Phase transitions and slow spin dynamics of slightly inverted A-site spinel CoAl2-xGaxO4.

We report the properties of an A-site spinel magnet, CoAl2-xGaxO4, and analyze its anomalous, low-temperature magnetic behavior, which is derived from inherent, magnetically frustrated interactions. Rietveld analysis of the x-ray diffraction profile for CoAl2-xGaxO4revealed that the metallic ions were randomly distributed in the tetrahedral (A-) and octahedral (B-) sites in the cubic spinel structure. The inversion parameterηcould be controlled by varying the gallium (Ga) composition in the range 0.055 ⩽η⩽ 0.664. The composition-induced Néel-to-spin-glass (NSG) transition occurred between 0.05 ⩽η⩽ 0.08 and was verified by measurements of DC-AC susceptibilitiesχand thermoremanent magnetization (TRM) below the Néel transition temperatureTN. The relaxation rate and derivative with respect to temperature of TRM increased at bothTNand the spin glass (SG) transition temperatureTSG. The TRM decayed rapidly above and below these transitions. TRM was highly sensitive to macroscopic magnetic transitions that occurred in both the Néel and SG phases of CoAl2-xGaxO4. In the vicinity of the NSG boundary, there was a maximum of the TRM relaxation rate atTmax

Demonstration of apoptosis in neuroblastoma and its relationship to tumour regression.

The in vivo occurrence of apoptosis in neuroblastomas was investigated. Histologically, a number of tumour cells showed typical apoptotic changes, including cell shrinkage, condensed and fragmented nuclei, eosinophilic cytoplasm, and absence of the inflammatory response. These cells coincided closely with the so-called karyorrhectic cells. An electrophoretic DNA ladder, a functional hallmark of apoptosis, was demonstrated in four of six tumours, and DNA fragmentation was detected in situ by terminal deoxytransferase-mediated nick end-labelling in 26 of 35 tumour specimens (74%). The labelled cell counts ranged from 5 to 62 per 5000 tumour cells (mean +/- SD: 15.0 +/- 14.5). Immunoperoxidase staining revealed that an apoptosis-suppressing protein, bcl-2, was expressed abundantly in advanced-stage tumours, whereas it was absent from karyorrhectic-apoptotic cells. Several tumours with the potential for spontaneous regression were bcl-2-deficient. Immunostaining of the Fas receptor for apoptosis demonstrated that the tumour cells expressed this molecule on their cell surfaces. Our results provide evidence of apoptosis in neuroblastomas and suggest that bcl-2 and the Fas receptor may play a role in its regulatory mechanisms.

Increased serum levels and sinusoidal expression of thrombomodulin in acute liver damage.

Thrombomodulin (TM) is a surface glycoprotein of endothelial cells involved in both anticoagulation and antifibrinolysis. In this study, we assessed the clinical significance of TM in acute liver damage by using a rat model induced by intraperitoneal injection of D-galactosamine (Gal-N). Serum TM levels were measured with enzyme immunoassay utilizing rabbit anti-rat TM antibody. Simultaneously, immunohistochemical examination was performed using the same antibody. Serum TM levels increased significantly after the injection of Gal-N compared with preinjection levels, peaking from 48 to 72 hours after injection and normalizing by 168 hours. Changes in parenchymal damage were synchronized with changes of TM, and changes of TM levels mirrored changes of liver weight. In immunohistochemical examination, TM immunoreactivity was observed only on the endothelial surfaces of both the artery and portal vein within Glisson's sheath in controls. After injection of Gal-N, TM immunoreactivity was gradually intensified, especially around the necrotic area and the central veins. These findings disappeared with improvement of parenchymal damage. Both the increase of serum TM levels and intensified TM immunoreactivity in the liver were synchronized with acute liver parenchymal damage induced by Gal-N. These findings on TM are related to endothelial damage with parenchymal necrosis and liver regeneration interacting with both homeostasis of microcirculation and healing of parenchymal damage.

Immunohistochemical expression of manganese superoxide dismutase in hepatocellular carcinoma, using a specific monoclonal antibody.

The expression of manganese superoxide dismutase (Mn-SOD) was studied immunohistochemically, using a specific monoclonal antibody, in surgically resected hepatocellular carcinoma (HCC) and noncancerous tissues from 47 patients (2 with well-differentiated HCC, 36 with moderately differentiated HCC, 8 with poorly differentiated HCC, and 1 with undifferentiated carcinoma). Cancer cells in 44 patients (93.6%) were positive for Mn-SOD. The staining pattern of cancer cells was mostly homogeneous in well-differentiated HCC, whereas it was heterogeneous in poorly differentiated HCC. Moreover, strongly positive immunoreactivity was observed in noncancerous liver tissues in all patients, especially in normal hepatocytes surrounding HCC, regenerative small hepatocytes in the tumor boundary, and mononuclear inflammatory cells in the necroinflammatory lesions. The positive immunoreactivity for Mn-SOD in patients with HCC appears to reflect increased production of the enzyme protein.

Synergistic effect of oral UFT in combination with cisplatin on DNA synthesis in rat hepatocarcinomas.

We investigated the synergistic efficacy of CDDP and UFT, an oral anticancer derivative of 5-fluorouracil, on DNA synthesis of 3'-MeDAB-induced hepatocarcinomas in rats. Chronic treatment with CDDP slightly reduced tissue activities of thymidylate synthetase and thymidine kinase in the hepatocarcinomas, and, moreover, simultaneous administration of a low dose of UFT with CDDP markedly suppressed both enzyme activities, i.e., UFT and CDDP showed a potent synergism on DNA synthesis in hepatocarcinomas.

Inhibition by 1-(2-tetrahydrofuryl)-5-fluorouracil in combination with uracil of hepatocarcinogenesis induced by 3'-methyl-4-dimethylaminoazobenzene in rats.

It is known that a high incidence of hepatocellular carcinoma in rat liver can be induced by 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB). The administration of 3'-MeDAB in combination with 1-(2-tetrahydrofuryl)-5-fluorouracil and uracil (UFT) delayed the appearance of oval cells and the formation of hyperplastic nodules, which were observed in the liver from 3 and 5 weeks, respectively, after the onset of 3'-MeDAB feeding, and also delayed the transient increase of serum alpha-fetoprotein level, which transiently peaked at 5 weeks, and completely suppressed the transient increase of tissue thymidylate synthetase activity, but not thymidine kinase, which were induced by 3'-MeDAB at 5 weeks, and finally reduced markedly the incidence of hepatocarcinomas. These results indicate that the suppression of de novo synthesis in pyrimidine metabolism prevents hepatocarcinogenesis.

Congenital hepatic fibrosis with fatal cholestatic liver damage.

A 23-year-old male with congenital hepatic fibrosis died because of progressive cholestatic liver damage. Pathologically, marked extension of fine fibers along the sinusoids in addition to fibrosis in Glisson's sheath, miniaturization and pseudo-glandular formation of hepatocytes as parenchymal damage, and nodular regenerative hyperplasia were considered as the cause of rapid aggravation of liver damage or portal hypertension.

Studies on the delayed neurotoxicity of organophosphorus compounds--(III).

TOCP (Tri-orthocresyl phosphate), an organophosphorus compound, has been implicated in producing neuropathy in the male S. D. rats. Repeated subcutaneous doses of TOCP (600 mg/kg) for up to 6 weeks produced ataxia, most striking at 50 days after final injection, followed by gradual recovery. Ultrastructurally, the internal structure of affected nerve fibers was primarily composed of altered smooth endoplasmic reticulum, tubular membrane system, and mitochondria, although myelin sheath was found to be essentially normal. In the histopathological examination, axonal and myelin degeneration was disclosed in the gracile nucleus and in the gracile fasciculus of the cords as well as in the sciatic nerves. The localization and degree of these changes were considered to be "dying back", showing systemic neuropathy. In addition, muscular lesion showed small group atrophy, corresponding to Type I fiber atrophy.

[Disappearance of Mallory bodies in the liver of autopsy cases with a history of heavy drinking].

Mallory bodies, the intra-cytoplasmic inclusions in hepatocytes, are thought to be a pathognomonic feature of alcoholic liver disease, particularly of alcoholic hepatitis. The presence of Mallory bodies is considered as a reflection of serious illness in alcoholic liver disease. Mallory bodies are thought to disappear relatively rapidly with the use of therapeutic agents after giving up alcohol drinking. However, histological vicissitudes of Mallory bodies have not been studied extensively. In the present study, 19 autopsied cases with a history of heavy drinking were clinicopathologically evaluated. All patients were admitted to our hospital, and stopped alcohol drinking. These period of non-drinking ranged from one day to 150 days (group A: 1-7 days, group B: 8-30 days, group C: 31-150 days). Histological evaluation was performed by hematoxylin and eosin staining, Luxol Fast blue staining and chromotrope aniline blue staining of formalin-fixed paraffin-embedded liver sections. Hepatocytes including Mallory bodies were counted. The incidence of Mallory body formation was as follows: Group A (50%), group B (100%), and group C (100%) respectively. Average count of Mallory bodies: Group A (12.3/10 fields), group B (141.4/10 fields), and group C (188.3/10 fields). Fatty change was more significant in group A than in group B or C, and bile stasis was more significant in group B or C than in group A. These findings suggest that Mallory bodies may remain for several months after giving up drinking.

[A case of pulmonary actinomycosis radiologically mimicking a lung cancer].

A 59-year-old male clerk consulted in general practitioner due to cough and hemoptysis. A mass shadow was pointed out in the left upper lung field on a chest radiograph. Patient was referred to our hospital for further treatment. Any definitive daiagnosis could not be made after examinations including sputum culture, cytology and TBLB. Because a lung cancer was strongly suspected, an exploratory thoracotomy was performed. Actinomyces was detected by pathological study of excised specimen, with no evidence of cancer. ABPC was administered for two months postoperatively. The patient is doing well without recurrence of actinomycosis 2.5 years after the surgery. Pulmonary actinomycosis presenting a mass shadow on a radiograph may mimick a pulmonary tumor, especially a lung cancer. Pulmonary actinomycosis should be considered in a differential diagnosis of pulmonary lesion thought to be malignant.

[Inhibitory effect of UFT on rat hepatocarcinogenesis induced by 3'-methyl-4-dimethylaminoazobenzene and phenobarbital promotion].

Inhibitory effect of UFT on hepatocarcinogenesis in rats induced by 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB) and phenobarbital (PB) promotion was studied. Donryu male rats were divided into four groups. Group A was fed a diet containing 0.06% 3'-MeDAB for 3, 5, or 7 weeks, and then fed normal diet for 2 weeks, subsequently received a diet containing 0.05% PB. Group B was given UFT (20 mg/kg/5 days a week) simultaneously with feeding 3'-MeDAB. Group C was given UFT simultaneously with feeding PB. Group D was given 3'-MeDAB alone. In all groups, the development of hepatocellular carcinoma was investigated 37 weeks later and the number and area per mm2 of induced glutathione S-transferase placental form (GST-P) positive foci were measured using an image processor. The number and area of GST-P positive foci in group B and group C were markedly decreased as compared with those in group A. These results seem to show that the administration of UFT inhibited the production of GST-P positive foci and that stronger inhibitory effect of UFT was observed by simultaneous administration of an initiator than by that of a promoter.

[Histological evaluation of the liver and response to interferon in chronic hepatitis C].

Liver histology was compared in patients with chronic hepatitis C to clarify the difference between responders and non-responders to interferon therapy. We have treated 50 patients with chronic hepatitis C by natural IFN-alpha 6.0 MU/day for 2 weeks, daily, followed by intermittent therapy for 3-6 months. The overall effect of IFN was a complete response (CR) in 16 (32%), transient response (TR) in 14 (28%), and no response (NR) in 20 (40%). According to the pre-treatment liver histology, CR had a lower total numerical scores than TR and NR. Histological difference between CR and TR appeared to be the degree of portal inflammation and piecemeal necrosis, though NR showed an increase in portal fibrosis compared of CR and also TR. Response to IFN may depend on the degree of liver fibrosis rather than other histological factors. To assess the degree of liver fibrosis is thought to be important for the prediction of the efficacy of IFN therapy.

New members of layered oxychloride perovskites with square planar coordination: Sr2MO2Cl2 (M = Mn, Ni) and Ba2PdO2Cl2.

New members of Ruddlesden-Popper type layered oxychloride compounds, Sr2MO2Cl2 (M = Mn, Ni) and Ba2PdO2Cl2, were synthesized under high-pressure conditions. Synchrotron XRD analysis revealed that all the phases adopt the tetragonal space group I4/mmm, where two-dimensional sheets composed of corner-sharing MO4/PdO4 squares were separated by rock-salt SrCl/BaCl layers.