Induction of allogeneic tumour- and lymphokine-activated lymphocytes against hepatocellular carcinoma

For clinical application of adoptive immunotherapy against hepatocellular carcinoma (HCC), it is not easy to prepare tumour specific effector cells such as cytotoxic T lymphocytes (CTL). To induce potent and broad-spectrum effectors, allogeneic cultured hepatoma cell lines (JHH-4 and HuH-6) were used as stimulators of peripheral blood lymphocytes (PBL) instead of autologous HCC cells. Allogeneic tumour- and lymphokine-activated killer cells (ATLAK) were generated by a mixed culture of lymphocytes and allogeneic cultured tumour cells with recombinant interleukin-2 (rIL-2). The tumour-killing activity of ATLAK induced by HuH-6 was confirmed against HuH-6 and other different HCC cell lines (JHH-2, HuH-7 and PLC). These activated lymphocytes were significantly more potent than lymphokine-activated killer cells (LAK) in [51Cr]-releasing assay. The JHH-4 stimulated ATLAK was reactive not only with JHH-4 but also with JHH-2. The lysis of allogeneic targets could be partially inhibited by anti-CD8 and anti-CD3 but not by anti-CD4. Anti-tumour cytotoxicity in these cultures might be mediated by CD3+CD56- and CD3+CD56+ effectors. These results imply that adoptive immunotherapy for HCC with ATLAK may be more feasible than that with LAK.     

Results of clinical surveillance during the Japanese first palivizumab season in 2002–2003

BACKGROUND: In Japan, palivizumab was approved in 2002 for prophylaxis of severe respiratory syncytial virus disease in high-risk infants. In order to evaluate the efficacy and safety of this drug, a questionnaire survey was conducted. METHODS: A questionnaire was sent to member institutions of the Japan Neonatologist Association. The subjects were premature infants who were considered possible candidates for treatment with palivizumab. RESULTS: A total of 6302 case reports, including those of 2806 infants receiving palivizumab (group P) and 3496 infants not receiving palivizumab (group NP), respectively, were retrieved. Background characteristics revealed significant lower gestational age (GA) and birthweight for group P (P < 0.0001). Sex ratio did not differ significantly, while use of oxygen and mechanical ventilation in the neonatal intensive care unit, and presence of chronic lung disease were significantly higher for infants in group P (P < 0.0001). When comparison of hospitalization rate for respiratory symptoms was performed with stratification by eligibility criteria, in the group of infants born at 29-35 weeks GA the hospitalization rate was 4.0% and 5.7% in groups P and NP, respectively (P < 0.05). Multivariate analysis also showed that prophylaxis with palivizumab was the only variable that significantly decreased rate of hospitalization (odds ratio 0.630, P= 0.0053). The incidence of adverse events associated with the administration of palivizumab was low. CONCLUSION: In this non-randomized questionnaire survey, multivariate analysis showed that palivizumab significantly decreased the rate of hospitalization due to respiratory symptoms for infants born prematurely at 29-35 weeks GA. These data confirmed the efficacy and safety of palivizumab.     

Oridonin induces human epidermoid carcinoma A431 cell apoptosis through tyrosine kinase and mitochondrial pathway

Oridonin, a diterpenoid isolated from the plant Rabdosia rubescens, induces human epidermoid carcinoma A431 cell death through apoptosis and tyrosine kinase pathway. To examine the pathway of oridonin-induced A431 cell death, morphologic observation, lactate dehydrogenase activity-based assay, DNA agarose gel electrophoresis and Western blot analysis were carried out. When A431 cells, which overexpress epidermal growth factor receptor (EGFR), were treated with oridonin, caspase-3 was activated followed by the degradation of caspase-3 substrates, inhibitor of caspase-activated DNase (ICAD) and poly(ADP-ribose) polymerase (PARP) in a time-dependent manner. Oridonin promoted the release of cytochrome c and the down-regulation of mitochondrial transmembrane potential (ΔΨm). Oridonin up-regulated the expression ratio of mitochondrial proteins, Bax/Bcl-2. In addition, the total tyrosine kinase activity of A431 cellular proteins and the expression of EGFR were markedly reduced after oridonin treatment. Taken together, oridonin induced apoptosis in A431 cells via mitochondrial pathway, activation of caspase-3 and inhibition of tyrosine kinase activities.     

Hemodynamic Consequences of Atrioventricular and Ventriculoatrial Pacing

The effect of atrialventricular versus ventricular pacing and contraction were studied in seven open-chest dogs. Cardiac output, left ventricular, left atrial, right atrial and pulmonary artery pressures were recorded. The right or left ventricular apical areas were consistently superior as ventricular pacing sites.
Appearance of cannon A waves within the pre- or ejection period produced a significant decrease in left ventricular and systemic blood pressure, and cardiac output with a concomitant increase in right atrial, ventricular and pulmonary pressures. Prominent "v" waves were also observed during these periods.
Reducing the basic driving cycle length from 400 to 300 msec caused a marlted deterioration of all hemodynamic parameters with the appearance of mechanical alternans. Random VA conduction or ventricular pacing in the presence of com-plete AV and VA heart block appeared to offer a more favorable hemodynamic result than constant 1:1 VA conduction. It is concluded that maintenance of a physiologic AV interval permitting atrial contraction to appear outside of pre- or ejection period of ventricular systole is an important determinant or ventriculor function during cardiac pacing.