of generations but in a regular sequence. Formulas for breed composition and heterosis in offspring from periodic rotations at equilibrium averaged over all generations of a cycle and for each generation of the cycle are presented. Coefficients of squares and products of breed differences and heterosis used to calculate inter-generational variance are also derived. Several specific periodic rotations utilizing a range of breed proportions were found to use from 70 to 95% as much heterosis as conventional rotations using the same number of breeds equally. Estimates of swine and cattle additive breed and heterosis effects taken from the literature were applied to the formulas. In both the swine and cattle examples, periodic rotations were found that equaled or exceeded the conventional rotations using the same number of breeds and also had lower inter-generational variance.

Animal Husbandry↗

Periodic rotational crosses. II. Optimizing breed and heterosis use.

Choice of the optimal number and sequence of breeds in a periodic cross was determined by comparing the trade-off between increased utilization of breed differences and decreased utilization of heterosis. It was shown that the change in mean efficiency resulting from adding the next best breed to the best conventional n-breed rotation is always less than the change in efficiency predicted from the increase in heterosis. Periodic rotations were generally optimized by decreasing the proportion of poorer performing breeds in the rotation. However, efficiency of periodic rotations can exceed that of the better breed even when the difference in additive breed effects for efficiency is almost twice the effect of heterosis on efficiency. The periodic rotation that was optimal also tended to have the lowest inter-generational variance. It was suggested that inter-generational variances of component traits, which are not necessarily minimized when crosses are selected on a combined efficiency trait, can be considered by including inter-generational variance in an index or by introducing maximum thresholds.

Animal Husbandry↗

Periodic rotational crosses. III. Sire-breed rotations with overlapping generations among dams.

Sire-breed rotations are defined as the changing of sire breeds ignoring the sire-breed pedigree of dams from overlapping generations. The limiting theoretical proportion of maximum potential heterozygosity maintained at equilibrium when there is no culling of dams was found to be equal to that of a composite population with the same breed composition. Heterozygosity was simulated with a deterministic model that assumed 20% of reproducing females in each age group were culled each mating period. Maximum age of reproducing females was varied from 3 to 10 mating periods (years for cattle and sheep, half-years for swine). Consecutive use of each sire breed in a sire-breed sequence from two to four mating periods maintained more heterozygosity than predicted by the limiting theoretical formula, which did not take the culling of females into account. Compared with complete sire and dam rotations, sire-breed rotations with the same breed sequence resulted in reductions of .03 to .13 of potential heterosis. Among two-breed, periodic rotations, the difference ranged from .03 to .08. The smaller differences were generally associated with younger maximum reproducing females ages and the larger differences with older maximum ages. Heterozygosity difference times heterosis is a measure of the expected returns for the more intensive management often needed for complete rotations. Scaled breed difference ranges over which one periodic rotation of sire breeds exceeds another are shifted by overlapping generations among the females. Breed utilization is unchanged by overlapping generations, but relative differences in heterosis utilization are altered.

Animal Husbandry↗