Biomedical subjects
Publications and source records attributed to K Ohtsubo.
A single or repeated administration of trichothecene mycotoxins to mice induced leukocytosis and leukopenia. Acute and sub-acute toxicosis of trichothecenes was characterized by hematological and pathological observations.
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Hepatotoxicity caused by furylfuramide in ddYS male mice was further investigated with following results. (1) Pretreatment with successive oral administration of non-toxic (non-necrotizing) dose (100 mg/day) of furylfuramide for 8 or 24 days alleviated the liver damage elicited by a necrotizing dose (250 mg/kg). The pretreatment resulted in the significant enhancement of the activity of aniline hydroxylase in the liver microsome, which was reduced markedly by a single administration of 250 mg/kg (without pretreatment). The result suggests that the acquired resistance to a toxic dose of furylfuramide is due to the acceleration of detoxication of the drug. (2) Simultaneous administration of CCl4, another hepatotoxic substance, with furylfuramide reduced the lethal effect of the latter. The LD50 values of furylfuramide were increased more than 2.4 times as compared with that of furylfuramide alone. Pretreatment with a small amount of CCl4 as short period as half an hour is more effective than simultaneous administration of both substances. This inhibitory effect of CCl4 on furylfuramide may be explained by an inhibition of the metabolic activation of the latter by the former.
A new cytochalasan compound, chaetoglobosin A produced by Chaetomium globosum, was studied for its toxicity to animals. By subcutaneous injection, 2 mg/kg body weight of chaetoglobosin A killed young Wistar rats acutely, and in the mouse of DDD strain, LD50 values of chaetoglobosin A were estimated 6.5 and 17.8 mg/kg for male and female, respectively. By oral administration, 400 mg/kg of chaetoglobosin A caused little adverse effect on mice and rats. Pathological examination of the mice, injected subcutaneously with 5 mg/kg of the toxin, revealed marked edema at the injection site which appeared in several hours after injection and subsided in a week. In other tissues necrosis of the thymus and spleen and degeneration of the spermatocytes in the testicles were noticeable. With characteristic cytotoxic effects like cytochalasin B, chaetoglobosin A is an interesting mycotoxin, although it may be of little significance as a food- or feed-borne toxin.
Laying Japanese quails were fed on diet of 1:1 mixture of basal diet and rice cultures of 2 strains of Aspergillus candidus. During 20 days of feeding, egg production was significantly reduced in these groups compared with the birds fed unmolded rice. The liver of the quails sacrificed at 20 days showed fatty degeneration of hepatic cells. Following withdrawal of the moldy rice, rate of egg production recovered in 5 days. The suppressive effect of egg production seems to be secondary to hepatic injury. In the other experiment, xanthoascin, a purified mycotoxin of A. candidus, was given subcutaneously between 2 to 5 mg/g body weight. In all groups mortality was about 80%. Survivors produced no eggs 10 days following the injection. The liver of quails that died in 1 to 4 days showed focal necrosis, fine droplet fatty degeneration and bile thrombosis of bile ductules. The features are similar to those observed previously in mice and rats, but the quail is far more sensitive to injected xanthoascin than rodents.
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Xanthoascin (1-4(hydroxyphenyl)-4-(2,2-dimethyl-6-chromanyl)-2,3-diisocyano-1,3-butadiene), a toxic metabolite recently isolated from rice grains infested with Aspergillus candidus L., caused acute hepatic injury with jaundice in mice. Following this, if the animals survived, degeneration of the myocardium developed over several weeks. Myocardial cells of dilated ventricular walls were diffusely vacuolated in routine H.E. sections. Electron microscopically, the vacuoles were filled with osmiophilic, concentric lamellar figures of varied size. Judging from observations in the early stages, this structure seems to develop in relation to mitochondrial membrane. The nuclei of the interstitial cells of the myocardium and pulmonary alveoli contained similar myelin-like figures. Recently it has been found that most strains of A. candidus produce terphenyllin, another toxic compound, and a smaller number of them produces, in addition to terphenyllin, xanthoascin. This may indicate that xanthoascin can be a candidate as a causative agent of primary myocardial diseases of men and contamination of foods with A. candidus and xanthoascin should be eargently examined.
Fifty isolates of Fusarium species from river sediments were examined on their producibility of mycotoxins such as trichothecenes and zearalenone. The most frequent fungal isolate was Fusarium oxysporum, followed by F. solani and F. lateritium. When cultured on Czapek-Dox medium supplemented with peptone, more than half of these strains were suspected to produce trichothecene mycotoxins through toxicity to mice and reticulocyte assay method. One of toxic isolates, F. lateritium 5036, was proved to produce the following five kinds of trichothecenes; diacetoxyscirpenol, 7alpha-hydroxydiacetoxyscirpenol, 7,8alpha-dihydroxy-diacetoxyscirpenol, 8alpha-hydroxydiacetoxyscirpenol (neosolaniol) and diacetylnivalenol. Three strains produced zearalenone on rice grain culture.
Aspergillus candidus Link, one of the commonest constituents of cereal mycoflora, produces two kinds of mycotoxins, terphenyllin and xanthoascin, which show different chemical and toxicological properties. The latter, xanthoascin, caused severe hepatic injury with jaundice and focal or confluent necrosis of hepatocytes, when given to mice in doses of 6 mg/kg b.w. or higher by a single subcutaneous injection. With higher doses above 15 mg/kg, myocardial degeneration and necrosis was induced after a week or two in addition to the hepatic injury. Vacuolation of the nuclei of the alveolar interstitial cells of the lung and myocardial interstitial cells was another characteristic lesion caused by this mycotoxin. Other organs including the testicles and thymus were widely involved. The unique nature of lesions in the liver and heart may necessitate further investigations in the field of mycotoxicology in relation to human diseases such as nutritional hepatitis and primary myocardial degeneration.
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Oral administration of furylfuramide (2-(2-furyl)-3-(5-nitro-2-furyl) acrylamide), used as an antimicrobial food preservative until recently, caused centrolobular coagulation necrosis of the liver of the mouse (ddYS, male) in the degree corresponding to the doses. The recovery process after a single oral administration was characteristic: the necrotic cells were laden with calcium and replaced by foreign body granuloma accompanied by multinucleate giant cells. Complete healing ensued in about a month. Phenobarbital pretreatment reduced injurious effect of furylfuramide on the liver with preservation of the centrolobular region. In this case necrosis occurred in the intermediate zone in a ring-like shape. This indicates enhanced detoxication of furylfuramide by microsomal drug metabolizing enzyme(s) of the liver cells induced by phenobarbital.
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BACKGROUND: Endosonographic features of c-kit-positive gastrointestinal stromal tumors (GISTs) were compared with those of leiomyomas and schwannomas. METHODS: Twenty-four patients with gastric mesenchymal tumors who underwent endoscopic ultrasonography (EUS) and surgical treatment were enrolled. GISTs were defined as c-kit (CD117)-positive tumors, leiomyomas as desmin-positive and c-kit-negative tumors, and schwannomas as S-100-positive and c-kit-negative tumors. Invasion to adjacent organs or more than 20 mitotic counts per 50 high power fields indicated malignancy. RESULTS: There were 19 GISTs, three leiomyomas, and two schwannomas. All five malignant tumors were GISTs. A marginal halo was found in 12 of 19 GISTs and in both of the schwannomas, but not in any of the three leiomyomas. The echogenicities of GISTs were low but higher than that of the normal proper muscle layer, whereas those of leiomyomas and schwannomas were usually low. Lobulation of the tumor surface was documented only in GISTs, particularly in malignant ones. The tumor doubling time of a malignant GIST was 9.3 months, and that of six benign GISTs was 18.7 months (range = 10.7-28.0 months). CONCLUSION: Marginal halo and relatively higher echogenicity on EUS might suggest GIST. Marginal lobulation and a short doubling time may be signs of a malignant GIST.
Presacral ganglioneuroma in a 70-year-old man with persistent constipation and its features on computed tomography, magnetic resonance, and endoscopic ultrasonography are presented. Barium enema study and laparotomy showed that constipation was caused mainly by extrinsic compression from this tumor. Computed tomography, magnetic resonance, endoscopic ultrasonographic features such as well-defined solid tumor with a cystic component and punctate calcifications may facilitate early diagnosis of this rare tumor.