Genetic changes and histopathological grades in human hepatocellular carcinomas

Loss of heterozygosity (LOH) on chromosomes 1p, 4q, 5q, 8p, 13q, 16q, 17p, and 22q, and mutation of the p53 gene were simultaneously analyzed in 63 hepatocellular carcinomas (HCCs) with distinct histopathological grades, 80% of the tumors being from patients who had been exposed to hepatitis B virus (HBV) or hepatitis C virus (HCV). The frequencies of LOH on 8 chromosomes were 0-25% in 10 well differentiated HCCs, LOH being observed on 4q, 5q and 17p, 21-53% in 26 moderately differentiated HCCs, LOH on 8p and 17p being high, and 29-75% in 27 poorly differentiated HCCs, LOH on 17p, 4q and 8p being the most frequent. p53 gene mutation was detected in moderately and poorly differentiated HCCs at 15% and 52%, respectively, but not at all in well differentiated HCCs. Of the mutations detected, 42% were transition mutation and only 5% were CpG transition, in contrast to the high frequencies of these types of mutations in colon tumors (78% and 54%, respectively). LOH on every chromosome and p53 mutation were more frequent in more advanced tumors, and accumulation of genetic changes increased with increase of the histopathological grade. Frequency of genetic changes in HCCs from HBV-positive patients was comparable to that from HCV-positive patients. The present results suggest that accumulation of genetic changes in multiple tumor suppressor genes, especially LOH on 17p, 4q and 8p, and mutation in p53 gene, are involved in the progression of liver cancer, and LOH on 17p and 4q precedes other genetic changes. Differences in the direction of p53 mutation between HCC and colon carcinoma suggest that liver carcinogens are distinct from colon carcinogens. Furthermore, mechanisms affecting the frequency of LOH in HCCs in HBV-infected patients may be similar to those in HCV-infected patients.     

Gangliosides minimize motor disabilities and histopathological changes in cortical lesioned and transplanted rats

The effect of bovine brain gangliosides was studied in rats lesioned by partial suction of the right somatosensory cortex and also in rats implanted with a piece of fetal brain tissue in this area. In both experiments a group of animals received 30 mg/kg i.p. of gangliosides daily for a period of 7 days after surgery. In lesioned rats, the untreated group showed a lower maintenance on a tight rope test at 7 as well as at 14 days, as compared with a sham-operated group (p < 0.05). In transplanted rats ganglioside treatment prevented the increase of the probability of falls from a horizontal bar at days 7 and 14 post-operations and the probability of slips on a vertical bar at day 7 (p < 0.05). Rats were killed at day 15 and brain coronal sections were obtained. Nuclear area and circularity were measured in a sample of cortical and grafted cells in a computer aid-image analyzer. Ganglioside protection on the normal size and shape of the nuclei in the ipsilateral cortex in lesioned as well as in transplanted rats (p < 0.01) was found. A higher nuclear area in ganglioside than in saline treated grafts was noted. Results suggest a protective action of the gangliosides against the lesion-induced motor dysfunction and secondary cortical cell degeneration.     

Cytogenetic changes in 67 cranial and spinal meningiomas: relation to histopathological and clinical pattern

The cytogenetic analysis of 67 meningiomas (58 intracranial and 9 spinal tumors) identified chromosomal abnormalities in 63% of cases. When chromosomes involved in numerical and structural changes with a frequency of more than one standard deviation above the mean were considered, distinct cytogenetic patterns could be identified according to sex, anatomical location and histology. The chromosomes more frequently affected were 1, 2, 3, 4, 8, 14, 15, 19, 22, Y. No conclusion could be drawn regarding the prognostic significance of these karyotypic alterations.     

Presenilin 1 intronic polymorphism is not associated with Alzheimer type neuropathological changes or sporadic Alzheimer's disease

BACKGROUND: A genetic association between the presenilin 1 (PS-1) intronic polymorphism and sporadic Alzheimer's disease has been a matter of controversy. Recent findings have suggested that the PS-1 polymorphism is not associated with Alzheimer's disease or amyloid beta-protein (Abeta) deposition in brains from patients with Alzheimer's disease. OBJECTIVES: To elucidate the influence of the PS-1 polymorphism on Alzheimer type neuropathological changes and the development of Alzheimer's disease, the relation between the PS-1 polymorphism and quantitative severity of Alzheimer type neuropathological changes in the brains from patients with Alzheimer's disease and non-demented subjects was studied. METHODS: The PS-1 and apolipoprotein E (ApoE) genotypes, were examined, together with the densities of the senile plaques, senile plaques with dystrophic neurites, and neurofibrillary tangles in the brains from 36 postmortem confirmed patients with sporadic Alzheimer's disease and 86 non-demented subjects. Association of the PS-1 polymorphism with sporadic Alzheimer's disease and ages at onset and duration of illness in Alzheimer's disease was also examined. RESULTS: The PS-1 polymorphism was not associated with the senile plaques, senile plaques with dystrophic neurites, or neurofibrillary tangles in Alzheimer's disease or non-demented subjects. There was no association of the PS-1 intronic polymorphism with Alzheimer's disease, ages at onset, or durations of illness in Alzheimer's disease. The results remained nonsignificant even when the PS-1 genotype groups were divided into the subgroups with different ApoE epsilon4 status. CONCLUSIONS: The PS-1 intronic polymorphism does not itself have a direct causal role in the formation of Alzheimer type neuropathological changes or in the development of sporadic Alzheimer's disease.     

The Alzheimer diseases

Our understanding of the etiologies of the Alzheimer diseases is advancing rapidly, led by the discovery of relevant genetic mutations for autosomal-dominant forms of the disease and widespread confirmation of the role played by apolipoprotein E, the major susceptibility gene for the common form of Alzheimer's disease. New hypotheses are being generated and old hypotheses are being modified to account for the wealth of new information.     

Time courses of hepatic injuries induced by chloroform and by carbon tetrachloride: comparison of biochemical and histopathological changes

The relationship was investigated between biochemical and morphological changes in chloroform (CHCl3)- and carbon tetrachloride (CCl4)-induced liver damage. The time courses of hepatic microsomal cytochrome P450 (CYP) content, hepatic microsomal CYP2E1 activity, hepatic reduced glutathione (GSH) content, plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were examined in relation to the liver morphology in rats orally treated with CHCl3 or CCl4 (3.35 mmol/kg). The CYP content and the activity of CYP2E1 markedly decreased in the CCl4-treated rats 3 h after treatment compared to much lower decreases in the CHCl3-treated rats. The hepatic GSH content was decreased to a similar extent in both groups of rats at 3 h after treatment; in the CCl4-treated rats, the GSH content continued to decrease, reaching a minimum at 24 h and without attaining the normal level at 72 h after treatment. By contrast, hepatic GSH content in the CHCl3-treated rats began to increase from 6 h, attaining complete recovery 48 h after treatment. Plasma ALT and AST activities were significantly elevated by CCl4 as early as 3 h after treatment, while the activities in the CHCl3-treated rats did not increase until 6 h after treatment. In both groups of rats, ALT and AST activities reached a maximum at 24 h, and gradually decreased, remaining at abnormal levels at 72 h. Hepatic cells in the CCl4-treated rats were found to be necrotic as early as 3 h post-treatment, whereas few or no morphological changes appeared in the liver of CHCl3-treated rats. The extent of necrosis was at a maximum 24 h after treatment in both CHCl3- and CCl4-treated rats. In addition, some necrotic cells remained in the liver of CCl4-treated rats 72 h after treatment, while the necrosis in the CHCl3-treated rats was almost negligible. The present results indicate that almost the same time-courses of biochemical and morphological changes were followed in rats of both the CHCl3- and CCl4-treated groups.     

Lanxide技术的研究与进展

针对最近国内外Ｌａｎｘｉｄｅ技术的研究工作进行了比较全面的评述，包括Ｌａｎｘｉｄｅ技术的起源与简介、材料制备过程、工艺优点、机理、发展现状，以及该领域当前的主要研究方向。     

Progression of HIV in haemophilia

A series of permeability thresholds to Ca2+ metabolites and macromolecules, occurring at different times when cells are attacked by complement, has been established by imaging HeLa cells transiently expressing a recombinant cytosolic fusion protein of firefly luciferase and aequorin (luciferase-aequorin) to measure changes in ATP and cytosolic free Ca2+. Nuclear fluorescence of propidium was used as a measure of permeability to small molecules, and luciferase activity imaged to assess lysis. The rise in cytosolic free Ca2+ observed after C9 attack preceded by at least 60 s both the increase in propidium fluorescence, measured in single cells, and the decrease in ATP monitored by luciferase light emission. These effects were dependent on the concentration of C9. At concentrations of C9 up to 4 micrograms/ml no loss of luciferase-aequorin protein was detected at the end of the experiment. Thus the membrane integrity of the cells remained intact, even though the cells were permeable to propidium. These results confirmed our earlier observations that propidium permeability in cells attacked by complement was not a reliable measure of cell death. They also show that it is vital to take account of cellular heterogeneity if the mechanisms by which cells respond to membrane pore former attack are to be correctly interpreted.     

Inhibition of Alzheimer beta-fibrillogenesis by melatonin

It is generally postulated that the amyloid beta protein (Abeta) plays a central role in the progressive neurodegeneration observed in Alzheimer's disease. Important pathologic properties of this protein, such as neurotoxicity and resistance to proteolytic degradation, depend on the ability of Abeta to form beta-sheet structures or amyloid fibrils. We report that melatonin, a hormone recently found to protect neurons against Abeta toxicity, interacts with Abeta1-40 and Abeta1-42 and inhibits the progressive formation of beta-sheets and amyloid fibrils. These interactions between melatonin and the amyloid peptides were demonstrated by circular dichroism and electron microscopy for Abeta1-40 and Abeta1-42 and by nuclear magnetic resonance spectroscopy for Abeta1-40. Inhibition of beta-sheets and fibrils could not be accomplished in control experiments when a free radical scavenger or a melatonin analog were substituted for melatonin under otherwise identical conditions. In sharp contrast with conventional anti-oxidants and available anti-amyloidogenic compounds, melatonin crosses the blood-brain barrier, is relatively devoid of toxicity, and constitutes a potential new therapeutic agent in Alzheimer's disease.     

Progression of asbestosis predicts lung cancer

STUDY OBJECTIVES: To explore whether the progression of asbestosis correlates with the risk of lung cancer among patients with asbestosis. DESIGN: A group of 85 asbestosis patients (78 men and 7 women) were radiographically followed up between 1979 and 1987. Two or three posteroanterior radiographs taken from each patient in 1978 to 1979, 1983 to 1984, and 1986 to 1987 were classified according to the International Labour Office 1980 classification and were used to divide the patients into progressors and nonprogressors. Follow-up for cancer was done automatically through the files of the Finnish Cancer Registry from the time of determination of the progression status to December 31, 1994. Predictors of lung cancer risk were studied with a logistic regression model, and the standardized incidence ratio (SIR) was calculated for lung cancer. RESULTS: Of the 24 male patients with progressive small opacity profusion, 11 (46%) developed lung cancer, as opposed to 5 (9%) of the 54 male patients without progression. The SIR for lung cancer was 37 (95% confidence interval, 18 to 66) for the progressors and 4.3 (1.4 to 9.9) for the nonprogressors. In both groups, all the lung cancer cases occurred among smokers or ex-smokers. None of the seven female patients showed progressive small opacity profusion. One of them developed lung cancer. In the logistic regression model including all 85 asbestosis patients, radiographic progression of small opacity profusion (p=0.0009) and current smoking (0.0021) were significant predictors of lung cancer morbidity. CONCLUSIONS: Asbestosis patients with radiographic progression of small opacity profusion over a few years are at a higher risk of lung cancer than those with a less aggressive course of the disease. The progression of pulmonary fibrosis may be an independent risk factor that, in addition to smoking history and the intensity of asbestos exposure, could be used to estimate lung cancer risk.     

Effects of an aldose reductase inhibitor, SNK-860, on the histopathological changes of retinal tissues in a streptozotocin-induced diabetic rat model

The efficacy of two protocols for the prevention of relapse using Mitomycin-C and alpha-Interferon in 56 patients with surface bladder carcinoma (stages Ta-T1) treated with TUR was compared in a prospective study. Relapse percentages and rates, related to the tumours' presentation characteristics (single, multiple, primary, recurrent), as well as their systemic and local toxicity, were evaluated. The study of statistical significance is made using the squared-chi test, and it is completed with a Fisher's test for groups containing few elements for accuracy. The results show no statistical differences (log rank p = 0.313) between the two groups of endovesical therapy, both confirming to be effective as adjuvant therapy to TUR in surface bladder tumours.