Disorders involving medicine and dentistry: the basal cell nevus syndrome.
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Biomedical subjects
Publications and source records attributed to R Wood.
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Dietary methyl-2-hexadecynoate appeared to inhibit fatty acid elongation in intact animals (Wood, R., Lee, T., and Gershon, H. (1980) Lipids 15, 141-150). Data from the present in vitro studies indicate that the microsomal elongation system is inhibited preferentially to the mitochondrial system. A series of metabolic acyl-CoA thioester intermediates has been isolated, characterized, and identified from microsomal and mitochondrial incubations with the 2-hexadecynoic acid (16 identical to 1 delta 2). The data support the following conclusions: 1) 16 identical to 1 delta 2 is activated to the CoA ester; 2) 16 identical to 1 delta 2 is acted on by an isomerase to produce a 2,3-allene; 3) either 16 identical to 1 delta 2 or the allene, or both, are hydrated to yield a beta-keto-CoA thioester after rearrangement; 4) the beta-keto ester is reduced to the beta-hydroxyacyl-CoA; 5) dehydration of the beta-hydroxy ester gives rise to trans-delta 2-hexadecenoate which accumulates; and 6) accumulation of the latter results from the inhibition of enoyl-CoA reductase by the 2,3-allene. The occurrence of cis and trans delta 3-hexadecenoates indicates the allene is reduced, after which the delta 3 monoene isomer may be isomerized to the delta 2 monoene by the acetylene isomerase or a different enzyme. Indirect evidence suggests that the fatty acid elongation systems may also be inhibited at another site.
The effects of 2-hexadecynoic acid on the growth and lipid metabolism of cultured 7288 (HTC) cells have been evaluated. Growth was inhibited by the acetylenic acid: the LD50 was 35-85 microM as determined by two methods at low and high cell densities. Reduced growth did not result from damaged plasma membranes as determined by alpha-amino isobutyrate leakage. DNA synthesis was unaffected by the acetylenic acid and the effect on RNA and protein synthesis appeared to be secondary to the effects on lipid metabolism. The 2-hexadecynoic acid inhibited lipid metabolism of the HTC cells at least at two levels. Data from both mass studies and radioactive acetate distributions in cellular and media lipids indicated that fatty acid elongation and acylation, especially triglyceride synthesis, were inhibited.
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The concentrations of the major neutral lipid and phospholipid classes in the plasma of rats bearing hepatoma 7288CTC were determined at various times after transplantation. The fatty acid composition of each lipid class was also analyzed quantitatively as tumor growth progressed. Generally, most lipid classes exhibited a slight decrease between the third and sixth day after transplantation, returned to near normal levels by the 15th day, increased dramatically and peaked between the 24th and 27th days before plummeting sharply. At peak concentrations, triglycerides were increased 5 times the normal levels, whereas cholesterol, cholesterly esters and phosphatidylcholines were increased 3-fold. The percentage of hexadecenoates decreased in all lipid classes as tumor growth progressed and generally, stearate levels increased. In addition to monounsaturated fatty acids, lysophosphatidylcholines and phosphatidylcholines showed relatively large decreases in the percentage of polyunsaturated fatty acids with increased tumor growth. These results indicate that hepatoma 7288CTC can cause perturbation of host animal plasma lipids in the early stages of growth which precedes the massive hyperlipidemia. The interpretation of these results suggests that the early changes in plasma lipids may result from alterations in the normal lipid metabolism of the host, and the hyperlipidemia that develops later may result from the mobilization of lipids to compensate for the altered metabolism.
Cis-hexadecenoates isolated from rat liver and hepatoma 7288CTC lipids were analyzed for positional isomers by ozonolysis and capillary gas liquid chromatography. In addition to the delta 6, delta 7, delta 9 and delta 11 isomers found in both tissues, the hepatoma neutral and polar lipids contained relatively high percentages of delta 12 and delta 14 hexadecenoates that were virtually absent from liver. The occurrence of these unusual fatty acids may result from an error in lipid metabolism in the hepatoma.
Normal and hepatoma bearing rats were fed a low level of methyl 2-hexadecynoate in a low fat diet for one month. The effect of the acetylenic acid on lipid metabolism as derived from mass analysis of lipid classes, fatty acids and positional monoene isomers isolated from the major lipid classes of liver and hepatoma has been assessed. Methyl 2-hexadecynoate caused a 25% decrease in body weight and the appearance of essential fatty acid deficiency symptoms within one week. Non-tumor-bearing animals contained a seven-fold increase in all neutral lipid classes, except cholesterol, while host animals did not contain fatty livers. The apparent protective effect of the host animal by the hepatoma also resulted in only marginal changes in the fatty acid and positional monoene isomers from host liver and hepatoma lipids. In contrast to host liver and hepatoma, methyl 2-hexadecynoate caused a massive accumulation of palmitate and hexadecenoates with a concomitant decrease in stearate and octadecenoates in most of the lipid classes from non-tumor-bearing animals. These changes were accompanied by a shift from the higher molecular weight triglycerides to lower molecular weights corresponding to carbon number 48. The high concentrations of hexadecenoates consisted predominantly of the delta 9 isomer. Despite the high concentrations of cis delta 9 hexadecenoate, precursor of cis delta 11 octadecenoate (vaccenate), total vaccenate levels of the five major lipid classes were lower than control values. All of these data strongly suggest that long-chain 2-ynoic acids inhibit elongation of saturated and monoene fatty acids.
Small bowel biopsy is a difficult procedure in infants and children, and the authors describe a new technique. The Quinton multipurpose suction biopsy instrument is incorporated into an Olympus GIF-P2 fiberoptic endoscope to allow positioning of the biopsy capsule under direct visual control. Fourteen children, 2 months to 4 years of age, have been biopsied, and tissue was successfully obtained in 20 of 21 procedures. Nine of 21 endoscopic examinations of duodenal mucosa were abnormal and gave additional diagnostic information.
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Underdevelopment of teeth after exposure to radiation has been observed since the early experiments with X rays. Two patients had been irradiated at young ages for embryonal rhabdomyosarcomas. For the patient treated with radiation at age 4 for a lesion in the submandibular area, root development of the mandibular teeth stopped, but the teeth nevertheless erupted. In the patient treated with radiation at age 9 for a tumor in the left cheek, bone apposition in the left side of the mandible failed to continue at the same rate as on the right side. Although new megavoltage radiation machines have reduced the chances of bone complications in adults, developing bone and structures are still significantly affected by radiation.
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The percentage distribution of the geometrical and positional isomers in the hexadecenoates and octadecenoates isolated from triglycerides, phosphatidylcholines, and phosphatidylethanolamines of brain, heart, kidney, liver, lung, muscle, spleen, and adipose tissues from normal rats maintained on a laboratory diet has been determined. All of the octadecenoates and most of the hexadecenoates from the lipid classes of all the tissues consisted of more than 95% cis isomers. Generally, palmitoleic was the predominant hexadeceonate, but many of the tissue phospholipids contained relatively high percentages of the delta 6 and delta 7 isomers. Oleate and vaccenate were the predominant octadecenoates in all tissues. Except for brain and adipose tissues, the oleate to vaccenate ratios differed for each lipid class, as well as between most tissues. In contrast to the monoenes of the phospholipids, the triglyceride monoenes exhibited the same approximate: percentage composition; percentage of geometrical isomers; and percentage distribution of hexadecenoate and octadecenoate positional isomers. These data add to our basic information about the percentage distribution of geometrical and positional isomers of naturally occurring unsaturated fatty acids in the major lipid classes of various normal tissues. Some new concepts were advanced as possible explanations to some of the observed positional isomer distributions.
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The effect of dietary cyclopropene fatty acids on the concentration of octadecenoate chain positional isomers in individual lipid classes of normal liver, host liver, and hepatoma 7288CTC has been determined. The data revealed the following: (a) Saturated and monoene fatty acid percentages of liver phosphatidylcholines and phosphatidylethanolamines were not affected, but the percentage of saturated fatty acids of the triglycerides and cholesteryl esters was increased while the monoene percentages decreased. (b) Oleate to vaccenate percentage ratios, previously shown to be characteristic of individual lipid classes, were completely disrupted. (c) Oleate concentrations of the two major liver phospholipids were elevated, and vaccenate levels were dramatically reduced. (d) Cyclopropene fatty acids appear to inhibit monoene elongation. (e) The elevated concentrations of oleate indicate that an alternate route of oleate biosynthesis must exist if the delta9 desaturation is inhibited by cyclopropene fatty acids as reported previously. (f) In contrast to liver, oleate and vaccenate concentrations in hepatoma were not affected by the dietary cyclopropene fatty acids.
Computed tomography detected the presence of dilated ducts in 15 of 18 cases with extrahepatic obstructive jaundice and demonstrated the obstructing lesion in 18 out of 25. The cause of the obstruction was detected in the absence of duct dilatation, and calculi which were radiolucent on conventional radiographs were demonstrated. Ulstrasound detected dilated ducts in eight of 10 cases, but demonstrated the cause of the obstruction in only one of 13 cases. Both techniques are capable of demonstrating dilated ducts in the majority of cases, but computed tomography is better at detecting the cause of the obstruction.
This study compared the effects of self-evaluation and adult-dispensed tokens on room-cleaning behavior of six predelinquent youths in a residential token-economy setting. The self-evaluation token system proved to be as effective as the external adult-administered system in increasing room-cleaning behavior and was more effective in maintaining performance after contingencies were withdrawn. The self-evaluation token system increased resistance to extinction, compared to the external token system, and appeared to be a useful component for a traditional token-economy system.
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