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Biomedical subjects

G M Hill

Publications and source records attributed to G M Hill.

At least 19 recordsLinked to original sources

Development of tolerance to class II-mismatched renal transplants after a short course of cyclosporine therapy in miniature swine.

Our laboratory has reported previously spontaneous acceptance of class II-matched, single haplotype (but not 2 haplotype), class I-mismatched renal allografts in miniature swine. All class II-mismatched animals rejected acutely regardless of class I matching. We have also demonstrated recently that a short course of high dose (10 mg/kg/day for 12 days) CsA uniformly induces donor-specific tolerance to 2-haplotype, class I-mismatched renal allografts. The survival of 2-haplotype, fully MHC mismatched renal allografts was prolonged by the same treatment, but tolerance was not induced, as all animals rejected eventually. We have now tested this short course of immunosuppressive therapy for its effect on renal allografts mismatched selectively for 2 haplotypes at class II. We have observed long-term graft survival in 5 of 7 animals under these conditions. Each of the 5 acceptor animals was demonstrated to be specifically tolerant by its response either to donor-matched skin grafts or to a second donor-matched kidney transplant without further immunosuppression. These data suggest the existence of a common pathway for induction of specific transplantation tolerance to MHC antigens when these antigens are recognized on vascular endothelium under conditions of altered cytokine production. They also suggest that tolerance induction under these conditions requires matching for either class I or class II antigens, which may have implications for the mechanism by which peripheral tolerance is induced, as well as practical implications for the extension of these results to potential clinical practice.

Animals

Rumen protected fat in kline barley or corn diets for beef cattle: digestibility, physiological, and feedlot responses.

A rumen protected fat product composed of Ca salts of fatty acids (CAF) was evaluated in beef cattle diets. Dietary treatments in a metabolism trial (six steers, 251 +/- 15 kg) and Feedlot Trial 1 (15 individually fed heifers, 355 +/- 11 kg) consisted of 62.1% corn and 3.2% soybean meal (C), 32.6% corn and 33.1% Kline barley (CB), and 28.2% corn, 33.1% barley, and 4.5% CAF (CBF) on a DM basis. Apparent DM and OM digestibilities were higher (P less than .05) and NDF digestibility was lower (P less than .05) for C than for CB and CBF. Apparent ether extract digestibility was higher (P less than .01) for CBF than for CB. Retention of N was higher (P less than .05) for C than for CB and CBF. On d 42, Feedlot Trial 1 ruminal fluid acetate:propionate ratio was lower (P less than .01) for C than for CB and CBF, and the ratio was lower (P less than .01) for CB than for CBF. Treatments did not affect (P less than .10) ADG and DMI of heifers, but feed/gain was lower (P less than .05) for C than for CB and CBF, and feed/gain was higher (P less than .05) for CBF than for CB. In Feedlot Trial 2, steers and heifers were fed the C diet or a 57% corn, 21.4% peanut hull, 4.1% soybean meal, and 4.5% CAF diet (CF) on an ad libitum basis for 50 d. Ruminal fluid acetate and propionate were unaffected (P greater than .10) by dietary treatments. Cattle ADG tended to be lower (P greater than .10), DMI was lower (P less than .05), and feed/gain tended to be improved (P greater than .10) for CF compared with C. Kline barley has potential as a feed grain for cattle, but CAF may not improve beef cattle performance, especially when diets contain barley.

Amino Acids

Nutritive characteristics of pearl millet grain in beef cattle diets.

Two trials were conducted to compare pearl millet grain with corn and grain sorghum in cattle diets. Grain portions of diets in metabolism and feedlot experiments contained 73% corn and 6% soybean meal (C); 76.2% grain sorghum and 2.8% soybean meal (GS); and 79% pearl millet (PM). In the metabolism trial (replicated 3 x 3 latin squares; six steers), apparent digestibilities of DM and OM were higher (P less than .05) for C than for GS or PM diets. Ether extract and CP digestibilities were higher (P less than .05) for C and PM than GS. Dietary TDN was higher (P less than .05) for C compared with GS or PM diets. Fecal N was higher (P less than .05) for GS than for C or PM, urinary N was higher (P less than .05) for PM than C or GS, but retained N was similar (P greater than .05) for C, GS and PM diets. In a 90-d feedlot trial (18 individually fed heifers), a trend was observed for higher (P less than .20) ADG on C compared with PM; however, feed/gain was similar for C, GS and PM diets (8.2, 9.1 and 8.5 kg feed/kg gain, respectively). Ruminal fluid acetate:propionate ratios were lower (P less than .05) at 3.5 and 7 h postfeeding for PM compared with C or GS diets on d 83. Pearl millet grain may be used as a feed grain for beef cattle, but diets should be formulated to efficiently utilize the high quantity of protein (about 14% of DM) in this grain as a substitute for supplemental protein.

Animal Feed

Pancreaticobiliary secretion of zinc and copper in normal persons and patients with Wilson's disease.

The objectives of this study were (1) to examine basal and cholecystokinin-stimulated pancreaticobiliary secretion of zinc in normal subjects with zinc-adequate and zinc-deficient diets, and (2) to investigate whether basal and stimulated secretion of zinc was abnormal in patients with Wilson's disease before and after zinc therapy. Gastroduodenal intubation was performed in six healthy subjects and five patients with Wilson's disease. After intravenous infusion of octapeptide of cholecystokinin (40 ng/kg/hr) the pancreaticobiliary secretion of zinc increased from a basal rate of 283.1 +/- 75.8 nmol/L/min to a peak of 716.6 +/- 175.3 nmol/L/min in normal subjects. Normal subjects with a zinc-deficient diet had both lower basal (66.8 +/- 15.8 nmol/L/min) and stimulated (559.5 +/- 31 nmol/L/min) pancreaticobiliary secretion of zinc than with a zinc-sufficient diet. In contrast to the markedly reduced pancreaticobiliary secretion of copper, patients with Wilson's disease not treated with zinc had normal basal (226.6 +/- 126 nmol/L/min) and stimulated (728.7 +/- 195.5 nmol/L/min) zinc secretion. These studies indicate that a considerable amount of zinc is being secreted in pancreaticobiliary fluid in healthy subjects and there was no impairment of zinc secretion in patients with Wilson's disease. Our data also indicate that pancreaticobiliary secretion of zinc is dependent on the zinc status of the subjects, suggesting that endogenous secretion of zinc may play a significant role in the homeostasis of zinc.

Acetates

Feedlot performance and pregnancy inhibition of heifers treated with depot-formulated melengestrol acetate.

In dose titration trials beef heifers received depot-formulated melengestrol acetate (DEPO-MGA) in single s.c. ear injections to determine effects on performance and pregnancy inhibition. In a 112-d feedlot trial, 105 heifers were assigned to light, medium and heavy weight blocks on five treatments: dietary MGA (.5 mg.hd-1.d-1), control (no MGA) or DEPO-MGA on d 1 at .5, 1.0 or 1.5 ml/hd (30, 60 or 90 mg MGA/hd, respectively). A high-energy cracked corn diet was fed to all heifers ad libitum. At d 56 and d 112, ADG and feed/gain were not affected (P greater than .05) by dietary MGA or DEPO-MGA treatments, although dietary MGA tended to increase 112-d ADG (1.67 vs 1.58 kg) compared with controls. In a pasture trial, 100 beef heifers were assigned by weight to five treatments: control (no MGA) or DEPO-MGA injected on d 1 at .5, 1.0, 1.5 or 2.0 ml/hd (30, 60, 90 or 120 mg MGA/hd, respectively). Heifers were pastured as a single herd and were exposed to fertile bulls from d 7 to d 181. Weights and pregnancy data were recorded at d 62, 90, 134, 181 and 225. Heifer ADG was not affected (P greater than .05) by DEPO-MGA treatment at any weighing date. By d 90, 90% of control heifers were pregnant, and 100% were pregnant by d 134. Pregnancy inhibition rates of 90% to 100% for each DEPO-MGA treatment at d 62, 90 and 134 were higher (P less than .01) than those in control heifers. Pregnancy was inhibited in 90% of heifers on 60-mg and 90-mg DEPO-MGA treatments through d 181, and in 95% of heifers on the 120 mg DEPO-MGA treatment through d 225.

Animals

Worsening of neurologic syndrome in patients with Wilson's disease with initial penicillamine therapy.

We describe a patient with Wilson's disease who presented with neurologic disease, was treated with D-penicillamine, and suffered sudden neurologic deterioration coincident with therapy. Replicate brain magnetic resonance imaging examinations after six weeks and 11 months of penicillamine therapy documented the development of new brain lesions during this period, while liver biopsy specimen data disclosed that excellent hepatic decoppering had occurred. To develop information on the relative rarity or frequency of neurologic worsening with the initiation of penicillamine therapy, we conducted a retrospective survey of 25 additional patients with Wilson's disease who met the criteria of presenting with neurologic disease and having been treated with penicillamine. The replies indicate that, at least from the patient's viewpoint, this syndrome occurs frequently. We suggest that the cause of this distressing syndrome, and ways to mitigate or circumvent it, must be discovered.

Adolescent

Dietary urea influences on digestibility and utilization of diets containing peanut skins by steers.

Metabolism and feedlot trials were conducted to evaluate increased dietary urea as a method of reducing detrimental effects of peanut skin (PS) tannins on nutrient digestibility and finishing steer performance. The PS fed in the trials contained 17.8% crude protein and 20.1% tannin. Urea (.7%) was included in a control (C) diet without PS, and with 15% PS in low-urea (.3%; LUPS), moderate-urea (.7%; MUPS) and high-urea (1.1%; HUPS) diets that contained ground corn and 15% peanut hulls. Apparent digestibility coefficients for dry matter, organic matter and crude protein were higher (P less than .05) for the C diet than for PS diets. Fecal N (g/d) was consistently higher (P less than .05) for PS diets than for the C diet. Retained N (g/d) was similar for steers fed C and HUPS diets, but lower (P less than .05) than C for LUPS and MUPS diets. Average daily gain at 91 d was highest (P less than .05) for C steers in the feedlot, intermediate (P less than .05) for MUPS and HUPS steers and lowest (P less than .05) for LUPS steers. Feed:gain ratio was 97% higher (P less than .05) for LUPS steers compared with C steers, but average daily feed intake was similar for all treatments. Rumen fluid propionic acid was lower (P less than .05) on all PS diets compared with the C diet on d 90. Plasma urea nitrogen (d 90) was reduced (P less than .05) by 48.5, 55.5 and 57.6%, respectively, on LUPS, MUPS and HUPS diets compared with the C diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed

Chemonucleolysis as an alternative to laminectomy for the herniated lumbar disc. Experience with patients in a private orthopedic practice.

Three hundred thirty-five patients with herniated lumbar intervertebral discs were injected with chymopapain. The overall success rate was 76%. The success rate was higher for private insurance patients (89%) than for Worker's Compensation patients (66%). There were no serious complications and patients spent fewer days in the hospital and returned to work faster than patients with laminectomies. Chemonucleolysis is an excellent alternative to open surgery for treatment of a herniated lumbar disc, especially if patients are selected carefully and good technique is strictly followed.

Adolescent

Treatment of Wilson's disease with zinc: III. Prevention of reaccumulation of hepatic copper.

Twelve patients with Wilson's disease, most of whom had received intensive treatment with penicillamine, were given zinc therapy as their sole medication for copper control. Serial liver biopsies were performed during a 12- to 20-month follow-up period to determine whether hepatic copper reaccumulates during zinc therapy. Mean baseline liver copper concentration was 255 micrograms/gm dry weight, whereas the mean value after therapy was 239 micrograms. No patient demonstrated hepatic reaccumulation of copper during zinc therapy. Copper balance, 24-hour urinary copper excretion, and nonceruloplasmin plasma copper concentration all indicated good copper control during zinc therapy. Hepatic zinc concentration increased twofold to threefold over baseline values but no toxicity was seen. Hepatic zinc concentrations appeared to reach a plateau after 12 to 18 months of zinc therapy. We conclude that oral zinc as the sole maintenance therapy in patients with Wilson's disease prevents hepatic reaccumulation of copper.

Copper

Treatment of Wilson's disease with zinc. II. Validation of oral 64copper with copper balance.

The efficacy of zinc as a therapeutic agent to control copper balance in Wilson's disease patients has been previously documented with balance studies. In an attempt to develop a simpler and faster tool for evaluating the adequacy of zinc therapy, a technique that measures the uptake into blood of a small oral dose of 64copper was studied in conjunction with copper balance. The mean peak 64copper uptake into blood of nine Wilson's disease patients on D-penicillamine, trien, or no medication was 6.04 +/- 2.74%, comparable with normal controls. Seven patients on zinc therapy had a markedly and significantly reduced mean uptake of 0.79 +/- 1.05% after treatment. The data demonstrate that the prevention of copper uptake into blood in Wilson's disease patients by zinc therapy can be evaluated by 64copper uptake and that peak uptakes of less than 1% occur in patients with neutral or negative copper balance.

Acetates

Influence of dietary crude protein on peanut skin digestibility and utilization by feedlot steers.

Peanut skins were fed at 15% of steer diets in metabolism and feedlot trials. Elevation of dietary protein using soybean meal or soybean meal plus urea and ammoniation of skins were evaluated as methods of overcoming detrimental performance and digestibility effects of tannins in peanut skins. Digestibility of dry matter, crude protein and energy were not different (P greater than .05) for steers fed a control diet with 11.4% crude protein with no skins compared with high-protein 15% peanut skin diets with soybean meal (15.5% crude protein) or soybean meal plus urea (16% crude protein). Dry matter, crude protein and energy digestibilities of control and of high-protein peanut skin diets were higher (P less than .05) compared with an 11.4% crude protein peanut skin diet and a 12.2% crude protein diet with ammoniated peanut skins. Ether extract digestibility was higher (P less than .05) for all peanut skin diets compared with the control. Nitrogen retention (g/d) was not different (P greater than .05) for control and high-protein peanut skin diets, and nitrogen retention on these diets was higher (P less than .05) compared with the lower protein and ammoniated peanut skin diets. Diets fed in the metabolism trial, except for the ammoniated peanut skin diet, were fed to 96 steers (345 kg initial wt) in a 109-d feedlot trial. Performance was lower (P less than .05) for steers fed the lower-protein peanut skin diet compared with other treatments through d 56; this diet was discontinued as a treatment on d 62.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed

Digestibility and utilization of ammonia-treated and urea-supplemented peanut skin diets fed to cattle.

A metabolism study and two feedlot trials were conducted to evaluate urea supplementation of peanut skin (PS) diets and ammoniation of PS as methods of reducing detrimental effects of tannins in PS on nutrient digestibility and performance of beef cattle. Tannin content of PS was reduced by 42% after ammoniation. Digestibility coefficients for dry matter, crude protein, nitrogen free extract, energy and total digestible nutrients were higher (P less than .05) for the control diet without PS compared with urea-supplemented PS (UPS) and ammoniated PS (APS) diets. Ether extract digestibility was higher (P less than .05) for UPS and APS diets compared with the control diet. Fecal N was higher (P less than .05) and N retention was lower (P less than .05) in steers fed UPS and APS diets compared with controls, which suggested that in UPS and APS diets dietary protein was being complexed with tannins and excreted. Steers fed the APS diet had lower (P less than .05) plasma urea nitrogen compared with control and UPS diets at 2, 4 and 6 h post-feeding. Eighteen heifers were fed control, UPS and APS diets individually for 84 d, resulting in similar (P less than .05) feedlot performance and carcass traits for heifers on all dietary treatments. Rumen fluid propionic acid levels were similar for control and APS heifers and somewhat lower (P greater than .05) for UPS heifers at 3 and 6 h post-feeding on d 62 of the trial. The experimental diets were fed to 54 steers (360 kg initial wt) ad libitum. After 98 d on dietary treatments average daily gains (ADG), final weights, carcass weights and carcass quality grades were not different (P greater than .05) for control and APS steers. Live weight and ADG were lower (P less than .05) for UPS steers on d 98 compared with control and APS steers, and UPS steers continued in the feedlot through d 147. After 98 d on control or APS diets 72.2% of the beef carcasses produced on each diet graded USDA Choice, and 100% of the carcasses of steers fed UPS graded USDA Choice after 147 d. A urea-supplemented PS diet or a diet containing ammoniated PS was ineffective in improving digestibility and N retention of PS diets when limit-fed to steers. However, ad libitum feeding of an ammoniated PS diet was effective in overcoming detrimental effects of tannins on feedlot performance of heifers and steers.

Ammonia

Effect of dietary cholesterol on erythrocyte peroxidant stress in vitro and in vivo.

The effect of dietary variation of plasma cholesterol concentrations on the susceptibility of erythrocytes to in vitro and in vivo peroxidant stress was studied in rats. Malonyldialdehyde, produced in vivo (endogenous malonyldialdehyde) or following in vitro exposure of cells to 10 mM H2O2 (H2O2 malonyldialdehyde), was used as a measure of peroxidant stress. After 5 weeks, the plasma cholesterol concentrations in rats receiving 1.2% cholesterol + 0.6% cholic acid in their diet rose to 6-times that of control rats receiving a diet without added cholesterol; at the same time, erythrocyte H2O2 malonyldialdehyde in the cholesterol-fed rats decreased significantly relative to the control rats. During subsequent exposure of both groups to in vivo peroxidant stress with phenylhydrazine in two separate dose trials, erythrocyte peroxidant stress remained significantly lower in the cholesterol-fed rats: at a dose of 100 mumol/100 g body weight, H2O2 malonyldialdehyde was lower; at a dose of 25 mumol/100 g body weight, both endogenous and H2O2 malonyldialdehyde were lower. Erythrocyte membrane cholesterol concentrations were 12% higher in the cholesterol-fed rats than in controls. The effects of in vivo peroxidant stress on plasma cholesterol were also studied. In vivo peroxidant stress at the higher dose of phenylhydrazine produced a decrease in plasma cholesterol concentrations of control rats. The lower dose had no effect on this group and the plasma cholesterol concentrations were unchanged in the cholesterol-fed rats during both treatments. The data suggest that elevated plasma cholesterol concentrations are protective against erythrocyte peroxidant stress. The mechanism of cholesterol's protective effect is probably mediated through elevated membrane cholesterol concentrations.

Animals

Interactions of trace elements: clinical significance.

We examined interaction of the trace element zinc with copper and lead. In sickle cell anemia, the usual situation is one of mild to moderate zinc deficiency owing to renal loss of zinc. Zinc deficiency seems to produce a mild overburden of copper and an increased ceruloplasmin level, probably by enhancing copper absorption. With zinc therapy, this process is reversed. Pharmacological doses of zinc, when administered in a way to ensure effectiveness (without food) will usually lead to copper deficiency. We have taken advantage of the copper-depleting effect of zinc to design a new therapy for Wilson's disease. Zinc, by inducing intestinal metallothionein, inhibits absorption of copper from food, and inhibits reabsorption of endogenously secreted copper, thereby producing a negative copper balance in Wilson's disease. Once we are certain that zinc blocks accumulation of copper in the liver of Wilson's disease patients, zinc therapy will be available as one approach for treating this fatal disease. The animal literature indicates that zinc protects against lead toxicity when both elements are given orally, no doubt through the intestinal metallothionein mechanism. In preliminary experiments in rats, we have not been able to show that toxicity from lead that arrives into the body through a nonoral route is affected by oral zinc supplements.

Anemia, Sickle Cell

Castration method and progesterone-estradiol implant effects on growth rate of suckling calves.

Eighty male calves nursing their dams and averaging 15 d of age were used to evaluate a method of nonsurgical castration and a growth implant in a 196-d experiment. On the 1st d of the experiment, 40 calves were castrated chemically using Chem-Cast (active ingredient: lactic acid 88% wt/wt), and 40 were castrated surgically. Twenty calves on each castration treatment were implanted with STEER-oid on d 1 and reimplanted on d 121 while 20 calves on each treatment were not implanted on either date. Chemical castration resulted in significantly lower scrotal edema and a trend toward increased rate of gain at d 28. Castration treatment did not affect 196-d rate of gain and weaning weights of calves. On d 121, bilateral castration was determined in 30 of 40 chemically castrated calves, a condition that persisted on d 196, resulting in a 75% castration rate. Implanted calves had rates of gain that were 14, 6, and 4% higher, respectively, on d 28, 121, and 196 compared with unimplanted calves.

Animal Population Groups

Plasma amino acid profiles and growth of the bovine fed different sources of nitrogen and levels of sulfur.

One-hundred-twenty calves were utilized in a 2 X 3 factorial design experiment of 140 days to determine the effects of dietary urea (U) or soybean meal (SBM) with added sulfur (S) plus corn silage on growth and plasma constituents. Total dietary crude protein (CP) of SBM-supplemented diets averaged 9.06%, and U-supplemented diets averaged 9.16% CP. Within each nitrogen source, S was added to supplements to provide 0.0, 0.15, or 0.30% added S based upon predicted intake. Calves fed SBM-supplemented diets had higher (P less than 0.05) gains and lower (P less than .05) plasma urea nitrogen levels compared to calves fed U-supplemented diets. The addition of S to SBM-supplemented diets did not significantly affect growth, efficiency or plasma nitrogen constituents. Calves fed the U-supplemented diets with added S had higher (P less than .10) gains and a trend toward improved efficiency compared with those supplemented with no added S. On day 28 plasma aspartic acid, threonine, serine, glutamic acid, glycine, methionine, total nonessential and total amino acid concentrations were increased (P less than .01 to P less than .10) by the addition of S to U-supplemented diets compared to the basal U diet. Isoleucine was higher (P less than .05) in calves fed SBM-supplemented diets compared to those fed U-supplemented diets. On day 140 higher (P less than .05) plasma threonine, valine, isoleucine, leucine, phenylalanine, lysine and total essential amino acids were observed in calves fed SBM compared to U-supplemented diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging