Tumor necrosis factor receptor type 1 (TNFR1) and c-Myc are important in signal transduction in tumor necrosis factor-a (TNF-a)-induced cytotoxicity, whereas activation of nuclear factor-kB (NF-kB) protects against TNF-a-induced apoptosis. This study investigated the expression of NF-kB, TNFR1, and c-Myc in human astrocytoma tissues by reverse transcriptase-polymerase chain reaction (PCR) and immunohistochemical analysis. TNFR1 messenger ribonucleic acid (mRNA) and c-Myc mRNA were frequently expressed in malignant astrocytomas, especially in glioblastomas, compared with low-grade astrocytomas by PCR analysis. TNFR1 and c-Myc mRNAs were barely detectable in normal brain tissues. NF-kB p50 and p65 subunit mRNAs were detected in various grades of astrocytomas, with frequent expression in malignant astrocytomas. The presence of activated NF-kB was confirmed by nuclear localization in neoplastic astrocytes as determined by immunohistochemistry. Both p50 and p65 subunits were inhomogeneously expressed in neoplastic astrocytes of glioblastoma, but only in a few scattered tumor cells in low-grade astrocytoma, and almost undetectable in normal brain tissues. These results indicate that TNFR1 and c-Myc are overexpressed in malignant astrocytomas, and this may increase the cellular sensitivity to the cytotoxic action of TNF-a. NF-kB p50 and p65 were simultaneously induced and activated in malignant astrocytomas. Our results suggest that the constitutive activation of NF-kB subunits in malignant astrocytoma, especially in glioblastoma, could be associated with the resistance to TNF-a immunotherapy, and indicates new therapeutic strategies for malignant astrocytomas.
We report seven patients with scalp arteriovenous malformations, including two patients with lesions > 10 cm in diameter, who were successfully treated. The principal complaint of each patient was a deforming mass. Each of four patients had a history of blunt traumatic injury. The lesions, each consisting of the nidus, feeders, and draining veins, evolved in all patients. The nidus consisted of fistulae, which exhibited various angioarchitectures as revealed by angiography. A hemangiomatous component was histologically recognized in one patient. In five patients, in whom the lesions were relatively small and whose nidi included only large fistulae, the malformations were remedied by surgical intervention alone or were cured with embolization alone using liquid adhesives. In the two patients with lesions > 10 cm, the nidi consisted of numerous large fistulae and plexiform fistulae in one patient and plexiform fistulae and a hemangiomatous component in the other patient. These patients were treated with a combination of transarterial embolization and surgical intervention. Preoperative embolization greatly reduced blood loss during resection. Total excision and scalp reconstruction using a soft tissue expander were performed in both patients. The cosmetic results were excellent in all of the patients, and no recurrence has been recognized during the follow-up period, which ranges from 31 to 99 months. The treatment of scalp arteriovenous malformations should strive to improve deforming features and to attain a permanent cure. Because each nidus includes a variety of anomalous angioarchitectural features, there should be different means and a combination of treatments for each patient. Embolization alone could be adequate treatment in relatively small lesions, the nidi of which consist only of several large fistulae. For malformations with more extensive, large fistulae or with anomalous components other than large fistulae, a combined endovascular and surgical approach and scalp reconstruction seems to be the best treatment.
To determine whether capsaicin-sensitive sensory nerves are involved in the swallowing reflex, we examined swallowing reflex in terms of the number of swallows elicited by injections of three different volumes (0.2, 0.4, and 0.6 ml) of distilled water, into the pharynx through a catheter in anesthetized guinea pigs pretreated with and without systemic capsaicin. The number of swallows was counted by submental electromyographic activity and visual observation of characteristic laryngeal movement. Injections of distilled water caused a volume-dependent increase in the number of swallows in animals treated with and without capsaicin. Capsaicin treatment significantly decreased the number of swallows elicited by all volumes of distilled water (p < 0.01). Exogenously administered substance P (SP) caused a dose-dependent increase in the number of swallows in all volumes but calcitonin gene-related peptide and acetylcholine were without effect. FK 888 (10(-5) M; 1 ml), a specific inhibitor of NK1 receptor, reduced the number of swallows elicited by distilled water to a similar degree as capsaicin treatment. Pharyngeal application of lidocaine (4%; 1 ml) also inhibited distilled water-induced swallowing. These results suggest that nonmyelinated C-fibers regulate the swallowing reflex through the release of SP in response to stimulation.
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