Gene/Protein Disease Symptom Drug Enzyme Compound
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 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acrylamide, widely employed as a vinyl monomer in the polymer industry, is a potent neurotoxin to man and to animals. The cumulative effect of prolonged, low-level exposure to acrylamide monomer is the insidious development of a progressive peripheral neuropathy. Sensory symptoms begin in the hands and feet (numbness, pins and needles), certain reflexes are lost and, with severe exposure, muscle weakness and atrophy occur in the extremities. The peripheral neuropathy may be supplemented by symptoms indicative of central nervous system damage (ataxia, tremor, somnolence and mental changes). The neuropathologic basis for this clinical picture has been determined in cats. Here, chronic acrylamide intoxication produces selective peripheral and central nerve fiber degeneration. Degeneration first occurs in the extremities of long and large nerve fibers which later undergo a progressive, seriate proximal axonal degeneration known as dying-back. Especially vulnerable are sensory axons supplying Pacinian corpuscles and muscle spindles in the hindfoot toepads, while adjacent motor nerve axons die back later. Distal central nerve fiber degeneration is seen in the medulla and the cerebellum. The neurotoxic property of acrylamide is of practical concern in two areas. One major problem is the protection of factory workers engaged in the manufacture of acrylamide. A sensitive test of neurologic function in these individuals, i.e., touch sensation, based on the experimental observation of the exquisite vulnerability of Pacinian corpuscles in acrylamide intoxicated cats, is presently under consideration. The second area for concern is the exposure of the populace to minute amounts of neurotoxic acrylamide monomer which contaminate acrylamide polymers currently deployed in the environment. Federal restrictions on the maximum permitted exposure to acrylamide, based on a largely clinical study of acrylamide neurotoxicity conducted ten years ago, may require a re-evaluation in the light of recent advances which have pinpointed the initial sites of nerve fiber degeneration.
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PMID:Nervous system degeneration produced by acrylamide monomer. 17 76

One of the critical issues confronting the evolving discipline of behavioral and neurological toxicology is the general lack of test validation in animal models. This paper seeks to provide a strategy aimed at resolving this important problem. It is proposed that test validation be accomplished by evaluating known neurotoxins in a battery of tests chosen to assess in animal models a wide range of effects on the basis of reported human toxicosis symptomatology. We propose to measure ongoing home cage motor activity, food consumption, water consumption, clay consumption (and the diurnal cycling of these), neurological/physiological indices (reflexes, autonomic signs, equilibrium/gait, balance, tremor, reactivity, and muscular strength), and aspects of cognitive and associative behavior involving both endogenous and exogenous (sensory) control of responding. An integrated, time-efficient scheme, covering 90 days of chemical treatment and 30 days of post-dosing recovery will be used. Chemical substances to be evaluated were chosen with the view of representing classes of neurotoxic effects. For initial study, triethyltin was chosen as an agent producing demyelination of nerves, acrylamide as an agent producing "dying-back" neuropathy, and methylmercury as an agent producing mixed central and peripheral neuropathies. Agents which attack specific loci in the nervous system and those producing anoxia will not be assessed in the first stages of this research due to lack of species generality of known effects, present lack of appropriate exposure facilities, or other problems. In addition, two drugs (amphetamine and sodium salicylate) will be investigated to support the generality of the testing procedures. By comparing the observed results of the neurotoxins in the animal models with the predicted effects based on reported human symptomatology, some decision concerning the validity of each procedure will be made. It is expected that the validation of tests to be used in behavioral and neurological toxicology will permit the meaningful assessment of more complex issues, such as the mechanisms by which neurotoxins act.
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PMID:Strategy for the assessment of neurobehavioral consequences of environmental factors. 72 Mar 19

To determine and compare the direct effects of prostaglandin F2a (PGF2a) and human chorionic gonadotropin (hCG) on luteal cell progesterone production in vitro, 9 human corpora lutea obtained at tubal ligation were minced and treated with collagenase to disaggregate luteal cells. Dispersed luteal cells (80% viable) were incubated in air at 37 degrees C in a shaking water bath for 3 h and total progesterone in the media and cells was determined by radioimmunoassay. Optimum progesterone production was obtained using 25,000 or more cells per incubate and an incubation time of 2-4 h. hCG-stimulated progesterone production increased significantly with 0.01 IU to as high as 100 IU. In the early luteal phase (days 1-5 post ovulation or days 15-20 of the luteal phase), PGF2a (10-1000 ng) significantly inhibited progesterone production but significantly stimulated progesterone production in the mid-luteal phase (days 21-25). PGF2a had no effect on luteal cell progesterone production in the late luteal phase (days 26-30). This age-dependent direct effect of PGF2a on human luteal cell progesterone production in vitro indicates a role for PGF2a in the total intragonadal regulation of progesterone output, possibly through a paracrine or autocrine manner directed towards synchronizing luteal progesterone secretion and endometrial preparation for nidation.
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PMID:Effect of human chorionic gonadotropin and prostaglandin F2a on progesterone production by human luteal cells. 260 39

Six monkeys were trained to report detection of a vibratory or electrical stimulus applied to the fingertip. The vibratory stimuli were presented at two frequencies (40 and 150 Hz). Thresholds were determined with a tracking procedure before, during, and after dosing. Each monkey served as its own control. Four monkeys were dosed orally with 10 mg/kg of acrylamide 5 days a week until the appearance of toxic signs. The total administered dose varied between 320 and 450 mg/kg. The other two monkeys served as time-matched controls. All the monkeys were observed 5 days a week. They were also weighed and presented with a visuomotor task (pickup test) twice a week. Weight loss usually preceded the onset of gross behavioral disturbances, such as loss of balance, tremor, or decreased activity. Impaired coordination, as revealed with the pickup test, paralleled weight loss. Electrical sensitivity was not affected. Vibration sensitivity, however, fell during dosing and remained impaired for several months after dosing ceased, outlasting all the other effects. Recovery of the other indices occurred relatively soon after dosing ended. These data indicate that vibration sensitivity testing can trace the time course of intoxication and recovery in toxic peripheral neuropathies. Furthermore, the differential results obtained with vibratory and electrical stimulation are consonant with a primary effect on end-organ receptors.
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PMID:Somatosensory thresholds in monkeys exposed to acrylamide. 663 91

We have developed techniques for the production of monoclonal antibodies using Coomassie blue-stained protein spots cut from high resolution 2-dimensional polyacrylamide gels. The gel spots were homogenized with Freund's adjuvant and injected sub-cutaneously into a mouse, at several places along the flank. After boosting twice the spleen cells were hybridized by standard methods. Hybrids, clones and ascitic fluids were also screened with antigen prepared from 2-dimensional gel spots. The spots were cut from gels, homogenized in the presence of guanidinium chloride, and extracted by shaking overnight. The acrylamide was removed, the sample dialyzed to remove denaturant and the protein labeled with 125I. An alternative method for the production of screening antigen using column chromatography is described. These techniques allow the production of monoclonal antibodies to specific protein components of complex mixtures, even in the presence of other immunodominant proteins.
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PMID:Development of monoclonal antibodies to proteins separated by two-dimensional gel electrophoresis. 665 45

1. Culture conditions for the production of rhizopuspepsin in liquid medium by Rhizopus chinensis have been investigated. 2. Optimum production was achieved in 24 hr shaking culture in 1% bovine serum albumin, 1% corn starch, 0.1% yeast extract and a salt mixture, pH 5. 3. Levels at 24 hr compared in isozyme pattern and in quantity to conventional solid culture on wheat bran.
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PMID:Liquid culture of Rhizopus chinensis for the production of acid protease rhizopuspepsin. 675 93

Optimum culture conditions for the production of exfoliative toxin by Staphylococcus hyicus (shET) were examined. High shET activity was obtained from the culture filtrate of HI and TY broth inoculated with S. hyicus. The pH in these two media ranged from 7 to 8.5 during bacterial culture, while the lowest pH in TS and BHI broth was less than 6. shET activity in the culture filtrate from TY broth inoculated with 10(7) CFU of S. hyicus per ml was higher than that in TY broth inoculated with 10(6) and 10(8) CFU of bacteria per ml. When shET activity in the culture filtrate was measured under various shaking conditions, the culture filtrate shaken at 75 oscillations per min had the highest shET activity of the five shaking conditions. shET activity of the culture filtrate of TY broth to which protease inhibitor had been added was the same as that of TY broth without inhibitor. shET activity in a shaking culture in an Erlenmeyer flask was also the same as that in sac culture and that in shaking culture using a shaking (Sakaguchi) flask. shET activity in TY broth supplemented with 100 mM glucose was significantly lower than that in TY broth without glucose. Based on the above results, the optimum culture conditions for the production of shET were as follows: inoculation of 3 x 10(9) CFU of S. hyicus strain P-1 into 300 ml of TY broth in a 2,000-ml Erlenmeyer flask, and incubation at 37 C with shaking at 75 oscillations per min.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Optimum culture conditions for production of exfoliative toxin by Staphylococcus hyicus. 855 67

The differential display of cDNA species defined by a combination of so-called anchored and arbitrary primers has been acknowledged as a powerful complex strategy to identify differences in gene expression, and depends in its original version, inaugurated by P. Liang and A. B. Pardee in 1992, on the use of radioactive-labelled nucleotides. As a non-radioactive methodological alternative, we established the use of polyesterfilm-backed 10% polyacrylamide gels for horizontal differential-display electrophoresis under non-denaturing conditions, with subsequent detection of cDNA bands by an optimized, semi-automated silver staining omitting any fixation step. Polyacrylamide gel slices carrying the silvered cDNA species of interest were cut out, chopped, squashed and incubated in an ammonium acetate/EDTA solution at 37 degrees C overnight under vigorous shaking. This procedure resulted in a 70% average success rate for subsequent PCR reamplification with regard to the number of cDNAs harvested from the differential-display gel. Novel sequence data of three cDNA clones are communicated, which under these methodological conditions were selected to be up- or down-regulated, respectively, by antipsoriatic dithranol in cultured HaCaT keratinocytes.
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PMID:Optimized visualization and PCR reamplification of differentially displayed cDNA bands detected by silver staining in polyacrylamide gels as established in the model of dithranol-treated keratinocytes. 1032 84

A variety of popular instant, ground, and brewed coffees were analyzed using a modified liquid chromatography-tandem mass spectrometry (LC-MS/MS) method specifically developed for the determination of acrylamide in foods. Coffee test portions were spiked with 13C3-labeled acrylamide as an internal standard prior to their extraction and cleanup. Ground coffees (1 g) and instant coffees (0.5 g) were extracted by shaking with 9 mL of water for 20 min. Brewed coffee test portions (9 mL) were taken through the cleanup procedure without further dilution with extraction solvent. Coffee test portions were cleaned up by passing 1.5 mL first through an Oasis HLB (hydrophilic/lipophilic copolymer sorbent) solid phase extraction (SPE) cartridge and then a Bond Elut-Accucat (cation and anion exchange sorbent) SPE cartridge. The cleaned up extracts were analyzed by positive ion electrospray LC-MS/MS. The MS/MS data was used to detect, confirm, and quantitate acrylamide. The limit of quantitation of the method was 10 ng/g for ground and instant coffees and 1.0 ng/mL for brewed coffee. The levels of acrylamide ranged from 45 to 374 ng/g in unbrewed coffee grounds, from 172 to 539 ng/g in instant coffee crystals, and from 6 to 16 ng/mL in brewed coffee.
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PMID:Analysis of coffee for the presence of acrylamide by LC-MS/MS. 1505 42

A study on the development of a process to form materials suitable for biomedical xenograft implants from bovine cancellous bone is presented. Bone cubes cut from the condyle portion of bovine femurs sourced from abattoir waste were subjected to a defatting and subsequent deproteination procedure to produce shape-modifiable materials in which the biocompatible mineral calcium hydroxycarbonate apatite component was preserved in the original osseous architecture of the bovine bone. Optimum defatting was achieved by (1) thawing of the precut bone cubes in water, (2) pressure cooking at 15 psi in water, (3) soaking in 0.1 mol l(-1) NaOH followed by a thorough rinse under running water, (4) microwave heating of the bone cubes in water, (5) refluxing in methyl acetate and finally (6) removal of internal liquid from the cubes by shaking and then air drying. Subsequent deproteination of the defatted bone cubes was optimally achieved by (1) soaking in 5% sodium hypochlorite solution at ambient temperature using ultrasonication, (2) thorough rinsing of the cubes in water followed by drying. The final product is a defatted/deproteinated, bleached material that can be molded into various shapes for implant use in the body. The bone specimens were characterized by a suite of analytical techniques (i.e. infrared, 31P and 13C solid magic-angle spinning (MAS) nuclear magnetic resonance (NMR), X-ray photoelectron spectroscopies, atomic absorption (AA) spectrometry, inductively coupled plasma (ICP) spectrometry, differential scanning calorimetry (DSC), and scanning electron microscopy (SEM)) in order to follow compositional changes during the various stages of processing. In general, bovine condyles proved to be the best source of xenograft materials with condyles from other animal species (i.e. deer, sheep and ostrich) being too small to constitute a utilizable source of cancellous bone. This study shows how value can be added to a hitherto underutilized abattoir by-product by using simple processing techniques.
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PMID:The processing and characterization of animal-derived bone to yield materials with biomedical applications: part 1: modifiable porous implants from bovine condyle cancellous bone and characterization of bone materials as a function of processing. 1534 8


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