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Biomedical subjects

M E Cook

Publications and source records attributed to M E Cook.

At least 55 records · Page 3Linked to original sources

Avian tibial dyschondroplasia: a morphological and biochemical review of the growth plate lesion and its causes.

Avian tibial dyschondroplasia is a disease found in fast growing strains of chickens, ducks, and turkeys worldwide in which growth plate cartilage accumulates in the metaphyseal region of the tibiotarsus; it is similar to mammalian osteochondrosis. Several biochemical and pathologic studies have shown that the growth plate chondrocytes do not reach their expected size in the hypertrophic zone and necroses prematurely. The chondrocytes also produce decreased amounts of extracellular proteins, such as collagen X and fibroblast growth factor-beta, that are necessary for cartilage maturation. This immature cartilage becomes highly cross-linked in the collagen molecules and apparently resistant to resorption and vascularization by the metaphyseal vessels. The dyschondroplastic cartilage remains in the metaphysis for several weeks. Not until the growth rate of the birds slows down is the cartilage able to be resorbed and replaced by trabecular bone. Many conditions have been found to induce tibial dyschondroplasia, including copper deficiency; fusarochromanone, thiram, and antabuse intoxication; excessive dietary levels of cysteine and homocysteine; metabolic acidosis; and bird rearing environment. However, the mechanism(s) by which these various methods induce tibial dyschondroplasia is presently not known. Current research is focusing on understanding the development of the disease and whether or not all these methods work by the same physiological chain of events. Recent biochemical evidence suggests that a copper deficiency might be caused by a different mechanism than genetically and thiram-induced tibial dyschondroplasia.

Animals↗

Evidence against the induction of immunological tolerance by feeding antigens to chickens.

A series of studies was conducted to determine whether oral tolerance shown to be inducible in rodents can be induced in chickens. A preliminary study was performed with male juvenile Sprague-Dawley rats to ascertain the ability of ELISA to detect oral tolerance induction. Two groups of six rats were provided water with or without 2 mg/mL BSA for 14 consecutive d to induce tolerance. Eight days following water treatment, the rats were challenged i.m. with 1 mg BSA. Serum collected from the rats 20 d later showed decreased (P < .01) anti-BSA ELISA titers in the group given BSA in the water relative to those given ordinary water. Three experiments were conducted to determine whether oral tolerance could be induced in chickens. Birds were given daily oral doses of 25 mg BSA for 14 d (Experiment 1), or fed 5% casein in their diet for 14 d (Experiment 2), or 1 mL of a 50% suspension of SRBC for 10 d (Experiment 3). All birds were challenged with the same antigen after oral dosing. Birds orally dosed with BSA prior to challenge with BSA had titers similar to birds not fed BSA prior to challenge with BSA. When chickens were fed casein (P < .05) or orally gavaged with SRBC (P < .1), titers were enhanced. These observations suggest that feeding antigens prior to injection with the same antigen leads to an enhanced humoral immune response in birds and not tolerance.

Animals↗

Factors influencing growth plate cartilage turnover.

A number of nutrients and chemicals have now been identified as consistent inducers of tibia dyschondroplasia (TD). Thiram, Antabuse, and fusarochromanone induce TD when fed at 30 to 75 ppm. Cysteine, cystine, homocysteine, and histidine induced TD when fed at .5 to 3% of the diet. Cation: anion imbalances resulting in acidotic diets also induced TD. Even though prevention of TD induced by these chemicals and nutrients has been established, reversal of the spontaneous TD lesion has not been clearly demonstrated. Thus, the etiology of the spontaneous lesion awaits elucidation. These model systems all suggest that TD is the result of decreased growth plate cartilage degradation. Recent work has shown that increased collagen cross-links in the accumulated cartilage, which makes collagen less susceptible to degradation. Cysteine-induced TD seems to decrease growth plate collagenase activity and production. A role of growth plate macrophages in paracrine signaling of collagenase production by chondrocytes has been presented.

Animals↗

The presence of lysylpyridinoline in the hypertrophic cartilage of newly hatched chicks.

The presence of lysylpyridinoline (LP) as a nonreducible cross-link in appreciable quantities has primarily been limited to the mineralized tissues, bone and dentin. However, the results reported here show that LP is not only present in the hypertrophic cartilage of the tibiotarsus isolated from newly hatched broiler chicks, but it is approx. 4-fold as concentrated as hydroxylysylpyridinoline (HP). Bone and articular cartilage surrounding the hypertrophic cartilage do not contain measurable quantities of LP. Purified LP has a fluorescent scan similar to purified HP and literature values, confirming that we indeed were measuring LP. Also, the cartilage lesion produced by immature chondrocytes from birds with tibial dyschondroplasia had LP but the HP:LP ratio was > 1. Thus, the low HP:LP ratio could be a marker for hypertrophic cartilage in avians.

Amino Acids↗

Immune modulation by altered nutrient metabolism: nutritional control of immune-induced growth depression.

The ability of conjugated isomers of linoleic acid (CLA) to prevent reduced growth rate following endotoxin (lipopolysaccharide, LPS) injection was studied in two chick trials and one rat trial. Chicks (10 per treatment) were fed a corn and soybean meal-based diet with or without .5% CLA. At 21 days of age, chicks were weighed and injected i.p. with 1 mg/kg BW Escherichia coli LPS and sterile PBS. Body weights were again determined 24 h later. Antibody responses to SRBC were also determined. Rats fed .5% stearic acid or CLA for 4 wk (seven per treatment) were also injected with LPS, and BW change over a 24-h postinjection period was determined. Antibody responses to BSA, phytohemagglutinin foot pad swelling, and phagocytosis of elicited peritoneal macrophages were also determined. The CLA had no adverse effects on any immune variables measured in the chicks and rats. The CLA enhanced the phytohemagglutinin response and macrophage phagocytosis in rats. Chicks fed CLA and injected with LPS continued to grow, whereas those not fed CLA either failed to grow or lost weight following LPS injection. Both control and CLA-fed rats lost weight over the 24-h period after LPS injection; however, the loss of weight in rats fed CLA was only half of the weight loss of the control rats. Thus, CLA is effective in preventing the catabolic effects of immune stimulation.

Animals↗

Excess levels of cysteine and homocysteine induce tibial dyschondroplasia in broiler chicks.

The effect of excessive levels of cysteine and homocysteine on tibial dyschondroplasia (TD) in broiler chicks was studied. In the first experiment, graded levels of L-cysteine as well as one level of L-homocysteine were supplemented to a corn-soybean-based diet adequate in sulfur amino acids. Levels equal to or above 0.5% supplemental cysteine increased the incidence of TD, and levels equal to or above 0.75% supplemental cysteine increased the severity of TD above that found in chicks fed the basal diet. Also, L-homocysteine at 0.5% induced TD. In the second experiment, graded levels of DL-homocystine were added to the basal diet to determine the threshold value of homocystine needed to induce TD, and a level of ammonium sulfate isosulfurous to 0.45% homocystine was added to a basal diet. The results showed that 0.45% DL-homocystine was the lowest level that increased the severity of TD above that found in chicks fed the basal diet and that sulfate did not induce TD. In the third experiment, a 2 x 2 factorial design was used to investigate the interaction between DL-homocystine and copper. Copper supplementation lessened the severity of TD caused by DL-homocystine. Copper supplementation also tended to improve growth, especially in birds fed DL-homocystine.

Ammonium Sulfate↗

Noncollagenous (NC1) domain of collagen VII resembles multidomain adhesion proteins involved in tissue-specific organization of extracellular matrix.

Type VII collagen (C7) is a stratified squamous epithelial basement membrane protein composed of three identical alpha chains, each consisting of a 145-kDa amino-terminal noncollagenous (NC1) domain and a 145-kDa carboxyl-terminal collagenous domain. Morphologic and biochemical studies have shown that tissue-specific aggregates of C7 dimers called anchoring fibrils may contribute to epithelial basement membrane organization and adherence by interacting with extracellular matrix (ECM) proteins such as type IV collagen. In this study, we cloned a cDNA encoding most of the NC1 domain of C7. The deduced amino acid sequence revealed motifs characteristic of multidomain ECM proteins that contribute to the tissue-specific organization of ECM including a region of 7 1/2 sequential fibronectin type III (Fn III) homology repeats, a potential collagen-binding region homologous to the A domain of von Willebrand factor (vWf) and an RGD sequence. A purified C7 fusion protein containing these motifs specifically bound to type IV collagen in a functional assay. These results suggest that regions within the NC1 domain of C7 mediate interactions with lamina densa and dermal ECM proteins including type IV collagen. Structural mutations and autoepitopes in these regions may represent mechanisms for the development of defective basement membrane organization and adherence in genetic and autoimmune forms of epidermolysis bullosa.

Amino Acid Sequence↗

High density lipoprotein deficiency syndrome in chickens is not associated with an increased susceptibility to atherosclerosis.

A spontaneous high density lipoprotein (HDL) deficiency syndrome in chickens associated with a Z-linked (sex-linked) mutation has been reported (F. Poernama et al, J Lipid Res 1990;31:955-963). The mutant, called WHAM (Wisconsin hypo-alpha mutant), has a 70-90% reduction in plasma HDL cholesterol and apolipoprotein A-I (apo A-I) concentrations. In the present study, the effect of the HDL deficiency on diet-induced or spontaneous atherosclerosis was assessed. Control chickens maintained on a high-cholesterol diet for 28 weeks experienced a 2.4-fold rise in the plasma very low density lipoprotein cholesterol concentration, while the same diet induced a 3.7-fold rise in the low density lipoprotein cholesterol concentration in WHAM chickens. The high-cholesterol diet did not elevate the plasma HDL cholesterol or apo A-I concentrations in either group. Both the aortic area of involvement and the width of lesions were quantified by gross and microscopic examination, respectively. Cholesterol feeding produced a significant increase in the area of the aorta with atherosclerotic lesions in both control and mutant chickens. The HDL deficiency in WHAM chickens did not correlate with a higher lesion area or increased lesion thickness. To assess the effect of HDL deficiency on spontaneous atherosclerosis, a separate group of control and WHAM chickens was maintained on a low-fat, cholesterol-free diet for 3 years. At the end of the 3-year period, the area and thickness of the spontaneous aortic lesions in control and WHAM chickens were not significantly different. Spontaneous HDL deficiency in chickens is therefore not associated with increased susceptibility to atherosclerosis.

Animals↗

Wheat middlings as an alternative feedstuff for laying hens.

Three long-term experiments were conducted to evaluate the possibility of using wheat middlings (WM) for laying hens and to study the responses of six strains of commercial laying hens fed WM diet. In Experiment 1,320 layers maintained in floor pens were fed diets containing 45% WM with .25 or .75% salt, or 89% WM with .25% or 1.5% salt. Salt supplementation did not show any beneficial effect on egg production. Hen-day egg production by hens fed the 45% WM diet was significantly higher for hens fed 45% WM than for those fed the 89% WM diet (79 versus 67.5%, 44-wk period). Feed, limestone, and water intakes were increased by the 89% WM diet. Yolk color, Haugh units, hen livability, and reproductive parameters were not different among the dietary treatments. In Experiments 2 and 3, laying hens from six commercial strains (four strains each experiment, 240 hens per strain) were maintained in laying cages in each year, and fed either a corn and soybean meal (CSM) or a 25% WM diet. Results show that neither diet nor strain had effects on hen-day egg production; however, egg weights from Strains A, C, and F were heavier than those from Strains B, D, and E. Feed intakes and feed utilizations were similar among the s trains. The 25% WM diet increased egg weight, feed intake, and feed utilization compared with the CSM diet. Livability of hens was 93.8 to 97.5% and was not affected by either strain or diet. It is concluded that commercial strains of laying hens can be fed diets containing 25 to 45% WM and still have normal hen-day egg production although feed utilization will be poorer.

Analysis of Variance↗

Nonreducible crosslink formation in tibial dyschondroplastic growth plate cartilage from broiler chicks fed homocysteine.

In the study of tibial dyschondroplasia, scientists have for a long time thought that an altered extracellular matrix might be involved in the etiology of the disease. The results presented in this paper show that the collagen content was increased in the dyschondroplastic cartilage when compared to normal growth plate and day-old hypertrophic cartilage. Furthermore, nonreducible crosslinks were found only in dyschondroplastic cartilage, with the greatest amounts occurring in the distal region of the lesion, approximately 10-fold higher than that found in the dyschondroplastic growth plate. Thus, intermolecular collagen bonding is altered in the extracellular matrix of dyschondroplastic cartilage. Possible models for the etiology of the disease are discussed.

Analysis of Variance↗

Therapeutic adherence in the elderly: transdermal clonidine compared to oral verapamil for hypertension.

This double-blind, double-dummy, randomized clinical trial, conducted in elderly patients with mild hypertension, compared adherence to treatment, efficacy, side effects, and quality of life during treatment with transdermal clonidine versus oral sustained-release verapamil (verapamil-SR). Blood pressure declined significantly--from 148/95 mm Hg at baseline to 139/84 after titration and 135/86 after maintenance--with transdermal clonidine (n = 29), and from 156/96 to 144/85 and 148/88, respectively, with verapamil-SR (n = 29). Adverse event rates and quality-of-life questionnaire responses were similar in the two treatment groups. Transdermal clonidine was worn as directed during more than 96% of patient-weeks of treatment. Compliance with the oral verapamil regimen was less consistent: Verapamil-SR was taken as directed during approximately 50% of patient-weeks of therapy, and individual compliance, assessed by tablet counts, varied from 50-120%. In all, 86% of subjects were satisfied or highly satisfied with the convenience of transdermal therapy; 87% reported that side effects were slightly or not bothersome; 65% indicated that transdermal patches were more convenient than oral therapy; and almost 60% preferred transdermal to oral therapy. In this study transdermal clonidine and oral verapamil were equally safe and effective. A substantial majority of patients preferred transdermal to oral therapy, and adherence to treatment was greater with transdermal therapy.

Administration, Cutaneous↗

Decreased immune response and increased incidence of tibial dyschondroplasia caused by fusaria grown on sterile corn.

Corn, feed, and litter samples reported to be associated with feed refusal, diarrhea, leg weakness, and mortality were evaluated for the presence of toxic substances. Intubated residues of ethyl acetate extracts of these samples did not cause gross lesions, diarrhea, or mortality in young New Hampshire x Single Comb White Leghorn crossbred chicks. Fusarium moniliforme was the predominant fungal species found in unpelleted feed and corn samples. Young broiler chicks, fed diets supplemented with 2 or 8% corn cultures of selected F. moniliforme isolates from a suspected toxic corn sample, failed to develop clinical signs of mycotoxicosis. However, some isolates resulted in decreased antibody responses to SRBC. Corn cultures of some Fusarium equiseti and Fusarium semitectum strains also decreased the immune response. Cultures of three F. equiseti strains from barley and potato induced tibial dyschondroplastic lesions in young broiler chicks. Other F. equiseti strains and strains of other Fusarium species did not cause this skeletal abnormality.

Animal Feed↗

Immune response of chicks fed various levels of zinc.

Five experiments were conducted to determine the effects of zinc intake on the immune response of chicks. Ancona chicks (Experiment 1), New Hampshire (Experiment 2), New Hampshire x Leghorn (Experiment 3), and broiler chicks (Experiments 4 and 5) were fed semipurified (Experiments 1, 2, 3, and 4) or corn and soybean meal diets (Experiment 5) containing from 8 to 88 micrograms zinc/g of diet. An extra group of chicks in Experiments 1, 2, and 4 were fed a diet adequate in zinc but at an intake similar to that of chicks fed the lowest zinc level in each respective experiment. Low zinc intake (less that 28 micrograms zinc/g of diet) suppressed body weight at all times measured. The effect of zinc intake on the size of lymphoid tissues was variable, but at 5 wk of age, chicks fed 8 micrograms zinc/g of diet had smaller bursae of Fabricius and thymi than those fed additional zinc. Zinc intake had no influence on the primary and secondary immune response to SRBC or delayed hypersensitivity to phytohemagglutinin-P (PHA) or human gamma globulin in Ancona and broiler chicks. However, zinc intake did have a small effect in chicks from the New Hampshire parents. In Experiments 1, 2, and 4 (at least at certain times), antibody titers were reduced in pair-fed chicks. Thus, although zinc supplementation at the levels of practical diets did not affect immune function, feed restriction did.

Animals↗

Research note: increased growth of chicks and poults obtained from hens injected with jackbean urease.

Two experiments were conducted using 120 Single Comb White Leghorn (SCWL) hens and 40 turkey hens. Hens were randomly assigned to two treatments: those injected with urease and controls injected only with adjuvant. At 22 wk of age, half of the SCWL hens were injected intramuscularly with 12 Sumner units of jackbean urease suspended in incomplete adjuvant six times in 26 wk. Turkey hens were injected twice at weekly intervals with 70 Sumner units. The other half of the breeders received adjuvant without urease (control). Urease injection into SCWL hens had no effect on feed consumption, feed conversion, and percentage fertility, hatchability, and hatch of all eggs set, but egg weight and body weight of chicks at hatch and at 3 wk of age were significantly higher as compared with the control hens. In the case of turkey hens, percentage hatchability and progeny body weight were significantly higher as a result of urease injection.

Animals↗

Fusarochromanone production by Fusarium isolates.

Sixty two Fusarium isolates representing nine species from many parts of the world were screened for fusarochromanone production. A simplified method for the detection of fusarochromanone in culture filtrates or grain cultures was used. Under UV irradiation (364 nm) the chloroform phase from fusarochromanone-positive culture extracts fluoresced a characteristic bright blue color. Results were confirmed by thin-layer-chromatography comparison with pure fusarochromanone standards. Detection was possible in cultures as young as 1 week old. Biosynthesis of fusarochromanone was rare in Fusarium spp. and was only detected in three isolates of Fusarium equiseti, namely R-4482 (barley [Federal Republic of Germany]), R-6137 (barley [Alaska]), and R-8508 (potato [Denmark]), among all the isolates tested from various geographic sources.

Amino Acids↗

Breeding-hen and progeny performance when hens are fed excessive dietary zinc.

Short-term (12 wk) and long-term (44 wk) studies were conducted to observe the effects of excessive Zn supplementation on the performance of breeding hens and their progeny. Zinc sulfate was added to a corn-soybean meal diet containing 28 mg of Zn/kg in order to provide Zn supplementation at 0, 20, 200, and 2,000 mg/kg. Each dietary treatment was fed to two groups of 20, Single Comb White Leghorn hens and one New Hampshire rooster. The hens were 56-wk old at the start of the short-term study and 24-wk old when the long-term study began. Determinations were made for: fertility, hatchability, progeny growth to 3 wk of age, Zn-related feather-fraying among the progeny as well as Zn, Cu, and Fe in the liver, pancreas, and right tibiotarsus. The Zn treatments had no effect on hen performance or on reproductive performance. Even though Zn was considerably elevated and Cu was reduced in the eggs collected from hens fed the highest level of Zn, chick performance and the tissue content of Zn, Cu, and Fe were not influenced by the maternal Zn nutritional status.

Animals↗