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Biomedical subjects

J B Taylor

Publications and source records attributed to J B Taylor.

At least 19 recordsLinked to original sources

Gross and histopathological observations of long-term catheterized vessels in experimental sheep.

Chronic indwelling central vessel catheters provide vascular access for compartmental infusion or sampling. However, complications with catheter patency during the postoperative and/or experimental period often arise. In order to identify physiological occurrences common with such complications, 10 multicatheterized sheep (61.8 +/- 7.8 kg BW), obtained from a previous nutrient flux study were used for gross and histopathological investigation. Catheters had been surgically placed in a hepatic portal vein (PVC), a hepatic vein (HVC), a distal mesenteric vein (MVC) and a mesenteric artery (MAC). In the previous study, catheters (PVC, HVC and MAC) were used to collect blood samples or infuse (MVC) p-aminohippurate. Catheters were maintained for a total of 58 days prior to necropsy. Histopathological findings indicated that catheter failures were associated with the following tissue responses: (i) thromboses with frequent focal vasculitis; (ii) euplastic tissues associated with extensive fibrosis; (iii) granulomas; (iv) neo-vascularization of the media; (v) calcification processes; and (vi) micro-abscesses. Additional studies are needed that address and incorporate improvement of catheter design and placement to minimize irritation of endothelium, improvement of catheter treatments and therapeutic regimes, and development and use of alternative anti-coagulants. A greater understanding of the mechanisms leading to failure will help researchers improve catheter performance and patency.

Animals↗

Effect of the chemical form of supranutritional selenium on selenium load and selenoprotein activities in virgin, pregnant, and lactating rats.

Virgin, pregnant, and lactating rats were used to assess the influence of selenomethionine and selenocystine, fed at four to seven times the daily Se requirement (supranutritional), on Se load and selenoprotein activities. Female Sprague Dawley rats (n = 48; age = 13 wk), reared on a low-Se torula yeast diet, were assigned to one of three reproductive states (n = 16 per reproductive state) to occur simultaneously: virgin, pregnant, and lactating. Once reproductive state was achieved, rats were fed (ad libitum) either l-selenomethionine (n = 24) or L-selenocystine (n = 24) diets providing 2.0 microg Se/g of diet (as-fed basis) for 18 d, and then killed. Lactating rats consuming selenomethionine had the greatest Se concentration in the brain, with pregnant rats being intermediate, and virgin rats having the least (P < 0.02). When selenocystine was fed, the concentration of Se in the brain was greater (P = 0.008) in lactating rats, but not different (P = 0.34) between pregnant and virgin rats. Selenium concentrations in the heart, liver, lung, muscle, spleen, plasma, placenta, uterus, and fetus were greatest (P < 0.001) in rats consuming selenomethionine. Brain, kidney, and liver thioredoxin reductase, and brain, erythrocyte, kidney, and liver glutathione peroxidase activities did not differ (P = 0.13 to P = 0.85) between Se treatments. Lactating rats exhibited the greatest (P < 0.006) Se concentration in the heart, lung, muscle, plasma, and spleen compared with pregnant and virgin rats. Thioredoxin reductase was greatest (P < 0.004) in the brain of pregnant rats, greatest (P < 0.004) in the liver of lactating rats, and greater (P < 0.03) in the kidney of lactating and pregnant vs. virgin rats. Regardless of reproductive state, supranutritional Se (2.0 microg/g of diet) fed as selenocystine resulted in less Se load, and when fed as selenomethionine, was equally available for thioredoxin reductase synthesis as the Se in selenocystine. Independent of dietary Se chemical form, thioredoxin reductase activity was responsive to reproductive state.

Animals↗

Effects of locoweed on serum swainsonine and selected serum constituents in sheep during acute and subacute oral/intraruminal exposure.

A study was conducted to evaluate the effects of acute and subacute locoweed exposure on serum swainsonine concentrations and selected serum constituents in sheep. Thirteen mixed-breed wethers (BW = 47.5 +/- 9.3 kg) were assigned randomly to 0.2, 0.4, or 0.8 mg of swainsonine x kg BW(-1) x d(-1) treatments. During acute (24 h) and subacute (19 d) exposure, serum swainsonine was detected in all treatments and was greatest (P < 0.03) in the 0.8 mg treatment. Serum alkaline phosphate (ALK-P) activity was increased (P < 0.01) for the 0.8 mg treatment compared with baseline (0 h) by 7 h and continued to increase throughout the initial 22 h following acute exposure to locoweed. A linear increase (P < 0.01) in serum ALK-P activity was noted, with the rate being 3.00 +/- 0.56 U x L(-1) x h(-1). Serum ALK-P activity was increased (P < 0.05) across treatments on d 7 over d -19, -12, 0, 1, 21, and 26; on d 14 over d -19, -12, 0, and 26; and on d 19 over d -19, -12, 0, 1, 21, and 26. By d 20, approximately 48 h after last exposure to swainsonine, serum ALK-P activities were no longer different (P = 0.13) than baseline (d -19, -12, and 0), and by d 26 values had generally returned to baseline. No linear (P = 0.98), quadratic (P = 0.63), or cubic effects of swainsonine with time from exposure were noted for serum aspartate aminotransferase. Similar to serum ALK-P activities, serum aspartate aminotransferase activities were increased (P < 0.05) across treatment levels on d 7, 14, 19, 20, 21, and 26 over those on d -19, -12, 0, and 1. Total serum Fe was decreased (P < 0.05) within the initial 22 h following the swainsonine exposure. On d 21 (48 h after swainsonine feeding ended), serum Fe increased to 472 mg/L. Concentrations of ceruloplasmin were lower (P < 0.10) on d 14 and 19 following exposure to locoweed. Recovery of ceruloplasmin levels coincided with similar changes in serum Fe. There was a linear (slope = 0.33 mg x dL(-1) x d(-1); P < 0.01) effect with time of exposure to locoweed (i.e., swainsonine) on serum triglyceride concentrations. Rapid changes in serum ALK-P and Fe concentrations without parallel changes in other damage markers indicate that acute exposure to swainsonine induces metabolic changes that may impair animal production and health before events of cytotoxicity thought to induce clinical manifestation of locoism.

Administration, Oral↗

Time-dependent influence of supranutritional organically bound selenium on selenium accumulation in growing wether lambs.

Crossbred wethers (n = 36; BW = 36.0 kg; SD = 3.4) were used to assess the time-dependent influence of supranutritional organically bound Se on Se accumulation. Four wethers were slaughtered before the trial began (d 0). The remaining wethers were fed diets containing adequate (0.2 microg of Se/g of DM) or supranutritional Se (2.9 microg of Se/g of DM; in the form of high-Se wheat grain) for 14, 28, 42, or 56 d before slaughter (four wethers per Se treatment at each slaughter day). The DMI was set at 3.1% of BW and adjusted weekly based on a targeted ADG of 150 g. Daily Se intake by wethers fed the adequate and supra-nutritional Se diets ranged from 5.3 to 5.9, and 79.0 to 95.0 microg of Se/kg of BW, respectively, and did not differ (P = 0.84 to 0.99) between slaughter day groups within Se treatment. Neither Se treatment nor Se treatment x slaughter day interactions were significant for BW, G:F, or liver, kidneys, and spleen weights (P = 0.06 to 0.84). Within the supranutritional Se treatment, Se contents of most organs and tissues from wethers slaughtered on d 14, 28, 42, and 56 were nearly twice the concentrations (P < 0.01) of wethers slaughtered on d 0. When regressed against the number of days the wethers were fed supranutritional Se, Se concentrations increased (P < 0.001) cubically in kidneys and plasma, quadratically in duodenum, lung, liver, and spleen, and linearly in heart, muscle, and wool. For total Se in kidneys, liver, and spleen, the response was quadratic (P < 0.03). Excluding skeletal muscle, heart, and wool, Se in other organs and tissues reached apparent steady-state concentrations 14 to 28 d after commencement of supranutritional Se diets. Selenium concentrations in skeletal muscle accumulated in a linear manner (P < 0.001) throughout the 56-d feeding period. High-Se grains can be used strategically to deliver supranutritional Se and rapidly enhance Se depots in sheep, a task that does not seem attainable with Se salts. Furthermore, a 100-g portion of uncooked loin (LM) from the wethers fed supranutritional Se contained 196 to 250% of the recommended Se requirement for humans.

Animal Feed↗

Effect of supranutritional and organically bound selenium on performance, carcass characteristics, and selenium distribution in finishing beef steers.

Dietary selenium influences the Se content in edible muscle of beef cattle. Limited data are available to describe the effects that feeds naturally high in Se have on production, carcass characteristics, and Se distribution in terminal tissues. Therefore, 43 crossbred steers (BW = 351 +/- 24 kg) were stratified by BW and assigned to one of four dietary treatments: Se adequate (CON; n = 12), Se provided as high-Se wheat (WHT; n = 9), high-Se hay (HAY; n = 11), or sodium selenate (SEO; n = 11). Daily selenium intake for WHT, HAY, and SEO diets was 65 microg/kg BW, whereas it was 9.5 microg/kg BW for CON. Diets were similar in ingredient composition (25% wheat, 39% corn, 25% grass hay, 5% desugared molasses, and 6% wheat middling-based supplement; DM basis), isonitrogenous and isocaloric (14.0% CP, 2.12 Mcal NEm/kg DM and 1.26 Mcal NEg/ kg DM), and offered once daily (1500) individually to steers in a Calan gate system for 126 d. At the end of the trial, steers were slaughtered; carcass data were recorded; and samples of the liver, kidney, spleen, semitendinosus, and hair were collected for Se analysis. Intake of DM, G:F, and ADG did not differ (P > 0.13). No differences (P > 0.12) were noted for hot carcass weight, organ weights, longissimus muscle area, back-fat thickness, marbling scores, or quality and yield grade. Kidney, pelvic, and heart fat tended to be higher (P = 0.06) in CON and WHT compared with SEO and HAY steers (2.9, 2.4, 2.5, 2.9 +/- 0.2% for CON, SEO, HAY, and WHT, respectively). Selenium concentrations in all tissues collected differed (P < 0.003) due to treatment. Distribution of Se to the kidney, spleen, and hair were similar with CON < SEO < HAY < WHT (8.40, 10.05, 10.86, 12.89 +/- 0.26 ppm for kidney; 2.00, 2.60, 3.82, 5.16 +/- 0.09 ppm for spleen; 1.80, 4.00, 5.93, 10.54 +/- 0.56 ppm for hair; P < 0.01). The distribution of Se in liver and muscle (DM basis) differed from that in other tissues, with CON < HAY < SEO = WHT (2.33, 6.56, 9.91, 10.79 +/- 0.80 ppm; P < 0.01) and CON = SEO < HAY < WHT (1.33, 1.55, 3.32, 4.41 +/- 0.18 ppm; P < 0.01), respectively. When providing dietary Se at supranutritional levels, source of Se did not affect production or carcass characteristics, but it altered the distribution and concentration of Se throughout the tissues of finishing beef steers.

Animal Feed↗

Effect of high-selenium wheat on visceral organ mass, and intestinal cellularity and vascularity in finishing beef steers.

Twelve crossbred steers (351 +/- 24 kg initial BW) were used to determine effects of high-Se wheat on visceral tissue mass, intestinal cell growth, and intestinal cellularity and vascularity. Steers were allotted randomly by BW to one of two treatments consisting of 75% concentrate diets that supplied 1) adequate Se concentration (7 to 12 microg x kg x BW(-1) x d(-1)) or 2) high-Se concentration (60 to 70 microg x kg x BW(-1) x d(-1)). Diets were similar in composition, including 25% grass hay, 25% wheat, 39% corn, 5% desugared molasses, and 6% wheat middlings supplement on a DM basis. In the Se treatment, high-Se wheat (10 ppm Se, DM basis) was replaced with low-Se wheat (0.35 ppm Se, DM basis). Diets were formulated to be similar in CP and energy (14.0% CP, 2.12 Mcal of NEm/kg, and 1.26 Mcal NEg/kg of DM) and were offered daily (1500) to individual steers in an electronic feeding system. Diets were fed at 2.38% BW. After 126 d, steers were slaughtered, and individual visceral tissue weights determined. Concentrations of DNA, RNA, and protein of duodenum, ileum, and total small intestine were not affected (P > or = 0.33) by treatment. Similarly, RNA:DNA and protein:DNA ratios in duodenum, jejunum, ileum, and whole small intestine were not (P > or = 0.33) affected by feeding high-Se wheat. Conversely, jejunal weight was greater (P < 0.002) in steers fed high-Se wheat than in controls (916 vs. 1,427 +/- 84 g). Jejunal DNA was increased (P < 0.04) in steers fed high-Se wheat (2.95 vs. 3.56 +/- 0.19 mg/g), suggesting increased cell number. Concentrations of jejunal RNA and protein were not altered by treatment; however, because the jejunal weight increased in high-Se steers, DNA, RNA, and protein contents (grams) were greater than in control steers (P < 0.05). Vascularity of jejunal tissue decreased (P < 0.10) with high-Se wheat; however, because jejunal mass was greater for the high-Se wheat treatment, total microvascular volume was not affected by treatment. Percentage of jejunal crypt cell proliferation was not affected (P = 0.48) by treatment; however, total number of cells proliferating within the jejunum was increased in steers fed high-Se wheat. Data indicate that the lower jejunal vascularity in the diet high in Se (provided from wheat) may have resulted in increased jejunal mass to meet physiological nutrient demand. Therefore, negative effects of Se level used in this study on productive performance of feedlot steers are not expected.

Animals↗

Torque on an ideal plasma.

Ripples in the confining field may exert a torque on a rotating plasma. Time reversal symmetry implies that this torque should vanish for an ideal plasma. However, even in an apparently ideal plasma, singularities can give rise to a nonzero torque. This torque is evaluated for a simple configuration. Although the primary force is magnetic, an essential contribution arises from other nonlinear terms in the equations of motion. The net force is confined to the singular layer, in the direction of the ripple wave vector and related to the energy absorbed in the layer.

Journal Article↗

Appearance and disappearance of swainsonine in serum and milk of lactating ruminants with nursing young following a single dose exposure to swainsonine (locoweed; Oxytropis sericea).

A series of experiments were conducted to investigate the elimination of swainsonine in the milk of lactating ruminants following a single dose oral exposure to swainsonine (locoweed; Oxytropis sericea) and to assess subsequent subclinical effects on the mothers and their nursing young. In a preliminary experiment, lactating ewes were gavaged with locoweed providing 0.8 mg swainsonine/kg BW (n = 4; BW = 75.8 +/- 3.6 kg; lactation = d 45) and lactating cows were offered up to 2.0 mg swainsonine/kg BW free choice (n = 16; BW = 389.6 +/- 20.9 kg; lactation = d 90). Serum and milk were collected at h 0 (before treatment), 3, 6, 12, and 24 for ewes, and h 0 (before treatment), 6, 12, 18, and 24 for cows. Swainsonine was highest (P < 0.05) by h 6 in the serum and milk of ewes. Consumption of at least 0.61 mg swainsonine/kg BW induced consistent (> 0.025 microg/mL) appearance of swainsonine in cow serum and milk. In response to the results obtained in the preliminary experiment, a subsequent experiment utilizing lactating ewes (n = 13; BW = 74.8 +/- 6.4 kg; lactation = d 30) and cows (n = 13; BW = 460.8 +/- 51.9 kg; lactation = d 90) was conducted. Each lactating ruminant was gavaged with a locoweed extract to provide 0 (control), 0.2, or 0.8 mg swainsonine/kg BW and individually penned with her nursing young. Serum and milk from the mothers and serum from the nursing young were collected at h 0 (before treatment), 3, 6, 9, 12, 24 and 48 (an additional sample was obtained at h 72 for ewes and lambs). Serum and milk swainsonine was higher (P < 0.05) in the 0.8 mg treated groups and maximal (P < 0.05) concentrations occurred from h 3 to 6 for ewes and h 6 to 12 h for cows (P < 0.05). Rises in alkaline phosphatase activity indicated subclinical toxicity in the treated ewes (P < 0.05). Following a single dose oral exposure to 0.2 and 0.8 mg swainsonine/kg BW provided by a locoweed extract, swainsonine was detected in the serum and milk of lactating ewes and cows, and rises in serum alkaline phosphatase activity were observed in the ewes. Neither swainsonine nor changes in alkaline phosphatase activity was detected in the serum of the lambs and calves nursing the ewes and cows dosed with swainsonine.

Alkaline Phosphatase↗

Effect of lonophore supplementation on selected serum constituents of sheep consuming locoweed.

The effects of ionophore supplementation on selected serum constituents of sheep consuming locoweed were investigated. Sixteen sheep were allotted by weight to a 2x2 factorial arrangement of treatments: 1) no locoweed, no lasalocid, 2) no locoweed, 0.75 mg lasalocid/kg BW, 3) 0.5 mg swainsonine/kg BW, no lasalocid, 4) 0.5 mg swainsonine/kg BW, 0.75 mg lasalocid/kg BW. Swainsonine was provided by locoweed (Oxytropissericea), and sheep were fed a blue grama based diet at 2.5% BW for a 35 d treatment period. Diets were formulated to be isocaloric and isonitrogenous. Blood samples were collected on d 1, 7,14, 21, 31 and 35 to determine serum swainsonine concentration, alkaline phosphatase, total iron, aspartate aminotransferase, g-glutamyltransferase, and lactate dehydrogenase activity and total cholesterol, and triglyceride concentrations. No lasalocid by locoweed interaction (P > 0.4) was noted for any response variable measured. Average daily gains (P = 0.4) and orts (P = 0.7) were not affected by the treatments. No lasalocid treatment (P = 0.7) or day (P = 0.1) effect of serum swainsonine was observed. A locoweed by day interaction (P < 0.0001) of serum alkaline phosphatase was detected. Alkaline phosphatase levels were elevated (P < 0.01) for locoweed treated sheep at 24 h following initial exposure and remained elevated throughout the trail. Total iron was suppressed (P < 0.08) in locoweed fed sheep. A day effect (P < 0.02) was observed for serum iron. However, no linear, quadratic, or cubic effects of day were noted (P >0.2). A locoweed by day interaction (P < 0.0001) of serum aspartate aminotransferase and g-glutamyltransferase was detected. Aspartate aminotransferase levels were elevated (P < 0.0001) by d 7 for locoweed treated animals and remained elevated throughout the trial. g--Glutamyltransferase levels were suppressed (P < 0.0001) by day 7 for locoweed treated animals and remained suppressed throughout the trial. A locoweed by day interaction (P = 0.06) of serum cholesterol was detected. However, no linear, quadratic, or cubic effects of day were detected (P = 0.2). Lasalocid treatment had no effect on any serum constituent measured. Use of lasalocid in grazing animals should not increase the likelihood of locoweed intoxication.

Alkaline Phosphatase↗

RGS14 is a bifunctional regulator of Galphai/o activity that exists in multiple populations in brain.

Members of the regulators of G protein signaling (RGS) family modulate Galpha-directed signals as a result of the GTPase-activating protein (GAP) activity of their conserved RGS domain. In addition to its RGS domain, RGS14 contains a Rap binding domain (RBD) and a GoLoco motif. To define the cellular and biochemical properties of RGS14 we utilized two different affinity purified antisera that specifically recognize recombinant and native RGS14. In brain, we observed two RGS14-like immunoreactive bands of distinct size (60 kDa and 55 kDa). Both forms are present in brain cytosol and in two, biochemically distinct, membrane subpopulations: one detergent-extractable and the other detergent-insensitive. Recombinant RGS14 binds specifically to activated Galphai/o, but not Galphaq/11, Galpha12/13, or Galphas in brain membranes. In reconstitution studies, we found that RGS14 is a non-selective GAP for Galphai1 and Galphao and that full-length RGS14 is an approximately 10-fold more potent stimulator of Galpha GTPase activity than the RGS domain alone. In contrast, neither full-length RGS14 nor the isolated RBD domain is a GAP for Rap1. RGS14 is also a highly selective guanine nucleotide dissociation inhibitor (GDI) for Galphai but not Galphao, and this activity is restricted to the C-terminus containing the GoLoco domain. These findings highlight previously unknown biochemical properties of RGS14 in brain, and provide one of the first examples of an RGS protein that is a bifunctional regulator of Galpha actions.

Animals↗

RGS7 is palmitoylated and exists as biochemically distinct forms.

Regulator of G protein signaling (RGS) proteins are GTPase-activating proteins that modulate neurotransmitter and G protein signaling. RGS7 and its binding partners Galpha and Gbeta5 are enriched in brain, but biochemical mechanisms governing RGS7/Galpha/Gbeta5 interactions and membrane association are poorly defined. We report that RGS7 exists as one cytosolic and three biochemically distinct membrane-bound fractions (salt-extractable, detergent-extractable, and detergent-insensitive) in brain. To define factors that determine RGS7 membrane attachment, we examined the biochemical properties of recombinant RGS7 and Gbeta5 synthesized in Spodoptera frugiperda insect cells. We have found that membrane-bound but not cytosolic RGS7 is covalently modified by the fatty acid palmitate. Gbeta5 is not palmitoylated. Both unmodified (cytosolic) and palmitoylated (membrane-derived) forms of RGS7, when complexed with Gbeta5, are equally effective stimulators of Galpha(o) GTPase activity, suggesting that palmitoylation does not prevent RGS7/Galpha(o) interactions. The isolated core RGS domain of RGS7 selectively binds activated Galpha(i/o) in brain extracts and is an effective stimulator of both Galpha(o) and Galpha(i1) GTPase activities in vitro. In contrast, the RGS7/Gbeta5 complex selectively interacts with Galpha(o) only, suggesting that features outside the RGS domain and/or Gbeta5 association dictate RGS7-Galpha interactions. These findings define previously unrecognized biochemical properties of RGS7, including the first demonstration that RGS7 is palmitoylated.

Animals↗

Convergence and plasticity of monoaminergic systems in the medial prefrontal cortex during the postnatal period: implications for the development of psychopathology.

A variety of observations have suggested that the dopamine and serotonin systems may play a role in the pathophysiology and treatment of major mental disorders of childhood, adolescence and early adulthood. A recent triple immunofluorescence study has demonstrated a convergence of serotonin and dopamine fibers onto both pyramidal cells and GABAergic interneurons in the rat medial prefrontal cortex (mPFCx). These findings are consistent with the results of an electrophysiological study conducted in another laboratory that suggested such a relationship exists in the pyriform cortex of the rodent brain. During postnatal development, the dopamine system shows a progressive ingrowth of fibers into this region that continues until the early adult period. In contrast, GABAergic neurons appear to complete their postnatal maturation by the fourth postnatal week (the early post-weanling period). As dopamine fibers infiltrate the rat mPFCx, they progressively increase their interaction with neural elements within the neuropil and with the cell bodies of both pyramidal cells and GABAergic interneurons. This process appears to be influenced by the serotonin system, since lesioning of the nucleus raphe dorsalis during the neonatal period results in a significant increase of dopamine fibers. This finding suggests that lesions of the serotonin system induce plasticity of the cortical dopamine system; however, it is not known whether this inferred suppressive effect of serotonin fibers occurs at brainstem levels or within the mPFCx itself. Taken together, these various studies suggest that the convergence of dopamine and serotonin fiber systems on intrinsic cortical neurons shows considerable plasticity during postnatal life that could theoretically contribute to the development of 'miswired' circuits in individuals with neuropsychiatric disorders.

Animals↗

Effect of subacute swainsonine (locoweed; Oxytropis sericea) consumption on immunocompetence and serum constituents of sheep in a nutrient-restricted state.

The subacute dose-response effects of swainsonine (SW) consumption on immunocompetence and serum constituents of sheep in a nutrient-restricted state were investigated. Sheep (23 wethers, 5 ewes) were assigned to 1 of 5 SW treatments (0, 0.2, 0.4, 0.8, or 1.6 mg swainsonine/ kg bw/d). Swainsonine was delivered by feeding locoweed (Oxytropis sericea) with grama grass and alfalfa hays for a 28-d treatment period followed by a 21-d recovery period without locoweed. Body weights were measured weekly and behavioral changes were monitored for clinical signs of SW toxicity. Venous blood was collected weekly for lymphoblastogenesis and serum constituent analyses. Clinical signs (sluggishness, decreased responsiveness) of swainsonine toxicity were observed from d 14 to 35 in the 0.8 and 1.6 mg treatments. Subacute oral exposure did not appear to affect lymphoblastogenic analyses. Acute and subacute alterations in various serum constituents did indicate subclinical effects of SW ingestion. Linear, quadratic and cubic dose-response relationships were detected for some serum constituents (e.g., alkaline phosphatase, aspartate aminotransferase). Subacute SW consumption at the levels investigated does not seem to affect the immunocompetence of nutrient restricted sheep. The lack of change in serum alkaline phosphatase at the 0.2 mg SW/kg bw/d dose indicates the potential for a no adverse effect level of SW consumption in nutrient restricted sheep. In combination with measurable SW in serum, rises in serum alkaline phosphatase and aspartate aminotransferase activities, and declines in serum Fe and cholesterol during subacute exposure to SW establish these markers as potential indicators of subclinical SW toxicosis.

Adjuvants, Immunologic↗

Forms and fallacies of memory in 19th-century psychology: Henry Holland, William Carpenter and Frances Power Cobbe.

Mid-19th-century mental scientists were intrigued by the phenomenon of memory, and self-reflexively applied associationist ideas to emerging concepts of unconscious mental reflex to explore it. They emphasized that the 'consciousness of agreement' between present and past states of consciousness was the basis of a coherent, well-managed identity. But they were also fascinated by forms of latent or unconscious memory, and they recognised that the analysis of memory lay at the heart of the study of consciousness itself, and the interconnections between the brain as a set of physiological processes and the mind responding to them. Here I contrast how two key figures in the emerging field of mental science --Henry Holland and William Carpenter--explore the interconnections between the act of recollection and the working of memory, and how their analysis of the limits of memory is taken up by Frances Power Cobbe.

History, 19th Century↗

In vitro effect of swainsonine on bovine and ovine lymphoblastogenesis.

Peripheral blood lymphocytes (PBL) were obtained from heifers and wethers to assess the in vitro effects of swainsonine. Stimulated and unstimulated PBL (2x10(5)/well; 96 well plates) were incubated in the presence of swainsonine (2, .2, .02, .002, and 0 microg/mL; n = 32) for 72 h. Mitogens used to stimulate PBL were concanavalin A (ConA; 5 microg/mL), phytohemagglutinin-P (PHA-P; 5 microg/mL), phytohemagglutinin-M (PHA-M; 5 microg/mL), pokeweed mitogen (PWM; 5 microg/mL), and lipopolysaccharide (LPS; 10 microg/mL). Controls received no swainsonine or mitogen. Effects of swainsonine are expressed as a percentage of stimulation relative to control (stimulation index; SI). Unstimulated bovine PBL treated with 2 microg/mL of swainsonine exhibited a depressed (P<.001; SI of 87 and 100 for 2 microg/mL and control, respectively; SE = 2.7) SI. At concentrations of .2 and 2 microg/mL, swainsonine inhibited (P<.001; SI of 351, 310, and 464 for .2, 2, and 0 microg/mL, respectively; SE = 27.1) bovine PBL proliferative response to PHA-P. Swainsonine had a mitogenic effect on unstimulated ovine PBL at .2 and 2 microg/mL (P<.05; SI of 118, 113, and 100 for .2 and 2 microg/mL and control, respectively; SE = 4.4). Swainsonine inhibited ovine proliferative responses to PHA-P at .2 and 2 microg/mL (P<.005; SI of 190, 178, and 228 for .2, 2, and 0 microg/mL, respectively; SE = 9.4) and to PHA-M at .002 and 2 microg/mL (P<.03; SI of 165, 167, and 192 for .002, 2, and 0 microg/mL, respectively; SE = 7.9). The opposing responses of unstimulated ovine (mitogenic) and bovine (antiproliferative) PBL to swainsonine indicates a differential species response. Swainsonine suppression of PHA-P-induced proliferation would indicate a negative effect on ovine and bovine T-cell function.

Adjuvants, Immunologic↗

Effects of nutrient supplementation in beef cows of poor body condition fed snakeweed (Gutierrezia spp).

Two replicate trials determined the effects of dietary supplementation on snakeweed toxicity in beef cows of poor condition. Cows were stratified by weight and randomly assigned to 3 dietary treatments. Dietary treatments were control (n = 3/trial; medium quality hay, 9.49% crude protein), corn supplementation (n = 3/trial; control diet + 628 g cracked corn), and protein supplementation (n = 3/trial; control diet + 800 g 42% protein supplement). Corn and protein dietary treatments were fed to be isocaloric. Each trial consisted of 2 phases (68 days/phase). Phase 1 consisted of dietary treatments without snakeweed. In phase 2 dietary treatments contained snakeweed as 10% of the dry matter. Phase 1 and 2 dietary treatments were isocaloric/isonitrogenous. Dry matter intake of the control diet was limited to 1.3% of body weight/d. Body condition score and back fat were measured on days 0, 21 and 68 of each phase. Serum samples were collected at the onset of each trial and on days 28, 42 and 56 of each phase. Serum bromosulphthalein (BSP) elimination half life (t1/2) was estimated during week 6 of each phase. Serum BSP elimination t1/2 was higher for the control diet versus corn and protein treatments. Increased blood urea nitrogen (BUN) was found by day 28 of phase 2. Serum total bilirubin increased by day 28 in phase 2 compared to baseline for the control and corn dietary treatments. Additionally, serum indirect bilirubin was higher by day 28 in phase 2. Likewise, serum direct bilirubin increased during phase 2 on day 28 in the corn diet, but decreased by day 28 for the protein diet. Alkaline phosphatase levels were higher (P < 0.05) in the controls by day 28, but lower in the protein treatment by day 28 in phase 2. Changes were noted during phase 2 for some of the serum clinical profiles; however, these changes appear due to dietary restriction. In contrast, changes during phase 2 point to possible hepatotoxic and renal toxic effects of snakeweed. Phase 2 data suggest a benefit of protein supplementation for improving animal tolerance to snakeweed.

Alanine Transaminase↗

Differential distribution of tyrosine hydroxylase fibers on small and large neurons in layer II of anterior cingulate cortex of schizophrenic brain.

A series of recent postmortem investigations of the anterior cingulate cortex in schizophrenic brain have suggested that there may be a loss and/or impairment of inhibitory interneurons in layer II. It has been postulated that changes of this type could secondarily result in a relative increase of dopaminergic inputs to GABAergic interneurons. To test this hypothesis, an immunoperoxidase technique was developed to extensively and reliably visualize tyrosine hydroxylase-immunoreactive (TH-IR) varicose fibers in human postmortem cortex. This method has been applied to the anterior cingulate (ACCx; Brodmann area 24) and prefrontal (PFCx: Brodmann area 10) cortices from a cohort of 15 normal control and 10 schizophrenic cases. The number of TH-IR varicosities in contact with large neurons (LN), small neurons (SN), and neuropil (NPL) was blindly analyzed using a computer-assisted microscopic technique. There was no significant difference in density of TH-IR varicosities in apposition with either LN or SN cell bodies observed in either ACCx or PFCx of schizophrenics when compared to normal controls. The density of varicosities was significantly reduced in NPL of layers V and VI in ACCx, but 2 neuroleptic-free cases did not show this change, suggesting that these decreases of TH-IR varicosities may be related to antipsychotic effects on corticostriatal projection cells in this region. When the density of TH-IR varicosities on SNs was compared to that observed on LNs, both groups showed a higher density on SNs. In ACCx, this pattern was much more pronounced for the schizophrenic group, particularly in layer II where the density on SNs was three times higher than that for LNs (P = 0.01). Unlike the changes in layer V, this latter change in layer II showed no relationship to neuroleptic exposure. There was a positive correlation between age and the density of TH-IR varicosities on SNs of layer II in ACCx; however, the patients were younger than the controls and would have been expected to show a lower density, rather than a higher one, if age considerations had accounted for the group differences. Overall, the results reported here suggest that there are no gross differences in the distribution of TH-IR varicosities in various laminae of the dorsolateral prefrontal cortex. In the anterior cingulate region, however, there may be a significant shift in the distribution of TH-IR varicosities from large neurons to small neurons that occurs selectively in layer II of schizophrenic subjects. Using size criteria, the majority of small neurons are likely nonpyramidal, while the majority of large neurons are predominantly pyramidal in nature. Taken together with other accumulating evidence of preferential abnormalities in this lamina of the cingulate region, the findings reported here are consistent with a model of schizophrenia in which a subtle "miswiring" of ventral tegmental inputs may result in a relative, though not absolute, hyperdopaminergic state with respect to an impaired population of GABAergic interneurons.

Cell Size↗

Glutathione S-transferase class Kappa: characterization by the cloning of rat mitochondrial GST and identification of a human homologue.

We have isolated a cDNA clone that encodes rat glutahione S-transferase (GST) subunit 13, a GST originally isolated from rat liver mitochondrial matrix by Harris, Meyer, Coles and Ketterer [(1991) Biochem. J. 278, 137-141]. The 896 bp cDNA contains an open reading frame of 678 bp encoding a deduced protein sequence of which the first 33 residues (excluding the initiation methionine residue) correspond to the N-terminal sequence reported by Harris et al. Hence like many other nuclear-encoded, mitochondrially located proteins, there is no cleavable mitochondrial presequence at the N-terminus. GST subunit 13 was originally placed into the Theta class of GSTs on the basis of sequence identity at the N-terminus; however, this is the only identity with the Theta class and in fact GST subunit 13 shows little sequence similarity to any of the known GST classes. Most importantly it lacks the SNAIL/TRAIL motif that has so far been a characteristic of soluble GSTs, although it does possess a second motif (FGXXXXVXXVDGXXXXXF) reported for GST-related proteins (Koonin, Mushegian, Tatusov, Altschul, Bryant, Bork and Valencia [(1994) Protein Sci. 3, 2045-2054]. Southern and Northern blot analyses of rat DNA and mRNA are consistent with GST subunit 13's being the product of a single hybridizing gene locus. Searches of EST databases identified numerous similar human DNA sequences and a single pig sequence. We have derived a human cDNA sequence from these EST sequences which shows a high nucleotide similarity (77%) to rat GST subunit 13. The largest open reading frame is identical in length with subunit 13 and yields a deduced protein sequence identity of 70%. Most unusually the 3' non-coding nucleotide sequence identity is also 77%. We conclude that these cDNAs belong to a novel GST class hereby designated Kappa, with the rat GST subunit 13 gene designated rGSTK1 and the human gene being called hGSTK1.

Amino Acid Sequence↗