Effects of Interleukin-12 on the Induction of Cytotoxic T Lymphocytes from the Regional Lymph Node Lymphocytes of Patients with Lung Adenocarcinoma

Lung cancer-specific cytotoxic T lymphocytes (CTL) were induced by repeated stimulations of regional lymph node lymphocytes (RLNL) in lung cancer patients with either autologous or HLA-A-locus-matched tumor cells. To investigate the effect of interleukin-12 (IL-12), IL-12 was added during the stimulation of RLNL from HLA A24 / adenocarcinoma patients with either autologous tumor cells or HLA A24-positive adenocarcinoma cells (PC-9) in combination with, or instead of interleukin-2 (IL-2), and then the cytotoxic activity, cytokine production and populations of the lymphocyte subsets were examined. The addition of IL-12, or the substitution of IL-2 by IL-12 was found to enhance the cytotoxic activity and the cytokine production (IFN-γ, GM-CSF) of the CTL as compared with IL-2 alone. The cytotoxic activity and cytokine production were both partially inhibited by anti-MHC-class I monoclonal antibody. The CTL thus induced by IL-12 had a higher proportion of CD3⁺/CD56⁺ cells than the CTL induced with IL-2 alone. The positively selected CD8⁺/CD56^– lymphocytes showed PC-9-specific cytotoxic activity, because the population did not show any cytotoxicity to K562 or A549 (HLA-A26/A30). However, the CD3⁺/CD56⁺ lymphocytes were cytotoxic to both PC-9 and K562. In conclusion, IL-12 is considered to be a useful cytokine for both the induction of lung-cancer specific CTL and the augmentation of non-MHC-restricted cytotoxicity against tumor cells, and may be applicable for adoptive immunotherapy using CTL.     

Therapeutic Potential of Monteplase in Acute Myocardial Infarction

Thrombolysis with conventional thrombolytic agents prior to percutaneous coronary intervention (PCI) has had no impact on the treatment of acute myocardial infarction (AMI). However, the development of mutant tissue type plasminogen activators (mt-PA) has prompted us to reassess the combination of thrombolysis and PCI. Monteplase is a newly developed mt-PA that can be administered as a single intravenous bolus injection. The results of the COMA (COmbining Monteplase with Angioplasty) trial, suggest that monteplase administration prior to emergent PCI in AMI improves 6-month outcomes and possibly the long-term prognosis of myocardial infarction. Combining monteplase administration on presentation at a community hospital with prompt transfer to a tertiary center for PCI would be an ideal strategy for the treatment of AMI.     

Localization of l-afadin at puncta adhaerentia-like junctions between the mossy fiber terminals and the dendritic trunks of pyramidal cells in the adult mouse hippocampus

We have recently found a novel cell-cell adhesion system at cadherin-based adherens junctions. This system consists of at least two components: nectin, an immunoglobulin-like cell adhesion molecule with Ca(2+)-independent homophilic binding activity, and l-afadin, an actin filament-binding protein that connects nectin to the actin cytoskeleton. In the present study, we investigated immunocytochemically the localization of l-afadin in the mouse hippocampus. At the light microscopic level, l-afadin immunoreactivity was demonstrated as flattened disks in the stratum lucidum of the CA3 area. By immunoelectron microscopy, signals for l-afadin were highly concentrated in a symmetrical manner at the puncta adhaerentia-like junctions between the mossy fiber terminals and the dendritic trunks of pyramidal cells. We furthermore immunostained the hippocampus with antibodies recognizing both l-afadin and s-afadin, a small splicing variant of l-afadin that is identical to AF-6. Immunoreactivity for l- and s-afadins was demonstrated not only as the flattened disks similar to that for l-afadin, but also as numerous fine dots widely distributed in all synaptic layers of the CA1 and CA3 areas. The latter finding may correspond with the recent report by Buchert et al. (1999, J. Cell. Biol. 144:361-371), who found that s-afadin (AF-6) and/or l-afadin was localized at the postsynaptic membranes of asymmetric synaptic junctions. Our present results indicate that l- and s-afadins are differentially distributed in the hippocampus and suggest that l-afadin localized at the puncta adhaerentia-like junctions in the mossy fiber terminals may regulate the structural and functional organization of these complex synaptic structures.     

Possible origin of suprasellar arachnoid cysts: neuroimaging and neurosurgical observations in nine cases

OBJECT: In this study the authors identify and investigate two new classifications of suprasellar arachnoid cysts. METHODS: The authors used computerized tomography cisternography, magnetic resonance (MR) imaging, and neuroendoscopy to investigate nine cases of suprasellar arachnoid cysts. A communicating cyst with early filling and early clearance of a radioopaque tracer was found in seven of nine cases; a communicating cyst with delayed filling and delayed clearance of the tracer was observed in one case; and a noncommunicating cyst was observed in the other. The MR findings indicated a variation in the position of the basilar artery (BA) bifurcation in relation to the ventral surface of the midbrain. A distance existed between the BA bifurcation and the ventral surface of the midbrain in a communicating cyst with early filling, whereas the BA bifurcation was posteriorly displaced in a communicating cyst with delayed filling and also in a noncommunicating cyst, leaving little space between the bifurcation and the ventral surface of the midbrain. Endoscopic observation revealed, in the case of communicating cysts with early filling and early clearance of tracer, that the BA bifurcation is located inside the cyst with no overlying membrane, whereas in a noncommunicating cyst, the BA and its branches can be observed through the transparent membrane of the lesion. CONCLUSIONS: The authors postulate two different types of suprasellar arachnoid cysts: a noncommunicating intraarachnoid cyst of the diencephalic membrane of Liliequist and a communicating cyst that is a cystic dilation of the interpeduncular cistern.     

Effect of ATP-potassium channel opener nicorandil on long-term cardiac preservation

BACKGROUND: ATP-sensitive potassium channels have been shown to be one of the important protective mechanisms for the ischemic myocardium. The purpose of this study was to evaluate the protective effect of nicorandil, an ATP-sensitive potassium channel opener, on myocardium during 6 hours hypothermic preservation. METHODS: Preserved rat hearts were randomly divided into 4 groups according to cardioplegia and preservation protocols as follows: (1) histidine-tryptophan-ketoglutarate solution (HTK) for both cardioplegic and immersing solutions (group A); (2) nicorandil-added HTK for cardioplegic solution and nicorandil-free HTK for immersing solution (group B); (3) nicorandil-free HTK for cardioplegic solution and nicorandil-added HTK for immersing solution (group C); and (4) nicorandil-added HTK for both cardioplegic and immersing solutions (group D). RESULTS: The recovery of postischemic cardiac function, including left ventricular developed pressure and end-diastolic pressure, was significantly improved in group B and group C as compared with the other groups (p<0.05). Postischemic intracellular calcium concentration was significantly lower in group B and group C than in group A (p<0.05). CONCLUSIONS: We concluded that nicorandil-induced hyperpolarizing arrest could reduce ischemia-derived myocyte injury and inhibit the influx of calcium into the myocytes in long-term cardiac preservation.     

Pleural retraction and intra-tumoral air-bronchogram as prognostic factors for stage I pulmonary adenocarcinoma following complete resection

BACKGROUND AND OBJECTIVES: We have retrospectively analyzed the postoperative prognostic factors for 116 patients with stage I adenocarcinoma, with special reference to pleural retraction and intra-tumoral air-bronchogram imaged by computed tomography, which may represent the biological features of pulmonary adenocarcinoma for the retraction of surrounding tissues due to central necrosis and air space-lining growth, respectively. METHODS: The subgroups divided according to the presence of pleural retraction and/or intra-tumoral air-bronchogram on pre-operative CT were compared with respect to the postoperative disease-free survival (DFS) and other clinico-pathological factors. RESULTS: The rates of DFS at 5 years associated with 61 patients with pleural retraction and with 55 patients without pleural retraction were 64.4% and 91.3%, respectively (P = 0.0052), and those associated with 83 patients with air-bronchogram-positive tumors and with 33 patients with air-bronchogram-negative tumors were 81.8% and 64.8%, respectively (P = 0.0040). The DFS at 5 years associated with T1 (73 patients) and T2 (43 patients) were 83.6% and 64.3%, respectively (P = 0.0153). The Cox proportional hazards model analysis revealed that the presence of pleural retraction and the absence of air-bronchogram were independent factors for poor prognosis with relative risks of 7.8 and 5.1, respectively. Pathological T factor was also a significant prognostic factor with a relative risk of 3.2. Seventeen patients with pleural retraction-positive and air-bronchogram-negative tumors showed the high recurrence rate of 47.5% and a poor prognosis with DFS at 5 years of 35.1%. CONCLUSION: These results suggested that, in stage I adenocarcinoma, the degree of malignant potential may be well figured by radiological imaging, with a significant affect on susceptibility of recurrence following complete resection.     

Role of Moraxella catarrhalis outer membrane protein CD in bacterial cell morphology and autoaggregation

Moraxella catarrhalis, an important pathogen in the human respiratory tract, causes otitis media and lower respiratory tract infections. M. catarrhalis outer membrane protein CD (OMPCD) is a major heat-modifiable OMP with demonstrable potential as a vaccine candidate. The gene encoding OMPCD of M. catarrhalis strains was subjected to nucleotide sequence analysis and then inactivated by insertional mutagenesis. The ompCD mutant strains exhibited a modest growth defect in comparison with the wild-type strains. In optical microscopy and scanning/transmission electron microscopy examinations, regarding morphology, the cell size and cell wall of the ompCD mutant strains were significantly larger and thinner, respectively, than those of the wild-type strain. Furthermore, the ompCD mutant strains exhibited significant autoaggregation and increased surface hydrophobicity, in addition to a reduction in the adherence to HEp-2 cells, compared to the wild-type strains. Strains repaired by replacing the mutated ompCD gene exhibited phenotypic characteristics very similar to those of the wild-type strains. These results indicate that M. catarrhalis OMPCD, in addition to its functions related to bacterial growth and adherence to human epithelial cells, plays a very important role in bacterial physiology and pathogenesis, including aspects such as stabilizing bacterial cell morphology and preventing autoaggregation by reducing surface hydrophobicity.