Differentiation inducing effects of vesnarinone on human glioma cells

The effects of 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-quinolinone (vesnarinone) on the growth of glioma cells were examined in vitro. Vesnarinone at a dose of 100 mug/ml suppressed the growth of four different glioma cell lines, U-251MG, U-373MG, U-87MG and A-172, by approximately 50%, with an elongation of the cytoplasmic process on day 5 of culture. The long-term culture of U-87MG with 10 mug/ml of vesnarinone was continued up to day 34. Although growth suppression was approximately 25% on day 5, it reached over 95% on day 34. An increase in the cyclic adenosine monophosphate content of glioma cells cultured with vesnarinone was observed by enzyme-linked immunosorbent assay (ELISA). The accumulation of glial fibrillary acidic protein was observed to occur with vesnarinone by ELISA. These findings suggest that vesnarinone suppressed the growth and induced differentiation of glioma cells in vitro.     

Skull metastasis of thyroid papillary carcinoma.

Skull metastasis of thyroid carcinoma is rare. The majority of skull metastases of thyroid carcinoma are of the follicular subtype, rather than thyroid papillary carcinoma. In this report, a 55-year-old woman with skull metastasis from thyroid papillary carcinoma is presented. The metastatic lesion of the skull was hypervascular and osteolytic, and the bleeding was profuse during resection. There have been only four reports of skull metastasis from thyroid papillary carcinoma. The mean period from the initial diagnosis of thyroid carcinoma until the detection of skull metastasis is 23.3 years, whereas in this patient, it was about 2 years. Therefore, in the clinical course of thyroid papillary carcinoma, skull metastasis should be considered, and the patient should be meticulously followed up.     

Immunohistochemical study of fibronectin, lysozyme, and alpha-fetoprotein (AFP) in human hepatocellular carcinoma

We have immunohistochemically localized fibronectin, lysozyme and alpha-fetoprotein (AFP) in 21 human hepatocellular carcinoma (HCC) tissues obtained by surgical resection at both light and electron microscopic levels. Three distinct distribution patterns of fibronectin (sinusoidal, periacinar, and pericellular patterns) were observed. The sinusoidal and periacinar patterns were mainly observed in HCC of pseudoglandular or trabecular patterns and of Edmondson's grade I or II, whereas the pericellular pattern was observed in HCC of compact or trabecular patterns and of Edmondson's III grade, suggesting that the pericellular fibronectin was rather associated with undifferentiated HCC. Electron microscopic observation of the pericellular fibronectin showed fibronectin to be present in the dilated intercellular spaces where microvilli were moderately developed. We observed intracytoplasmic staining of fibronectin in 2 of the 21 HCC cases. By immunoelectron microscopy, fibronectin was observed in the endoplasmic reticulum (ER) of some HCC cells. In the 21 HCC cases, lysozyme-positive cancer cells were observed in 10 cases, and AFP in 6 cases. At the ultrastructural level, lysozyme was identified in the ER and the perinuclear spaces of HCC cells, suggesting that lysozyme was synthesized by these cells. Lysozyme-positive cases tended to be more frequently observed in cases with the pericellular pattern of fibronectin rather than those with sinusoidal or periacinar patterns.     

Plasma thrombomodulin level in very low birthweight infants at birth

Objective: Plasma soluble thrombomodulin level reflects endothelial damage. The plasma thrombomodulin level at birth is increased in asphyxiated full-term infants. There is no report of plasma thrombomodulin level in premature infants. To determine the thrombomodulin level in premature infants and whether it might reflect endothelial damage, we examined the plasma thrombomodulin level in very low birthweight (VLBW) infants at birth. Methods: Forty-five VLBW infants, of whom 14 had perinatal asphyxia complications, were recruited. As a control, 50 full-term infants wimout complications were also studied. Plasma thrombomodulin concentration, pH, base deficit, serum creatinine and D-dimer concentration, platelet count and fibrinogen concentration were measured within 1 hour after birth. Results: There were significant differences in plasma pH, creatinine concentration, platelet count, antithrombin in activity and D-dimer concentration between VLBW infants and full-term infants. Plasma thrombomodulin concentration (39. 0 (16. 6–93. 7) vs 27. 0 (16. 6–39. 1) μg/L, p < 0. 0001) and plasma taombomodulin-to-serum creatinine ratio (0. 82 (0. 19–2. 65) vs 0. 47 (0. 24–0. 70) μg/μmol, p < 0. 0001) were significantly higher in VLBW infants than those in full-term infants. By univariate analyses for all neonates, there were significant relations between plasma thrombomodulin concentration and gestational age, birthweight, plasma pH, creatinine concentration, platelet count and antithrombin in activity. A stepwise multiple linear regression model using the above variables as dependent factors showed only birthweight contributed significantly to plasma thrombomodulin concentration (plasma thrombomodulin concentration (μg/1) = 45. 677–0. 006 (birthweight; g), r²= 0. 323, p < 0. 0001, n= 94). Plasma thrombomodulin concentration and plasma thrombomodulin-to -serum creatinine ratio in VLBW infants with asphyxia were higher than in those without asphyxia, but not significantly different (43. 2 ± 17. 7 vs 38. 3 ± 8. 5 μg/1 and 0. 92 ± 0. 60 vs 0. 83 ± 0. 37 μg/μmol). Conclusion: Plasma thrombomodulin level in VLBW infants shows a high value at birth, and we consider the main factor responsible for this elevation may be endothelial damage or low clearance rate of thrombomodulin, which may be related to early gestational age.     

Genetic alteration in carcinoid tumors of the lung.

Surgically resected specimens of 13 carcinoid tumors of the lung including nine typical carcinoids and four atypical carcinoids, and eight salivary gland type carcinomas (six mucoepidermoid carcinomas and two adenoid cystic carcinomas) were analyzed regarding p53 expression, loss of heterozygosity (LOH) in chromosome 3p, 9p, and K-ras mutation. The overexpression of p53 was identified in four atypical carcinoid tumors, one mucoepidermoid carcinoma, and one adenoid cystic carcinoma, however, none of typical carcinoids showed p53 immunoreactivity. LOH in 3p14 was demonstrated in three of seven informative cases in all tumors. LOH in 9p was demonstrated in two of five informative cases in all tumors. Two of three cases with LOH at 3p14 had a poor prognosis, one of which also had LOH at 9p. No mutation of the K-ras gene was observed in any of these tumors. These data thus indicate that p53 overexpression might distinguish atypical carcinoid tumors from typical tumors and might therefore be useful as an adjunct modality in the differential diagnosis of pulmonary carcinoid tumors. The presence of LOH at 3p14 or 9p may thus help to identify lung cancer patients with a poor prognosis.     

Clinical evaluation of autoantibodies to liver cell membrane specific antigen, liver specific lipoprotein, and Tamm-Horsfall glycoprotein in autoimmune chronic active hepatitis

An enzyme-linked immunosorbent assay was developed to detect circulating autoantibodies to three liver cell membrane surface antigens, i.e., liver cell membrane specific antigen (LCM), liver specific lipoprotein (LSP), and Tamm-Horsfall glycoprotein (THGP). In autoimmune chronic active hepatitis (autoimmune CAH), the positive rate and mean titer (normal range, less than 5.5 units) for anti-LCM were 100% and 13.5 units before corticosteroid treatment and 100% and 9.9 units during the treatment. The corresponding values for anti-LSP were 84% and 11.8 units, and 81% and 8.9 units, and those for anti-THGP were 84% and 12.3 units, and 81% and 7.9 units. In an autoimmune CAH patient, elevation of the plasma levels of autoantibodies during the treatment apparently preceded the elevation of alanine aminotransferase (ALT). However, the ALT elevation induced by transcatheter arterial embolization was not associated with the elevation of these autoantibodies in an autoimmune CAH patient with hepatocellular carcinoma. In primary biliary cirrhosis, drug-induced hepatitis, and non-hepatic immunological disorders, the production of the three autoantibodies did not directly correlate with liver cell damage. These findings suggest that the elevation of autoantibodies against LCM, LSP, and THGP can be a useful guide for the prednisolone treatment of autoimmune CAH.     

Inhibition of HIV-1 infectivity with curdlan sulfate in vitro

Polymethoxylated flavones and C-glycosyl derivatives isolated from medicinal plants besides other flavonoid compounds were studied for their influence on lipid peroxidation induced by FeSO4+ cysteine in rat liver microsomes. A number of hydroxyflavones (e.g. luteolin); C-glycosyl-flavones (e.g. orientin); methoxyflavones (e.g. gardenin D) and flavonols (e.g. datiscetin), as well as the flavanol leucocyanidol and the biflavone amentoflavone behaved as inhibitors of non-enzymic lipid peroxidation. Structure-activity relationships were established and it was observed that the structural features for active polyhydroxylated compounds were different from those of polymethoxylated flavones, antiperoxidative flavonoids possessing a high lipophilicity.