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Biomedical subjects

G L Bennett

Publications and source records attributed to G L Bennett.

At least 73 records · Page 4Linked to original sources

Hepatocyte proliferation and serum hepatocyte growth factor levels in patients with alcoholic hepatitis.

BACKGROUND/METHODS: Hepatocyte growth factor is thought to be important in stimulating growth of the liver following injury. In this study we have measured serum levels of hepatocyte growth factor together with hepatocyte proliferation in liver biopsies, by detection of the Ki-67 antigen, in 23 patients with alcoholic hepatitis. RESULTS: Serum hepatocyte growth factor was elevated in all patients (median 0.9 ng/ml; range 0.6-7.7 ng/ml; normal < 0.5 ng/ml) and there was a positive correlation between hepatocyte growth factor levels and hepatocyte proliferation in the biopsies. CONCLUSIONS: These results demonstrate that in acute alcoholic hepatitis the liver proliferates in response to injury and suggest that hepatocyte growth factor may be one of the growth factors responsible for this proliferative activity.

Adult↗

Human hepatocyte growth factor in alcoholic liver disease: a comparison with change in alpha-fetoprotein. Department of Veterans Affairs Cooperative Study Group 275.

To evaluate the hepatic regenerative response in patients with alcoholic liver disease, sera from 263 patients with severe alcoholic hepatitis and/or cirrhosis were analyzed for hepatocyte growth factor (HGF) and alpha-fetoprotein (AFP). HGF concentration was elevated above healthy controls in 95% of the patients (median level = 2.4 ng/ml), whereas AFP tended to be depressed below controls (median level = 4.1 ng/ml). Correlations with parameters of liver injury (i.e., ascites, encephalopathy, AST bilirubin, and protime) all showed a more significant correlation with HGF concentrations than those of AFP. Patients with HGF levels below the mean (4 ng/ml) exhibited significantly better survival (median survival = 35 months vs. 8.5 months for those with HGF > or = 4 ng/ml; p = 0.007). Serum HGF levels were associated with various specific histologic features of alcoholic hepatitis that included, but were not exclusively related to, necrosis.

Energy Intake↗

Agenesis of the corpus callosum: prenatal detection usually is not possible before 22 weeks of gestation.

PURPOSE: To determine whether agenesis of the corpus callosum can be diagnosed prenatally with standard ultrasonographic (US) evaluation before 22 weeks of gestation. MATERIALS AND METHODS: Initial scans obtained on or before 22 weeks and follow-up scans obtained in the third trimester were selected from all cases of agenesis of the corpus callosum diagnosed prenatally at the authors' laboratory. Follow-up was attained by means of review of the medical records and included imaging, karyotype, and clinical outcome. RESULTS: Among 15 fetuses with callosal agenesis confirmed by means of third-trimester scans, 10 had completely normal US scans at 16-22 weeks and five had other US abnormalities. Isolated callosal agenesis was identified in six children with normal development (except one with polydactyly). Among the others, four were developmentally delayed, three died, and two others had abnormal karyotype. CONCLUSION: Standard second-trimester US before 22 weeks of gestation may not show isolated callosal agenesis. Fetuses with this abnormality can have normal second-trimester scans and develop abnormal US findings in the third trimester.

Agenesis of Corpus Callosum↗

Subchorionic hemorrhage in first-trimester pregnancies: prediction of pregnancy outcome with sonography.

PURPOSE: To determine the effects of subchorionic hematoma size, gestational age, and maternal age on pregnancy outcome in patients with vaginal bleeding in the first trimester of pregnancy. MATERIALS AND METHODS: A retrospective review was performed with ultrasound images obtained in 516 patients with vaginal bleeding, a live fetus, and a subchorionic hematoma in the first trimester. Hematoma size was graded according to the percentage of the chorionic sac circumference elevated by the hematoma. Patients were also classified according to gestational age and maternal age. Logistic regression analysis was used to determine the effect of each variable on pregnancy outcome. RESULTS: The overall spontaneous abortion rate was 9.3% (48 of 516 patients). The rate nearly doubled when the separation was large (18.8%) compared with small and moderate hematomas (7.7% and 9.2%, respectively). A large separation was found to be associated with an almost three-fold increase in risk of spontaneous abortion. The spontaneous abortion rate was approximately twice as high for women aged 35 years or older versus younger women (13.8% and 7.3%, respectively) and for women with bleeding at 8 weeks gestation or less compared with those with bleeding at greater than 8 weeks gestation (13.7% vs 5.9%). CONCLUSION: For women with a subchorionic hematoma that is sonographically identified, fetal outcome is dependent on size of the hematoma, maternal age, and gestational age.

Abortion, Spontaneous↗

Analysis of cryotherapy penetration: a comparison of the plaster cast, synthetic cast, Ace wrap dressing, and Robert-Jones dressing.

Four groups were studied to determine the cooling effect at skin level of ice application over common ankle bandages and casts. The plaster cast, synthetic cast, and Ace wrap dressing groups had 18 participants and the Robert-Jones dressing group had four participants. In a standardized fashion, ice bags were applied over each bandage or cast and skin temperatures were measured with a thermocouple over a 90-min period. The average final skin temperature was 16.5 degrees in the plaster cast, 18.8 degrees in the synthetic cast, 21.2 degrees in the Ace wrap dressing, and 28.7 degrees in the Robert-Jones dressing. The temperature curves showed that ice application effectively decreased skin temperatures through the plaster cast, synthetic cast, and Ace wrap dressing. The cooler temperature did not adequately penetrate the Robert-Jones dressing.

Adult↗

Triple arthrodesis: a biomechanical evaluation of screw versus staple fixation.

The subtalar, talonavicular, and calcaneocuboid joints were internally fixed to simulate triple arthrodesis was performed on eight matched pairs of human cadaver feet. Feet were randomly assigned such that one specimen in each pair was internally fixed with cobalt-chrome staples and one specimen with stainless steel screws. Liquid metal strain gauges were placed in a perpendicular fashion across the three joints of each specimen. Each foot was then secured to the Shore Western Materials Test System where a series of 10 increasing eversion stresses across the foot was created. Displacement was measured at each joint with every increase in eversion stress. Our results show that there is no statistical difference in fixation strength between screws and staples at the talonavicular, calcaneocuboid, or subtalar joints (P = 0.862). Although many studies determining the strength to failure of different implants have been performed, shear stress and micromotion at the joint surfaces have not been evaluated, to our knowledge, and no single implant in this study has shown superior immobilization characteristics to recommend its use as the implant of choice in triple arthrodesis.

Arthrodesis↗

Genetic (co)variances among birth weight, 200-day weight, and postweaning gain in composites and parental breeds of beef cattle.

Genetic and environmental (co)variances for birth weight, adjusted 200-d weight, and postweaning gain were estimated in nine parental and three composite populations of beef cattle. The parental breeds were Angus (A), Braunvieh (B), Charolais (C), Gelbvieh (G), Hereford (H), Limousin (L), Pinzgauer (P), Red Poll (R), and Simmental (S). The composites were MARC I (1/4 B, 1/4 C, 1/4 L, 1/8 H, 1/8 A), MARC II (1/4 G, 1/4 S, 1/4 H, 1/4 A), and MARC III (1/4 R, 1/4 P, 1/4 H, 1/4 A). Heritabilities of additive direct genetic effects for birth weight (.50) and postweaning gain (.49) were greater than for 200-d weight (.32). Heritabilities of additive maternal effects of .09 for birth weight and .10 for 200-d weight were much smaller than direct effect heritabilities. Heritabilities were larger in composites than in parental breeds for additive direct effects of all three traits but smaller for maternal 200-d weight. Correlations were high and positive for direct genetic effects of the three weight traits and higher in composites than in the parental breeds. Correlations between direct and maternal genetic effects for both birth weight and 200-d weight were near zero. Some differences in variances among populations were correlated with differences in weight and milk yield. Heavier populations had larger variances, supporting the use of logarithmic transformation of weights to stabilize variances among genetic groups. Increased average milk yield was correlated with decreased phenotypic variance of 200-d weight. Average milk yield was also implicated in the expression of direct and maternal genetic effects for 200-d weight and their covariance. Comparison of univariate and multivariate estimates of genetic variances suggested that it is important to include birth weight in multivariate analyses of all weight traits to account for increased preweaning mortality of calves with extremely heavy or light birth weights. Based on heritability estimates, within-herd selection in composites should be at least as effective as in purebreds. Some differences among populations in genetic parameters were indicated, especially maternal 200-d weight and its correlations with other traits.

Animals↗

Hepatocyte growth factor and hepatocyte growth factor receptor in the lacrimal gland, tears, and cornea.

PURPOSE: The purpose of this study was to characterize the expression of hepatocyte growth factor (HGF) and HGF receptor proteins in lacrimal gland, tears, and cornea. METHODS: The reverse transcription-polymerase chain reaction method was used to detect HGF and HGF receptor messenger RNA in human lacrimal gland tissue. HGF and HGF (c-met) receptor monoclonal antibody specificity was demonstrated with fluorescent antibody sorting of cells engineered to express HGF or HGF receptor compared with control cell lines, enzyme-linked immunoadsorbent assay (ELISA), immunoprecipitation, and immunohistology with preabsorption. Immunohistochemistry was applied to study the distribution of HGF and HGF receptor expression in rabbit lacrimal gland tissue and in wounded and unwounded rabbit cornea. An ELISA was used to detect HGF in pooled samples of human tears and individual aliquots of tears collected from patients 1 day after anterior segment surgery. RESULTS: Amplification products of the expected size for HGF and HGF receptor mRNAs were detected in lacrimal tissue and were confirmed to be specific by hot blotting and nucleic acid sequencing. Hepatocyte growth factor protein was detected in interalveolar and interlobular connective tissue cells adjacent to glandular alveolar (acinar) cells and associated with the cells lining the interlobular ducts. Hepatocyte growth factor receptor protein was expressed in the glandular alveolar and interlobular ductal cells in the lacrimal gland and all three cell types of the cornea. It was detected in keratocyte and endothelial cells, and expression was increased in keratocytes after epithelial wounding. Hepatocyte growth factor was not present in corneal epithelial cells, but in the unwounded cornea a strong signal was associated with the epithelial cell surface. It was detected by ELISA in pooled normal tears at levels 186 to 290 pg/ml and in individual postoperative tear samples at 453 to 619 pg/ml. In some tear samples, HGF levels were below the sensitivity of the assay (97.5 pg/ml). CONCLUSIONS: The distribution of HGF receptor protein expression in the lacrimal gland suggests that HGF secreted by interalveolar connective tissue cells traverses the acinar cells and modulates functions in acinar and ductal epithelial cells. Hepatocyte growth factor likely collects within the interlobular ducts and becomes a component in normal tears. Thus, lacrimal gland HGF probably modulates corneal epithelial cell proliferation, motility, and differentiation. Its expression in keratocytes is upregulated after corneal epithelial wounding and probably contributes to the epithelial wound healing process.

Animals↗

Direct and maternal genetic covariances by age of dam for weaning weight.

Weaning weights of calves of dams at ages in years of 2, 3, and older were modeled to be three separate traits. Fixed effects were sex of calf-year of birth combinations for nine pure breeds and sex of calf-year of birth-generation for three composite populations. Random effects fitted for each trait were correlated direct and maternal genetic, maternal permanent environmental, and temporary environmental. Direct and maternal effects were correlated across traits. A multiple-trait, derivative-free REML algorithm was used to estimate the 30 (co)variance components. Number of animals per breed group ranged from 1,244 to 4,326. For the three traits for pure breeds, average proportions of phenotypic variance were .34, .31, and .27 for direct genetic; .16, .15, and .12 for maternal genetic; and .18, .20, and .17 for maternal environmental effects. Average correlations among the three traits were .84 for direct genetic, .78 for maternal genetic, and .71 for maternal environmental effects. Average of direct-maternal genetic correlations for pure breeds was .05. For the composite breeds, average proportions of phenotypic variances were .44, .46, and .36 for direct genetic; .06, .06, and .05 for maternal genetic; and .16, .14, and .14 for maternal environmental effects. Average correlations among the three traits were .93 for direct genetic, .76 for maternal genetic, and .85 for maternal environmental effects. Average direct-maternal genetic correlation was .09 for composites. No evidence was found for greater direct-maternal genetic correlation for earlier than for later ages of dam. Sign and magnitudes of direct-maternal genetic correlations seemed to differ among pure breeds and were reflected in composites from those parent breeds.

Aging↗

Immunohistochemical visualization of brain-derived neurotrophic factor in the rat brain.

A purified polyclonal antibody preparation was made against recombinant brain-derived neurotrophic factor (BDNF) in guinea pig and characterized for use in immunoassays and immunohistochemistry. The anti-BDNF antibodies specifically recognized BDNF in Western blots and immunoprecipitation. There was no cross-reactivity with the other known mammalian members of the neurotrophin family, nerve growth factor, neurotrophin-3 and neurotrophin-4/5. In immunohistochemical analysis, the anti-BDNF recognized exogenous BDNF injected into the brain of rats, whereas no signal was obtained with the other neurotrophins. Preabsorption with native BDNF abolished the immunoreactivity in brain sections. These studies identify the anti-BDNF as a tool for immunocytochemistry and the development of an immunoassay. Immunohistochemical analysis revealed widespread neuronal localization of BDNF in many brain areas. BDNF was localized in all subpopulations of hippocampal neurons. The distribution in the hippocampus suggests localization in the cytoplasm of cell bodies and dendrites.

Animals↗

Sulfated oligosaccharides promote hepatocyte growth factor association and govern its mitogenic activity.

Hepatocyte growth factor (HGF) is a potent mitogen, motogen, and morphogen for various epithelial cell types. The pleiotropic effects of HGF are mediated by its binding to a specific high affinity receptor, c-Met. In addition, HGF binds to heparan sulfate proteoglycans on cell surfaces and within the extracellular matrix. Incubation of HGF with 0.1, 1.0, and 10 micrograms/ml of heparin, heparan sulfate, or dextran sulfate resulted in a concentration-dependent increase in mitogenic potency in a primary rat hepatocyte bioassay, whereas sodium sulfate or fucoidan did not. Although co-incubation of HGF with sulfated compounds that enhanced HGF-dependent mitogenesis did not alter the binding isotherm of HGF for the c-Met receptor in a solid phase assay, an increase in autophosphorylation of the c-Met receptor in intact A549 cells was observed upon their addition. A series of chemically sulfated malto-oligosaccharides varying in unit size and charge was tested in the bioassay in order to provide additional insights into the nature of the HGF-heparin interaction. While sulfated di-, tri-, tetra-, and pentasaccharides did not significantly potentiate HGF-dependent mitogenesis, larger oligosaccharides such as the sulfated hexa-, hepta-, or a sulfated oligosaccharide mixture containing decasaccharides resulted in an approximate 2-, 4-, and 7-fold enhancement, respectively. We observed a correlation between the sulfated oligosaccharide preparations that enhanced mitogenic potency and those that promoted HGF oligomerization in vitro, as measured by gel filtration and analytical ultracentrifugation. These findings indicate that heparin-like molecules can stabilize HGF oligomers, which may facilitate c-Met receptor dimerization and activation.

Animals↗

The CT small bowel faeces sign: description and clinical significance.

OBJECTIVE: To describe a new CT sign of the GI tract: the small bowel faeces sign, and discuss its significance. METHODS: The small bowel faeces sign consists of gas bubbles mixed with particulate matter in dilated segments of small bowel. This was a retrospective study of 22 patients demonstrating this sign from 1989 to 1993. Final diagnosis was established by surgical, medical or laboratory findings. To determine the prevalence of the sign, the CT examination of 120 consecutive separate control patients were evaluated. RESULTS: All 22 of the patients demonstrating this sign required hospitalization with surgical or medical intervention. Eighteen of 22 had mechanical small bowel obstruction. The remaining four patients had other abnormalities of small bowel to account for the finding on CT. Twelve of the 22 patients were treated with surgery and the remaining 10 patients were treated with nasogastric tubes (n = 6) or other medical therapy (n = 4). None of the 120 control patients demonstrated the sign. CONCLUSION: The presence of gas and particulate material resembling faeces in a dilated segment of small bowel on CT is abnormal. Most (18/22; 82%) patients with this sign had small bowel obstruction.

Aged↗

Engineering linear F(ab')2 fragments for efficient production in Escherichia coli and enhanced antiproliferative activity.

We developed a novel bivalent antibody fragment, the linear (L-) F(ab')2, comprising tandem repeats of a heavy chain fragment VH-CH1-VH-CH1 cosecreted with a light chain. Functional humanized L-F(ab')2 directed against p185HER2 was secreted from Escherichia coli at high titer (> or = 100 mg/l) and purified to homogeneity. The L-F(ab')2 binds two equivalents of antigen with an apparent affinity (Kd = 0.46 nM) that is within 3-fold of the corresponding thioether-linked F(ab')2 fragment. The N-terminal site binds antigen with an affinity (Kd = 1.2 nM) that is approximately 4-fold greater than that for the C-terminal site, as shown by the comparison of L-F(ab')2 variants containing a single functional binding site. L-F(ab')2 has greater antiproliferative activity than the thioether-linked F(ab')2 against the p185HER2-overexpressing tumor cell line BT474. Linear and thioether-linked F(ab')2 have very similar pharmacokinetic properties in normal mice, and their serum permanence times are respectively 7- and 8-fold longer than the corresponding Fab fragment. L-F(ab')2 offers a facile route to bivalent antibody fragments that are potentially suitable for clinical applications, and that may have improved biological activity compared with thioether-linked F(ab')2 fragments.

Animals↗

Induction of liver growth in normal mice by infusion of hepatocyte growth factor/scatter factor.

Hepatocyte growth factor/scatter factor (HGF/SF) is a potent stimulator of DNA synthesis in a variety of epithelial cells, including hepatocytes, and has been implicated in liver regeneration. We show here that combining dextran sulfate with HGF/SF markedly increases the plasma concentrations of HGF/SF that are achieved during intraperitoneal infusion. Three days of administration of HGF/SF by this mechanism caused a dose-dependent increase in liver wet weight. Mitotic figures were rarely observed in control livers but were abundant in livers exposed to HGF/SF, and liver DNA content was elevated. Serum levels of triglycerides, cholesterol, total protein, and albumin were also dose dependently increased, whereas alkaline phosphatase was reduced. From these data we conclude 1) that combining HGF/SF with dextran sulfate provides a novel method for delivering HGF/SF in a continuous manner, 2) that HGF/SF can induce liver growth in an intact animal, and 3) that HGF/SF-induced liver enlargement is associated with changes in serum biochemistry.

Animals↗

Morton's interdigital neuroma: a comprehensive treatment protocol.

One hundred fifteen patients with signs and symptoms of Mortons' interdigital neuroma were studied in an attempt to evaluate the efficacy of a staged treatment program. The first stage consisted of patient education, footwear modifications, and metatarsal head relief. The second stage consisted of a steroid/local anesthetic injection into the affected interspace. The third stage was surgical excision of the inflamed interdigital nerve. Overall, 97 of 115 patients (85%) believed that they had improved with the treatment program. Twenty-four patients (21%) eventually required surgical excision of the nerve and 23 of 24 patients (96%) had satisfactory results. The results of the staged treatment protocol were very satisfactory and patient satisfaction was high.

Adolescent↗

Application of a computer model to predict optimum slaughter end points for different biological types of feeder cattle.

A bioeconomic model was developed to predict slaughter end points of different genotypes of feeder cattle, where profit/rotation and profit/day were maximized. Growth, feed intake, and carcass weight and composition were simulated for 17 biological types of steers. Distribution of carcass weight and proportion in four USDA quality and five USDA yield grades were obtained from predicted carcass weights and composition. Average carcass value for each genotype was calculated from these distributions under four carcass pricing systems that varied from value determined on quality grade alone to value determined on yield grade alone. Under profitable market conditions, rotation length was shorter and carcass weights lighter when the producer's goal was maximum profit/day, compared with maximum profit/rotation. A carcass value system based on yield grade alone resulted in greater profit/rotation and in lighter and leaner carcasses than a system based on quality grade alone. High correlations ( > .97) were obtained between breed profits obtained with different sets of input/output prices and carcass price discount weight ranges. This suggests that breed rankings on the basis of breed profits may not be sensitive to changes in input/output market prices. Steers that were on a grower-stocker system had leaner carcasses, heavier optimum carcass weight, greater profits, and less variation in optimum carcass weights between genotypes than steers that were started on a high-energy finishing diet at weaning. Overall results suggest that breed choices may change with different carcass grading and value systems and postweaning production systems. This model has potential to provide decision support in marketing fed cattle.

Abattoirs↗

Simulated influence of postweaning production system on performance of different biological types of cattle: I. Estimation of model parameters.

Breed parameters for a computer model that simulated 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, were estimated for 17 biological types of cattle (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). One value for the maximum fractional growth rate of fat-free matter (KMAX) was estimated and used across all breed types. Mature fat-free matter (FFMmat) was estimated from data on mature cows for each of the 17 breed types. Breed type values for a fattening parameter (THETA) were estimated from growth and composition data at slaughter on steers of the 17 breed types, using the previously estimated constant KMAX and breed values for FFMmat. For each breed type, THETA values were unique for given values of KMAX, FFMmat, and composition at slaughter. The results showed that THETA was most sensitive to KMAX and had similar sensitivity to FFMmat and composition at slaughter. Values for THETA were most sensitive for breed types with large THETA values (Chianina, Charolais, and Limousin crossbred steers) and least sensitive for breed types with small THETA values (purebred Angus, crossbred Jersey, and Red Poll steers).(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Simulated influence of postweaning production system on performance of different biological types of cattle: II. Carcass composition, retail product, and quality.

A computer simulation model was used to characterize the response in carcass composition, retail product, and quality of 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, and finished at either a low (1.0 kg) or high (1.36 kg) ADG. The backgrounding systems were a high ADG (.9 kg) for 111, 167, or 222 d, a medium ADG (.5 kg) for 200, 300, or 400 d, a low ADG (.25 kg) for 300 or 400 d and 0 d backgrounding. For specific genotype x production system combinations, results showed that carcasses of compensating steers may be either leaner, not different in fatness, or fatter than carcasses of steers put on a finishing diet directly after weaning. Systems in which steers gained a greater proportion of the final slaughter weight over long durations of growth restriction resulted in leaner carcasses. There were 12 common production systems in which 13 of the genotypes produced a carcass with a maximum of 28% fat or with a marbling score of 11 or greater. These results suggest sire breeds used to produce these steers can be used over a wide range of nutritional and management environments, and that a mixed group of steers can be fed and managed similarly from weaning to slaughter to produce a carcass with a specified composition, retail product, or quality.

Aging↗