Endotoxin preconditioning protects against the cytotoxic effects of TNFalpha after stroke: a novel role for TNFalpha in LPS-ischemic tolerance.

Lipopolysaccharide (LPS) preconditioning provides neuroprotection against subsequent cerebral ischemic injury. Tumor necrosis factor-alpha (TNFalpha) is protective in LPS-induced preconditioning yet exacerbates neuronal injury in ischemia. Here, we define dual roles of TNFalpha in LPS-induced ischemic tolerance in a murine model of stroke and in primary neuronal cultures in vitro, and show that the cytotoxic effects of TNFalpha are attenuated by LPS preconditioning. We show that LPS preconditioning significantly increases circulating levels of TNFalpha before middle cerebral artery occlusion in mice and show that TNFalpha is required to establish subsequent neuroprotection against ischemia, as mice lacking TNFalpha are not protected from ischemic injury by LPS preconditioning. After stroke, LPS preconditioned mice have a significant reduction in the levels of TNFalpha (approximately threefold) and the proximal TNFalpha signaling molecules, neuronal TNF-receptor 1 (TNFR1), and TNFR-associated death domain (TRADD). Soluble TNFR1 (s-TNFR1) levels were significantly increased after stroke in LPS-preconditioned mice (approximately 2.5-fold), which may neutralize the effect of TNFalpha and reduce TNFalpha-mediated injury in ischemia. Importantly, LPS-preconditioned mice show marked resistance to brain injury caused by intracerebral administration of exogenous TNFalpha after stroke. We establish an in vitro model of LPS preconditioning in primary cortical neuronal cultures and show that LPS preconditioning causes significant protection against injurious TNFalpha in the setting of ischemia. Our studies suggest that TNFalpha is a twin-edged sword in the setting of stroke: TNFalpha upregulation is needed to establish LPS-induced tolerance before ischemia, whereas suppression of TNFalpha signaling during ischemia confers neuroprotection after LPS preconditioning.     

A case of surgical excision of intracerebral cavernous angioma in a patient with thrombasthenia

A case of thrombasthenia (Glanzmann) associated with an intracerebral cavernous angioma in a 32-year-old woman is reported. Since her childhood, the patient had experienced a tendency to develop purpura following minor trauma. But she had not had major bleeding even during pregnancy and delivery. On April 4, 1987, she presented generalized convulsion. A high density mass in the right temporal lobe was demonstrated with CT scan. Carotid angiogram was normal except that the right anterior choroidal artery was stretched. Inhomogeneous signal intensities in T1- and T2-weighted MRI images were seen in the tumor locus. The clinical diagnosis was cavernous angioma which was complicated with intracerebral hemorrhage. The patient had a disorder of platelet function without thrombocytopenia. Her bleeding time was markedly prolonged. Because of this, we did not try surgical excision at first. During the 13-month observation period, however, intracerebral bleeding occurred 5 times. We decided to operate on the patient using fresh blood and platelet transfusion. The postoperative course was uneventful and pathological diagnosis confirmed cavernous angioma. We would like to emphasize possible pitfalls in treating cases of intracerebral angioma with thrombasthenia.     

Chromosomal Mapping of Genetic Locus Associated with Thymus-size Enlargement in BUF/Mna Rats

The thymoma-prone rat of the BUF/Mna strain is a useful model for human thymoma. In this strain thymoma development is regulated by a single autosomal susceptible gene, Tsr-1. At pre-thymoma age, BUF/Mna rats have extremely large thyrauses, when compared to those of other strains of rats. Genetic studies in crosses between BUF/Mna rats with large thymuses and WKY/NCrj rats with small thymuses suggested the presence of a major autosomal gene, Ten-1 , which contributes to thymus enlargement in a backcross population. Linkage studies between Ten-1 and microsatellite markers in backcross rats of (WKY/NCrj×BUF/Mna)Fl×BUF/Mna have led to the localization of Ten-1 in chromosome 1. This result may provide an approach to clone Tsr-1 , which could be allelic to Ten-1.     

The Sistrunk median cervical cyst operation using a cecal foramen pointer

The cecal foramen pointer was invented for a Sistrunk median cervical cyst operation. The instrument consists of three elements, namely: The cecal foramen holder, the giraffe shaped connector and the pointer needle. First of all, the cecal foramen is held by the holder which is reconstructed from hemostatic forceps. The one end of the connector is joined to the holder's handle. Then the other end of the connector comes along the patient's chin, in front of the neck. The cyst and mid-portion of the hyoid bone are dissected, followed by coring out of the thyroglossal duct toward the cecal foramen. In the coring out process, the pointer needle is pierced through the tunnel of the connector's opposite end, so that the needle top reaches to the bottom of operative wound. Then the needle shows exactly the direction to the cecal foramen and the distance from the bottom of the wound to the cecal foramen. By using this instrument the operation was successfully performed for a case of a recurrent median cervical cyst with a complete fistula to the cecal foramen.     

Chemo-endocrine therapy in patients with stage D2 prostate cancer

There have only been a few studies of chemo-endocrine therapy compared with endocrine therapy alone in newly diagnosed prostate cancer patients. We assessed the effects of these two therapies by comparing long-term survival rates. One hundred and twenty-nine patients were entered in this study between November 1977 and March 1992. Seventy-seven patients were treated with endocrine therapy alone. Other 52 patients received chemo-endocrine therapy, which included orchiectomy and/or diethylstilbestrol diphosphate (DES-DP) plus Cisplatin, with or without other cytotoxic agents. All patients had bone metastasis at the beginning of the study. There was a significant difference in survival between patients who received endocrine therapy and chemo-endocrine therapy (P = 0.0078). That is, survival rate was superior for the chemoendocrine therapy patients throughout the entire follow-up period. These data suggest that early chemo-endocrine therapy containing Cisplatin, with or without maintenance chemotherapy, is a potentially effective treatment for newly diagnosed metastatic prostate cancer and is worth further investigation via a randomized trial.     

Regeneration of periodontal ligament and cementum by BMP-applied tissue engineering

Previously, we demonstrated that the inductive properties of bone morphogenetic protein (BMP) highly depend on the nature of the carrier material used for implantation. In this paper, we show that administration of BMP incorporated in a fibrous collagen membrane can help to regenerate periodontal ligament and cementum both in cat canines and in monkey molars. The partially purified bovine BMP was combined with one or two layers of a fibrous collagen membrane. Although the single layer approach showed partial regeneration of periodontal defects, it also quite often led to ankylosis. The double layer technique in artificially prepared class III furcation defects in monkey molars gave favorable results. After 12 wk, not only the alveolar process but also the periodontal ligament and cementum had regenerated along the entire treated dentin surface. Collagen fibers were arranged more or less perpendicular to the surface of the new cementum. Ankylosis was not seen. It is concluded that the double-layer approach is superior to the single-layer technique in regenerating cementum.     

Comparison of computed tomographic scanning and magnetic resonance imaging in the diagnosis of trigeminal schwannoma. Report of four cases

Four cases of trigeminal schwannoma with different clinical presentations are reported. Two patients had root-type tumors and two ganglion-type tumors. Computed tomography demonstrated the mass in each case, but extension of the tumor into Meckel's cave, displaced but uninvolved seventh and eighth cranial nerves, extension of the tumor into the orbit or into the infratemporal fossa, and other anatomical details were far more clearly shown by magnetic resonance imaging, which provided confirmation of the mass lesions in the base of the brain and within the posterior fossa.