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Biomedical subjects

C C McCormick

Publications and source records attributed to C C McCormick.

At least 37 records · Page 2Linked to original sources

Metalloforms of metallothionein induced by parenteral copper: the influence of route of administration.

Previous results regarding the two metalloforms of MT which accumulate in chick liver following the parenteral administration (ip) of copper were discussed. One metalloform, which is exclusively zinc, was suggested to reflect the marked accumulation of hepatic zinc following copper injection. The present report shows that there is a marked difference in hepatic zinc accumulation if copper is administered iv. Under these conditions there is virtually no change in hepatic zinc and thus MT produced under these conditions appears to contain only copper. We suggest the the changes in zinc metabolism as effected by copper when given intraperitoneally reflect a secondary response analogous to that observed when iron is similarly administered.

Animals↗

Facet joint arthrography in lumbar spondylolysis: anatomic basis for spread of contrast medium.

Facet arthrograms in patients with lumbar spondylolyses show spread of contrast medium through pars interarticularis defects into the adjacent ipsilateral facet joint space and across the midline into the contralateral joint space. Transverse and sagittal sections of facet joints from 141 postmortem lumbar spines were studied. Five examples of spondylolysis were found. Anatomic studies of the relationship of the joint recesses to the pars interarticularis demonstrated the basis for the patterns of spread of contrast medium observed radiographically in this and previous series. The pars interarticularis forms the only boundary between the inferior recess of one facet joint and the superior recess of the adjacent joint. Fracture through the pars interarticularis establishes communication between adjacent ipsilateral joints and opens a communication to the retrodural space, through which contrast medium can track to the contralateral joint.

Arthrography↗

Amino acid sequence and comparative antigenicity of chicken metallothionein.

The complete amino acid sequence of metallothionein (MT) from chicken liver is reported. The primary structure was determined by automated sequence analysis of peptides produced by limited acid hydrolysis and by trypsin digestion. The comparative antigenicity of chicken MT was determined by radioimmunoassay using rabbit anti-rat MT polyclonal antibody. Chicken MT consists of 63 amino acids as compared to 61 found in MTs from mammals. One insertion (and two substitutions) occurs in the amino-terminal region, a region considered invariant among mammalian MTs. Eighteen of the 20 cysteines in chicken MT were aligned with cysteines from other mammalian sequences. Two cysteines near the carboxyl terminus are shifted by one residue due to the insertion of proline in that region. Overall, the chicken protein showed approximately equal to 68% sequence identity in a comparison with various mammalian MTs. The affinity of the polyclonal antibody for chicken MT was decreased by 2 orders of magnitude in comparison to that of a mammalian MT (rat MT isoforms). This reduced affinity is attributed to major substitutions in chicken MT in the regions of the principal determinants of mammalian MTs. Theoretical analysis of the primary structure predicted the secondary structure to consist of reverse turns and random coils with no stable beta or helix conformations. There is no evidence that chicken MT differs functionally from mammalian MTs.

Amino Acid Sequence↗

The toxicity of parenteral copper in the chick: dependence on route of administration.

Preliminary work in our laboratory suggested that the route of parenteral copper administration influences the acute toxicity of copper (Cu). The present work examined the effects of Cu given either intraperitoneally (i.p.) or intravenously (i.v.) on mortality, feed intake, peritoneal fluid and hepatic accumulation of Cu and zinc (Zn) in chicks. We also studied the potential interaction of prior Zn loading on these parameters. Four-wk-old chicks were pretreated by injection (subcutaneous) with Zn acetate (5 mg Zn/kg) or sodium acetate 24 h prior to Cu treatments. Copper as Cu acetate was given either i.p. or i.v. at a dose of 1.84 mg Cu/kg. Mortality was markedly greater in those chicks given Cu i.p. compared to those given Cu i.v. (46.1% vs. 3.9%). Zinc pretreatment had no effect on any of the parameters associated with copper treatments. The accumulation (24 h) of copper in either total hepatic tissue or cytosol was comparable for both routes of injection. However, marked differences in Cu-induced hepatic Zn accumulation were observed. Massive peritoneal fluid (41% of total plasma volume) was observed 1 to 3 h following the administration of Cu i.p. None was observed in those given Cu i.v. Thus, this effect was associated with the route-dependent mortality observed in the present study. We suggest that our data highlight the gratuitous effects of reactive agents given intraperitoneally.

Animals↗

Tissue-specific accumulation of metallothionein in chickens as influenced by the route of zinc administration.

The effect of the route of zinc (Zn) administration on the induction of metallothionein (MT) in various tissues of chicks was examined. Four-week-old, male chicks were assigned to one of four treatments: 5 mg Zn/kg intraperitoneal (i.p.) injection, 5 mg Zn/kg intravenous (i.v.) injection, 16 mg Zn oral (O) dose or a saline control (C). Chicks were fasted overnight, treated and killed 24 h later. 109Cd radioassay analysis of liver (L), kidney (K) and pancreas (P) showed a significant elevation of MT in all tissues except K of i.v. chicks. Comparing tissue MT accumulation within treatments showed that L was induced to a greater extent than P for the i.p. treatment (P/L ratio = 0.69 +/- 0.04), while the reverse effect was seen for both O (1.51 +/- 0.10) and i.v. (1.67 +/- 0.14) chicks, reflecting greater P than L accumulation. Zn injected i.p. did not result in significantly greater total peritoneal exudate cell (PEC) or macrophage (M) numbers than saline-injected controls. Sephadex, while causing massive increases in PEC and M, did not induce tissue MT, demonstrating the lack of correlation between PECs or Ms and MT accumulation. Feed intake by chicks during the 24-h period following i.p. Zn treatment was only 30% of that by controls. A subsequent experiment demonstrated that a similar restriction in feed intake increased L but not P MT. This increase accounted for 17.8% of the L induction due to i.p. Zn injection. This does not fully account for the reduction in P/L that is characteristic of i.p. treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

The ontogeny and induction by zinc of hepatic chick embryo metallothionein.

To avoid the maternal influences inherent in mammalian models, the chick embryo was examined for the effects of development on the ontogeny of hepatic metallothionein (MT) induction. Livers from embryos were examined for total and cytosolic zinc (Zn) and copper (Cu), and cytosolic MT on 12, 14, 16, and 18-21 days of incubation (DI) as well as 1, 7, and 14 days posthatch (ph). Cytosolic Zn levels fell, from a high on 12 DI (45.04 +/- 1.05 ng/micrograms DNA), to 25.79 +/- 1.05 ng/micrograms DNA on 19 DI and then increased to 44.73 +/- 3.47 ng/micrograms DNA by 1 day ph. Cytosolic Cu followed a reverse pattern, with a high of 24.10 +/- 0.74 ng/microgram DNA on 16 DI. Both 109Cd radioassay analysis and gel filtration chromatography of hepatic cytosols showed a developmental pattern for MT similar to that of cytosolic Zn. These results are in contrast to the developmental pattern of the rat. To establish if yolk Zn levels limit hepatic MT in the 1-day neonate, the yolks of unincubated fertile eggs were supplemented with 26, 52, or 78% of the endogenous Zn (768 micrograms/yolk). As a result, hepatic MT of 1-day neonates increased by 3.9-, 4.7-, and 7.1-fold, respectively. Thus the initial level of Zn in the yolk has a significant impact on the final concentration of MT in neonatal liver. A study of MT induction in the 18-DI embryo revealed that yolk sac administration of Zn (550, 2750, 4950 micrograms/yolk) increased hepatic MT by 5.8-, 23-, and 39-fold, respectively. This demonstrates the inducibility of MT even at the point of minimum endogenous MT (18 DI). In summary, our results show that (1) a marked difference exists between the developmental patterns of MT in avian and mammalian species, and (2) chick embryo hepatic MT is highly responsive to exogenous Zn introduced into the yolk.

Animals↗

Iron-induced accumulation of hepatic metallothionein: the lack of glucocorticoid involvement.

The process(es) by which parenteral iron effects the accumulation of hepatic metallothionein (MT) is not known. The present study examined glucocorticoids as potential mediators of this process. Chicks were given either one injection (ip) of iron (+1FE) at 10 mg Fe/kg, two injections of iron (+2FE) given 24 hr apart, or a single injection of saline. Plasma corticosterone was evaluated at various times following the last injection. Plasma corticosterone increased approximately 50% following +1FE but more than 200% at 2 and 4 hr following a second injection of iron (+2FE). Plasma zinc showed a transient increase followed by a considerable depression. Coincidentally, the accumulation (determined at 24 hr) of zinc MT in liver of +2FE chicks was three times higher than that of +1FE chicks. In another experiment, markedly greater changes, at similar time intervals, in plasma corticosterone were effected by multiple subcutaneous injections of adrenocorticotropic hormone (ACTH) (either 5 IU ACTH or 20 IU ACTH/kg). Subsequent analysis of hepatic zinc MT showed only minor changes as a result of ACTH injections. These results indicate that a change in the plasma glucocorticoid corticosterone is not a primary component in the process(es) by which parenteral iron effects an increase in hepatic zinc MT.

Adrenocorticotropic Hormone↗

Performance and physiological profiles of high dietary zinc and fasting as methods of inducing a forced rest: a direct comparison.

Equal periods of fasting or high zinc feeding as a means of inducing a forced rest were examined. Single Comb White Leghorn hens (60 weeks of age) were fasted (F) or fed a layer diet containing 20,000 ppm zinc (Zn) for either 4 or 10 days in a 2 X 2 factorial arrangement of treatments. Feed intake was markedly depressed in the first day of high zinc feeding and averaged 10.7 and 6.1 g/hen-day during the 4 or 10 days of Zn feeding. Body weight losses of hens fasted or fed high dietary zinc were not significantly different. Egg production rate was highest for hens treated 10 days (both F and Zn) in the immediate weeks following the rest. However, over the entire 6-month experimental period, there were no significant differences among the four treatments. Ovary and oviduct regressed similarly in F and Zn hens. Tissue zinc concentration greatly increased during zinc feeding, especially in the pancreas, and rapidly returned to normal upon refeeding a normal layer diet. Fasting also caused a substantial increase in tissue zinc. The results show that the effectiveness of zinc as a forced-resting agent for hens is related to changes in feed intake.

Animals↗

Quantitation of chick tissue zinc-metallothionein by gel electrophoresis and silver stain enhancement.

Discontinuous gradient gel electrophoretic systems were developed to quantitate zinc-metallothionein (Zn-MT) in chick tissues, liver and pancreas. Gels were stained with Coomassie Blue initially, then enhanced by silver stain. At least 4 micrograms of Zn-MT could be detected after Coomassie Blue stain, and 1 microgram Zn-MT detected following silver stain enhancement. Significant linearity (correlation coefficient = 0.99) of a standard curve was established in the Coomassie Blue stained gels. The results of our experiment suggest that electrophoretic analysis is a simple and feasible method for the quantitation and identification of Zn-MT in chick tissues.

Animals↗

Effects of cage and floor pen management on behavior, production, and physiological stress responses of laying hens.

Behavior, physiology, health, egg production, and egg quality characteristics of laying hens housed either 1/1394-cm2 cage (S), 2/1394-cm2 cage (HD), 2/2788-cm2 cage (LD), or in floor pens (P), each containing 25 hens, were monitored in order to assess hen welfare in different management systems. Egg production was highest in P and S hens. There were no differences among treatment groups in feed efficiency, egg weight, or egg taste, although egg shell breaking strengths were lower in HD hens despite their relatively low egg production. Blood spots were most common in eggs from caged hens. With respect to behavior, penned hens locomoted more, spent less time in stationary exploration than caged birds, and utilized nest boxes for activities in addition to egg laying. The HD hens fed less frequently than did the LD, and HD cage pairs engaged less frequently in simultaneous feeding, drinking, and resting behavior than LD pairs. Plasma corticosterone levels were initially found to be higher in pens than cages; this difference disappeared when the use of trap-nesting to capture P birds for sampling was discontinued. Nighttime corticosterone levels were higher in HD hens. In contrast, primary and secondary hemagglutination titers to sheep erythrocyte (SRBC) antigen, heterophil to lymphocyte ratios, hepatic zinc metallothionein, serum zinc, and body weights did not differ among treatments. Mortality, however, was lower in pens. It was concluded that, although there were striking dissimilarities in behavior between the pen and cage environments, physiological and production data did not provide evidence of stress associated with cage housing per se. High density caging, however, may be a stressor; this is discussed with reference to other research.

Animals↗

Induction and accumulation of metallothionein in liver and pancreas of chicks given oral zinc: a tissue comparison.

The present study was undertaken to compare apparent zinc metabolism in two organs, the liver and pancreas. Four-week-old chicks received an oral dose of saline or an equal volume of zinc solution containing 4, 8 or 16 mg zinc. The accumulation of zinc metallothionein (MT) was determined 24 hours postgavage in hepatic and pancreatic cytosol. The rate of MT synthesis was determined in both tissues by a pulse labeling technique. In response to orally administered zinc, plasma zinc increased sharply (by 3 hours) and in proportion to the amount of zinc given. At 12 hours there was little difference in plasma zinc. The concentration of zinc MT in pancreatic cytosol relative to liver was nearly fivefold higher in control chicks and increased at approximately twice the rate when chicks were given zinc. Despite this marked difference in both the rate and extent of zinc MT accumulation there was little evidence of a difference in the rate of MT synthesis. Quantitation of MT by anion-exchange chromatography demonstrated an apparent maximum in the rate of MT synthesis at 6 hours, which was apparently the same in pancreas and liver. Our data suggest that when compared to liver, the pancreas possesses a markedly higher concentration of MT-bound zinc and a greater propensity to accumulate zinc MT when zinc status is acutely elevated. This tissue difference appeared not to be due to a greater capacity to synthesize MT.

Animals↗

The tissue-specific accumulation of hepatic zinc metallothionein following parenteral iron loading.

The synthesis in various tissues of the unique metal-binding protein, metallothionein, can be influenced by the administration of certain trace elements. Zinc and cadmium, both of which bind to metallothionein, are most widely recognized as potent inducers. Preliminary results in our laboratory suggested that iron loading causes a marked accumulation of hepatic zinc metallothionein. We present in this report the effects of parenteral iron administration on metallothionein concentration in various tissues. Male chicks (300-350 g) received (ip) either a single injection (+1 Fe) of iron (10 mg Fe/kg, as FeCl3), two injections (+2 Fe) given 24-hr apart, three injections (+3 Fe) each given 24-hr apart, or an equivalent volume of 0.9% saline (control). Twenty-four hours following the final injection, chicks were killed and tissues analyzed for cytoplasmic zinc and metallothionein (Zn-MT). The parenteral administration of ferric iron, FeCl3, resulted in a marked tissue-specific accumulation of zinc as metallothionein. In chicks given +2 Fe, hepatic Zn-MT increased more than 10-fold with a third injection (+3 Fe) causing no further change. The concentration of Zn-MT in renal and pancreatic tissue was unaffected by iron loading. An increase in hepatic Zn-MT was evident prior to detectable changes in total hepatic iron. The administration of other ferrous iron compounds at a similar rate produced comparable changes in hepatic Zn-MT. Feeding excess dietary iron, however, had no effect on liver Zn-MT levels even though similar hepatic iron concentrations were attained. Our results indicated that parenteral administration, but not feeding, of various iron compounds causes a marked increase in zinc metallothionein, specifically in liver tissue.

Amino Acids↗

High dietary zinc and fasting as methods of forced resting: a performance comparison.

A study was conducted to compare fasting and high dietary zinc as procedures to induce a forced rest of laying hens. Five to six replicates (25 hens each) of Single Comb White Leghorn hens laying approximately 60% were fasted for 10 days (fasted) or fed either 10,000 ppm zinc (10 Zn) or 20,000 ppm zinc (20 Zn) for a period of 4 days. A fourth treatment consisted of feeding 20,000 ppm zinc for 8 days (20 Zn-8). During the rest-inducing period, hens consumed little of either high zinc diet. Four-day intake by 20 Zn hens averaged 17.6 +/- .2 g/hen/day compared to 32.6 +/- 1.5 g/hen/day (means +/- SEM) for 10 Zn hens. Those fed 20 Zn-8 consumed the least amount, 12.6 +/- .2 g/hen/day during the 8 days of high zinc feeding. Body weight loss of hens in this last group was comparable to hens fasted for 10 days (fasted), i.e., 24.6 +/- .3% vs. 27.6 +/- .4%. Weight loss of hens in the remaining two groups reflected, to some extent, differences in feed consumption. The 20 Zn hens lost significantly more body weight during the 4-day period when compared with 10 Zn hens (16.2 +/- .4% vs. 11.9 +/- .5%). Each treatment resulted in a sharp drop in egg production. By the 5th day, fasted, 20 Zn, and 20 Zn-8 hens had ceased producing eggs. Egg production by 10 Zn hens declined at a slightly slower rate. There were considerable differences in post-rest egg production among the various treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Forced resting by high dietary zinc: tissue zinc accumulation and reproductive organ weight changes.

An experiment was conducted to investigate the effects of high dietary zinc, as a means of inducing a forced-rest, on selected organ accumulation of zinc and reproductive function in terms of ovary and oviduct weight in the laying hen. Single Comb White Leghorn hens laying approximately at 60% production were fed either 10,000 ppm zinc as zinc oxide (10 Zn) or 20,000 ppm zinc (20 Zn) for a period of 4 days. At the initiation of the experiment (Day 0), five hens were killed and organs obtained for analysis. On 4, 10, 16, and 22 days afterward, similar samples were obtained from 5 hens per treatment. Ovary and oviduct weights were determined and zinc analysis performed on the latter as well as liver, kidney, and pancreas. The brief 4-day feeding of either high zinc diet caused a marked 80% reduction in ovary weight by Day 10. The oviduct, although less affected, was still reduced approximately 60% in weight after feeding either 10 Zn or 20 Zn for 4 days. The oviduct exhibited a statistically significant elevation in zinc concentration on Day 4 but was normal by Day 10 (6 days following the refeeding of a normal diet) and not different between treatments. There was extensive accumulation of zinc in kidney, liver, and especially pancreas after 4 days of feeding either 10 Zn or 20 Zn. The level of dietary zinc had no effect on the extent of accumulation in any tissue. The depletion of tissue zinc roughly corresponded to the magnitude of increase in the concentration of zinc observed at Day 4. Possible ramifications of the dramatic increase observed in pancreatic zinc were discussed. We concluded that feeding either 10 Zn or 20 Zn as a means of inducing a forced rest effects a marked and rapid reduction in ovary and oviduct weight as well as an extensive increase in renal, hepatic, and especially pancreatic zinc.

Animals↗

Developmental asymmetry of roots of the cauda equina at metrizamide myelography: report of seven cases with a review of the literature.

The myelographic findings of developmental asymmetry of the lumbo-sacral nerve root sheaths are described in seven patients and details of the clinical presentation and management are presented. Six of the seven patients had referred pain to the leg on the side of the anomaly. There were no significant associated plain film findings. Adherence to recommended techniques of metrizamide myelography is stressed, with particular reference to horizontal beam decubitus oblique projections, which profile the root sheaths to best effect. Minimal signs in the frontal projection are also described, which may be the initial clue to diagnosis. The possibility of erroneous diagnosis of lateral disc protrusion is emphasised if this anatomical variant is not recognised.

Adult↗

The interaction of phosphorus nutrition and fasting on the survival time of young chickens acutely exposed to high temperature.

Phosphorus nutrition and fasting are dependent factors which markedly influence the tolerance of young chickens to high temperature. A study was conducted to further characterize the nature of this interaction. Male chicks fed low phosphorus diets and fasted 24 hr exhibited significantly shorter survival time after exposure to acute heat when compared to fasted chicks previously fed adequate dietary phosphorus. When chicks were fasted for 48 hr, the effect of previous diet was considerably more pronounced. These results showed that the effect of low phosphorus nutrition was potentiated by fasting 48 hr which in itself improved survival time over that of chicks fasted 24 hr. The apparent metabolic responses of chicks to heat as indicated by changes in plasma glucose and total ketones were not related to the observed dietary effects. Plasma phosphate (Pi) and calcium (Ca) decreased significantly during heat exposure. The Ca/pi molar ratio was increased significantly at heat induced exhaustion, indicating a relatively greater heat induced change in Pi. From the initiation of heat exposure to heat exhaustion, the percent change in Pi, but not Ca, was similar in all groups despite marked differences in the time within which this occurred. We concluded that the effect of low phosphorus nutrition on heat tolerance of young chickens persists after a 48-hr fast. In addition, the effects of previous diet were somewhat more pronounced in 48-hr fasted chicks when compared to those fasted 24 hr.

Animal Feed↗