We present morphological data of the early stage of tumor invasion in the central nervous system. C6 rat glioma cells were injected into the caudate-putamen of rat brain using glass micropipettes to minimize traumatic reactions. Four days after the inoculation, we examined the tumor-brain interface using light and electron microscopy. Ultrastructurally the tumor processes were attached to the perivascular basement membrane instead of the astroglial end-feet. At the tumor periphery, the vessel walls were in contact with both tumor processes and astroglial end-feet. Astrocytes withdrew their processes from the vascular walls and changed into a reactive phenotype, while the neuronal cells remained virtually intact, even when surrounded by tumor cells. Immunohistochemical study using C6 cells labeled with bromodeoxyuridine showed migration of the cells toward the perivascular space that was distant from the site of injection. These observations represent the earliest morphologically detectable changes of the tumor-brain interface, and suggest that the C6 cells possess the characteristics of high affinity to the endothelial basement membrane and invade along the preexisting blood vessels with brain parenchymal infiltration.
The mechanism of glial proliferation in the developing nervous system, as well as in response to injury, inflammation, and tumor invasion, is unknown. Several growth factors and extracellular matrices have been shown to stimulate the proliferation of cultured cells of various origin, including astrocytes. We investigated the effect of extracellular matrix components, including fibronectin (FN), laminin (LN), and collagen types I and IV, on the growth of astrocytes during stimulation by various growth factors. When astrocytes were grown on FN- and LN-coated wells in a serum-free, chemically defined medium, their increase in number significantly exceeded that of cells grown on plastic wells. The addition of platelet-derived or basic fibroblast growth factor to cells cultured on FN- or LN-coated wells significantly potentiated astrocyte proliferation. The collagen preparations had no such effect. These observations indicate that FN and LN have a fundamental part in converting the quiescent astrocyte into the proliferating phenotype, which may be required for remodelling damaged brain tissues in vivo.
Two cases of intracerebral hemorrhage in patients with prosthetic heart valves receiving anticoagulant therapy without preceding embolic cerebral infarction are reported. Phytonadione and fresh frozen plasma were immediately given, and the intracerebral hematoma evacuated successfully. In one case, intractable bleeding occurred perioperatively until the thrombotest value reached 40% or more. This patient later developed fatal massive multiple intracerebral hemorrhages.
Sick leave due to mental disorders is a societal problem. It carries a high cost in terms of loss of labor productivity and absenteeism. Partial remission increases the risk of relapse after a return to work. There is sometimes a difference between the ability to return to work as judged by a general practitioner (GP) and the needs of the workplace. GPs are the main controllers of treatment and tend to protect their patients. Communication and agreement by GPs and occupational physicians play an effective role in the return to work. However, it requires considerable effort for both of them to make time to do this. We have developed a concise set of files for a smooth return to work. The files consist of three parts: “Suggestions for corresponding with employees taking sick leave”; “Checklist for smooth return to work”; and “Pattern of living”. We put them into practice among 20 companies in Japan from January 2012 to October 2013. The companies had 8244 workers in total and 116 workers were on sick-leave due to mental disorders. Our set of files contributed to sharing the written basic policy of return to work among employees on sick leave with mental disorders, GPs, occupational physicians and personnel officers. That sharing led to facilitating a smooth return to work. Although there are differences in the legal and medical systems between Japan and other countries, our concept of sharing the written basic policy may give some help to occupational physicians in other parts of the world as well.
Extracellular matrix (ECM) constituents likely play an important role in cell proliferation and the invasion of malignant human gliomas. We examined the formation of stress fibers and the growth of the human glioblastoma cell lines A172 and T98G cultured on collagen types I, IV, and V, laminin (LN), and fibronectin (FN). A172 cells cultured on LN and FN formed complete F-actin filaments after 24 h of culture and grew logarithmically after 48 h. In contrast, T98G cells on LN and FN reorganized only short F-actin filaments after 24 h of culture and grew rapidly after 72 h. However, on the collagen preparations, neither cell line formed definite stress fibers and both showed lower rates of cellular proliferation. Significantly positive correlation was observed between the relative intensity of F-actin filaments and the cell proliferation. The results indicate that the ability of ECM components to modulate the growth and differentiation of malignant glioma cells may be mediated, in part, by the assembly and disassembly of F-actin filaments.
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