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

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.

A clinicopathological study of acute hepatitis in heavy drinkers, unrelated to hepatitis A, B, or C viruses.

BACKGROUND: There are six histological classifications of alcoholic liver disease (ALD) in Japan. However, it is unclear whether all cases of the disease conform to these criteria. This study investigated the clinicopathological features of eight histologically unusual cases of ALD. METHODS: The characteristic features of alcohol drinking behavior, subjective and objective symptoms, laboratory data on admission, and progress after admission were analyzed for eight patients with acute-onset hepatitis. RESULT: The eight patients showed histologically acute hepatitis, with much spotty necrosis that contained granular ceroid pigment by Kupffer cells, which indicated acute parenchymal damage of the liver, but with no Mallory bodies and unremarkable intrasinusoidal neutrophilic infiltration. The only etiological factor for all the cases was habitual alcohol consumption, with increased consumption just before the onset of symptoms. In five cases that were tested, the patients were negative for hepatic viral markers, which included hepatitis G virus RNA and TT virus DNA. CONCLUSION: Some cases of ALD may not conform to the current histological classifications in either Japan or Western countries. It seems natural to consider that these cases are developed by other, unknown causes that overlap with ALD rather than as a result of damage from alcoholic overload.

Mechanisms of alcoholic liver disease: cytokines.

This article represents the proceedings of a workshop at the 2000 ISBRA Meeting in Yokohama, Japan. The chair was Manuela G. Neuman. The presentations were (1) New aspects of hepatic fibrosis, by D. A. Brenner; (2) Cellular immune response in hepatitis C models, by B. Rehermann; (3) The role of interleukin-10 in acute alcoholic hepatitis, by J. Taieb, S. Chollet-Martin, M. Cohard, J. J. Garaud, and T. Poynard; (4) Cytokine-mediated apoptosis in vitro, by M. G. Neuman; (5) Signaling for apoptosis and repair in vitro, by G. G. Katz, R. G. Cameron, N. H. Shear, and M. G. Neuman; (6) Interferons activate the P42/44 mitogen-activated protein kinase and Janus Kinase signal transducers and activation of transcription (JAK-STAT) signaling pathways in hepatocytes: Differential regulation by acute ethanol via a protein kinase C-dependent mechanism, by B. Gao; (7) Genetic polymorphisms of interleukin-1 in association with the development of Japanese alcoholic liver disease, by M. Takamatsu, M. Yamauchi, M. Ohata, S. Saito, S. Maeyama, T. Uchikoshi, and G. Toda; and (8) Increased levels of macrophage migration inhibitory factor in sera from patients with alcoholic liver diseases, by T. Kumagi, S. M. F. Akbar, M. Abe, K. Michitaka, N. Horiike, and M. Onji.

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.

[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.

Hepatic veno-occlusive lesions and other histopathological changes of the liver in severe alcoholic hepatitis--a comparative clinicohistopathological study of autopsy cases.

BACKGROUND: The clinicopathological features of veno-occlusive lesions (VOL) in the liver were studied in 18 autopsy cases of severe alcoholic hepatitis (sALH). All the cases were heavy drinkers and died of liver failure or variceal rupture. METHODS: We performed histological evaluation by examining stained sections of liver blocks from each case. The severity of VOL was compared with the clinical findings and histopathological changes of alcoholic liver diseases (ALD). RESULTS: Clinically, as the severity of VOL increased, the amount of ascites observed during autopsy increased significantly (p = 0.001) and the time from hospitalization to death was significantly longer (p < 0.05). The peripheral leukocyte count tended to increase and the serum bilirubin level increased significantly (p < 0.05) with increased VOL severity, after we excluded one case that was complicated by acute respiratory distress syndrome and bacterial endocarditis. Histopathologically, the appearance of Mallory bodies increased significantly as VOL became more severe (p < 0.05), but the VOL severity did not correlate with sinusoidal neutrophil infiltration. Fatty degeneration tended to be milder as VOL increased in severity although the difference was not significant, whereas bile retention tended to be more marked. CONCLUSIONS: We conclude that investigation of VOL is clinicopathologically important when assessing the pathophysiology and severity of sALH.

Genetic polymorphisms of interleukin-1beta in association with the development of alcoholic liver disease in Japanese patients.

OBJECTIVE: Cytokine interleukin-1beta plays a central role in the inflammation process. Serum levels of IL-1beta are elevated in patients with alcoholic liver disease (ALD), especially in those with cirrhosis and alcoholic hepatitis. Recently, the presence of genetic polymorphisms of this cytokine was confirmed. The aim of this study was to determine whether IL-1beta polymorphisms are associated with the development of ALD. METHODS: We examined the frequency of two polymorphisms in the IL-1beta gene located in promoter -511 and exon 5 +3953 locus by restriction fragment length polymorphisms in 142 male patients with ALD, 30 heavy drinkers without ALD, and 218 healthy controls. RESULTS: The carriers of -511 IL-1beta allele 2 were present significantly more often in patients with alcoholic cirrhosis than in those with noncirrhotic ALD (p = 0.026), heavy drinkers without ALD (p = 0.001), and healthy controls (p = 0.032). The frequencies of allele 2 and heterozygotes of +3953 polymorphism were both significantly higher in heavy drinkers without ALD than in patients with ALD (allele, p = 0.030; genotype, p = 0.027) and healthy controls (allele, p = 0.047; genotype, p = 0.043). The haplotype, IL-1beta -511 allele 2/+3953 allele 1 was associated with the development of alcoholic cirrhosis (p < 0.05). CONCLUSIONS: These results suggest that IL-1beta polymorphisms may be related to the development of ALD in Japanese alcoholics.

Apoptosis in favourable neuroblastomas is not dependent on Fas (CD95/APO-1) expression but on activated caspase 3 (CPP32).

The mechanisms of apoptosis in neuroblastomas have been investigated by examining the expression profiles of Fas, Fas ligand (FasL), and caspase 3 in 42 primary tumour tissues. Immunohistochemically, no or weak Fas expression was detected in 25 out of 29 neuroblastomas (86 per cent), whereas high levels of expression of FasL and pro-caspase 3 were noted in 30 and 29 of 42 tumours, respectively (approximately 70 per cent). Overexpression of pro-caspase 3, but not FasL, correlated significantly with a younger age and low tumour stage. Western blot analysis of ten neuroblastomas confirmed the lack of Fas expression and the presence of strong FasL expression in all samples and pro-caspase 3 expression in five tumours, of which four belonged to the favourable type. These favourable tumours also showed vigorous Asp-Glu-Val-Asp (DEVD) hydrolytic, or caspase 3-like activities, while the unfavourable tumour lacked such activity. Moreover, immunostaining for the p17 subunit of the caspase 3 heterodimer showed that active caspase 3 was mainly localized in apoptotic tumour cells. Combined together, our results suggest that caspase 3, activated via a Fas-independent pathway, may play important roles in apoptosis, suppression of growth, and, in some cases, regression of favourable neuroblastomas.

[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.

Hepatic veno-occlusive lesions in severe alcoholic hepatitis and alcoholic liver cirrhosis: a comparative histopathological study in autopsy cases.

Clinicopathological features of veno-occlusive lesions in hepatic veins were studied in autopsy cases of severe alcoholic hepatitis (15 cases) and alcoholic liver cirrhosis (15 cases). All the cases were heavy drinkers and died of liver failure or variceal rupture. The frequency and degree of veno-occlusive lesions, and the diameter and number of hepatic veins were studied from stained sections of liver blocks from each case. The hepatic veins observed ranged from 60 to 3000 microm in diameter. The veno-occlusive lesions were found in hepatic veins mainly 60 to 1200 microm in diameter. These findings were recognized in the majority of severe alcoholic hepatitis cases and alcoholic liver cirrhosis cases. Furthermore, more severe veno-occlusive lesions were noted in severe alcoholic hepatitis, compared with alcoholic liver cirrhosis. In the cases with obstruction in hepatic veins of >400 microm, a decrease in the number of hepatic veins and zonal necrosis were noted. In addition, some of the veno-occlusive lesions were recognized focally in the same cases. Clinical findings also indicated that ascites increased with the progression of the veno-occlusive lesions. We conclude that investigation of veno-occlusive lesions in severe alcoholic liver disease has clinicopathological significance.

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 analysis of TrkA neurotrophin receptor expression in human non-neuronal carcinomas.

The Trk family of tyrosine protein kinase receptors plays a significant role in the development and maintenance of neural tissues. It has been recently shown that Trk receptors are also expressed by a wide range of normal non-neuronal tissues in humans in a cell type-specific manner. In the present study, the expression patterns of TrkA in 337 non-neuronal invasive carcinomas of 15 different human tissues were investigated immunohistochemically. Overall, 133 (39%), 101 (30%) and 103 (31%) tumors exhibited strong, moderate and no TrkA immunoreactivity, respectively. Esophageal and thyroid carcinomas expressed high levels of TrkA, whereas the levels in gastric and colon cancers were low. TrkA expression was detected not only in carcinomas originating from TrkA-positive normal counterpart tissues, including the esophagus, breast, lung and uterus, but also in those from TrkA-negative tissues/cells of the thyroid, liver and ovary. Immunostaining for nerve growth factor-beta, the specific ligand for TrkA, in esophageal and breast carcinomas demonstrated its immunoreactivity in stromal fibroblasts and some TrkA-expressing tumor cells. These results suggest that paracrine/autocrine regulation via stromal/tumoral NGF-tumoral TrkA interaction may be involved in the growth of certain non-neuronal carcinomas.

Treatment of extensive hypomelanosis with autologous cultured epithelium.

Successful repigmentation was achieved in 6 patients with three types of hypomelanosis (vitiligo, piebaldism, and albinism) by transplantation of fresh, autologous cultured epithelium with melanocytes. A small piece of uninvolved skin was taken for cultivation from a site adjacent to the lesion. Epidermal cells were cultured according to Green's technique. The lesions were abraded superficially and autologous cultured epithelium was applied. The grafts with functional melanocytes took completely and the wounds healed with minimal scarring. Repigmentation was visible within 6 to 8 months. The skin color resembled the surrounding normal skin except in the albinistic patient, in whom the donor skin was taken from a hyperpigmented area. Histochemical examination revealed dopa-positive melanocytes 12 to 17 days after grafting in the basal layer of the epidermis and the dermis. These cells grew in the basal layer of the epidermis and the hair follicles. Melanistic granules were visible in the keratinocytes in 1.5 months. A normal number of dopa-positive melanocytes and melanistic granules were seen in approximately 8 months. Thus, the autologous cultured epithelial grafting procedure is a promising treatment for patients with hypomelanosis.

Favorable donor site for epidermal cultivation for the treatment of burn scars with autologous cultured epithelium.

It is very important to determine from where we select the donor skin for epidermal cultivation in the treatment of burn scar disfigurement. To prove this point, we compared the appearance and histology of grafted sites according to the different donor sites. Thirty-eight patients with skin color difference and irregular contours of matured burn scars were superficially abraded and underwent autologous cultured epithelial grafting. These patients were followed more than 2 years. The donor skin for epidermal cultivations was taken from the buttock (group 1, 8 patients), sole (group 2, 6 patients), and adjacent to the site of the scar (group 3, 24 patients). In group 3, skin elasticity was also measured after 2 years. Hypo- and hyperpigmentation were well treated with autologous cultured epithelial grafting. The most favorable results in terms of color match were obtained in group 3, where the skin color resembled surrounding normal skin. The skin tension returned to almost normal. In group 2, the histology of the grafted site resembled the sole epidermis. It was concluded that the general principle of conventional skin grafting (i.e., "closer is best") was also correct in cultured epithelial grafting. Furthermore, it was revealed that cultured epithelium has a site specificity even after grafting.

Immunologic reaction and genetic factors in biliary atresia.

The characteristic histopathological features seen in the livers of patients with biliary atresia (BA) are very similar to those of primary biliary cirrhosis, which is an autoimmune disease. To clarify whether BA liver possess an immunological response similar to that in primary biliary cirrhosis, we studied HLA-DR expression in liver tissue of BA patients, using a HLA-DR staining method, and determined the frequency of HLA types in BA patients and their families. HLA-DR was expressed by the bile duct epithelium in 11 of 16 liver specimens obtained from 13 BA patients. By contrast, HLA-DR was not expressed in liver specimens from 6 patients with congenital biliary dilatation. Among the HLA types seen in BA patients and their families, HLA-A33, -B44 and -DR6 were frequently expressed in blood. These results suggest that certain immunological factors and disease-susceptible genes might be involved in the etiology of BA.

Expression of the G2-M checkpoint regulators cyclin B1 and cdc2 in nonmalignant and malignant human breast lesions: immunocytochemical and quantitative image analyses.

We investigated the in vivo expression of cyclin B1 and Cdc2 (key molecules for G2-M transition during the cell cycle) in nonmalignant and cancerous human breast lesions using immunohistochemistry and quantitative proliferative index (PI) analysis. Breast epithelial cells co-expressed cyclin B1 and Cdc2 in their cytoplasm in the G2 phase and in their nuclei in the M phase. Cyclin B1, but not Cdc2, immunostaining rapidly disappeared from the nuclei during the mitotic metaphase to anaphase transition. Static image analysis revealed the mean proliferative index for cyclin B1/cdc2 for each type of lesion to be as follows: normal glands (n = 20), 2.0/2.5%; benign lesions, including typical ductal hyperplasia (n = 76), 2.5/5.8%; atypical ductal hyperplasia (n = 21), 3.0/6.6%; carcinomas in situ (n = 70), 7.4/14.0%; and invasive carcinomas (n = 58), 10.0/22.9%. Proliferative index data for atypical hyperplasia were virtually identical to those for benign lesions and were significantly lower than those for breast cancer, suggesting that expression levels of cyclin B1 and Cdc2 may be used to distinguish premalignant human breast lesions from advanced disease. Furthermore, the proliferative index for cyclin B1 for comedo-type ductal carcinomas in situ agreed with that for invasive ductal carcinomas (mean, 10.1% versus 9.5%), apparently explaining the clinicopathological aggressiveness of this tumor at the molecular level.

Correlation between intrasinusoidal neutrophilic infiltration and ceroid-lipofuscinosis in alcoholic liver fibrosis with or without fatty change: clinicopathological comparison with nutritional fatty liver.

A histopathological study was conducted on alcoholic liver fibrosis with fatty change (21 cases) and alcoholic liver fibrosis without fatty change (18 cases) in comparison with nutritional fatty liver (27 cases). The diagnoses of alcoholic liver fibrosis groups were clinically fulfilled according to the criteria established by the Alcohol and Liver Research Group (Chief: Professor Takeuchi) of the Ministry of Education of Japan. Histological diagnosis of alcoholic liver fibrosis with fatty change was based on moderate and/or greater fatty metamorphosis of the hepatic lobules, alcoholic liver fibrosis without fatty change on a lesser degree of fatty metamorphosis than alcoholic liver fibrosis with fatty change, and nutritional fatty liver on clinicopathological features. All 66 cases were negative for viral markers of hepatitis B surface antigen and anti-hepatitis C virus in serum. Intrasinusoidal neutrophil infiltrations were significant in cases of alcoholic liver fibrosis groups more often than in cases of nutritional fatty liver. The degree of intrasinusoidal neutrophil infiltration in cases of alcoholic liver fibrosis groups was higher in cases who had last consumed alcohol recently, compared with those with longer abstinence. In alcoholic liver fibrosis with fatty change and nutritional fatty liver groups, mild-to-moderate degrees of ceroid-lipofuscinosis were recognized, but both fatty change and ceroid-lipofuscinosis were decreased according to the deterioration of fibrotic changes in alcoholic liver fibrosis with fatty change cases. On the other hand, it is significant that the frequency of ceroid-lipofuscinosis in alcoholic liver fibrosis without the fatty change group was lower than those of the alcoholic liver fibrosis with fatty change and nutritional fatty liver groups. Distribution of ceroid-lipofuscinosis has a tendency to be recognized around the central zone (zone III) of alcoholic liver fibrosis with fatty change cases with mild fibrosis, as in nutritional fatty liver cases, and the ceroid-lipofuscinosis disperses with the progression of fibrosis. These results suggest that fibrosis and fatty droplet deposition lead to microvascular heterogeneity. Therefore, the degree and distribution of fatty droplets, ceroid-lipofuscinosis, and intrasinusoidal neutrophil infiltration differ, depending on the etiology of fatty liver, and are an important histopathological barometer in cases of alcoholic liver fibrosis with fatty change and alcoholic liver fibrosis without fatty change, thus indicating the degree of fibrosis and the period since last alcohol intake.

Expression of beta-catenin in normal breast tissue and breast carcinoma: a comparative study with epithelial cadherin and alpha-catenin.

Expression of beta-catenin was investigated in normal breast tissue and 66 breast carcinomas in conjunction with expression of epithelial cadherin (E-CD) and alpha-catenin. In normal mammary ducts and acini, intense beta-catenin immunoreactivity was present at the basolateral surfaces of luminal epithelium and weak immunoreactivity was observed at the lateral borders of myoepithelial cells. No beta-catenin was revealed at the myoepithelial basal surface. The intercellular expression of beta-catenin, as well as of E-CD and alpha-catenin, was also observed in carcinoma tissues with varying staining intensity. Almost all of 10 intraductal carcinomas and approximately 70% of 41 invasive ductal carcinomas expressed the three molecules at the same level as in normal glands, whereas approximately 80% of 13 invasive lobular carcinomas showed severe deficiency of them. Two lobular carcinomas in situ showed complete absence of all of the proteins. Some of these findings were confirmed biochemically by immunoblotting analysis. In invasive ductal carcinomas, alpha-catenin was reduced more frequently in diffuse than in solid type tumours, whereas the level of expression of beta-catenin and E-CD was unchanged between them. No correlation was present between reduced expression of the adhesion molecules and lymph node metastasis.