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Biomedical subjects

A B Johnson

Publications and source records attributed to A B Johnson.

At least 19 recordsLinked to original sources

Effect of dietary cobalt supplementation on cobalt metabolism and performance of dairy cattle.

Three studies were conducted with dairy cattle fed diets with added Co. The first study examined cow age and added dietary Co on Co in liver and blood. Nonpregnant, nonlactating Holstein cows were blocked by age (2.5 or 6.5 yr) and assigned to either a control diet or a diet supplemented with 9 mg Co per day. The Co concentration of liver, taken on d 60, was not affected by dietary Co but was higher in the younger cows. The cytosolic fraction of liver contained the most Co, and the subcellular distribution of Co was not affected by total Co in liver. In a second study, Holstein cows were assigned to one of three treatments of dietary Co from 21 d prepartum until 120 d postpartum. There was an interaction of time x treatment x parity such that milk yield response to Co supplementation differed between multiparous cows and primiparous cows. Supplemental Co did not increase Co in serum, colostrum, milk, or liver. Primiparous cows secreted colostrum and milk with higher Co concentrations than did multiparous cows. Likewise, serum B12 levels were higher in primiparous than multiparous cows and declined with increasing days in milk (DIM). Serum Co also decreased from 7 to 120 DIM. In a final study, a Co supplement in the starter diet did not affect Co in serum or liver of young calves. In conclusion, supplemental dietary Co did not affect secretion of Co in milk, tissue retention, or subcellular distribution of Co within the liver. Primiparous and multiparous cows differed in their milk yield response to dietary Co supplementation.

Aging↗

Molecular findings in symptomatic and pre-symptomatic Alexander disease patients.

BACKGROUND AND OBJECTIVE: Alexander disease is a slowly progressive CNS disorder that most commonly occurs in children. Until recently, the diagnosis could only be established by the histologic finding of Rosenthal fibers in brain specimens. Mutations in the glial fibrillary acidic protein (GFAP) gene have now been shown in a number of biopsy- or autopsy-proven patients with Alexander disease. A prospective study on patients suspected to have Alexander disease was conducted to determine the extent to which clinical and MRI criteria could accurately diagnose affected individuals, using GFAP gene sequencing as the confirmatory assay. METHODS: Patients who showed MRI white matter abnormalities consistent with Alexander disease, unremarkable family history, normal karyotype, and normal metabolic screening were included in this study. Genomic DNA from patients was screened for mutations in the entire coding region, including the exon-intron boundaries, of the GFAP gene. RESULTS: Twelve of 13 patients (approximately 90%) were found to have mutations in GFAP. Seven of those 12 patients presented in infancy with seizures and megalencephaly. Five were juvenile-onset patients with more variable symptoms. Two patients in the latter group were asymptomatic or minimally affected at the time of their initial MRI scan. The mutations were distributed throughout the gene, and all involved sporadic single amino acid heterozygous changes that changed the charge of the mutant protein. Four of the nine changes were novel mutations. CONCLUSIONS: In symptomatic and asymptomatic patients with a predominantly frontal leukoencephalopathy by MRI, GFAP gene mutation analysis should be included in the initial diagnostic evaluation process for Alexander disease.

Adolescent↗

Mitochondrial abnormalities in Alzheimer's disease.

The finding that oxidative damage, including that to nucleic acids, in Alzheimer's disease is primarily limited to the cytoplasm of susceptible neuronal populations suggests that mitochondrial abnormalities might be part of the spectrum of chronic oxidative stress of Alzheimer's disease. In this study, we used in situ hybridization to mitochondrial DNA (mtDNA), immunocytochemistry of cytochrome oxidase, and morphometry of electron micrographs of biopsy specimens to determine whether there are mitochondrial abnormalities in Alzheimer's disease and their relationship to oxidative damage marked by 8-hydroxyguanosine and nitrotyrosine. We found that the same neurons showing increased oxidative damage in Alzheimer's disease have a striking and significant increase in mtDNA and cytochrome oxidase. Surprisingly, much of the mtDNA and cytochrome oxidase is found in the neuronal cytoplasm and in the case of mtDNA, the vacuoles associated with lipofuscin. Morphometric analysis showed that mitochondria are significantly reduced in Alzheimer's disease. The relationship shown here between the site and extent of mitochondrial abnormalities and oxidative damage suggests an intimate and early association between these features in Alzheimer's disease.

Adolescent↗

Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease.

Alexander disease is a rare disorder of the central nervous system of unknown etiology. Infants with Alexander disease develop a leukoencephalopathy with macrocephaly, seizures and psychomotor retardation, leading to death usually within the first decade; patients with juvenile or adult forms typically experience ataxia, bulbar signs and spasticity, and a more slowly progressive course. The pathological hallmark of all forms of Alexander disease is the presence of Rosenthal fibers, cytoplasmic inclusions in astrocytes that contain the intermediate filament protein GFAP in association with small heat-shock proteins. We previously found that overexpression of human GFAP in astrocytes of transgenic mice is fatal and accompanied by the presence of inclusion bodies indistinguishable from human Rosenthal fibers. These results suggested that a primary alteration in GFAP may be responsible for Alexander disease. Sequence analysis of DNA samples from patients representing different Alexander disease phenotypes revealed that most cases are associated with non-conservative mutations in the coding region of GFAP. Alexander disease therefore represents the first example of a primary genetic disorder of astrocytes, one of the major cell types in the vertebrate CNS.

Adolescent↗

Alexander disease: new insights from genetics.

Prior to finding that GFAP mutations underlie many cases of Alexander disease, it was unclear whether the disease originated in astrocytes or if the formation of Rosenthal fibers was a response to an external insult. It was also unclear whether the etiology of the disease was environmental or genetic. For many cases of Alexander disease, these questions have now been answered. An immediate clinical benefit of this discovery is the possibility of diagnosing most cases of Alexander disease through analysis of patient DNA samples, rather than resorting to brain biopsy. In addition, fetal testing is now an option for parents who have had an Alexander disease child with an identified mutation and who wish to have additional children. For the future, these mutations should provide a unique window for illuminating the mechanism of the disease.

Brain↗

Effects of supplementing combinations of inorganic and complexed copper on performance and liver mineral status of beef heifers consuming antagonists.

Performance, immune response, and liver trace mineral status were measured in growing heifers supplemented with different copper (Cu) concentrations and sources when diets contained the Cu antagonists Mo, S, and Fe. Sixty Angus x Hereford heifers were managed in two groups for 112 d and were either individually fed diets and mineral treatments using individual feeding stalls (Stall) or pen-fed grass hay and individually supplemented mineral treatments (Pen). The basal diet of grass hay, rolled barley, and soybean meal was analyzed to contain 6 mg Cu/kg DM. The treatments consisted of 1) no supplemental Cu (Control); 2) 49 mg Cu/kg DM from Cu sulfate (i.e. approximately five times NRC recommendation for Cu from CuSO4) (5X-SO4); 3). 22 mg Cu/kg DM from CuSO4 (2X-SO4); 4). 22 mg Cu/kg DM from a combination of 50% CuSO4 and 50% Cu-amino acid complex (50-50); and 5). 22 mg Cu/kg DM from a combination of 25% CuSO4, 50% Cu-amino acid complex, and 25% Cu oxide (CuG) (25-50-25). All heifers were supplemented with the Cu antagonists Mo (10 mg/kg DM), S (2,900 mg/kg DM), and Fe (500 mg/kg DM). These diets resulted in dietary Cu:Mo ratios that averaged 0.5:1 for Control, 4.5:1 for the 5X-SO4, and 2.4:1 for 2X-SO4, 50-50, and 25-50-25. Rate and efficiencies of gain and cell-mediated immune function were not different (P > 0.10) among treatments. Data suggest supplements containing combinations of inorganic and complexed Cu interacted differently in the presence of Mo, S, and Fe. Heifers consuming the 25-50-25 supplement in the Stall group initially lost hepatic Cu rapidly but this loss slowed from d 50 to d 100 compared to the Control (P = 0.07), 50-50 (P < 0.05), and 2X-SO4 (P < 0.05) heifers and was similar (P > 0.10) to that in the 5X-SO4 heifers. In the Pen group, total hepatic Cu loss tended to be greater for 25-50-25 and 2X-SO4 compared to 5X-SO4 heifers (P = 0.09 and P = 0.06, respectively); Cu loss in the 50-50 heifers was similar (P > 0.10) to that in the 5X-SO4 heifers. This suggests that supplementing combinations of inorganic and amino acid-complexed Cu was as effective in limiting hepatic Cu loss during antagonism as was increasing dietary Cu levels to five times the NRC recommendation. A combination of 25% CuSO4 , 50% Cu-amino acid complex, and 25% CuO limited liver accumulation of Mo compared to supplements without CuO and could provide a strategic supplementation tool in limiting the systemic effects of Cu antagonism in beef cattle.

Animal Feed↗

Effects of inorganic and organic copper supplemented to first-calf cows on cow reproduction and calf health and performance.

Two experiments were conducted to determine whether the supplementation of Cu in the organic or inorganic form to 2-yr-old cows, before and after calving, affects reproduction rate, calf health and performance, passive transfer of immunoglobulin, or liver and serum Cu concentrations compared with unsupplemented controls. Cows (n = 75 in 1997; n = 120 in 1998) were randomly assigned by estimated calving date and body condition score to one of three treatments: 1) Control, control; 2) Inorganic, inorganic Cu supplement (200 mg Cu from CuSO4); 3) Organic, organic Cu supplement (100 mg Cu from AvailaCu). In 1998, a fourth treatment was added; 4) CU-ZN, organic Cu and Zn (400 mg Zn from AvailaZn in the Organic diet). Cows were fed a hay-based diet and individually fed supplements for approximately 45 d before and 60 d after calving (approximately January 15 to May 15 each year). Liver biopsies were obtained from cows before supplementation began, and from cows and calves at 10 and 30 d after calving. Blood samples were obtained from both cows and calves at calving, and colostrum samples were collected for IgG and mineral content. Cow liver Cu concentrations before supplementation began were 58 mg/kg in 1997 and 40 mg/kg (DM basis) in 1998. By 10 d after calving, liver Cu concentrations of Control cows had decreased (P < 0.05) to 24 mg/kg (Cu deficient) in both years, whereas liver Cu concentrations of Cu-supplemented cows increased (P < 0.05) in both years. Calf liver Cu concentrations at 10 d of age were similar (P > 0.10) for all treatment groups. No differences (P > 0.10) were found in colostrum Cu concentrations, or in calf health among treatments. No differences (P > 0.10) were found in cow BW change, calf serum Cu concentrations, calf weaning weights, or in cow 60-d pregnancy rates among treatments in either year. In 1998, cows in the Organic group had higher (P < 0.05) 30-d pregnancy rate than Control cows. Neither serum samples nor placental tissue were reliable indicators of Cu status in cows. Feeding supplemental Cu (either inorganic, organic, or organic with extra Zn) to cows with liver Cu concentrations of approximately 50 mg/kg before calving did not improve cow 60-d pregnancy rates or the health and performance of their calves when compared with unsupplemented cows.

Animal Feed↗

Foamy cells with oligodendroglial phenotype in childhood ataxia with diffuse central nervous system hypomyelination syndrome.

Childhood ataxia with diffuse central nervous system hypomyelination syndrome (CACH) is a recently described leukodystrophy of unknown etiology. To characterize the neuropathological features and gain insight as to the pathogenesis of this disorder, we studied cerebral tissue from six patients with the CACH syndrome. Evaluation of toluidine blue-stained, semithin sections of white matter from CACH patients disclosed unusual cells with "foamy" cytoplasm, small round nuclei and fine chromatin. Electron microscopy (EM) revealed cells in the white matter with abundant cytoplasm containing many mitochondria and loosely clustered, membranous structures, but lacking the lysosomal structures seen in macrophages. Further analysis of tissue sections with antibodies and special stains demonstrated that the abnormal cells with abundant cytoplasm labeled with oligodendroglial markers, but did not react with macrophage or astrocytic markers. Double immunolabeling with macrophage and oligodendroglial markers clearly distinguished macrophages from the "foamy" oligodendroglial cells (FODCs). Proteolipid protein (PLP) mRNA in situ hybridization demonstrated PLP mRNA transcripts in a high proportion of oligodendrocytes in CACH patients compared to control patients, and PLP mRNA transcript signal in cells, morphologically consistent with FODCs. Normal and pathological brain control tissues did not contain FODCs. These neuropathological findings will be useful pathological identifiers of CACH, and may provide clues to the pathogenesis of this disorder.

Ataxia↗

Choice of insufflating gas influences on wound metastasis.

BACKGROUND: Laparoscopic cancer surgery is limited by concerns about port-site metastasis. No study has definitively addressed the behavior and growth of tumor cells after the use of specific laparoscopic gases. METHODS: In athymic rats, 10,000 colon cancer cells were injected intraperitoneally. The rats received either no pneumoperitoneum (pneumo) or pneumo (8 mmHg, 10 min) with carbon dioxide (CO(2)), nitrous oxide (N(2)O), or air. Two full-thickness incisions were made and closed in the upper abdomen of each animal. After 4 weeks, implants were identified grossly at necropsy, and invasiveness was scored according to penetration through the layers of the abdominal wall. RESULTS: Rats receiving pneumo had more frequent implants (p < 0.01) with deeper penetration (p < 0.001) than rats not receiving pneumo. Implants were more common after air pneumo than after CO(2) (p < 0.05) or N(2)O (p = 0.07) pneumo, and were less penetrating after CO(2) pneumo than after air (p < 0.001) or N(2)O (p < 0.05) pneumo. CONCLUSIONS: Carbon dioxide gas may limit the viability and invasiveness of free intraperitoneal tumor cells, as compared with air or N(2)O.

Abdominal Muscles↗

Thyroid and sympathetic influences on plasma leptin in hypothyroidism and hyperthyroidism.

OBJECTIVES: To determine the dependence of plasma leptin concentrations upon circulating noradrenaline (NA) and thyroid hormones (TH) in humans. DESIGN: Cross-sectional study in 40 newly diagnosed untreated patients with primary thyroid disease, and 69 lean and obese euthyroid control subjects. MEASUREMENTS: Plasma leptin, NA, free T3 (fT3) and TSH in the fasting state. Anthropometry and % body fat (electrical bioimpedance). RESULTS: Leptin levels were highest in 37 obese euthyroid and 22 hypothyroid (median [interquartiles]31.5 [19.0- 48.0], 19.2 [11.5-31.5] ng ml(-1)), and lowest in 32 lean euthyroid and 18 hyperthyroid subjects (6.6 [3.9-14.4], 8.9 [5.5-11.1]; ANOVA, P< 0.0001). Plasma NA was similar in all groups (P= n.s.). In obese controls, TSH correlated with % body fat and leptin (r= 0.67, r= 0.61; P< 0.001). Treatment of hypothyroidism (n= 10) with T4 reduced leptin from 20.8 [11.8-31.6] to 12.9[4.6-21.2] (P= 0.005) with no change in BMI. CONCLUSIONS: Thyroid status modifies leptin secretion independently of adiposity and NA. The data suggest leptin-thyroid interactions at hypothalamic and adipocyte level.

Female↗

Impact of redox conditions on metolachlor and metribuzin degradation in Mississippi flood plain soils.

The effect of soil redox conditions on the degradation of metolachlor and metribuzin in two Mississippi soils (Forrestdale silty clay loam and Loring silt loam) were examined in the laboratory. Herbicides were added to soil in microcosms and incubated either under oxidized (aerobic) or reduced (anaerobic) conditions. Metolachlor and metribuzin degradation under aerobic condition in the Forrestdale soil proceeded at rates of 8.83 ngd(-1) and 25 ngd(-1), respectively. Anaerobic degradation rates for the two herbicides in the Forestdale soil were 8.44 ngd(-1) and 32.5 ngd(-1), respectively. Degradation rates for the Loring soil under aerobic condition were 24.8 ngd(-1) and 12.0 ngd(-1) for metolachlor and metribuzin, respectively. Metolachlor and metribuzin degradation rates under anaerobic conditions in the Loring soil were 20.9 ngd(-1) and 5.35 ngd(-1). Metribuzin degraded faster (12.0 ngd(-1)) in the Loring soil under aerobic conditions as compared to anaerobic conditions (5.35 ngd(-1)).

Acetamides↗

Digital characteristics in commercial dairy herds fed metal-specific amino acid complexes.

Five commercial dairy herds in Central New York fed metal-specific amino acid complexes were selected to evaluate digital characteristics. During the first year (period 1), herds were evaluated by a specific procedure by one individual. Three herds were not supplemented and two herds were supplemented with zinc methionine. During the subsequent year (period 2) all herds were switched to a combination of zinc methionine, copper lysine, manganese methionine, and cobalt glucoheptonate and evaluated in the same way as during period 1. There was no effect of period on incidence of heel erosion and interdigital dermatitis. During period 2, there was a reduced incidence of double soling, white line separation, sole hemorrhages, sole ulcers, and papillomatous digital dermatitis, and the incidence of wall ridges tended to be reduced compared with period 1. There was no effect of period on the incidence of abaxial wall lesions, digital arthritis, or foot rot, although the overall incidence of these disorders was low. During period 2, when cows were fed a combination of complexed trace minerals, there was a general reduction in the incidence of digital disorders associated with the laminitis syndrome complex compared with period 1; however, other time-related differences existed that may confound interpretation.

Amino Acids↗

AMPA receptor protein expression and function in astrocytes cultured from hippocampus.

Glutamate receptors guide the proliferation, migration, and differentiation of glial cells. Here, we characterize AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid) and NMDA receptor protein expression and function and mRNA expression in hippocampal glial cultures. By immunocytochemistry, GluR2 (the subunit that limits the Ca(2+) permeability of AMPA receptors) exhibited prominent labeling in hippocampal glial cultures. Double-labeling of GluR2 with GFAP and with A2B5 revealed GluR2 subunit expression on type-1 and type-2 astrocyte lineage cells. GluR1 subunit expression was more prominent in type-1 than in type-2 astrocytes. To characterize functional properties of glutamate receptors expressed in cultured hippocampal astrocytes, we performed whole-cell patch clamp recording. Application of L-glutamate, AMPA, and kainate, but not NMDA, to small, rounded cells (morphologically identified as type-2 astrocytes) elicited inward currents which were blocked by the AMPA/kainate antagonist 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX). Cyclothiazide potentiated AMPA- and kainate-elicited currents, indicative of AMPA-preferring receptors. Current voltage analysis indicated that type-2 astrocyte AMPA receptors were electrically linear, indicative of GluR2-containing, Ca(2+)-impermeable AMPA receptors. By Northern blot analysis, GluR1 mRNA was highest in astrocyte cultures from cerebellum and hippocampus and moderate in astrocyte cultures from neocortex and striatum. GluR3 mRNA was detectable in astrocyte cultures from cerebellum and neocortex. GluR2 and NR1 mRNA expression were not detected in astrocytes cultured from any brain region examined. In situ hybridization studies showed wide expression of GluR1 mRNA in cultured astrocytes; GluR2 and GluR3 mRNAs were near background levels. Thus, cultured type-2 astrocytes express functional AMPA receptors in a cell-specific and region-specific manner, consistent with their role in neuronal-glial communication.

Animals↗

Fundoplications resist reflux independent of in vivo anatomic relationships.

BACKGROUND: Antireflux operations restore lower esophageal sphincter (LES) function and hiatal anatomy; however, the relative contributions are unclear. METHODS: We measured the competency of fundoplications, exclusive of in vivo variables, in gastroesophageal explants from 8 cadavers. Using a multichannel manometer, esophageal, LES, and intragastric pressures were recorded during transpyloric distension. Data were compared at baseline, and after Nissen (360 degrees) and Toupet (270 degrees) fundoplications. RESULTS: Before fundoplication, stomachs refluxed immediately upon distension. Nissen fundoplications never refluxed before gastric rupture (46.8 +/- 15.0 mm Hg). LES pressure averaged 2.0 +/- 0.5 times intragastric pressure during distension. Toupet fundoplications refluxed at intragastric pressure <2 mm Hg, then became competent until gastric rupture (49.9 +/- 15.0 mm Hg). LES pressure averaged 2.4 +/- 1.0 times intragastric pressure during distension. CONCLUSIONS: Nissen and Toupet fundoplications increase LES pressure linearly at 2 to 2.5 times intragastric pressure, independent of in vivo variables. Toupet fundoplication lacks the competency of Nissen fundoplication at low intragastric pressures.

Aged↗

Fundoplication provides effective and durable symptom relief in patients with Barrett's esophagus.

BACKGROUND: Columnar-lined esophagus with intestinal metaplasia (IM), also called Barrett's esophagus, is a manifestation of severe gastroesophageal reflux (GER) and may predict poor symptom relief and high failure rate after fundoplication. We compared symptom scores and reoperation rates in GER patients with and without Barrett's esophagus. METHODS: Between July 1992 and July 1997, 646 patients underwent fundoplication (626 laparoscopic). Of 150 endoscopic biopsies of suspected columnar-lined esophagus, 80 confirmed IM, 50 identified cardiac or fundic epithelium, and 20 revealed only esophagitis. Typical GER symptoms were scored by patients preoperatively and postoperatively (0 to 4 scale). We compared symptom response (Wilcoxon rank sum test) and failure rates (t test) in patients with IM and GER controls without IM. Preoperative data were available for 74 IM patients and 496 controls. One-year follow-up was available in 45 IM patients and 301 controls. Intermediate follow-up (2 to 5 years) was available in 20 IM patients and 99 controls. RESULTS: Preoperatively and postoperatively, patients with IM reported heartburn, regurgitation, and dysphagia scores similar to controls. Procedure failure, requiring redo fundoplication, appeared more likely in IM patients than controls (6.3% versus 2.5%), but this difference did not reach statistical significance (P = 0.061). CONCLUSION: Fundoplication provides equivalent symptom relief for patients with and without IM.

Barrett Esophagus↗

Current activities at the Centers for Disease Control and Prevention's National Diabetes Laboratory.

In 1997, the Centers for Disease Control and Prevention established the National Diabetes Laboratory in order to help prevent and treat type 1 diabetes. This state-of-the-art laboratory collaborates with research scientists and key national and international organizations throughout the world to identify and study risk factors for type 1 diabetes by developing measurements for glycosylated proteins, developing and evaluating technology for measuring genetic risk factors for the disease, and working to standardize autoantibody measurements. Developing improved technologies for diagnosing and managing diabetes and developing reference materials for properly calibrating and standardizing blood glucose meters are also critical aspects of the laboratory's work. In addition, the laboratory provides quality storage for valuable collections of biologics and other materials and facilitates sharing of specimens, associated epidemiologic data, and test results. Working with our partners in diabetes research, we are improving the diagnosis, treatment, and prevention of type 1 diabetes.

Autoantibodies↗

Effects of supplementation of organic and inorganic combinations of copper, cobalt, manganese, and zinc above nutrient requirement levels on postpartum two-year-old cows.

The objective of this study was to determine whether a combination of Cu, Co, Mn, and Zn in an organic or inorganic form fed at higher than nutrient recommendations for 2-yr-old cows from calving to breeding would affect pregnancy rate, calving date, calf performance, and cow liver and serum mineral concentrations. Crossbred 2-yr-old cows were used after calving in 1994 (n = 127) and 1995 (n = 109). Cows were blocked by calving date to one of three treatments: 1) no supplemental minerals (CTL), 2) organic minerals (ORG), or 3) inorganic minerals (ING). Minerals were fed for the same daily intake for both organic and inorganic treatments: Cu (125 mg), Co (25 mg), Mn (200 mg), and Zn (360 mg). Cows were individually fed a mineral-protein supplement with grass hay from calving (February-March) to before breeding (May 15). Hay intakes were calculated using chromium oxide boluses to determine fecal output. Fecal excretion of minerals was calculated following trace element analysis of feces. Liver biopsies were obtained before calving, after calving (start of supplementation), at the end of supplementation, and in midsummer. Over 2 yr, more cows did not become pregnant (P < .01) in ORG (11/78) and ING (11/78) treatments than in CTL (0/80) treatments. A treatment x year interaction was found for day of conception. Cows in the ORG group conceived later (P < .01) than cows in the ING or CTL groups in 1994. In 1995, there was no difference (P > .10) in day of conception among groups. Liver Zn and Mn concentrations were not different (P > .10) and Cu concentrations increased (P < .01) for the ORG and ING groups. Cows in the ORG and ING groups had higher (P < .01) concentrations of Cu, Mn, and Zn in the feces than the CTL cows. Trace elements in the feces did not differ for ORG and ING groups. Results indicate that combinations of Cu, Co, Mn, and Zn fed at higher levels than are required reduced reproductive performance.

Animal Feed↗