[Sclerosing polycystic adenosis of the parotid gland : surgical treatment of an extensive lesion of deep tissue without superficial damage]. / Adénose sclérosante polykystique de la parotide : traitement chirurgical d'une lésion extensive du lobe profond sans atteinte superficielle.

Sclerosing polycystic adenosis (SPA) is a rare benign epithelial lesion of the salivary glands, of unknown etiology, mainly affecting the parotid gland. We report the first clinical case of SPA involving the deep parotid gland with extension in the parapharyngeal space and the masticatory region. It has been resected by an external parotidectomy approach exclusively, despite the median extension of the lesion. The objective of this article is to complete the small series of cases described in the literature, and to update the knowledge of this rare disease.

L'adénose sclérosante polykystique (SPA) est une lésion épithéliale bénigne rare des glandes salivaires, d'étiologie inconnue, atteignant principalement la glande parotide. Nous rapportons le premier cas clinique de SPA dont l'origine est le lobe profond de la parotide et qui envahit la région masticatrice et l'espace parapharyngé. Elle a été réséquée par une voie d'abord externe de parotidectomie, exclusivement, malgré l'extension médiane de la lésion. L'objectif de cet article est de compléter la petite série de cas décrits dans la littérature, et d'actualiser les connaissances de cette pathologie rare.

Evolution in the management of oropharyngeal squamous cell carcinoma: systematic review of outcomes over the last 25 years.

The treatment of oropharyngeal squamous cell carcinoma (SCC) has evolved over the last 25years, from open surgery to combined chemoradiotherapy, and now to the development of minimally invasive procedures, but evidence for the best treatment is lacking. We therefore did a systematic search of the MEDLINE database for studies published between 1992 and 2017 that reported oncological or functional outcomes, or both. Predefined inclusion and exclusion criteria were used for screening and selection, and 45 studies were chosen. Only one was a randomised controlled trial, all the rest were prospective or retrospective case series. The heterogeneities in their characteristics made meta-analysis impossible and only qualitative analysis was feasible. We found no conclusive evidence to suggest the advantage of one therapeutic approach over another, so we still cannot offer patients the "ideal" treatment. We have, however, raised the possibility of there being two different entities: human papillomavirus (HPV)-positive and HPV-negative disease.

The secretion of apolipoprotein E by human monocyte-derived macrophages.

The secretion of newly synthesized apolipoprotein E (apo E) by human monocyte-derived macrophages (HMD macrophages) was measured in the medium of cells which had been incubated for 24 h with or without either native or acetylated low-density lipoproteins (LDL or AcLDL, respectively), and subsequently with [35S]methionine in the presence of high-density lipoproteins (HDL, 350 micrograms/ml) for 24 h, by isolating the lipoprotein fraction by centrifugation for 48 h at a density adjusted with KBr to 1.21 g/ml (d = 1.21). The d less than 1.21 medium was subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) or precipitation with trichloroacetic acid (TCA). Fluorography of the gels demonstrated that the d less than 1.21 fraction of the medium contained one major labeled band, which migrated with an apparent molecular weight of approximately 35,000. Immunoprecipitation of the d less than 1.21 fraction showed that the labeled band was precipitated by anti-apo E, but not by anti-HDL. As the apo E band appeared to be the only labeled band in the d less than 1.21 fraction, the amount of apo E secreted by the cells was quantitated by scintillation counting of the TCA-precipitable radioactivity in the d less than 1.21 fraction as compared with that in the whole medium. The proportion of secreted apo E to the total secreted protein was similar whether the cells had been in culture for 3 or 16 days, but was increased if the cells had been incubated with LDL or AcLDL. The proportion of apo E of the secreted proteins was always more than 6% and was as much as 16% when the cells were preincubated with lipoproteins, suggesting that the increased cholesterol influx induced apo E secretion.

Mechanism of induction of cytochrome P-450 by phenobarbital.

Treatment of rats with phenobarbital (PB) leads to a substantial increase in the hepatic levels of translatable polysomal poly(A) + cytochrome P-450 mRNA. An enriched fraction of P-450 mRNA was obtained by agarose gel electrophoresis and used to prepare a cDNA probe by differential hybridization to total mRNA from control and PB-treated rats. The majority of the sequences within the probe hybridized to recombinant DNA plasmids which contained a bona fide P-450 cDNA insert identified by positive hybridization selection and in vitro translation. The cDNA probe was used to demonstrate that PB treatment leads to a 30-fold increase in polysomal P-450 mRNA, which is not due to more efficient utilization of previously existing mRNA but to the appearance of new messenger in the cytoplasm. The induction of cytoplasmic P-450 mRNA by PB was rapid, with increases detected within 3 h of PB injection and steady state levels reached in approximately 20 h. The data suggest that the increase in cytoplasmic P-450 protein levels observed after PB treatment may be totally accounted for by an enhanced rate of synthesis resulting from translation of higher cytoplasmic levels of its specific mRNA. The P-450 mRNA was almost exclusively segregated into the membrane-bound polysome compartment was expected for an mRNA coding for an integral membrane protein of the endoplasmic reticulum.

Segregation of specific classes of messenger RNA into free and membrane-bound polysomes.

Analysis of mRNA populations from rat liver rough microsomes and free polysomes by homologous and heterologous cDNA . mRNA hybridization shows that the two mRNA populations are distinct, demonstrating that specific mRNA classes are efficiently segregated for translation in association with endoplasmic reticulum membranes. We estimate that approximately 90% of the mRNA in membrane-bound polysomes contains a diverse set of messengers with a minimum of 500--2000 different species although approximately 5--8 messengers may constitute 25--30% of the mRNA mass. The complexity of the mRNA population of free polysomes appears to be comparable to that estimated for total liver poly(A) + mRNA by other investigators, and is likely to be substantially greater than that of the bulk of bound mRNA. In addition, mRNA in free polysomes lacks the high abundance class characteristic of mRNA-bound polysomes. The substantial complexity of the bound mRNA population suggests that the segregation of polysomes in rough microsomes is not limited to a small class specialized in manufacturing secretory proteins, but extends to polysomes engaged in the synthesis of proteins for intracellular distribution. The segregation of specific messengers into the free and membrane-bound classes was abolished when polysome disassembly was induced by administration of ethionine. Thus, messenger RNA molecules themselves lacked the capacity for segregation, although they contain information for segregation which is expressed during translation. These findings are consistent with the presence of signal sequences in nascent polypeptides which determine the attachment of ribosomes to endoplasmic reticulum membranes.

Time dependence of ethionine-induced changes in rat liver transfer RNA methylation.

Methyl-deficient transfer RNA (tRNA) and subnormal levels of tRNA-methylating enzymes were found in the livers of female rats that had received injections of 250 mg DL-ethionine per kg body weight per day and 120 mg adenine per kg body weight per day for 2 days. Adenine alone had no effect. When the ethionine plus adenine injections were continued for longer periods of time, liver tRNA-methylating enzyme activity measured in vitro gradually increased and exceeded that of the controls. Concurrently, the relative methyl deficiency of liver tRNA decreased. The latter was evident because of the decreased ability of the tRNA to accept methyl groups during in vitro methylation catalyzed by homologous enzymes. Liver tRNA from animals that were treated with ethionine for 7 days could accept only about 40% as many methyl groups as could tRNA from animals that had received ethionine for only 2 days. No further significant change in methyl deficiency of the tRNA was seen when ethionine administration was extended to a total of 14 days. Enzyme preparations from ethionine-treated, but not control, rat livers contained dialyzable substances that inhibited the tRNA methylases and altered the base specificity of these enzymes. Although S-adenosylhomocysteine and S-adenosylethionine were found to be present in the liver preparations, neither of these substances could account for the observed changes in specificity.

Ethionine-induced changes in rat liver transfer RNA methylation.

We have confirmed the finding by Rajalakshmi that transfer RNA (tRNA) from livers of ethionine-treated rats can act as a substrate for homologous tRNA-methylating enzymes in vitro. This methyl-deficient tRNA from liver can be methylated in vitro by enzymes from normal or ethionine-treated rats. The in vitro inhibition of tRNA methylation that follows ethionine treatment can be at least partially relieved in vitro. The liver extracts from ethionine-treated animals contained a low-molecular-weight inhibitor of tRNA methylation. Dialysis of enzyme preparations from ethionine-treated, but not control, rats resulted in large increases in tRNA methylase activity, with either Escherichia coli or homologous tRNA's as substrate. Furthermore, the tRNA methylase activity of control rat liver enzyme extracts was greatly depressed by dialysate from liver homogenates of ethionine-treated rats. After 5 days of ethionine administration the liver tRNA methylase activities were significantly higher than those of control preparations despite the continued presence of the dialyzable inhibitor(s). The liver tRNA's from these animals were poorer methyl acceptors than those from 3-day-treated rats, although still better than tRNA's from untreated rats. These observations have been interpreted to indicate that ethionine causes the accumulation in the liver of inhibitors of tRNA methylation. Early in the course of ethionine administration, methyl-deficient tRNA can be isolated. When the period of ethionine treatment is extended, the organism attempts to maintain homeostasis by production of increased amounts of tRNA-methylating enzymes. The increased quantities of these enzymes are able to overcome, at least partially, the effects of the inhibitors and to decrease the extent to which methyl-deficient tRNA is produced.

Inhibition of methylated nucleoside synthesis in vivo: accumulation of incompletely methylated transfer RNA in ethionine-treated cells of Escherichia coli B.

tRNA prepared from cells of E. coli B that had been incubated with 0.5% DL-ethionine (Ethio sRNA) was found to accept methyl groups from 14CH3-S-adenosyl-methionine in the enzymatic reaction catalyzed in vitro by tRNA methyl transferases from untreated cells of the same organism. tRNA from cells that were not exposed to ethionine did not accept a significant level of methyl groups when incubated with the same enzyme system. Base ratio analysis of the product obtained after in vitro addition of methyl groups to Ethio sRNA by enzymes from normal E. coli B indicated that a high proportion of uracil sites in this tRNA were available for enzymatic methylation. These results indicated that tRNA from ethionine-treated organisms was recognized by the homologous enzymes to be incompletely methylated, while, as previously shown, all methyl-acceptor sites on tRNA from normal cells were already filled, and that Ethio sRNA was preferentially deficient in methyl groups on uracil moieties in the RNA molecules. Ethionine thus appears to interfere with normal tRNA modification in vivo.