Biomedical subjects
L W Smith
Publications and source records attributed to L W Smith.
Movement of cadmium in rat submaxillary slices.
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Excretion of cadmium and mercury in rat saliva.
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Structure and toxicity of the alkaloids of Russian comfrey (symphytum x uplandicum Nyman), a medicinal herb and item of human diet.
Eight pyrrolizidine alkaloids of hepatotoxic type have been indentified in leaves of Symphytum X uplandicum. The combined alkaloids exhibit chronic hepatotoxicity in rats.
Movement of mercury in rat submaxillary slices.
The movement of 203Hg2+ (as HgCl2) was studied in slices of rat submaxillary gland. A steady-state distribution was reached within 60 min. N2 or metabolic inhibitors (2,4-DNP, NaCN, NaF or ouabain) failed to decrease tissue uptake. Increasing the concentration of Hg2+ produced a corresponding increase in tissue metal. Decreasing the incubation temperature decreased uptake. Cd2+ and Fe2+ decreased uptake by Zn2+, Cu2+, and Fe2+ were without effect. Efflux experiments indicated a firm binding of Hg2+. The data suggest a passive uptake for hg2+ with unsaturable, temperature-sensitive binding sites in the interior of the cell.
In vitro stimulation of oxygen consumption in rat submaxillary gland by pilocarpine.
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Arsenic in tissues of sheep and milk of dairy cows fed arsanilic acid and 3-nitro-4-hydroxyphenylarsonic acid.
Arsenic from two sources--arsanilic acid and 3-nitro-4-hydroxyphenylarsonic acid (3-nitro)--was fed to mature wethers and lactating dairy cows, and the uptake and depletion of arsenic in tissues and milk were determined. In experiments with sheep, arsenic concentration in liver, kidney and blood increased as the level of arsenic from arsanilic acid and 3-nitro was increased in feed. Muscle arsenic was relatively unaffected by the level of arsenic in feed from either source. No statistically significant differences in arsenic levels were observed between liver and kidney tissue, over all levels fed, or for either source of arsenic. When comparisons were made within each tissue, arsenic levels were found to be significantly lower in sheep fed 3-nitro. This difference between 3-nitro and arsanilic acid within tissues was not observed in muscle or blood. The depletion rates for arsenic were the same for all tissues, and the time required for tissue to return to pretreatment arsenic levels was dependent on the initial tissue concentration. Within 6 days of removal of arsenic from the sheep diets, 85% of the arsenic in the liver of sheep fed arsanilic acid and 81% of the arsenic in the liver of sheep fed 3-nitro was depleted. Arsenic levels in the kidneys of sheep fed arsanilic acid and 3-nitro were depleted by 87 and 83%, respectively. In the experiments with lactating dairy cows, significantly higher levels of arsenic in milk were observed for cows fed either 3.2 or 4.8 mg of arsenic per kilogram of body weight from arsanilic acid or 3-nitro. In the experiment in which 3-nitro was fed at a level of 4.8 mg/kg of body weight for 28 days, arsenic levels plateaued after 14 days of feeding and remained constant for the next 14 days. Milk arsenic from 3-nitro returned to pre-experiment levels within 5 days after arsenic was removed from the feed. In the experiment conducted with arsanilic acid, arsenic feeding was stopped after 5 days and milk arsenic levels returned to pre-experiment levels within 7 days. Because of the short duration of this study, no plateauing effect was observed.
Phomopsin A production by Phomopsis leptostromiformis in liquid media.
Phomopsis leptostromiformis WA1515 produced 75 to 150 mg of phomopsin A per liter in stationary cultures in a Czapek-Dox medium supplemented with 5 to 10 g of yeast extract per liter. pH and temperature optima were approximately 6.0 and 25 degrees C, respectively. A commercial tryptic digest of casein was a satisfactory alternative to the yeast extract, but poor growth and very little phomopsin were obtained when the yeast was replaced by vitamin-free Casamino Acids or a mixture of 18 amino acids. Approximately 95% of the phomopsin A produced was found in the cutlure liquid. No phomopsin was detected in shaken cultures. No phomopsin B was found in any culture. Methods are described for recovery and estimation of phomopsin A from culture liquids.
An analysis of the G-banded chromosomes of the golden hamster.
Chromosomes from 20 G-banded karyotypes of golden hamster cheek pouch cells were precisely measured to determine total lengths and arm ratios. Mean values were used to establish an idiogram which may serve as the basis for a standard hamster karyotype.
Isolation of toxic metabolites of Phomopsis leptostromiformis responsible for lupinosis.
Two metabolites of P. leptostromiformis (phomopsins A and B) have been isolated as a crystalline mixture from a culture of the fungus on lupin seed. The mixture has been shown to be capable of inducing lupinosis in sheep and in young rats. Key steps in the isolation were the transfer of the phomopsins from crude aqueous solution to tetrahydrofuran and chromatography on macroreticular polystyrene resin. The bioassays used in monitoring fractions were based on inhibition of cell cultures and the mitosis-arresting effect of the metabolites on liver cells in vivo.
Oral cancer in 57,518 industrial workers of Gujarat, India: a prevalence and followup study.
In Gujarat, India, 57,518 industrial workers over 35 years old were examined for oral lesions. At a two-year interval, 43,654 workers were re-examined. Biopsies were taken from 13,223 lesions. In the initial examination, 29 oral cancers were diagnosed, representing a prevalence rate of 50/100,000. After two years, 22 new oral cancers were diagnosed, representing an incidence rate of 25/100,000 per year. Over 90% were squamous carcinomas, with the majority of lesions occurring in the oropharynx and tongue. All patients who developed squamous carcinomas had tobacco habits, while 85% of the entire study population had oral habits in some form. Their most common habits were smoking tobacco alone or in combination with chewing "pan"/"supari." Of the carcinomas that developed during a two-year interval, 62% appeared in previously normal appearing mucosa. Leukoplakia was the only oral lesion that proved to be precancerous, with a transformation rate of 0.13% in a two-year interval.
Malignant transformation and natural history of oral leukoplakia in 57,518 industrial workers of Gujarat, India.
In Gujarat, India, 6718 industrial workers, over 35 years of age, with oral leukoplakia (confirmed clinically and microscopically), were studied. After 2 years, 4762 (71%) of the individuals were re-examined. The buccal mucosa was the most common site of occurrence; 98.3% of these individuals had oral habits, with smoking alone or smoking in combination with "pan" or "supari" chewing accounting for 74.9% of the habit forms. Six individuals (0.13%) with oral leukoplakia developed oral carcinomas within 2 years. This incidence of malignant transformation was equivalent to 63/100,000 per year, which far exceeds that of new oral cancers expected even in high-risk populations. While 57.3% the leukoplakic lesions remained unchanged during a 2-year interval, 31.6% disappeared and 11% had an altered appearance. This study confirmed the precancerous nature of oral leukoplakia.
Hepato- and pneumotoxicity of pyrrolizidine alkaloids and derivatives in relation to molecular structure.
62 pyrrolizidine alkaloids and derivatives have been screened for acute and chronic hepato- and pneumotoxicity by the single dose method previously described. This procedure is satisfactory for the compounds of medium to high hepatotoxicity but failed to detect toxicity in certain other compounds of known, low hepatotoxicity. New findings significant in relation to hepatotoxicity are as follows: (i) On a molar basis, diesters of heliotridine and retronecine are about 4 times as toxic as the respective mono-esters and heliotridine esters are 2-4 times as toxic as retronecine esters. (ii) Crotanecine esters are less toxic than retronecine esters, and the 6,9-diester madurensine, 2-4 times less toxic than the 7,9-diester anacrotine (the difference being ascribed to there being only one reactive alkylating centre in the toxic metabolite from madurensine). (iii) Hepatotoxicity was confirmed for 7-angelylheliotridine but not observed for 9-angelyheliotridine and 7- and 9-angelylretronecine. (iv) Other significant compounds failing to induce hepatotoxicity were 9-pivalyl- and 7,9-dipivalyheliotridine, the alpha- and beta-epoxides of monocrotaline, 7-angelyl-1-methylenepyrrolizidine and the methiodides of monocrotaline and senecionine. The following compounds are readily converted by rat liver microsomes in vitro into dehydroheliotridine (or dehydroretronecine): 7- and 9-angelyheliotridine, 7- and 9-angelylretronecine, 7,9-dipivalylheliotridine and otosenine. 7,9-Divalerylheliotridine, the alpha- and beta-epoxides of monocrotaline, and retusamine yield pyrrolic metabolites more slowly. The preparation and characterisation of several alkaloid derivatives are described. Chronic lung lesions were produced by most compounds which gave chronic liver lesions, although a higher dose was required in some instances. This requirement may sometimes mean that chronic lung lesions cannot be induced because of the intervention of acute or peracute deaths. Apart from this factor, structure activity requirements for pneumotoxicity are the same as for hepatotoxicity, consistent with their being both caused by the same toxic metabolites.
Urinary excretion and metabolism of salts of 2-pyridinethiol-1-oxide following intravenous administration to female Yorkshire pigs.
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Recycling and degradation of anabolic agents in animal excreta.
A variety of anabolic agents are currently added to animal feeds to increase growth rate and improve feed efficiency. These compounds and their metabolites are largely excreted. Prior to the use of anabolic agents as feed additives and the advent of confined livestock production, natural recycling occurred which generally resulted in benefit to the animal with no known adverse effects on consumer health. However, the current interest in the use of animal excreta in livestock feed and the possible presence of anabolic agents and their metabolites from this practice has created an additional need for information on the occurrence of anabolic agent residues in consumer products. This report will consider the definition of anabolic agents in its broadest sense and discuss the research on hormones used in animal feed that may be found in animal excreta. In addition to feed additive residues, endogenous compounds may also be found in animal excreta. Endogenous estrogens and androgens have been detected in excreta from domestic livestock and poultry. Research results suggest that substantial estrogenic and androgenic activity may be detected in fresh animal excreta. However, little is known about the effects of various processing methods of excreta such as heat drying and fermentation on its hormonal activity. The effects of feed additive residues and endogenous hormones in excreta used for feed will be discussed relative to their impact on animal health and occurrence in animal products.
Teachers as models in programs for school dental health; an evaluation of "The Toothkeeper".
An evaluation of the effectiveness of the Toothkeeper program was performed in Houston to determine if participation in the program by elementary school children would result in their having cleaner teeth and better gingival health than seen in similar children not in the program. Assessments for plaque and gingivitis were made at the beginning, at the completion of the formal 16-week program, and again after a second 16-week period. In this particular setting, the Toothkeeper was found to be ineffective. Possible reasons for the ineffectiveness of the program are discussed and several suggestions for modifying the program are offered.
Oral cancer and precancerous lesions in 57,518 industrial workers of Gujarat, India.
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A follow up study of oral cancer and precancerous lesions in 57,518 industrial workers of Gujarat, India.
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