Phalloidin-induced alterations of bile canaliculi.

Phalloidin, a toxin from the plant Amanita phalloides, irreversibly polymerizes actin filaments and causes cholestasis. Three-dimensional structural changes induced by phalloidin in the bile canaliculi and the intra-acinar localization of these changes were studied in the rat liver by scanning and transmission electron microscopy. After 3 days of treatment, canalicular changes appeared mainly in zones 2 and 3 of Rappaport's acinus, but after 7 days of treatment changes occurred in bile canaliculi of the whole acinus. The changes in the bile canaliculi included tortuosity, saccular dilatation, loss of microvilli, bleb formation and elongation of canalicular side branches. Some side branches extended near to Disse's space, leaving only a thin cytoplasmic rim between the canalicular lumen and Disse's space. Kupffer cells were occasionally situated near such extended bile canaliculi and protruded their processes into the hepatic cord. These results suggest that bile canaliculi in zone 3 are more susceptible to phalloidin toxicity than those in zone 1 and that biliary constituents may leak from such altered bile canaliculi.</p

Preparation of Thick Amorphous Alloy Sheets in Multicomponent Fe-based Systems and Their Thermal and Magnetic Properties

Thick amorphous sheets with thickness up to about 200μm were formed for the Fe_Al_5Ga_2P_C_6B_4Si_1 alloy with a wide supercooled liquid region of 58 K before crystallization. The glass transition temperature (T_g), crystallization temperature (T_x) and supercooled liquid region ΔT_x(=T_x-T_g) remain unchanged in the entire thickness range. However, the heat of structural relaxation decreases from 2.2 kJ/mol for the 22μm thick ribbon to 0.48 kJ/mol for the 160μm thick ribbon, accompanying the increase in T_c from 597 K to 619 K. In comparison with the other amorphous alloy ribbons in the same Fe-(Al, Ga)-(P, C, B, Si) system, there is a clear tendency for the maximum sample thickness for glass formation (t_) to increase with increasing ΔT_x. The Fe-Al-Ga-P-C-B-Si amorphous sheets have high saturation magnetization of about 180x10^ Wbm/kg and low coecivity of about 5 A/m in the annealed state and their values remain unchanged in the thickness range up to 200μm. The permeability (μ_e) at 1 kHz shows the high values of 12000 for the 30μm thick ribbon and decreases to about 7000 for the 200μm thick ribbon. It is to be noticed that the good soft magnetic properties of 5 A/m for H_c and 7000 for μ_e as well as the wide supercooled liquid region of 58 K are obtained for the thick amorphous sheets with thickness of 150 to 200μm. These characteristics for the thick amorphous ribbons have not been obtained for Fe-based amorphous alloys previously reported. It is therefore expected that the thick amorphous ribbons cause a further extension of the application fields of ferromagnetic amorphous alloys

Three-dimensional arrangement of ductular structures formed by oval cells during hepatocarcinogenesis.

The three-dimensional arrangement of ductular structures formed by oval cells in rats fed 2-acetylaminofluorene (2-AAF) was studied by scanning electron microscopy (SEM) of biliary tract casts and light microscopy of sections of liver injected with india ink via the biliary tract. Both resin and india ink were well injected up to bile ductules, and the findings of each method correlated with each other. By the second week after 2-AAF administration, a few oval cells appeared in the periportal areas forming ductular structures which connected with the portal bile ducts. At the 4th week, increased ductular structures occupied two thirds of the lobule and formed networks communicating with each other, and with the portal bile ducts. At the 8th week, such ductular structures were compressed around hyperplastic nodules and appeared like a basket in biliary casts examined by SEM. Although a histochemical study of gamma-glutamyl transpeptidase revealed activity both on the luminal side of the ductular structures and hepatocytes in hyperplastic nodules, no transition was observed between these two cell populations. These results suggest that oval cells have characteristics more similar to those of biliary epithelia than of hepatocytes, and have no relation to the development of hyperplastic nodules.</p

Effect of acute ether or restraint stress on plasma corticotropin-releasing hormone, vasopressin and oxytocin levels in the rat.

Ether and restraint stress-induced peripheral plasma corticotropin releasing hormone (CRH), arginine vasopressin (AVP), oxytocin (OXY) and adrenocorticotropin (ACTH) levels were measured by radioimmunoassays. Plasma CRH, AVP, OXY and ACTH rose to approximately twice the level of control rats 2 min after the onset of a 1-min exposure to ether. Plasma CRH rose further 5 min after the onset of ether stress, while plasma AVP and OXY returned to the baseline levels at 5 min. Plasma CRH, OXY and ACTH showed significant elevation 2 min after the onset of restraint stress, while plasma AVP did not show a significant change. Plasma OXY and ACTH rose further 5 min after the onset of restraint stress, whereas plasma CRH returned to baseline levels. CRH and OXY concentrations in the hypothalamic median eminence decreased 5 min after the onset of ether exposure and restraint, while the AVP concentration did not differ from control levels. The results, including the discrepancy between plasma CRH and ACTH 5 min after stress, suggest that CRH in the peripheral plasma is derived from both hypothalamic and extrahypothalamic tissues. The levels of stress-induced CRH in the peripheral plasma were sufficient to stimulate ACTH release. These results suggest that ether and restraint stress elevate plasma CRH shortly after the onset of the stress, and that this elevation in the plasma CRH level is at least partly responsible for stress-induced ACTH secretion.</p

GLUTATHIONE S-TRANSFERASE PLACENTAL FORM IS A MARKER FOR BILE DUCT CARCINOMA, BUT NOT HEPATOCELLULAR CARCINOMA, IN HUMANS.

Immunohistochemical studies using anti-human glutathione S-transferase placental form (GST-π) rabbit antibody were carried out to investigate various hepatobiliary diseases in humans. Hepatocytes in fetal and adult liver without disease were negatively or positively stained while intra-or extrahepatic bile duct epithelial cells were positively or strongly positively stained with GST-π. Hepatocytes in regenerated nodules in liver cirrhosis were positively stained. Hepatocellular carcinomas were not strongly positively stained, while cholangiocarcinomas and cancers of the biliary tract were positively or strongly positively stained. These results indicate that GST-π staining is a useful marker for the diagnosis of intra-or extra-hepatic bile duct carcinomas in humans, and that enzyme activity is not phenotypically expressed in hepatocellular carcinomas

MALIGNANT ONCOCYTOMA OF THE PARANASAL SINUS

A case of malignant oncocytoma developing in the paranasal sinus of a 37-year-old Japanese man with a habit of heavy smoking is described. The primary tumor was found in the right maxillary sinus with local invasion to the nose and right ethmoidal sinus ; it was composed of nests of large oncocytic cells, with finely granular and eosinophilic cytoplasm, nuclear pleomorphism and prominent nucleoli, surrounded by proliferation of spindle-shaped cells in some areas. Electron microscopically, the cytoplasm of oncocytic tumor cells was characterized by abundant mitochondria, and immunohistochemical investigation revealed positive binding for antibodies to S-100 protein and α₁-antitrypsin, but a negative reaction for both cytokeratin and vimentin. At autopsy, metastatic nodules of tumor in the lungs, liver and pancreas independently exhibited both oncocytic cell- and sarcomatous cell compartments. This phenomenon is rare, and to the authors' knowledge, this would be histologically an ususual report of malignant oncocytoma with sarcomatous metastatic nodules arising from the paranasal sinus to be described in the literature

Combined anterior pituitary function test using CRH, GRH, LH-RH, TRH and vasopressin in patients with non-functioning pituitary tumors.

We examined 8 normal subjects and 16 patients with non-functioning pituitary tumors with a combined anterior pituitary test to evaluate the clinical usefulness of the test. Diagnoses included 9 of chromophobe adenoma, 3 of craniopharyngioma, 2 of Rathke's cleft cyst, and 1 each of intrasellar cyst and tuberculum sella meningioma. All subjects received hypothalamic releasing hormones: 1 micrograms/kg corticotropin releasing hormone (CRH), 1 micrograms/kg growth hormone releasing hormone (GRH), 500 micrograms thyrotropin-releasing hormone (TRH), 100 micrograms luteinizing hormone releasing hormone (LH-RH), and a relatively small dose (5 mU/kg) of lysine vasopressin (LVP). In the normal subjects, the addition of LVP potentiated the secretion of adenocorticotropic hormone (ACTH) induced by CRH, but had no significant effect on the secretion of other anterior pituitary hormones. In the combined test with 5 releasing hormones, the plasma ACTH and cortisol responses were not impaired in the majority of the patients before pituitary surgery. Serum thyroid-stimulating hormone (TSH), prolactin (PRL) and follicle-stimulating hormone (FSH) responses were not impaired in 82%, 70% and 67% of the patients, respectively, while the serum LH and GH responses were impaired in 67% and 73% of the patients, respectively. Following pituitary surgery, responses of these hormones to combined testing were similarly impaired in more than 75% of the patients. These results indicate that plasma ACTH, cortisol and serum TSH responses are fairly good before pituitary surgery but are impaired significantly after surgery. No subjects experienced any serious adverse effects related to the testing. These results suggest that combined testing with hypothalamic hormones is a convenient and useful method for evaluating pituitary function.</p