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Biomedical subjects

L F James

Publications and source records attributed to L F James.

At least 73 records · Page 4Linked to original sources

Reduced progesterone and altered cotyledonary prostaglandin values induced by locoweed (Astragalus lentiginosus) in sheep.

Feeding 300 or 400 g of dried spotted locoweed, Astragalus lentiginosus per day to 11 pregnant Columbia ewes from the 20th to the 50th days of their gestations resulted in dead and edematous fetuses. Aspartate aminotransferase values were increased, whereas serum progesterone values were significantly diminished (P less than 0.05) in a dose-dependent manner by locoweed ingestion. Cotyledonary 6-keto-prostaglandin (PG)F1 alpha (400 g/day only) and PGF2 alpha (300 and 400 g/day) values were significantly increased (P less than 0.05), whereas PGE values were not affected by the treatment. Alterations in PG values in these sheep may be a mechanism for altering corpus luteum function and inducing fetal death, which would ultimately result in abortion.

6-Ketoprostaglandin F1 alpha↗

Locoweed-induced neuronal storage disease characterized by meganeurite formation.

Golgi staining was performed on cerebral cortex and thalamus of adult animals chronically intoxicated with an alpha-mannosidase inhibitor found in locoweed (Astragalus lentiginosus). The widespread occurrence of large, aspiny meganeurites was discovered on cortical pyramidal and thalamic principal neurons but aberrant spines and neurite growth were not observed. Ectopic neurite growth is known to be characteristic of alpha-mannosidosis of early onset in inherited and induced feline models. The absence of neuritogenesis in a storage disease known to be so characterized when induced in younger animals suggests that this unusual phenomenon is in some way linked to normal developmental processes associated with brain maturation.

Animals↗

Swainsonine-induced oligosaccharide excretion in sheep. Time-dependent changes in the oligosaccharide profile.

Urinary oligosaccharides isolated from locoweed-intoxicated sheep were separated and quantified by reversed-phase high pressure liquid chromatography of the perbenzoylated alditols. Mannose-containing oligosaccharides were elevated as early as day 3 of feeding, but maximum levels (approx. 1 mumol/ml) were not attained until after 6 weeks of feeding. The relative abundance of individual oligosaccharides changed over the course of the feeding period. Man3GlcNAc2 reached a peak on day 3 and then rapidly declined. Two isomers were shown to be present in this fraction and the relative proportions altered with the duration of locoweed treatment. The major isomer present at early time points (less than 8 days) co-eluted with synthetic Man(alpha 1-3)[Man(alpha 1-6)]Man(beta 1-4)GlcNAc(beta 1-4)GlcNAc, was digested by endo-beta-N-acetyl-glucosaminidase D, and is probably derived from the trimannosyl core of complex glycoproteins synthesized prior to locoweed treatment. Man3GlcNAc2 isolated from day 53 urine was resistant to endo-beta-N-acetylglucosaminidase D digestion but was cleaved by endo-beta-N-acetylglucosaminidase H. This isomer has the probable structure Man(alpha 1-3)Man(alpha 1-6)Man(beta 1-4)GlcNAc(beta 1-4)GlcNAc, indicative of its origin from hybrid or high-mannose glycoproteins. Man5GlcNAc2 reached a peak on day 13 and then slowly declined, whereas Man4GlcNAc2 increased concomitantly. The rapid increase in Man5GlcNAc2 can probably be attributed to the breakdown of hybrid glycans produced as a result of swainsonine inhibition of Golgi alpha-D-mannosidase II. The onset of observable clinical signs on day 38 closely correlated with the time point at which the level of Man4GlcNAc2 exceeded Man5GlcNAc2. After locoweed feeding was discontinued, the amount of urinary oligosaccharides declined rapidly and reached baseline levels within 12 days.

Acetylglucosaminidase↗

The similar effects of swainsonine and locoweed on tissue glycosidases and oligosaccharides of the pig indicate that the alkaloid is the principal toxin responsible for the induction of locoism.

A neurological condition resembling that observed in hereditary mannosidosis occurs in animals ingesting spotted locoweed and plants of the genus Swainsona. Swainsonine has been isolated from these plants and has been suggested to be the primary causative agent in inducing the pathological condition. This alkaloid has also been found to increase tissue acid alpha-D-mannosidase levels in rats while lowering liver Golgi mannosidase II levels. In the present study, the effects of locoweed and swainsonine were directly compared for the first time, with the pig as experimental animal. Both increased most lysosomal acid glycosidase activities in most tissues, decreased liver Golgi mannosidase II levels, increased plasma hydrolase levels, and greatly increased tissue oligosaccharide, especially Man5GlcNAc2 and Man4GlcNAc2. These results indicate that swainsonine is the agent in locoweed responsible for the enzymatic and oligosaccharide changes. The behavior of the animals was also similarly affected by swainsonine and locoweed.

Alkaloids↗

Effect of repeated locoweed feeding on peripheral lymphocytic function and plasma proteins in sheep.

Seven healthy, adult, crossbred yearling ewes were given (orally) 340 g of locoweed (Astragalus lentiginosus) every day for 10 weeks. Another 7 ewes were not fed the plant, but were housed similarly (controls). Blood samples were obtained once a week to evaluate the mitogen-induced lymphocytic responsiveness. For the locoweed-exposed ewes, there was decreased activity in the presence of phytohemagglutinin (a T-cell mitogen). This effect, although not statistically significant at all times, was consistent and became significant after 7 weeks. A similar response was observed in the blood cell cultures in the presence of pokeweed mitogen, but the differences were not statistically significant at most time points. For the locoweed-exposed ewes there also were gradual numerical decreases in total leukocyte and lymphocytes in peripheral blood. Peripheral leukocytes had cytoplasmic vacuolation. The results indicated that a selective effect may occur on cell-mediated immune responses. Serum proteins and gamma-globulins were not affected by locoweed treatment. Locoweed, certain species of Astragalus and Oxytropis, causes considerable economic loss to the livestock industry of western United States. Locoweed consumption by livestock can result in neurologic problems, emaciation, habituation, and reproductive alterations. The reproductive alterations include abortions, birth defects, and some interference with spermatogenesis and oogenesis. Signs of poisoning are CNS depression, rough dry coat, dull eyes, irregular gait, and excitement when stressed. The microscopic lesions are neurovisceral cytoplasmic vacuolations. Microscopic lesions are also observed in the fetuses and newborns of dams which were fed locoweed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Induced mannosidosis-excretion of oligosaccharides by locoweed-intoxicated sheep.

Daily urine samples were collected from a locoweed-fed sheep, and the oligosaccharide content examined by thin-layer and liquid chromatography. An unusual pattern of urine oligosaccharides was observed, which appears to be characteristic of loco intoxication. Changes in the pattern could be correlated with the onset of visible disease, which occurred approximately 5 weeks after the typical urine sugars were first detected. HPLC showed that these sugars consisted of two homologous series of oligosaccharides containing one and two residues of 2-acetamido-2-deoxy-D-glucose, respectively.

Animals↗

Characterization of oligosaccharides from the urine of loco-intoxicated sheep.

Two major oligosaccharides were isolated by preparative HPLC from the urine of a locoweed-fed sheep. Analysis by gas-liquid chromatography and mass-spectrometry indicated compositions of (Man)4(GlcNAc)2 and (Man)5(GlcNAc)2, respectively. Structures were determined by digestion with alpha-D-mannosidase and endo-beta-N-acetylglucosaminidases D and H, and comparison of the products by HPLC with synthetic standards, and oligosaccharides isolated from human mannosidosis urine. Incubation with an exo-beta-N-acetylglucosaminidase was without effect.

Acetylglucosamine↗

Kochia scoparia poisoning in cattle.

Cattle consuming only high-sulfate water (2.3 g/L) and Kochia scoparia in a marginal pasture in southeastern Colorado were periodically monitored by serum chemical profiles. Serum glutamic oxaloacetic transaminase, serum sorbitol dehydrogenase, and serum bilirubin values were abnormally high over extended periods, suggesting chronic toxicosis, but the toxicosis seemed accentuated after substantial rains, when plant growth was accelerated, and flowering, pollination, and early seed development were occurring. Clinical disease was manifested primarily as photosensitization. Polioencephalomalacia was also produced. Evidence of a thiamin-destructive principle in K scoparia was obtained.

Animals↗

Effects of herbicides on the concentration of poisonous compounds in plants: a review.

Herbicides may raise, lower, or not affect the concentration of poisonous compounds in plants. Herbicides, 2,4,5-T and silvex controlled Wasatch milkvetch (Astragalus miser var oblongifolius) and markedly reduced the concentration of miserotoxin, a poisonous aliphatic nitro compound. The concentration of phototoxic furocoumarins in the leaves of spring parsley (Cymopterus watsonii) decreased to nontoxic concentrations 4 to 5 weeks after treatment with 2,4-D. The hydrocyanic acid content of wild cherry (Prunus spp) decreased after treatment with 2,4-D and 2,4,5-T, but increased in Sudangrass (Sorghum halapense) after treatment with 2,4-D. The alkaloid concentration in Barbey larkspur (Delphinium barbeyi) increased after treatment with 2,4,5-T or silvex, decreased in horsetail (Equisetum palustre) after treatment with MCPA, and was unaffected in Datura after treatment with several herbicides. The effect of herbicides on nitrate concentration in plants was dependent upon the species of plant and the herbicide used.

Alkaloids↗

Teratogenic plants.

Abnormal, defective offspring are a significant problem in livestock as well as in humans. Congenital malformations have been observed since ancient times and were once thought to be primarily of genetic origin. Knowledge relating to congenital anomalies has greatly increased in recent years. Numerous hazardous plants are abundant on many of the ranges grazed by livestock. Many of the plants, when ingested during certain stages of gestation, induce congenital defects. The defects can vary from minor changes to striking abnormalities. The final manifestations of abnormal intrauterine differentiation and development are death, resulting in reabsorption or abortion, malformation, suppression of growth, and disordered function. It appears that the type of malformation induced in a conceptus depends more upon the developmental stages in which the injurious agent operates than upon the type of the agent. The etiology and pathogenesis of congenital defects are complex. With time, and additional studies, other plants will probably prove to be teratogenic. Teratogenic studies and findings in animals have had beneficial influences for the livestock industry and for veterinary and human medicine.

Animals↗

Relationship between ingestion of the locoweed Oxytropis sericea and congestive right-sided heart failure in cattle.

In field observations of young cattle grazing on certain high-altitude ranges infested with the locoweed Oxytropis sericea, a high frequency of clinical congestive right ventricular failure was identified. At necropsy of affected calves, there were right ventricular hypertrophy and dilation, subcutaneous edema, hydrothorax, diarrhea, and chronic passive congestion of liver. Microscopically, there was neurovisceral foamy cytoplasmic vacuolation, characteristic of locoism. An experiment was set up to test the relationship of O sericea to congestive right-ventricular failure. Preliminary investigation supports the field observation.

Altitude↗

Astragalus bisulcatus--a cause of selenium or locoweed poisoning?

Certain plants accumulate selenium at levels that render them toxic. One of the principle groups of selenium-accumulating plants is the selenium-accumulating Astragalus. Reports in early literature suggest that selenium is the only toxin in these plants. Sheep fed Astragalus bisulcatus, a selenium-accumulating plant, had signs similar to those observed in locoweed poisoning, and the microscopic lesions from tissues collected from these sheep were similar to those of locoweed poisoning rather than selenium poisoning. This suggests this group of plants contains toxin compounds in addition to selenium.

Animals↗

Limb deformities in foals associated with ingestion of locoweed by mares.

Five of 26 pregnant mares observed ingesting locoweed (Astragalus mollisimus) subsequently aborted and another 10 produced foals with various limb deformities. Seven of the foals had deformities of a flexion-extension type and 3 had angular deformities. Four foals were normal. The limb deformities either resolved spontaneously (5 cases) or were treated successfully (in 4 of the other 5 cases). The problems of abortion and limb deformities were attributed to locoweed ingestion on the basis of the mares having eaten the plants, and the similarity of the syndrome to that previously reported in sheep and cattle.

Abortion, Veterinary↗

Locoweed embryotoxicity in rats.

In an effort to develop a laboratory animal assay for locoweed (Astragalus lentiginosus and Astragalus wootoni) teratogenicity, different amounts of the plant were administered either in feed pellets or by gavage to rats. In preliminary experiments with A. lentiginosus in feed pellets, we found dose-dependent effects on the number of pups born alive and on birth weight of pups. In the primary experiment, 1 gm of A. lentiginosus or A. wootoni administered by gavage on Days 7 through 17 of gestation produced similar results. A. lentiginosus reduced pup birth weights by 13% less than that of controls; this weight differential persisted for at least 4 weeks. A. lentiginosus also reduced the number of offspring born alive (34.9% fewer than those of controls) and the number of survivors to weaning (86.4% fewer than that of controls). No gross malformations were observed. Behavioral tests, however, showed that activity patterns of 30-day-old offspring of dams fed locoweed differed from those of pups of control dams. A test of learning indicated no differences. At 80 days of age, offspring of treated dams showed no significant differences from those of control dams. The same behavioral tests also showed no differences among the dams at the time of testing. Microscopic examination of tissues from pups whose mothers had been given locoweed revealed lesions only in the newborn pups. Neural lesions were not observed even in the newborn pups. Dose-dependent and species-dependent embryotoxic effects of locoweed were observed in rats.

Animals↗

Field and experimental studies in cattle and sheep poisoned by nitro-bearing Astragalus or their toxins.

Various species of nitro-containing Astragalus, and the toxic principle of these plants, 3-nitropropionic acid or 3-nitro-1-propanol, were fed to sheep and cattle at doses which produced chronic or acute intoxication. The signs of intoxication produced were similar to those observed in poisoning that occurs under field conditions. The signs of intoxication were emphysema and difficulty in locomotion. Primary microscopic lesions were observed in the lungs and CNS. The lungs had varying degrees of alveolar emphysema and there were varying degrees of wallerian degeneration of the spinal cord.

1-Propanol↗