Incidental prostatic carcinoma: Morphometry correlated with histological grade

Summary The histological grades of prostatic carcinoma, as defined by Gleason, were correlated with three methods of morphometry in 254 step-sectioned prostates obtained at autopsy. The variables studied were 1) the number of tumours in each prostate; 2) bilaterality and 3) tumour volume. Each characteristic yielded a statistically significant correlation with histological grade. The strongest correlations were obtained using tumour volume. These autopsy studied help to explain the inconsistent results obtained from morphometric analyses of surgical material, and lend support to the Gleason system as a means of predicting tumour behavior.Supported in part by research contracts PH 64-10, NCI-72-3213, N01-CP-53521; Grant R01-CA-33644; and the Grant-in-Aid for Cancer Research (33) from the Ministry of Health and Welfare     

Allergen-induced biphasic bronchoconstriction in rats

The development of an allergic bronchoconstriction model in rats is described. In actively sensitized Donryu strain rats, there was a remarkable biphasic increase in airway resistance within 10 min after antigen challenge on day 9 to day 21. The increase in airway resistance, correlated with the IgE titer and the dose of antigen, was inhibited by disodium cromoglycate (DSCG) or by aminophylline. This bronchoconstriction was remarkably blocked by methysergide (25 and 100 micrograms/kg) while pyrilamine inhibited it partially at the same dose. Serotonin (greater than 30 micrograms/kg) but not histamine (less than 1,000 micrograms/kg) induced a bronchoconstriction. FPL-55712 (1,10 mg/kg) inhibited it significantly. The content of thromboxane B2 (TxB2) in plasma increased during the bronchoconstriction while the content of peptide-leukotrienes (p-LTs) in plasma did not increase significantly. OKY-046 inhibited not only allergic bronchoconstriction but also the increase in TxB2 levels in plasma. The late phase of the bronchoconstriction was more susceptible to OKY-046. In conclusion, this model seems to be useful for the screening of antiasthma drugs because of a relationship with the dose of antigen, IgE titer and the susceptibility to an antiallergic drug or a bronchodilator. It is demonstrated that the major part of this allergic bronchoconstriction depends on serotonin, and it is also suggested that thromboxane A2 may play an important role in the late phase of the bronchoconstriction.     

Social isolation stress augments angiogenesis induced by colon 26-L5 carcinoma cells in mice

We have previously shown that tumor necrosis factor-α (TNF-α), which is an important angiogenesis-related factor, was over-secreted in male BALB/c mice under social isolation stress as compared with the control, and closely associated with a remarkable elevation of tumor invasion and metastasis of colon 26-L5 carcinoma cells. In the present study, we explored the effect of isolation stress on the angiogenesis caused by colon 26-L5 carcinoma cells in vivo and in vitro. Social isolation lead to the enhancement of tumor growth after intrahepatic implantation with a fragment of colon 26-L5 tumor. Angiogenic response (number of vessels oriented towards tumor mass) and tumor growth (size) were significantly increased in the socially isolated mouse relative to that in the group-housed mice. Furthermore, higher protein level of hepatic TNF-α was found in the stressed mice than that in the control. Expression of mRNA for vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) were also elevated in the tumor regions and liver tissues of the stressed mice in comparison with that in group-housed mice. On the other hand, hepatic sinusoidal endothelial (HSE) cells treated with TNF-α exhibited a marked promotion of the migration, invasion, expression of mRNA for matrix metalloproteinase (MMP)-9, and tube-like formation, but no cytotoxicity against the cells in vitro. The above data suggest that the social isolation stress augmented the tumor-induced angiogenesis probably by up-regulating the angiogenesis-related factors, including TNF-α, VEGF and HGF, and consequently mediating the functions of endothelial cells such as migration, invasion, and tube-like formation.     

Role of tight junctions of polarized epithelial MDCK cells in the replication of herpes simplex virus type 1

Before completion of polarization, Madin-Darby canine kidney (MDCK) cells showed high infectivity and progeny production of herpes simplex virus type 1 infection. After polarization or formation of tight junctions, the infectivity and virus replication in MDCK cells was restricted significantly. The disruption of tight junctions by depletion of Ca²⁺ resulted in increasing virus infectivity and productivity. Mechanical disruption of tight junctions by scratching the cell monolayers with injection needle allowed markedly the replication of HSV-I in the cells aligned along the injured area. In polarized MDCK cells the progeny were released preferentially from the apical surface of the cells. These data suggest that because polarized MDCK cells mimic the epithelial cell layers, this cell line is helpful for determining the factors which regulate viral transmission in the human body. © Wiley-Liss, Inc.     

Anaplastic carcinoma of the thyroid gland. An ultrastructural study on four cases.

Four cases of anaplastic carcinoma of the thyroid, composed of one small cell carcinoma and three giant cell carcinomas, were studied with electron microscope. In the case of small cell carcinoma, fine cytoplasmic interdigitations and junctional complex between apposing cytoplasmic membranes of neighbouring tumor cells and a few microlumina within tumor cell clusters surrounded by well-defined basal lamina were seen. In the cases of giant cell carcinoma, occasional cytoplasmic interdigitations as well as desmosomal structures were detected even in tumor cells markedly pleomorphic and anaplastic. Abundant cytoplasmic organelles including profiles of Golgi apparatus, rough endoplasmic reticulum and a few mitochondria were seen in the cytoplasm of tumor cell of all four cases. Of interest to note was that all giant cell carcinomas demonstrated evidences of fairly well differentiated tumor within anaplastic carcinoma, indicating probable pre-existing either benign or malignant epithelial neoplasm more differentiated, with its subsequent anaplastic transformation. Findings in the present study support an assumption that these anaplastic tumors are derived from the follicular epithelium of the thyroid gland. In addition, it can be said that tumor cells of the small cell carcinoma provide evidences suggesting functional differentiation of carcinoma cells to a certain extent, yet unable to produce thyroglobulin.     

Cross-linking of Fc(gamma)-receptor on monocytes inhibits hepatitis C virus-specific cytotoxic T-lymphocyte induction in vitro.

In hepatitis C virus (HCV) infection, immune complex (IC)-type virus particles are frequently observed in circulation. The IC leads to cross-linking of Fcgamma receptors (FcgammaR) on monocytes and exerts immunoinhibitory function. To test the roles of IC in HCV-specific cytotoxic T lymphocyte (CTL) induction, we generated HCV CTL from peripheral blood mononuclear cells of chronic hepatitis C patients with or without HCV-IC- or immunoglobulin G (IgG)-coated culture plates and compared their lytic activities. HCV-IC or adherent IgG, which induces FcgammaR cross-linking, significantly reduced CTL activity. Expression of B7-1 on monocytes decreased on adherent IgG. In addition, tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) production increased from cells on adherent IgG and their mRNA expression in monocytes was enhanced. Anti-TNF-alpha antibody during induction on adherent IgG inhibited lysis; however, anti-TGF-beta completely reversed its inhibitory effect. These results demonstrated that HCV-IC or adherent IgG impaired HCV-CTL induction in vitro. The FcgammaR-mediated CTL suppression occurred via decreased expression of monocyte B7-1 and/or enhanced production of TGF-beta1.