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Biomedical subjects

L F James

Publications and source records attributed to L F James.

At least 55 records · Page 3Linked to original sources

Lentiginosine, a dihydroxyindolizidine alkaloid that inhibits amyloglucosidase.

Lentiginosine, a dihydroxyindolizidine alkaloid, was extracted from the leaves of Astragalus lentiginosus with hot methanol and was purified to homogeneity by ion-exchange, thin-layer, and radial chromatography. A second dihydroxyindolizidine, the 2-epimer of lentiginosine, was also purified to apparent homogeneity from these extracts. Gas chromatography of the two isomers (as the TMS derivatives) showed that they were better than 95% pure; lentiginosine eluted at 8.65 min and the 2-epimer at 9.00 min. Both compounds had a molecular ion in their mass spectra of 157, and the NMR spectra demonstrated that both were dihydroxyindolizidines differing in the configuration of the hydroxyl group at carbon 2. Lentiginosine was found to be a reasonably good inhibitor of the fungal alpha-glucosidase, amyloglucosidase (Ki = 1 x 10(-5) M), but it did not inhibit other alpha-glucosidases (i.e., sucrase, maltase, yeast alpha-glucosidase, glucosidase I) nor any other glycosidases. The 2-epimer had no activity against any of the glycosidases tested.

Alkaloids↗

Natural plant toxicants in milk: a review.

Elimination of plant toxicants via milk by lactating animals is considered a minor route of excretion; however, it may be important when the health of the neonate or food safety in humans is considered. Among plant toxicants excreted in milk is tremetol or tremetone, the toxin in white snakeroot (Eupatorium rugosum) and rayless goldenrod (Haplopappus heterophyllus). These plants have been responsible for intoxication of cows and their suckling calves and for many human poisonings. Other plant toxins excreted through the milk that pose a toxicity hazard include pyrrolizidine alkaloids in Senecio, Crotalaria, Heliotropium, Echium, Amsinckia, Symphytum (comfrey), Cynoglossum (hounds tongue) and Festuca (tall fescue); piperidine alkaloids in Conium, tobacco and others; quinolizidine alkaloids in Lupinus; sesquiterpene lactones of bitterweed and rubber weed; and glucosinolates in Amoracia (horseradish), Brassica (cabbage, broccoli, etc.), Limnanthes (meadowfoam), Nasturtium (watercress), Raphanus (radish) and Thlaspi (stinkweed). Many plants such as Astragalus, Oonopsis, Stanleya, Xylorrhiza, Aster, Atriplex, Sideranthus and Machaeranthera accumulate selenium and may cause intoxication when grazed. Selenium is found in the milk at concentrations relative to the amounts ingested by the lactating animal. Excretion of selenium via the milk is important in the deficiency state, but when in excess it may cause toxicity to offspring.

Animals↗

Feed preferences and habituation of sheep poisoned by locoweed.

Livestock addiction to locoweed is commonly cited as a clinical sign of locoweed poisoning. However, there have been no physiological or pathological explanations for the reported addiction. Four hypotheses were tested to evaluate locoweed's (Astragalus lentiginosus) addictive nature: 1) animals become psychologically addicted to locoweed; 2) animals have an innate preference for locoweed; 3) animals become habituated to locoweed in the sense of acquiring an acceptance or liking for it; and 4) intoxicated animals lose the ability to discriminate between feeds and eat whatever is present. Two feeding trials were conducted to evaluate these hypotheses. In 1987, 20 ewes were fed a pelleted basal feed consisting of alfalfa with 20% locoweed to induce locoweed poisoning. Five control ewes were fed pelleted alfalfa. In 1988, seven ewes were fed a basal feed consisting of alfalfa and 15% locoweed, and five control ewes were fed pelleted alfalfa. At 2- to 3-wk intervals, ewes from both trials were placed on cafeteria trials and offered a choice of four feeds (100% locoweed pellets, 15% or 20% locoweed pellets, mixed grain pellets and alfalfa pellets) to evaluate their preferences at increasing levels of intoxication. Sheep did not seek out locoweed, which would have indicated a psychological addiction. Locoweed was not innately palatable to sheep. One ewe habituated to 100% locoweed and two ewes habituated to the 15% locoweed diet. The rest of the ewes rejected the 100% locoweed pellets and the 15% or 20% locoweed basal feed when the choice of feeds was offered, even though they were severely intoxicated. Sheep show neither initial preference nor addiction to locoweed but may acquire preference (habituation).

Animal Feed↗

Premature bovine parturition induced by ponderosa pine: effects of pine needles, bark and branch tips.

Three components of Ponderosa pine trees were administered via gavage to pregnant cows to determine their ability to induce premature parturition. When tips of branches, bark or needles were administered (2.7 kg/day) starting at 250 d of pregnancy, early parturition was induced in an average of 3.4, 5.0 and 9.1 d, respectively, compared to 31.8 d for water gavaged controls (P less than 0.01). Less pine material was required to induce parturition with tips and bark (9.4 and 11.2 kg/cow, respectively) than with needles (25.0 kg/cow P less than 0.05). Cows fed pine material retained fetal membranes longer after parturition; 13.0 d for needles, 10.5 d for bark and greater than 3.0 d for tips versus less than 0.5 d for controls (P less than 0.01). However, 2 of the cows fed tips died within 48 hours after parturition with fetal membranes intact and the other 2 cows fed tips became depressed, pyrexic and emaciated. They survived after extended veterinary care with antibiotic and fluid therapy. Administration of pine materials modified serum progesterone concentration profiles; there was significant elevation in progesterone 1-3 days after pine material was administered. Subsequently, pine material induced a premature decline in progesterone levels prior to parturition, which occurred more rapidly in cows fed bark and tips suggesting a dose response relationship. Pine material also modified serum cortisol concentration profiles; the main difference was a prolonged elevation in cows receiving tips. Branch tips and bark from Ponderosa pine are more potent in inducing parturition than needles.

Animals↗

Pine needle abortion in cattle: a review and report of 1973-1984 research.

Research has verified field observations that cows grazing ponderosa pine needles may abort. The incidence and nature of the abortions produced experimentally simulate very closely those reported by livestock producers and veterinarians. The incidence of experimentally-produced abortions varied markedly from year to year even though the needles were collected in the same general area each year. This suggests that the abortifacient compound(s) in the needles vary from year to year, probably due to environmental and site conditions. The impact of stress (cold and nutrition) as a factor in the abortions was examined. It was concluded that the only effects would be on the willingness of cows to eat the needles. The pine needle abortion problem, what is known of the etiology, and mechanisms of the abortion are reviewed. The usefulness of bioassay systems to study pine needle abortions is discussed.

Abortion, Veterinary↗

Transient testicular degeneration in rams fed locoweed (Astragalus lentiginosus).

Locoweed (Astragalus lentiginosus) fed to mature rams induced transient degenerative changes in the seminiferous, epididymal and vas deferens epithelium. There were changes in behavior and loss of condition in the treatment rams. Observed libido was reduced. Estimated percent abnormal sperm was significantly (P less than 0.05) higher in the locoweed-fed rams than in the controls. Increased retained proximal cytoplasmic droplets, separation of the heads and tails of the spermatozoa, and reduced sperm motility were observed. Serum SGOT (serum glutamic oxaloacetic transaminase) levels were significantly (P less than 0.01) elevated, and WBC (white blood cell) counts were decreased (P less than 0.01). Grossly no changes were observed. Histologically there were advanced lesions of foamy cytoplasmic vacuolation in all tissues taken at necropsy, but particularly in the epithelium of the seminiferous tubules, epididymis and vas deferens. Reduced spermatozoa production was evident. Testicular changes were transient and rams appeared clinically normal 70 days after locoweed feeding was terminated; however, there was slight residual atrophy of the germinal epithelium at necropsy.

Animals↗

Toxicosis in pigs fed selenium-accumulating Astragalus plant species or sodium selenate.

Three groups of 5 pigs each were fed a high selenium (Se) diet by mixing either Astragalus praelongus (31.6 ppm Se in feed), A bisulcatus (31.7 ppm Se in feed), or sodium selenate (26.6 ppm Se in feed) with commercial hog feed. Ten control pigs were fed only commercial hog chow containing trace selenium (0.44 ppm Se). Pigs were fed for 9 weeks and necropsied when they had ataxia or paralysis. Blood was collected for hematologic and serum biochemical determinations, and samples of various tissues were collected and fixed in neutral-buffered 10% formalin for histologic evaluation or frozen for determination of selenium concentration. All forms of selenium induced clinical signs of weight and hair loss, with cracked hooves and inflamed coronary bands developing in all Na2SeO4-fed pigs and 1 A praelongus-fed pig, but not in A bisulcatus-fed pigs. Serum calcium, phosphorus, and albumin concentrations were unchanged or significantly decreased from prefeeding values in groups fed selenium. Serum aspartate transaminase (AST) activities in Astragalus species-fed groups, and amylase activities and PCV in all groups of pigs fed selenium, were increased. Serum alkaline phosphatase and creatine kinase activities were significantly increased in the A praelongus-fed pigs and significantly decreased in Na2SeO4-fed pigs. Terminal tissue and body fluid selenium concentrations were determined in all groups of pigs fed selenium and compared with values in control pigs. Urine and bile concentrations were increased by the greatest factor (40 to 100x), with tissue concentrations of selenium increased by a lesser factor (6 to 17x).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Pine needle abortion in cattle: associated changes in serum cortisol, estradiol and progesterone.

Nineteen spring-calving cows were used in an experiment to study the effect of feeding pine needles on incidence of premature parturitions (abortions) and the associated changes in serum cortisol, estradiol-17 beta and progesterone. The study was conducted over 2 years (1983, seven cows fed pine needles and three controls; 1984, six cows fed pine needles and three controls). Experimental feeding started at an average of 250 d of gestation and continued until parturition. Daily blood samples were taken from the start of feeding through 2 to 4 d after parturition. Feeding pine needles shortened gestation by 16 d and induced a premature normal rise in cortisol and estradiol-17 beta associated with parturition. Cortisol concentrations were also high at the beginning of the bleeding period and remained higher in pine needle-fed cows. An abrupt rise in progesterone concentration occurred after the start of pine needle feeding which then decreased sharply for 7 to 8 d before parturition and did not decrease to control concentrations until after parturition. We conclude that feeding pine needles to pregnant cows in late gestation causes abortions and that these abortions are directly caused by or are associated with changes in steroid metabolism.

Abortion, Veterinary↗

Pine needle abortion in cattle: pathological observations.

Grazing of ponderosa pine needles by pregnant cows may cause abortion. The abortions are frequently accompanied by retained placenta. Death is not uncommon in cows that abort. Ten cows were placed on a ponderosa pine needle experiment. Six of these cows were fed pine needles and four served as controls. All six cows receiving pine needles aborted, and three of them died shortly after the abortion. Death was due to a severe septicemia. Although the cows were necropsied shortly after death, all tissues were necrotic. Other lesions are described. Three of the six calves died shortly after the abortion. The other three were small and weak but survived due to intensive care.

Abortion, Veterinary↗

The structures of oligosaccharides excreted by sheep with swainsonine toxicosis.

Eleven oligosaccharides were purified form the urine of sheep with swainsonine toxicosis induced by the feeding of Astragalus lentiginosus. Oligosaccharides were extracted by charcoal adsorption, chromatographed on Bio-Gel P-2, and partially fractionated by preparative-layer chromatography. Separation into individual compounds was completed by semi-preparative high pressure liquid chromatography. Structures were determined by a combination of high pressure liquid chromatography and exo- and endo- glycosidase action, methanolysis followed by gas-liquid chromatography, methylation analysis, and high resolution nuclear magnetic resonance spectroscopy. Two homologous series of oligosaccharides were identified: (a) alpha-D-Manp-(1----6)-beta-D-Manp-(1----4)-D-GlcpNAc, alpha-D-Manp(1----3)-[alpha-D-Manp-(1----6)]-beta-D-Manp+ ++-(1----4)-D-GlcpNAc, alpha-D-Manp-(1----2)-alpha-D-Manp(1----3)-[alpha-D-Manp+ ++-(1----6)]-beta-D-Manp-(1----4)-D-GlcpNAc, and alpha-D-Manp-(1----2)-alpha-D-Manp-(1----2)-alpha-D-Manp+ ++-(1----3)-[alpha- D-Manp-(1----6)]-beta-D-Manp-(1----4)-D-GlcpNAc (minor series); (b) alpha-D-Manp-(1----6)-beta-D-Manp-(1----4)-beta-D-GlcpNAc- (1----4)-D-GlcpNAc, alpha-D-Manp-(1----3)-[alpha-D-Manp-(1----6)]-beta-D-Manp -(1----4)-beta-D-GlcpNAc-(1----4)-D-GlcpNAc, alpha-D-Manp(1----3)-alpha-D-Manp-(1----6)-beta-D-Manp -(1----4)-beta-D-GlcpNAc- (1----4)-D-GlcpNAc, alpha-D-Manp-(1----6)-alpha-D-Manp-(1----6)-beta-D-Manp++ +-(1----4)-beta-D-GlcpNAc - (1----4)-D-GlcpNAc, alpha-D-Manp-(1----3)-alpha-D-Manp-(1----6)-[alpha-D-Manp -(1----3)]-beta-D- Manp-(1----4)-beta-D-GlcpNAc-(1----4)-D-GlcpNAc, alpha-D-Manp-(1----3)-[alpha-D-Manp-(1----6)]-alpha-D-Man p-(1----6)-beta-D- Manp-(1----4)-beta-D-GlcpNAc-(1----4)-D-GlcpNAc, and alpha-D-Manp-(1----3)-[alpha-D-Manp-(1----6)]-alpha-D-Man p-(1----6)- [alpha-D-Manp-(1----3)]-beta-D-Manp-(1----4)-beta-D-GlcpNAc- (1----4)-D- GlcpNAc (major series).

Alkaloids↗

Production of hybrid glycoproteins and accumulation of oligosaccharides in the brain of sheep and pigs administered swainsonine or locoweed.

Swainsonine and swainsonine-containing plants produce biochemical and neurological changes in several mammalian species. The toxin is a potent inhibitor of liver lysosomal alpha-D-mannosidase and Golgi mannosidase II. The inhibition of the latter enzyme causes the production of abnormal glycoproteins containing hybrid oligosaccharides instead of complex types in a variety of cultured cells. In view of the widespread occurrence and biological importance of N-linked glycoproteins in the central nervous system, we initiated studies to determine the structure of oligosaccharides in glycoproteins prepared from the brain of control, swainsonine-fed, and locoweed-fed animals. The results presented here indicate that the feeding led to alteration in the structure of brain glycoproteins. Over 25% of the glycoproteins which presumably contained complex-type oligosaccharides were modified and now contained hybrid oligosaccharides. The structure of the N-linked oligosaccharide (glycopeptide) was established by (a) studying the binding properties of the glycopeptide to immobilized lectins of known sugar specificity, and (b) comparing the size of the glycopeptide before and after treatment with exo- and endoglycosidases. The production of hybrid oligosaccharides occurred despite the apparent absence of mannosidase II in brain. The relationships of the altered structure of brain glycoproteins, accumulation of mannose-rich oligosaccharides in the brain, and abnormal behavior of the animals administered swainsonine or locoweed are discussed.

Acetylglucosamine↗

In vivo induction of gliadin-mediated enterocyte damage in rats by the mannosidase inhibitor, swainsonine: a possible animal model for celiac disease.

Simultaneous feeding of gliadin and swainsonine, an inhibitor of alpha-D-mannosidases, in rats disturbed enterocytic maturation as shown by a marked loss of activities of alkaline phosphatase and gamma-glutamyltransferase. Morphologically, simultaneous treatment with gliadin and swainsonine caused destruction and decreased density of microvilli, as shown by electron microscopy. Neither gliadin nor swainsonine when given alone had significant effects on enterocytic enzyme activities or enterocytic morphology. Binding of enterocytic glycoproteins to both gliadin-Sepharose and concanavalin A-Sepharose was significantly increased in rats treated with swainsonine. Because swainsonine causes the formation of hybrid-type oligosaccharides with a high binding affinity to mannose-specific lectins, the observed alterations of enterocytic maturation and morphology are presumably caused by the increased binding of gliadin to enterocytic glycoproteins. A possible analogy in the etiology of celiac disease is discussed.

Alkaline Phosphatase↗

Cattle grazing Wahweap milkvetch in southeastern Utah.

Cattle's grazing of the locoweed Wahweap milkvetch (Astragalus lentiginosus var. wahweapensis) was evaluated on desert and foothill winter range during the winter of 1986 to 1987. Dry, dead stalks of Wahweap milkvetch that had grown in 1985 and 1986 made up 15% of cattle diets overall, and 24% of diets when cattle grazed gravelly benches where it was abundant. Nutritional quality of Wahweap milkvetch was higher than of most associated forage, but its alkaloid concentration varied among the senescent stages. One cow aborted and two cows developed clinical signs of locoweed poisoning, including water belly (hydrops amnii). Microscopic lesions consisting of cytoplasmic foamy vacuolation were evident in both the dam and fetus. Because senescent stalks of Wahweap milkvetch are palatable and readily grazed by cattle, ranchers should not permit cattle to graze infested sites until other green forage is available in the spring.

Animal Feed↗

The relationship of Oxytropis sericea (green and dry) and Astragalus lentiginosus with high mountain disease in cattle.

All calves fed locoweed (green and dry Oxytropis sericea Nutt and dry Astragalus lentiginosus Dougl) at high elevation developed clinical signs, gross and microscopic lesions of congestive right heart failure. Clinical signs and microscopic lesions of locoweed intoxication were also evident. Control calves did not develop the clinical signs, gross or microscopic lesions demonstrated in the locoweed fed calves.

Altitude Sickness↗

Ultrasonographic imaging to monitor fetal and placental developments in ewes fed locoweed (Astragalus lentiginosus).

Ultrasonographic imaging was used to monitor the effects of locoweed (Astragalus lentiginosus) on fetal, placental, and cotyledonary developments in pregnant ewes and proved to be a useful noninvasive method of monitoring the effects of locoweed poisoning on fetal and placental development. Ultrasonographic imaging may be a good research technique to observe the effects of toxicants on fetal movement, fetal heart action, and growth and development of the fetus and placenta. Known effects of locoweed poisoning in pregnant ewes, such as fluid accumulation in the placenta (hydrops allantois, hydrops amnii), altered cotyledonary development, and fetal death were observed with ultrasonographic imaging. A previously unknown effect of locoweed on fetal heart action also was observed. Locoweed decreased fetal heart rates, caused cardiac irregularity, and decreased the strength of heart contractions. All ewes, except No. 3525, fed locoweed aborted. At necropsy, aborted fetuses had hypertrophy of the heart, right ventricular dilatation, rounded at the apex of the heart, and generalized edema.

Animals↗

Locoweed (Oxytropis sericea) poisoning and congestive heart failure in cattle.

Locoweed (Oxytropis sericea), when fed to calves at high elevations, increased the prevalence and severity of congestive heart failure. Forced exercise did not increase the prevalence of congestive heart failure, but it did increase severity. Calves consuming locoweed at high elevations developed signs and gross lesions of congestive heart failure and microscopic lesions of congestive heart failure and locoweed poisoning. Calves fed locoweed at low elevations developed only signs and lesions of locoweed poisoning.

Altitude↗