Efficacy of transdermal nicotine patches for eosinophilic pustular folliculitis.
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Administration, Cutaneous↗
Biomedical subjects
Y Mera
Publications and source records attributed to Y Mera.
Selenium deficiency: report of a case.
We report an 18-month-old Japanese boy with selenium deficiency. He had dry skin with irregularly shaped, erythematous changes on the cheeks, groin, hip, and extremities, erosions on the external urethral and anal orifices, and sparse, short, thin, light-coloured hair. He had received parenteral nutrition for 5 months because of juvenile polyposis. At presentation, his serum selenium level was less than 2.0 microg/dL (normal range, 10.6-17.4 microg/dL). His skin lesions responded well to supplementary treatment with sodium selenite. His skin symptoms were similar to those attributable to a deficiency of zinc which, like selenium, is an essential trace element. According to the literature, selenium deficiency is responsible for cardiomyopathy, which was diagnosed in our patient. The clinical similarity to zinc deficiency and the literature yielded important clues for a diagnosis of selenium deficiency in this patient.
Diagnosis, Differential↗
Plexiform schwannoma.
We present a case of plexiform schwannoma, a rare benign peripheral nerve sheath tumour characterized by a multinodular and plexiform growth pattern, that had slowly grown for 40 years on the trunk of a 64-year-old woman. Preoperative biopsy findings, such as a high cellularity and the extent of nuclear atypia of the tumour, led us to suspect a malignant peripheral nerve sheath tumour; but ultimately a benign plexiform schwannoma was diagnosed based on an immunohistochemical review of the excised tumour using various markers including S-100 and Ki67 (MIB1).
Biomarkers, Tumor↗
A case of mastocytosis with chorea.
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Adult↗
Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 3). Effects of repeated doses of ethinylestradiol for 2 and 4 weeks on the male reproductive organs.
Male Sprague-Dawley rats were subcutaneously administered 0.3 and 3.0 mg/kg/day of ethinylestradiol for 2 and 4 weeks. Two weeks treatment decreased body weight gain, food consumption, absolute weights of testis, epididymis, prostate and seminal vesicle, and relative weights of epididymis, prostate and seminal vesicle. On the other hand, it increased absolute and relative weights of pituitary and adrenal glands, and induced atrophy of Leydig cells, degeneration/necrosis of pachytene spermatocytes, vacuolar degeneration of Sertoli cells, and retention of spermatids. In addition to the changes found after 2 weeks treatment, 4 weeks treatment induced exfoliation of germinal cells, decreases in spermatid and multinucleated giant cell formation and relative weights of testis. These results suggest that examination of prostate and seminal vesicle weights and histopathological changes in the testis are important for evaluation of male reproductive toxicity of ethinylestradiol and 2 weeks treatment is sufficient to detect toxicity on male reproductive organs.
Adrenal Glands↗
ATP-dependent proteolysis in yeast mitochondria.
An ATP-dependent proteolysis system in yeast mitochondria was characterized by examining the hydrolysis of mitochondrial translation products in isolated mitochondria. Degradation of [35S]methionine-labeled polypeptides synthesized in isolated yeast mitochondria was activated by exogenously added ATP. ADP, GTP, and CTP substituted for ATP to some extent, but nonhydrolyzable ATP analogues did not. Adenosine-5'-O-(3'-thio-triphosphate) effectively competed with ATP as activator. Carboxyatractyloside, an inhibitor of adenine nucleotide translocation across the mitochondrial inner membrane, and the metal chelator o-phenanthroline inhibited the ATP-dependent proteolysis. The latter inhibition was abolished by subsequent addition of Mn2+ or Co2+ but not Ca2+ or Zn2+. Hemin inhibited the ATP-dependent proteolysis of mitochondrial translation products with a half-maximum inhibition at 12 microM. Analysis by SDS-polyacrylamide gel electrophoresis showed that [35S]methionine-labeled polypeptides were rapidly degraded into low-molecular-weight species. Submitochondrial particles retained the ATP-dependent proteolytic activity and had the same spectrum of inhibitors as intact mitochondria except for a reduced effect of carboxyatractyloside. These results indicate that yeast mitochondria contain an ATP-dependent and hemin-sensitive proteolysis system which is associated with the inner membrane and can hydrolyze mitochondrial translation products, and that a chelator-sensitive protease is probably involved in this system.
Adenosine Triphosphate↗
Divalent metal ion-dependent mitochondrial degradation of unassembled subunits 2 and 3 of cytochrome c oxidase.
Intracellular protein degradation plays an important role in maintaining the stoichiometry of the different subunits of an oligomeric enzyme. In a Saccharomyces cerevisiae mutant defective in cytochrome c oxidase subunit 4 encoded in nuclear DNA, mitochondrial-encoded subunits 2 and 3 cannot assemble normally [Dowhan et al. (1985) EMBO J. 4, 179-184]. In this study, we show that those unassembled forms of subunits 2 and 3 in this strain are eliminated rapidly by degradation. Reduction of the intracellular ATP level by inhibiting the glycolytic pathway, or inhibition of the entry of ATP into mitochondria by bongkrekic acid, both of which are expected to reduce the intramitochondrial ATP level in respiratory-deficient cells such as WD1, significantly suppressed the degradation, suggesting that the degradation requires intramitochondrial ATP. The degradation was also inhibited by o-phenanthroline, a membrane-permeable metal chelator, and this inhibitory effect was suppressed by addition of an excess amount of Co2+, Mn2+, or Zn2+, but not by Ca2+ or Mg2+, suggesting a novel metal-dependence of the degradation of unassembled Cox II and Cox III which has not been reported previously for mitochondrial metabolic protein degradation systems. A potential advantage of using this strain for identifying the factor(s) involved by a genetical approach is discussed.
Adenosine Triphosphate↗
[The gastric mucosal adhesiveness of Z-103 in rats with chronic ulcer].
The gastric mucosal adhesiveness of Z-103 in rats with acetic acid ulcer was studied macroscopically, histologically, and biochemically. From macroscopical observations, when Z-103 was orally administered to an acetic acid ulcer model, there was adhesion of Zn to the normal mucosa as well as the ulcerous site under both the fasting condition and after feeding. It was also proven that the strength and duration of adhesiveness were increased dose-dependently under fasting conditions. In addition, histological localization of Zn was noted from the covering epithelial cell layer to the gastric lamina propria mucosae in the normal tissue and in the most superficial ulcerous layer and the granulous layer of the ulcerous site. Measurement of the gastric tissue Zn content after oral administration of 100 mg/kg of Zn showed that the Zn content was significantly increased for 6 hr at the normal site and for 24 hr at the ulcerous site. On the other hand, although ZnSO4 and ZnSO4+carnosine combination macroscopically produced generally the same level of adhesiveness as Z-103, when the gastric tissue Zn content for Z-103 and ZnSO4 were compared, the Zn content of ZnSO4 was lower than that for Z-103 at both the normal and ulcerous site. In summary, Z-103 shows a long-term adhesive and permeable action on the gastric mucosa in acetic acid ulcer rats, and it has a comparable high affinity at the ulcerous site.
Acetates↗
Localization of 14C-nizatidine in the gastric wall of rats.
Nizatidine (N-[2-[[[2- [(dimethylamino)methyl]- 4-thiazolyl]methyl]thio]ethyl]-N'-methyl-2-nitro-1,1-ethenediamine , CAS 76963-41-2) has a selective and competitive antagonism against histamine H2-receptors. The localization of 14C-nizatidine to the parietal cells of gastric mucosa which is the effective site of nizatidine, was studied. After oral administration of 14C-nizatidine to rats, the radioactivity was rapidly distributed at higher levels in the gastric mucosa than in the plasma. The mucosal level of nizatidine at 6 h after administration was still 63.3 ng/g tissue, being similar to the effective plasma concentrations in dogs and man. Nizatidine was confirmed to be retained as an unchanged drug in the gastric mucosa, supporting the duration of pharmacological effects of nizatidine. The localization of the drug in gastric wall after intraduodenal administration was examined by means of microautoradiography. The radioactivity of 14C-nizatidine absorbed as the fine developed silver granules was widely localized into the parietal cells in the mucosal layer through the gastric wall at 30 min after administration. Also at 2 h after administration, when the suppression of gastric acid secretion was strongest, the silver granules were almost uniformly localized all over the gastric wall, but the localization was generally less dense than at 30 min.
Animals↗
Repeated dose toxicity studies on catena-(S)-[mu-[N alpha-(3-aminopropionyl) histidinato(2-)-N1,N2,O:N tau]-zinc] in rats.
Thirteen- and 52-week oral toxicity studies of Z-103 (catena-(S)-[mu- [N alpha-(3-aminopropionyl) histidinato (2-)-N1,N2,O:N tau]-zinc], CAS 107667-60-7) were carried out in rats. In a 13-week repeated dose toxicity study (37.5, 75, 150, 300, 600 or 1200 mg/kg/d), deterioration of the general condition was observed at 300 mg/kg/d or more, a decrease in body weight gain at 600 mg/kg/d or more. Approximately 40% of the animals were found dead or sacrificed in a moribund state at 1200 mg/kg/d. Furthermore, in the 600 mg/kg group changes in urine volume, blood urea nitrogen and weight of kidneys were observed, suggesting that Z-103 may have had adverse effects on the kidney. No sex difference was noted. From these results the no-effect dose level was estimated to be 150 mg/kg/d under the conditions of this experiment. In a 52-week repeated dose toxicity study (18.75, 37.5, 75 or 150 mg/kg/d), proliferation of small duct and atrophy of acinar cells in the pancreas were observed in both sexes of the 150 mg/kg/d group. No other dose-related changes were observed throughout the administration period. Therefore, the no-effect dose level was estimated to be 75 mg/kg/d under this condition.
Animals↗
Stable phenotypic expression of glutathione S-transferase placental type and unstable phenotypic expression of gamma-glutamyltransferase in rat liver preneoplastic and neoplastic lesions.
Using immunohistochemical demonstration of glutathione S-transferase placental type (GST-P) and histochemical demonstration of gamma-glutamyltransferase (gamma-GT), the long-term development of preneoplastic and neoplastic lesions was followed in rats over a 50-week period. Rats were given a single i.p. injection of 200 mg/kg body weight of diethylnitrosamine (DEN), and then 2 weeks later were administered 0.02% 2-acetylaminofluorene (2-AAF) (group 1), 0.05% phenobarbital (PB) (group 2), 2.0% butylated hydroxyanisole (BHA) (group 3) or no supplement (group 4) in their diet for 6 weeks, all rats being subjected to partial hepatectomy at week 3. Hepatocellular proliferated lesions were classified as foci, nodules and hepatocellular carcinomas. Development of foci, nodules and hepatocellular carcinomas was enhanced strongly by 2-AAF and weakly by PB, and inhibited by BHA. Almost all foci and nodules were GST-P positive, although 5-10% of the GST-P-positive foci were gamma-GT negative. The areas of GST-P-positive foci and nodules increased with time in all groups. In contrast, while the areas of gamma-GT-positive lesions also increased with time in groups 2-4, they decreased from week 12 in group 1. As the percentage gamma-GT-positive area in GST-P-positive foci significantly decreased with time in all groups, the rate of phenotypic reversion of gamma-GT in foci in group 1 was revealed to be larger than the focus growing rate, whereas that in groups 2-4 was smaller. Gamma-GT-negative and GST-P-positive micro-nodules of altered morphology appeared within gamma-GT- and GST-P-positive nodules in later stages. All hepatocellular carcinomas found in this experiment consisted of GST-P-positive cells. In contrast, 37% (13/35) of the hepatocellular carcinomas were negative for gamma-GT. The results indicate GST-P to be the most accurate marker enzyme for detection of initiated cells during liver carcinogenesis and gamma-GT to be more appropriate for indicating changes of phenotypic expression in each lesion type.
Animals↗
Reciprocal relationship between development of glutathione S-transferase positive liver foci and proliferation of surrounding hepatocytes in rats.
The effects of 2-acetylaminofluorene (2-AAF), phenobarbital (PB) and butylated hydroxyanisole (BHA) on the competitive proliferation of glutathione S-transferase (GST-P) positive liver cell foci induced by diethylnitrosamine (DEN) and surrounding hepatocytes were studied. Rats were given a single i.p. injection of 200 mg/kg body wt of DEN and from 2 weeks later were given a diet containing 0.02% 2-AAF (group 1), 0.05% PB (group 2), 2.0% BHA (group 3), or no supplement (group 4) for 6 weeks. All rats were subjected to partial hepatectomy (PH) at the end of week 3. Animals from each group were killed 1, 2, 3 or 4 days or 1, 2, 3 or 5 weeks after PH. Sequential changes in cellular proliferations after PH were investigated by immunohistochemical staining for GST-P and autoradiography of [3H]thymidine. The development of GST-P positive foci was enhanced strongly by 2-AAF and slightly by PB and was inhibited by BHA. In the group treated with 2-AAF, proliferation of hepatocytes adjacent to foci was almost completely inhibited [labelling index (LI) = 0.4-1.5], but GST-P positive foci cells had a high LI (16.2-26.1) 1 week after PH. In the group treated with PB, proliferation of surrounding hepatocytes was slightly inhibited (LI one day after PH = 16.0) compared with that of control (LI = 24.2), but proliferation of cells in GST-P positive foci was not inhibited (LI one day after PH = 11.3; control value = 11.0). BHA retarded recovery of the LI (LI 4 days after PH = 8.1; control value, 4.0) and did not inhibit proliferation of surrounding hepatocytes. These results indicated an inverse relationship between the development of GST-P positive foci and proliferation of surrounding hepatocytes.
2-Acetylaminofluorene↗
Induction of tumors in the liver, urinary bladder, esophagus and forestomach by short-term treatment with different doses of N,N'-dibutylnitrosamine in rats.
The multipotential carcinogen N,N'-dibutylnitrosamine (DBN) was given to F344 male rats for 2 weeks at three dose levels to study the concentration dependence of its organ specificity. Groups of 20 rats were given water containing 0.25, 0.125 or 0.063% DBN for 2 weeks and then tap water only to drink until they were killed 52 weeks after the start of the experiment. DBN induced preneoplastic lesions in the liver, esophagus, forestomach and urinary bladder. Carcinoma was found only in the liver. Induction of preneoplastic focal hepatocyte lesions positive for the P-form of glutathione S-transferase (GST-P) was quantitatively dependent on the dose of DBN. In the urinary bladder, the incidences of papillary or nodular hyperplasia (PNH) and papilloma of transitional cells tended to increase at higher doses. The incidence and number per unit length of basal cell-type hyperplasias of the esophageal epithelium were significantly higher in all DBN groups than in the control group, through the increase did not show a clear dose-dependency. The incidence of epithelial basal cell hyperplasia of the forestomach was significantly increased at all doses and the increase was apparently dose-related. These results indicate that even in a short-term experiment, DBN exerted multipotential carcinogenic effects. Thus, this system could be used for assay of the modifying effects of compounds administered subsequently on carcinogenesis in different organs.
Animals↗
Patterns of epithelial proliferation revealed by continuous administration of bromodeoxyuridine during urinary bladder carcinogenesis in rats.
The patterns of epithelial proliferation in the urinary bladder during carcinogenesis were examined sequentially in rats given drinking water supplemented with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 12 weeks and then water without BBN for 18 weeks. Animals received 120 micrograms of bromodeoxyuridine (BrdU) per hour continuously via an osmotic minipump for 4 days before sacrifice and labeled cells were detected immunohistochemically using monoclonal antibody against BrdU. Two types of BBN-induced epithelial lesions were distinguishable: reversible changes characterized by proliferation of basal cells only, and irreversible changes with high and irregularly distributed incorporation of label throughout the epithelium. Simple hyperplasia, and papillary or nodular hyperplasia consisted of areas of reversible and/or irreversible changes, whereas papilloma and cancer consisted of areas of irreversible changes.
Animals↗
Immunohistochemical demonstration of pyloric gland-type cells with low-pepsinogen isozyme 1 in preneoplastic and neoplastic tissues of rat stomachs treated with N-methyl-N'-nitro-N-nitrosoguanidine.
The appearance of pyloric gland-type cells with a low pepsinogen isozyme 1 (Pg 1) content in the stomach mucosa of F344/Du rats during stomach carcinogenesis was examined by a combination of paradoxical concanavalin A (Con A) staining and immunohistochemical staining for Pg 1. Male F344 rats were given drinking water containing 100 micrograms N-methyl-N'-nitro-N-nitrosoguanidine [(MNNG) CAS: 70-25-7]/ml for 30 weeks and then normal tap water and were killed in week 10, 20, 30, 40, 50, or 70. Untreated rats were killed in week 30 or 70. Serial sections of pyloric mucosa were stained by paradoxical Con A staining and Pg 1 immunostaining. After MNNG treatment, tissues showing changes were classified into normal-looking pyloric mucosa with a low Pg 1 content, mucosa showing atrophic or hyperplastic changes, adenomatous hyperplasia, and adenocarcinoma. From the results of paradoxical Con A staining and Pg 1 immunostaining, the cells in lesions were classified into gastric types (surface mucous cell type and pyloric gland cell type) and intestinal types (intestinal-absorptive cell type and goblet cell type). In this experiment, the cells in lesions were mainly of the gastric cell types. All pyloric glands of control rats in weeks 30 and 70 contained class III mucins and had a high Pg 1 content demonstrated immunohistochemically. After MNNG treatment, class III mucin-positive pyloric glands with a low Pg 1 content in normal-looking pyloric mucosa were found from week 10; subsequently, their number increased with time. Changed mucosa was found from week 20, and the area of cells of the pyloric gland cell type with little or no Pg 1 in changed mucosa was about 30% of the area of cells of the pyloric gland cell type. Adenomatous hyperplasias were found from week 30; adenocarcinomas were found from week 50. Almost all cells of the pyloric gland cell type (greater than 95%) in areas of adenomatous hyperplasia and adenocarcinomas had little or no Pg 1 content. The present results suggested that the appearance of pyloric glands with a low Pg 1 content in normal-looking mucosa might be an immunohistochemically detectable preneoplastic change preceding morphologically detectable preneoplastic changes in stomach carcinogenesis.
Animals↗
Ornithine decarboxylase activity and DNA synthesis in rats after long term treatment with butylated hydroxyanisole, sodium saccharin or phenobarbital.
Ornithine decarboxylase (ODC) activity and DNA synthesis were measured in the forestomach, urinary bladder and liver of rats given diet containing 2% butylated hydroxyanisole (BHA), 5% sodium saccharin (SS) or 0.05% phenobarbital (PB) for 21 weeks. ODC activity was not increased significantly in any of these organs in any of the groups, but the labeling index (LI) of the forestomach epithelium was increased by BHA and PB, and that of the urinary bladder epithelium by SS. PB did not increase the LI of the liver. These results do not indicate any relation between the effects of promoters, and the ODC activity or DNA synthesis in non-initiated target organs.
Animals↗
Immunohistochemical demonstration of induction of pyloric glands with low pepsinogen 1 (Pg 1) content in rat stomach by N-methyl-N'-nitro-N-nitrosoguanidine.
Three groups of male Fischer rats were given single doses of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) at 160 mg (group 1), 80 mg (group 2) and 40 mg (group 3)/kg body weight by gastric intubation. A fourth group was given drinking water containing 100 micrograms/ml of MNNG for 2 weeks, and a fifth group served as a control. Rats were killed in weeks 5, 8 and 12. Serial sections of the pyloric mucosa were examined by paradoxical concanavalin A (Con A) staining and pepsinogen isozyme 1 (Pg 1) immunostaining. All pyloric glands contained class III mucin as detected by paradoxical Con A staining. Most pyloric glands had a high Pg 1 content, but a few stained only weakly if at all. The percentage and number (No./500 normal-looking pyloric glands) of pyloric glands with a low Pg 1 content were 50.0 and 0.2 +/- 0.4 (week 5), 87.5 and 0.5 +/- 0.4 (week 8) and 100.0 and 1.2 +/- 1.0 (week 12) in group 1, 50.0 and 0.2 +/- 0.3 (week 8) and 87.5 and 0.5 +/- 0.4 (week 12) in group 2, and 30.0 and 0.2 +/- 0.4 (week 12) in group 4. No pyloric glands with a low Pg 1 content were found in groups 3 and 5. Thus the results showed significant dose-dependent induction (P less than 0.05-0.01) of altered pyloric glands demonstrating reduced Pg 1 content and their earlier appearance in groups given higher doses of MNNG. The results suggest that the appearance of pyloric glands with a low Pg 1 content may be a preneoplastic change in gastric carcinogenesis.
Animals↗
Histologic and autoradiographic studies on the forestomach of hamsters treated with 2-tert-butylated hydroxyanisole, 3-tert-butylated hydroxyanisole, crude butylated hydroxyanisole, or butylated hydroxytoluene.
The inductions of hyperplasia and neoplastic lesions in the forestomach of Syrian golden hamsters by 2-tert-butylated hydroxyanisole [(2-tert-BHA) CAS: 121-00-6], 3-tert-butylated hydroxyanisole [(3-tert-BHA) CAS: 88-32-4], crude butylated hydroxyanisole [(BHA) CAS: 25013-16-5], and butylated hydroxytoluene [(BHT) CAS: 128-37-0] were compared histopathologically and autoradiographically. In hamsters fed the 2-tert-BHA diet, severe hyperplasia developed from week 4, reaching a maximum level in week 16 of 0.56 cm/10 cm basement membrane (bm), and papillomatous lesions appeared in week 16 (0.13 cm/10 cm bm). In hamsters fed 3-tert-BHA or crude BHA, severe hyperplasia developed from week 1, which reached a maximum level in week 4 of 3.63 cm/10 cm bm with 3-tert-BHA and 5.10 cm/10 with crude BHA; it then decreased. Papillomatous lesions were found in week 3 in hamsters fed 3-tert-BHA and in week 4 in hamsters fed crude BHA; they increased to maximum levels in week 16 of 0.50 cm/10 cm bm with 3-tert-BHA and 0.29 cm/10 cm bm with crude BHA. Mild hyperplasia occurred slightly more often in hamsters fed the BHT diet than in the control group. BHT induced no severe hyperplasia and papillomatous lesions. Changes in the labeling index of the forestomach epithelium paralleled the histologic changes, except in hamsters fed the BHT diet in which no significant increase in the labeling index was observed throughout the experiment. These data suggest that the tumorigenic action of crude BHA on hamster forestomach is largely due to 3-tert-BHA and that BHT does not induce forestomach tumors in hamsters.
Animals↗