Brain microglia are a major source of inflammatory cytokines, such as tumor necrosis factor-␣ (TNF-␣), which have been implicated in the progression of neurodegenerative diseases. Recently, microglia were revealed to be highly responsive to ATP, which is released from nerve terminals, activated immune cells, or damaged cells. It is not clear, however, whether released ATP can regulate TNF-␣ secretion from microglia. Here we demonstrate that ATP potently stimulates TNF-␣ release, resulting from TNF-␣ mRNA expression in rat cultured brain microglia. The TNF-␣ release was maximally elicited by 1 mM ATP and also induced by a P2X 7 receptorselective agonist, 2Ј-and 3Ј-O-(4-benzoylbenzoyl)adenosine 5Ј-triphosphate, suggesting the involvement of P2X 7 receptor. ATP-induced TNF-␣ release was Ca 2ϩ -dependent, and a sustained Ca 2ϩ influx correlated with the TNF-␣ release in ATP-stimulated microglia. ATP-induced TNF-␣ release was inhibited by PD 098059, an inhibitor of extracellular signal-regulated protein kinase (ERK) kinase 1 (MEK1), which activates ERK, and also by SB 203580, an inhibitor of p38 mitogen-activated protein kinase. ATP rapidly activated both ERK and p38 even in the absence of extracellular Ca 2ϩ . These results indicate that extracellular ATP triggers TNF-␣ release in rat microglia via a P2 receptor, likely to be the P2X 7 subtype, by a mechanism that is dependent on both the sustained Ca 2ϩ influx and ERK/p38 cascade, regulated independently of Ca 2ϩ influx. Key Words: Microglia-Tumor necrosis factor-␣-ATP-P2X 7 receptor-Ca 2ϩ -Mitogenactivated protein kinase. J. Neurochem. 75, 965-972 (2000).

Hepatic vein (HV) thrombosis causes ascites, hepatomegaly, and severe congestion of the liver (Budd‐Chiari syndrome [BCS]). Severe hepatic fibrosis develops in this syndrome with a variety of histological patterns. Some livers have a pattern of cirrhosis in which there is fibrous bridging between HVs and portal tracts (veno‐portal cirrhosis). Other livers have a pattern of “reversed‐lobulation cirrhosis” (veno‐centric cirrhosis), in which fibrous bridging between HVs and portal tracts is minimal. The prevalence and pathogenesis of these forms of cirrhosis and the effect of portal vein (PV) thrombosis in this disease have not been studied. We examined 15 resected livers from patients with BCS to determine the distribution of vascular obstruction and the character of the parenchymal response. Six livers had veno‐portal cirrhosis, and all of these had severe PV obliteration caused by thrombosis. Three livers had veno‐centric cirrhosis and had normal medium and large PVs. The remaining six livers had mixed veno‐centric/veno‐portal cirrhosis and had moderate PV obliteration. The nodules in veno‐centric cirrhosis had evidence of an unusual circulation with small arteries supplying a midzonal venous plexus that appeared to drain retrogradely into patent small PVs. Nine livers had large regenerative nodules histologically similar to focal nodular hyperplasia. PV thrombosis is a frequent occurrence in BCS. The correlation between PV thrombosis and the pattern of cirrhosis suggests a role for PV obliteration in the genesis of veno‐portal bridging fibrosis in this disease and possibly in other diseases leading to cirrhosis.

The CMU RSTA Project has been developing a video-rate stereo machine that has the capability of generating a dense depth map at the video rate. The performance bench marks of the CMU video-rate stereo machine are: 1) multi image input of up to 6 cameras; 2) throughput of 30 million point × disparity range per second; 3) frame rate of 30 frame/ sec; 4) a dense depth map of up to 256 × 240 pixels; 5) disparity search range of up to 60 pixels; 6) high precision of depth output up to 8 bits (with interpolation). The capability of passively producing such a dense depth map (3D representation) of a scene at the video rate can open up a new class of applications of 3D vision: merging real and virtual worlds in real time.

We clinicopathologically studied 23 surgically resected cases of combined hepatocellular and cholangiocarcinoma (HCC-CC). The frequency of this cancer in our subjects, who had primary liver cancer and who underwent hepatectomy, was 6.3%. The mean age of patients was 64.0 years old and the male: female ratio was 1.9:1. Serum alpha-fetoprotein was positive in 70% of cases and its levels were relatively low (< or = 1000 ng/mL) in most cases. The positive rate of serum carcinoembryonic antigen was 18% and its levels were also low. In regard to hepatitis virus markers, 17% of the 20 combined HCC-CC cases were positive to HBs antigen and 70% were positive to the HCV antibody. Of the 23 combined HCC-CC cases, 9 cases (39%) were associated with liver cirrhosis. Tumours were classified macroscopically into a separated type (HCC and CC are clearly separated 17%), a HCC-predominant type (resembles HCC 49%), and a CC-predominant type (resembles CC 34%). The separated and HCC-predominant types were associated with liver cirrhosis in 50 and 55% of cases, respectively. These cases with liver cirrhosis presented the features of HCC more apparently, while those without liver cirrhosis presented the features of CC. Histologically, all cases were classified into either Type I (HCC and CC were clearly distinguished; 17%), Type II (HCC and CC were contiguous and shared transitional features; 66%), and Type III (cancer cells were able to be evaluated as either HCC or CC and were considered to be an intermediate type; 17%). Immunohistological stains for cytokeratin were useful to distinguish HCC and CC. Specifically, CC was positive to cytokeratin 7 and 19. The tumour, in which HCC and CC were almost indistinguishable, such as Type III), indicates the presence of intermediate tumour cells that can differentiate either to HCC or CC.